Hospice & Palliative Medicine

Managing heart failure is a challenge. To aid clinicians in this task, the American College of Cardiology Foundation (ACC) and the American Heart Association (AHA) publish evidence-based guidelines, most recently in 2013.¹ Since then, new drugs and devices have been shown to improve survival and reduce hospitalizations.

See related editorial

This paper reviews the ABCs of outpatient management of systolic heart failure (or heart failure with reduced ejection fraction), including the results of major trials and recommendations.

A common and serious condition

Heart failure is a debilitating syndrome that takes a significant physical and mental toll on those affected.

And it is common. An American age 40 or older faces a 20% lifetime risk of heart failure.¹ An estimated 5.1 million Americans have clinical signs and symptoms of heart failure, and 900,000 new cases are diagnosed each year.² By 2030 the prevalence of heart failure is projected to increase by 46%, and 9 million Americans will have been diagnosed with it.²

The severity of heart failure can be described using either the functional classification devised by the New York Heart Association (NYHA; Table 1) or the stages defined by the ACC and AHA.^1,3 Though survival rates have improved, there is a direct correlation between worsening symptoms and death.⁴

Heart failure is the leading cause of hospitalizations annually. It accounts for $30 billion in healthcare costs, with direct medical costs accounting for 68% and another $1.8 billion associated with clinic visits, most often with primary care providers. By 2030, the cost is projected to increase by 127% to $69.7 billion—$244 per person in the United States.²

ACE inhibitors

The renin-angiotensin-aldosterone system has been studied for over 100 years.⁵

In heart failure with reduced ejection fraction, this system is upregulated as an adaptive mechanism to maintain hemodynamic homeostasis.^6–8 However, prolonged activation of the renin-angiotensin-aldosterone system can lead to deleterious cardiovascular effects such as myocyte hypertrophy, myocardial fibrosis, sodium conservation, and fluid overload.^8,9 Angiotensin II is a potent vasoconstrictor and plays a role in cardiovascular remodeling, leading to worsening progression of heart failure.⁶

CONSENSUS (the Cooperative North Scandinavian Enalapril Survival Study) examined the effect of the angiotensin-converting enzyme (ACE) inhibitor enalapril on survival in 253 patients with NYHA class IV heart failure. Participants were randomized to receive either enalapril or placebo. At 6 months, the mortality rate was 26% in the enalapril group vs 44% in the placebo group, an 18% absolute risk reduction and a 41% relative risk reduction (P = .002). At 12 months, the relative risk reduction in mortality was 30% (P = .001).¹⁰

SOLVD (the Study of Left Ventricular Dysfunction) extended the use of ACE inhibitors to all patients with heart failure, not just those in NYHA class IV. It randomized 1,284 patients with heart failure of any NYHA class and an ejection fraction less than 35% to receive either enalapril or placebo, and demonstrated a 16% relative risk reduction in mortality in the enalapril group, with mortality rates of 36% vs 39.7% (P = .0036).¹¹

Recommendations. The benefits of ACE inhibition have been demonstrated in patients with mild, moderate, and severe heart failure. Thus, the guidelines recommend ACE inhibitors (Table 2) for all patients with heart failure with reduced ejection fraction.¹

Angiotensin II receptor blockers

Angiotensin II receptor blockers (ARBs) (Table 3) have been proven to be suitable alternatives for patients with heart failure with reduced ejection fraction who cannot tolerate ACE inhibitors.

Val-HefT (the Valsartan HF Trial)¹² randomized 5,010 patients in a double-blind fashion to receive either valsartan or placebo, with background therapy that included beta-blockers, digoxin, diuretics, and ACE inhibitors. There was a 13% reduction of the combined primary end point of mortality and morbidity and a 24% reduction in heart failure hospitalizations in the valsartan group.¹²

Subgroup analysis compared patients on the basis of use of ACE inhibitors and beta-blockers at study entry. Valsartan had a favorable effect in the subgroups using beta-blockers alone, ACE inhibitors alone, and neither drug. However, when patients received all three (a beta-blocker, an ACE inhibitor, and valsartan), the mortality rate was significantly increased (P = .009).¹² This finding conflicted with those of other studies, which found a small benefit of combining an ACE inhibitor and an ARB.

CHARM-Added (the Candesartan in HF Assessment of Reduction in Mortality and Morbidity trial)¹³ investigated whether adding the ARB candesartan to an ACE inhibitor would improve clinical outcomes. In the study, 2,548 patients in NYHA class II, III, or IV with a left ventricular ejection fraction of less than 40% who were receiving ACE inhibitors were randomized to either candesartan or placebo. The addition of candesartan resulted in a significant reduction in cardiovascular mortality and heart failure hospitalizations, but with the downside of higher rates of hyperkalemia and serum creatinine elevation.¹³

Recommendations. The 2013 guidelines recommend that ARBs be used in patients who cannot tolerate an ACE inhibitor due to cough. However, routine combined use of ARBs, ACE inhibitors, and aldosterone antagonists is not recommended and may cause harm.¹

Aldosterone receptor antagonists

Elevated levels of aldosterone lead to fluid retention, loss of magnesium and potassium, and myocardial fibrosis.

RALES (the Randomized Aldactone Evaluation Study)¹⁴ tested the hypothesis that the aldosterone receptor antagonist spironolactone (25 mg daily) would reduce deaths from all causes in patients with severe heart failure receiving standard medications including an ACE inhibitor. RALES included 1,663 patients in NYHA class III or IV with a left ventricular ejection fraction of 35% or less, randomized to receive 25 mg of spironolactone or matching placebo. This study found a 30% relative risk reduction and an 11% absolute risk reduction in all-cause mortality, a 31% relative risk reduction and a 10% absolute risk reduction in cardiac mortality, and 30% fewer cardiac-related hospitalizations in the spironolactone group.¹⁴

Eplerenone, an aldosterone receptor antagonist that lacks the antiandrogenic side effects of spironolactone, has also been shown to be beneficial. Its efficacy in patients with left ventricular systolic dysfunction was first established in postmyocardial infarction patients.¹⁵

EMPHASIS-HF (the Eplerenone in Mild Patients Hospitalized and Survival Study in Heart Failure)¹⁶ broadened the application of eplerenone (and aldosterone antagonists in general), investigating the effects of eplerenone in 2,737 NYHA class II patients, regardless of ischemic etiology. The composite end point of cardiovascular death or heart failure hospitalization occurred in 18.3% of the eplerenone group vs 25.9% of the placebo group (P < .001). A total of 12.5% of patients in the eplerenone group died, compared with 15.5% in the placebo group (P = .008). Hospitalizations were also fewer in the eplerenone group.

Recommendations. The 2013 guidelines recommend aldosterone receptor antagonists (Table 4) for patients with NYHA class II, III, or IV heart failure who have an ejection fraction of 35% or less, to reduce morbidity and mortality (class IA recommendation).¹ The guidelines also recommend that these agents not be used in patients with renal insufficiency (serum creatinine > 2.5 mg/dL in men or > 2.0 mg/dL in women; an estimated glomerular filtration rate < 30 mL/min/1.73 m²); or a serum potassium level above 5 mmol/L.¹

Angiotensin-neprilysin inhibitor (the future)

Research has identified neprilysin as another potential target in the treatment of heart failure and has sought to combine inhibition of angiotensin and neprilysin.

Neprilysin, a neutral endopeptidase, is associated with degradation of several natural vasoactive peptides such as natriuretic peptide, bradykinin, and adrenomedullin. Neprilysin inhibition increases these substances and counters the neurohormonal overactivation that leads to vasoconstriction, sodium retention, and cardiac remodeling.¹⁷

The ARB valsartan has been combined with the neprilysin inhibitor sacubitril to create the first angiotensin-neprilysin inhibitor (ARNI) (Table 5). The combination was selected to minimize the potential for angioedema.

PARADIGM-HF (the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure trial)¹⁷ examined whether combined angiotensin-neprilysin inhibition was superior to ACE inhibition alone with enalapril in patients with chronic heart failure.

In PARADIGM-HF, 10,521 patients with NYHA class II, III, or IV heart failure were randomized to receive either sacubitril-valsartan or enalapril. The group receiving sacubitril-valsartan had significantly fewer deaths from cardiovascular causes and heart failure hospitalizations.¹⁷ An improvement in quality of life and NYHA functional class was also observed in the sacubitril-valsartan group.¹⁷

Sacubitril-valsartan underwent priority review by the US Food and Drug Administration and has been approved. Currently, it is indicated for the treatment of heart failure with reduced ejection fraction and NYHA class II, III, or IV symptoms. It should be avoided in patients who have previously experienced angioedema with an ACE inhibitor or ARB, in patients receiving aliskiren for diabetes, and in patients with hypersensitivity reactions to either of its components. Simultaneous use of sacubitril-valsartan and an ACE inhibitor should be avoided, and a washout period is recommended when transitioning from an ACE inhibitor to this combined agent.

Beta-blockers

In heart failure, there is increased sympathetic activation and associated elevations in norepinephrine levels, which may lead to deleterious long-term effects on cardiac function and structure. Beta-adrenergic receptor blockade is now known to be cardioprotective, but it was not always so; beta-blockers used to be contraindicated in patients with heart failure.

An early experience using beta-blockers in heart failure was described in 1975.^18,19 The first study to report a survival benefit of treating systolic heart failure with a beta-blocker was published in 1979.²⁰ Later, small controlled trials demonstrated a reduction in heart failure symptoms and improvement in left ventricular function and in NYHA functional class.²¹ Larger clinical trials have demonstrated a tremendous survival benefit with beta-blockers in heart failure, specifically carvedilol, extended-release metoprolol, and bisoprolol.

The US Carvedilol Heart Failure Study Group trial²² evaluated whether beta-blocker use in heart failure patients would reduce the rates of morbidity and mortality.²² The trial included 1,094 patients with symptomatic heart failure for at least 3 months and a left ventricular ejection fraction of 35% or less on background therapy including vasodilators, ACE inhibitors, and digoxin. Patients were randomized to receive either carvedilol or placebo. Carvedilol use was associated with a dramatic 65% risk reduction in mortality (7.8% with placebo vs 3.2% with carvedilol, P < .001) and a 27% risk reduction in hospitalizations (19.6% vs 14.1%, P = .036), leading to early trial termination.

CIBIS-II (the Cardiac Insufficiency Bisoprolol Study II)²³ investigated the effects of beta-blockers on survival and morbidity. CIBIS-II included 2,647 NYHA class III or IV patients with a left ventricular ejection fraction less than 35% on background medical therapy that included diuretics and ACE inhibitors. This trial was also terminated early, after demonstrating a significant survival benefit with bisoprolol.

MERIT-HF (the Metoprolol Extended Release Randomized Intervention Trial in Congestive Heart Failure)²⁴ evaluated if once-daily metoprolol would lower mortality rates  in patients with symptomatic heart failure. The study enrolled 3,991 NYHA class II–IV patients with chronic heart failure and a left ventricular ejection fraction of 40% or less. Like the previous two beta-blocker trials, MERIT-HF was terminated early, as it demonstrated a 34% reduction in all-cause mortality (7.2% risk of death per patient-year vs 11.0%, P = .00009).

The beta-blocker trials have shown that when added to background therapy, beta-blockers improve survival and reduce hospitalizations. However, when prescribing a beta-blocker, it is important to understand that not all beta-blockers are equal in the treatment of heart failure.

COMET (the Carvedilol or Metoprolol European Trial)²⁵ was the only head-to-head randomized control trial evaluating clinical outcomes in patients receiving carvedilol or metoprolol tartrate (not metoprolol succinate). In COMET, 1,511 patients with NYHA class II, III, or IV heart failure with a left ventricular ejection fraction of 35% or less were randomized to carvedilol or metoprolol tartrate. The primary end point of all-cause mortality occurred in 34% of the carvedilol group and 40% of the metoprolol tartrate group (P = .0017). There was no significant difference with regard to the composite end point of mortality and all-cause admissions.

Recommendations. The 2013 guidelines give a class IA recommendation for starting a beta-blocker (carvedilol, bisoprolol, or metoprolol succinate, Table 6) in patients with current or prior symptoms of heart failure.¹ Beta-blockers should be initiated with caution or avoided in patients with acutely decompensated heart failure with evidence of fluid overload.

Brain-type natriuretic peptide

Brain-type natriuretic peptide (BNP) or its amino-terminal cleavage product (NT-proBNP) originates in cardiomyocytes and is released by several triggers, most commonly cardiomyocyte stretch in the setting of volume or pressure overload.²⁶ The biologic significance of BNP includes natriuresis and vasodilation, renin-angiotensin system inhibition, and sympathetic nervous system modulation.²⁶

TIME-CHF (the Trial of Intensified vs. Standard Medical Therapy in Elderly Patients With Congestive HF)²⁷ investigated whether 18-month outcomes would be better if treatment were guided by N-terminal BNP levels rather than by symptoms. The BNP-guided strategy was not associated with a reduction in hospitalization or a survival benefit.

BATTLESCARRED (the NT-proBNP-Assisted Treatment to Lessen Serial Cardiac Readmissions and Death trial)²⁸ in 2009 showed that a BNP-guided management strategy significantly reduced mortality rates in patients under age 75 compared with standard medical therapy.

PROTECT (the Use of NT-proBNP Testing to Guide HF Therapy in the Outpatient Setting study)²⁹ also showed that a BNP-guided strategy was superior to usual care and was associated with reduced cardiovascular events and improved quality of life.²⁹

GUIDE IT-HF (the Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure study), currently ongoing, is designed to assess the safety, efficacy and cost-effectiveness of a biomarker-guided strategy in 1,100 high-risk patients with heart failure with reduced ejection fraction. 

Recommendations. The 2013 ACC/AHA guidelines give a class IA recommendation for the use of BNP to support clinical decision-making, particularly in cases of clinical uncertainty.¹ BNP can also be used to establish prognosis or disease severity in chronic heart failure and to achieve optimal dosage of goal-directed medical therapy for euvolemic patients followed in a structured heart failure program.¹

Heart failure clinics

Continuity of care upon discharge from the hospital is currently in a state of evolution. Those diagnosed with heart failure can now experience more comprehensive posthospital care by virtue of disease management clinics. The name may vary by institution, but whether it is called a “diuresis clinic,” “bridge clinic,” or “heart failure clinic,” the goal is to improve guideline-driven care, educate the patient, and reduce heart failure hospitalizations. Heart failure clinics are designed to provide a smooth transition from inpatient to outpatient care and to encourage patient self-accountability in health maintenance thereafter.

Studies have shown that heart failure clinics are associated with better medication dosing, fewer hospitalizations, and lower healthcare costs.^30–32

Chronotropy: I_f inhibition

An elevated resting heart rate has been shown to be associated with increased cardiovascular morbidity and mortality.³³ Studies have shown that slowing the heart rate improves myocardial contraction and energy supply and reduces energy expenditure.³⁴ Ivabradine, a selective I_f (the f is for “funny”) channel inhibitor, slows the heart rate without other known cardiovascular effects.

SHIFT (the Systolic Heart Failure Treatment With the I_f Inhibitor Ivabradine Trial)³⁵ investigated whether isolated heart rate reduction with ivabradine would reduce adverse clinical outcomes in patients with symptomatic heart failure. SHIFT randomized 6,505 patients with a left ventricular ejection fraction of 35% or less, in sinus rhythm, with a heart rate of at least 70 beats per minute, on optimal medical therapy, and hospitalized within 12 months of enrollment to receive ivabradine or placebo. The primary end point was a composite of cardiovascular mortality and hospital admission for worsening heart failure. Outcomes varied by heart rates achieved, with the best outcomes in those with the lowest heart rates at trial conclusion.

Ivabradine (Table 7) is indicated for patients with symptomatic heart failure with a left ventricular ejection fraction less than 35%, in sinus rhythm, with a resting heart rate of at least 70 beats per minute, and either on a maximally tolerated beta-blocker or with a contraindication to beta-blockers.

Ivabradine should be avoided in patients who are in acute decompensated heart failure or are hypotensive (blood pressure < 90/50 mm Hg), as well as in patients with a significant conduction abnormality (sick sinus syndrome, sinoatrial block, third-degree atrioventricular block), hepatic impairment, or bradycardia (resting heart rate < 60 beats per minute).

Digoxin

Digoxin has been used in treating systolic heart failure for more than 70 years.^36,37

DIG (Digoxin Investigative Group trial)³⁸ evaluated the long-term effect of digoxin on rates of mortality and hospitalization for heart failure over a 3-year period. In patients with  a left ventricular ejection fraction less than 45%, digoxin had no effect on overall mortality when combined with diuretics and ACE inhibitors. However, the risk of hospitalization for worsening heart failure was significantly reduced with digoxin treatment.³⁸

Recommendations. Digoxin should be considered when patients are on guideline-recommended therapy but heart failure symptoms persist. It is commonly initiated at a dose of 0.125 to 0.25 mg. The target therapeutic range for digoxin is 0.5 to 0.9 ng/mL.¹ Digoxin toxicity can occur in patients with renal impairment, hypokalemia, hypomagnesemia, and hypothyroidism.

The 2013 ACC/AHA guidelines give a class IIA recommendation (treatment is “reasonable”) for digoxin in patients with heart failure with reduced ejection fraction unless contraindicated, to decrease hospitalizations for heart failure.¹

Diuretics

Clinical manifestations of volume overload in patients with heart failure are from excess salt and water retention leading to inappropriate volume expansion in both the vascular and extravascular space. Diuretics (Table 8) are the foundation of heart failure treatment. Most patients are first initiated on a combination of a loop diuretic and a low-sodium diet to improve symptoms.

The 2013 ACC/AHA guidelines give a class I recommendation for diuretics in patients with heart failure with reduced ejection fraction who have evidence of fluid retention, unless contraindicated, to improve symptoms.¹

Devices: ICDs

Patients with heart failure are at increased risk of sudden death and ventricular arrhythmias.³⁹ Previously, antiarrhythmic drugs were considered the standard of care for nonsustained ventricular tachycardia after myocardial infarction.

MADIT (the Multicenter Automatic Defibrillator Implantation Trial) investigated whether prophylactic implantation of an internal cardiac defibrillator would improve 5-year survival rates in patients with heart failure. Eligible patients had had a Q-wave or enzyme-positive myocardial infarction within 3 weeks of study entry. They also had had an episode of asymptomatic nonsustained ventricular tachycardia unrelated to an acute myocardial infarction. Additionally, the patients had a left ventricular ejection fraction less than 35%, and inducible, sustained, nonsuppressible ventricular tachyarrhythmia on electrophysiologic testing.⁴⁰

During the study, 15 patients in the defibrillator group died vs 39 in the conventional therapy group (P = .009).⁴⁰

MADIT II evaluated the potential survival benefit of a prophylactically implanted defibrillator in the absence of electrophysiologic testing to induce arrhythmias.⁴¹ MADIT II included 1,232 patients with prior myocardial infarctions and a left ventricular ejection fracton of 30% or less. Patients were randomized to receive an implanted cardioverter-defibrillator or conventional medical therapy. The primary end point was death from any cause.⁴¹

The mortality rate was 19.8% in the conventional therapy group vs 14.2% in the defibrillator group (hazard ratio 0.69, P = .016).⁴¹ Thus, MADIT-II confirmed the benefits of prophylactic implantable cardioverter-defibrillator therapy seen in the original MADIT, and additionally eliminated the need for an electrophysiology test prior to device implantation.

SCD-HeFT (the Sudden Cardiac Death in Heart Failure Trial) evaluated whether amiodarone or a conservatively programmed shock-only, single-lead implanted cardioverter-defibrillator would decrease the risk of death (all-cause) in a population with mild to moderate heart failure with ischemic and nonischemic causes.⁴² In this trial, 2,521 patients with an ejection fraction of 35% or less, in NYHA class II or III, and with stable heart failure were randomized to receive a single-chamber implantable cardioverter-defibrillator,  amiodarone, or placebo.

There were 244 deaths in the placebo group, 240 deaths in the amiodarone group (P = .53 compared with placebo), and 182 deaths in the defibrillator group (P = .007 compared with placebo).⁴²

Recommendations. The 2013 ACC/AHA guideline¹ gives implantable defibrillator therapy a class IA recommendation for the primary prevention of sudden cardiac death in selected patients with nonischemic cardiomyopathy or ischemic cardiomyopathy at least 40 days after a myocardial infarction and 90 days after percutaneous coronary intervention or coronary artery bypass grafting; with a left ventricular ejection fraction of 35% or less; and NYHA class II or III symptoms on chronic goal-directed medical management.

This therapy receives a class IB recommendation for primary prevention of sudden cardiac death to reduce total mortality in selected patients at least 40 days after myocardial infarction with a left ventricular ejection fraction of 30% or less and NYHA class I symptoms while receiving goal-directed medical therapy.

Implantable cardioverter-defibrillators are not recommended in patients who otherwise have a life expectancy of less than 1 year.

Devices: Cardiac resynchronization therapy

From 25% to 30% of heart failure patients have an intraventricular conduction abnormality,^43,44 which can result in abnormalities of systolic and diastolic function. Biventricular pacing, in which a pacing lead is placed in the coronary sinus in addition to the right atrium and right ventricle, optimizes synchronization of ventricular contraction.^43,44

MUSTIC (the Multisite Stimulation in Cardiomyopathies study) was a randomized trial designed to assess the efficacy of biventricular pacing (also known as cardiac resynchronization therapy) in heart failure patients.⁴⁴ Entry criteria included NYHA class III heart failure for at least 1 month, left ventricular ejection fraction less than 35%, left ventricular end-diastolic diameter greater than 60 mm, and QRS duration longer than 150 ms. Patients were followed up at 9 and 12 months with 6-minute walking distance, peak oxygen consumption, changes in NYHA class, and left ventricular systolic function by echocardiography or radionuclide testing. Quality of life was assessed by the Minnesota Living With Heart Failure Questionnaire.

At 12 months, patients could walk significantly farther in 6 minutes, and their peak oxygen consumption had increased. They also reported significant improvement in quality of life, and NYHA class improved by 25%. MUSTIC was the first study to show a benefit in exercise tolerance, quality of life, improvement in cardiac performance, and reduction in heart failure symptoms with the use of biventricular pacing at 1 year.

MIRACLE (the Multicenter InSync Randomized Clinical Evaluation) validated the findings seen in MUSTIC by using a larger population size and a double-blinded method.⁴⁵ Compared with a control group, patients who underwent cardiac resynchronization therapy could walk farther in 6 minutes and scored better in NYHA class, quality of life, and left ventricular ejection fraction.⁴⁵

Recommendations. The 2013 ACC/AHA guidelines¹ give cardiac resynchronization therapy a class IA/B indication for NYHA class II, III, or IV patients on goal-directed medical therapy in sinus rhythm with left ventricular ejection fraction 35% or less, left bundle branch block, and QRS duration of 150 ms or more.¹

Devices: Implantable sensors

The future of ambulatory heart failure management may include implantable pulmonary artery pressure sensors.

The CardioMEMS is a permanently implantable pressure measurement system designed to provide daily pulmonary artery pressure measurements in an ambulatory setting with a goal of reducing heart failure-related hospitalizations. Through a transvenous delivery system, an implantable, battery-free sensor is positioned in the distal pulmonary artery.^46,47

CHAMPION (the CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Patients trial) was one of the first major trials to assess the safety and efficacy of implantable pulmonary artery pressure monitoring systems.⁴⁶ The study device was associated with a significant reduction in mean pulmonary artery pressures, fewer heart failure hospitalizations, and better quality of life. The length of stay for heart failure-related hospitalizations was also significantly shorter in the CardioMEMs group.⁴⁶

Exercise

Patients with heart failure routinely experience a decline in functional capacity. This decline manifests as reduced exercise tolerance and poor quality of life, usually resulting in a physician recommendation to rest and paradoxical deconditioning and possible progression of symptoms.

Several studies have shown that cardiac rehabilitation has improved outcomes in heart failure patients.⁴⁸ Cardiac rehabilitation is a supervised program that helps patients with exercise training, healthy living, education, and psychosocial counseling.

HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) is the largest randomized trial performed to determine whether aerobic exercise training reduces all-cause mortality or all-cause hospitalization and improves quality of life in patients with stable heart failure.⁴⁹ Although the reduction in end points was initially not statistically significant, after adjusting for highly prognostic predictors of poor outcomes (cardiopulmonary exercise time, left ventricular ejection fraction, atrial fibrillation, and depression), exercise training was found to reduce the incidence of all-cause mortality or all-cause hospitalization by 11% (P = .03).⁴⁹

Recommendations. Based on the results of HF-ACTION and several smaller studies, the ACC/AHA guidelines give exercise training a class IA recommendation as a safe and effective activity for patients with heart failure who are able to participate, to improve functional status.¹ A class IIA recommendation is given to cardiac rehabilitation for the improvement of functional capacity, exercise duration, quality of life, and mortality rates.¹

End-stage heart failure: Recognition

Despite adequate titration of goal-directed medical therapy, a portion of patients with heart failure with reduced ejection fraction ultimately progress to stage D, also termed “advanced” heart failure. The 5-year survival rate for patients with heart failure overall is 50%, but the 1-year mortality rate for those with advanced heart failure exceeds 50%.⁵⁰

Because the high rates of morbidity and mortality can potentially be lowered, recognition of heart failure disease progression is imperative so that patients can be promptly referred for therapies such as inotropic infusion, mechanical circulatory support, and cardiac transplant, as well as end-of-life care such as hospice.¹

The ACC/AHA¹ have published clinical events and findings useful in identifying patients with advanced heart failure:

• Two or more hospitalizations or emergency department visits for heart failure in the past year
• Progressive deterioration in renal function (eg, elevation in creatinine or blood urea nitrogen)
• Weight loss without other cause
• Intolerance to ACE inhibitors due to hypotension or worsening renal function
• Inability to tolerate beta-blockers due to worsening heart failure or hypotension
• Systolic blood pressure often below 90 mm Hg
• Persistent dyspnea with dressing or bathing requiring rest
• Inability to walk one block on level ground due to dyspnea or fatigue
• Recent need to escalate diuretics to maintain volume status, often reaching daily dose equivalent to furosemide more than 160 mg/day or use of supplemental metolazone
• Progressive decline in serum sodium, usually to below 133 mmol/L
• Frequent shocks from implanted cardiac defibrillator.

End-stage heart failure: Left ventricular assist devices

For patients with refractory heart failure despite optimal medical management, advanced therapies such as heart transplant or ventricular assist devices have been proven to be durable options. These mechanical circulatory support devices “unload” the diseased ventricle and maintain cardiac output to vital organs.⁵¹ They were initially designed as temporary support to allow ventricular recovery or as a bridge to cardiac transplant. However, they have also evolved into permanent (“destination”) therapy.⁵²

REMATCH (the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive HF trial) was the landmark study that showed that left ventricular assist device implantation resulted in a survival benefit and an improved quality of life in patients with advanced heart failure ineligible for cardiac transplant, compared with medical management.⁵⁰ Implantation of a left ventricular assist device was associated with a 27% absolute reduction in the 1-year mortality rate.⁵⁰

Since the National Institutes of Health’s artificial heart program was launched in 1964, there has been tremendous progress in the development of mechanical circulatory devices.⁵⁰ The results of REMATCH were promising, but the 2-year survival rate was still only 23%, leaving a lot to be desired.

The HeartMate II (Thoratec) trial compared an axial continuous-flow device vs the previously established pulsatile left ventricular assist device, and noted a 2-year survival of 58% with the continuous flow device vs  24% with the pulsatile device (P = .008).⁵³

ADVANCE (Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure) showed similar efficacy of the HVAD (Heartware), a centrifugal continuous-flow LVAD currently in use.⁵⁴

The next generation of continuous-flow left ventricular assist devices are currently in clinical trials in the United States and include the axial flow MVAD (Heartware) and centrifugal flow Heartmate III (Thoratec).

We emphasize the importance of early identification of patients with advanced disease who may qualify for and benefit from such therapies.

The management of heart failure is evolving. In the 1960s, the standard heart failure medical regimen included digoxin, diuretics, and the recommendation of rest. This contrasts with the current era, in which medical regimens include neurohormonal blockade, diuretics, and the promotion of physical activity.⁵⁵ Since the publication of the 2013 heart failure guidelines, new medical and device options have emerged that have been proven to either improve survival or reduce hospitalizations. The development of clinical guidelines promotes evidence-based practice and overcomes the inertia of practice patterns based on anecdotal evidence.

Several approaches to the management of heart failure have been recommended. A major effort should be made to identify those at risk for heart failure (stage A) and to implement risk factor modification. Treatment of hypertension, diabetes mellitus, and dyslipidemia decreases the risk of heart failure.¹

For patients with evidence of structural heart disease with and without symptoms, Figure 1 summarizes a guideline approach to the management of heart failure. It should be stressed that guidelines are meant to guide management, but do not serve as a substitute for sound clinical judgment.

Heart failure is the common final pathway of all cardiac pathology, and understanding the neurohormonal response and maladaptive physiology has led to the development of novel therapeutics and devices. At present, the field of cardiology may not be able to remove the “failure” from heart failure, but we can make every effort to prevent failure of treatment delivery and reduce resource utilization and morbidity associated with this syndrome.

Acknowledgments: We would like to thank Chankya Dahagam and Cynthia Obenwa for their valuable contribution in the preparation of this manuscript.

Managing heart failure is a challenge. To aid clinicians in this task, the American College of Cardiology Foundation (ACC) and the American Heart Association (AHA) publish evidence-based guidelines, most recently in 2013.¹ Since then, new drugs and devices have been shown to improve survival and reduce hospitalizations.

See related editorial

This paper reviews the ABCs of outpatient management of systolic heart failure (or heart failure with reduced ejection fraction), including the results of major trials and recommendations.

A common and serious condition

Heart failure is a debilitating syndrome that takes a significant physical and mental toll on those affected.

And it is common. An American age 40 or older faces a 20% lifetime risk of heart failure.¹ An estimated 5.1 million Americans have clinical signs and symptoms of heart failure, and 900,000 new cases are diagnosed each year.² By 2030 the prevalence of heart failure is projected to increase by 46%, and 9 million Americans will have been diagnosed with it.²

The severity of heart failure can be described using either the functional classification devised by the New York Heart Association (NYHA; Table 1) or the stages defined by the ACC and AHA.^1,3 Though survival rates have improved, there is a direct correlation between worsening symptoms and death.⁴

Heart failure is the leading cause of hospitalizations annually. It accounts for $30 billion in healthcare costs, with direct medical costs accounting for 68% and another $1.8 billion associated with clinic visits, most often with primary care providers. By 2030, the cost is projected to increase by 127% to $69.7 billion—$244 per person in the United States.²

ACE inhibitors

The renin-angiotensin-aldosterone system has been studied for over 100 years.⁵

In heart failure with reduced ejection fraction, this system is upregulated as an adaptive mechanism to maintain hemodynamic homeostasis.^6–8 However, prolonged activation of the renin-angiotensin-aldosterone system can lead to deleterious cardiovascular effects such as myocyte hypertrophy, myocardial fibrosis, sodium conservation, and fluid overload.^8,9 Angiotensin II is a potent vasoconstrictor and plays a role in cardiovascular remodeling, leading to worsening progression of heart failure.⁶

CONSENSUS (the Cooperative North Scandinavian Enalapril Survival Study) examined the effect of the angiotensin-converting enzyme (ACE) inhibitor enalapril on survival in 253 patients with NYHA class IV heart failure. Participants were randomized to receive either enalapril or placebo. At 6 months, the mortality rate was 26% in the enalapril group vs 44% in the placebo group, an 18% absolute risk reduction and a 41% relative risk reduction (P = .002). At 12 months, the relative risk reduction in mortality was 30% (P = .001).¹⁰

SOLVD (the Study of Left Ventricular Dysfunction) extended the use of ACE inhibitors to all patients with heart failure, not just those in NYHA class IV. It randomized 1,284 patients with heart failure of any NYHA class and an ejection fraction less than 35% to receive either enalapril or placebo, and demonstrated a 16% relative risk reduction in mortality in the enalapril group, with mortality rates of 36% vs 39.7% (P = .0036).¹¹

Recommendations. The benefits of ACE inhibition have been demonstrated in patients with mild, moderate, and severe heart failure. Thus, the guidelines recommend ACE inhibitors (Table 2) for all patients with heart failure with reduced ejection fraction.¹

Angiotensin II receptor blockers

Angiotensin II receptor blockers (ARBs) (Table 3) have been proven to be suitable alternatives for patients with heart failure with reduced ejection fraction who cannot tolerate ACE inhibitors.

Val-HefT (the Valsartan HF Trial)¹² randomized 5,010 patients in a double-blind fashion to receive either valsartan or placebo, with background therapy that included beta-blockers, digoxin, diuretics, and ACE inhibitors. There was a 13% reduction of the combined primary end point of mortality and morbidity and a 24% reduction in heart failure hospitalizations in the valsartan group.¹²

Subgroup analysis compared patients on the basis of use of ACE inhibitors and beta-blockers at study entry. Valsartan had a favorable effect in the subgroups using beta-blockers alone, ACE inhibitors alone, and neither drug. However, when patients received all three (a beta-blocker, an ACE inhibitor, and valsartan), the mortality rate was significantly increased (P = .009).¹² This finding conflicted with those of other studies, which found a small benefit of combining an ACE inhibitor and an ARB.

CHARM-Added (the Candesartan in HF Assessment of Reduction in Mortality and Morbidity trial)¹³ investigated whether adding the ARB candesartan to an ACE inhibitor would improve clinical outcomes. In the study, 2,548 patients in NYHA class II, III, or IV with a left ventricular ejection fraction of less than 40% who were receiving ACE inhibitors were randomized to either candesartan or placebo. The addition of candesartan resulted in a significant reduction in cardiovascular mortality and heart failure hospitalizations, but with the downside of higher rates of hyperkalemia and serum creatinine elevation.¹³

Recommendations. The 2013 guidelines recommend that ARBs be used in patients who cannot tolerate an ACE inhibitor due to cough. However, routine combined use of ARBs, ACE inhibitors, and aldosterone antagonists is not recommended and may cause harm.¹

Aldosterone receptor antagonists

Elevated levels of aldosterone lead to fluid retention, loss of magnesium and potassium, and myocardial fibrosis.

RALES (the Randomized Aldactone Evaluation Study)¹⁴ tested the hypothesis that the aldosterone receptor antagonist spironolactone (25 mg daily) would reduce deaths from all causes in patients with severe heart failure receiving standard medications including an ACE inhibitor. RALES included 1,663 patients in NYHA class III or IV with a left ventricular ejection fraction of 35% or less, randomized to receive 25 mg of spironolactone or matching placebo. This study found a 30% relative risk reduction and an 11% absolute risk reduction in all-cause mortality, a 31% relative risk reduction and a 10% absolute risk reduction in cardiac mortality, and 30% fewer cardiac-related hospitalizations in the spironolactone group.¹⁴

Eplerenone, an aldosterone receptor antagonist that lacks the antiandrogenic side effects of spironolactone, has also been shown to be beneficial. Its efficacy in patients with left ventricular systolic dysfunction was first established in postmyocardial infarction patients.¹⁵

EMPHASIS-HF (the Eplerenone in Mild Patients Hospitalized and Survival Study in Heart Failure)¹⁶ broadened the application of eplerenone (and aldosterone antagonists in general), investigating the effects of eplerenone in 2,737 NYHA class II patients, regardless of ischemic etiology. The composite end point of cardiovascular death or heart failure hospitalization occurred in 18.3% of the eplerenone group vs 25.9% of the placebo group (P < .001). A total of 12.5% of patients in the eplerenone group died, compared with 15.5% in the placebo group (P = .008). Hospitalizations were also fewer in the eplerenone group.

Recommendations. The 2013 guidelines recommend aldosterone receptor antagonists (Table 4) for patients with NYHA class II, III, or IV heart failure who have an ejection fraction of 35% or less, to reduce morbidity and mortality (class IA recommendation).¹ The guidelines also recommend that these agents not be used in patients with renal insufficiency (serum creatinine > 2.5 mg/dL in men or > 2.0 mg/dL in women; an estimated glomerular filtration rate < 30 mL/min/1.73 m²); or a serum potassium level above 5 mmol/L.¹

Angiotensin-neprilysin inhibitor (the future)

Research has identified neprilysin as another potential target in the treatment of heart failure and has sought to combine inhibition of angiotensin and neprilysin.

Neprilysin, a neutral endopeptidase, is associated with degradation of several natural vasoactive peptides such as natriuretic peptide, bradykinin, and adrenomedullin. Neprilysin inhibition increases these substances and counters the neurohormonal overactivation that leads to vasoconstriction, sodium retention, and cardiac remodeling.¹⁷

The ARB valsartan has been combined with the neprilysin inhibitor sacubitril to create the first angiotensin-neprilysin inhibitor (ARNI) (Table 5). The combination was selected to minimize the potential for angioedema.

PARADIGM-HF (the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure trial)¹⁷ examined whether combined angiotensin-neprilysin inhibition was superior to ACE inhibition alone with enalapril in patients with chronic heart failure.

In PARADIGM-HF, 10,521 patients with NYHA class II, III, or IV heart failure were randomized to receive either sacubitril-valsartan or enalapril. The group receiving sacubitril-valsartan had significantly fewer deaths from cardiovascular causes and heart failure hospitalizations.¹⁷ An improvement in quality of life and NYHA functional class was also observed in the sacubitril-valsartan group.¹⁷

Sacubitril-valsartan underwent priority review by the US Food and Drug Administration and has been approved. Currently, it is indicated for the treatment of heart failure with reduced ejection fraction and NYHA class II, III, or IV symptoms. It should be avoided in patients who have previously experienced angioedema with an ACE inhibitor or ARB, in patients receiving aliskiren for diabetes, and in patients with hypersensitivity reactions to either of its components. Simultaneous use of sacubitril-valsartan and an ACE inhibitor should be avoided, and a washout period is recommended when transitioning from an ACE inhibitor to this combined agent.

Beta-blockers

In heart failure, there is increased sympathetic activation and associated elevations in norepinephrine levels, which may lead to deleterious long-term effects on cardiac function and structure. Beta-adrenergic receptor blockade is now known to be cardioprotective, but it was not always so; beta-blockers used to be contraindicated in patients with heart failure.

An early experience using beta-blockers in heart failure was described in 1975.^18,19 The first study to report a survival benefit of treating systolic heart failure with a beta-blocker was published in 1979.²⁰ Later, small controlled trials demonstrated a reduction in heart failure symptoms and improvement in left ventricular function and in NYHA functional class.²¹ Larger clinical trials have demonstrated a tremendous survival benefit with beta-blockers in heart failure, specifically carvedilol, extended-release metoprolol, and bisoprolol.

The US Carvedilol Heart Failure Study Group trial²² evaluated whether beta-blocker use in heart failure patients would reduce the rates of morbidity and mortality.²² The trial included 1,094 patients with symptomatic heart failure for at least 3 months and a left ventricular ejection fraction of 35% or less on background therapy including vasodilators, ACE inhibitors, and digoxin. Patients were randomized to receive either carvedilol or placebo. Carvedilol use was associated with a dramatic 65% risk reduction in mortality (7.8% with placebo vs 3.2% with carvedilol, P < .001) and a 27% risk reduction in hospitalizations (19.6% vs 14.1%, P = .036), leading to early trial termination.

CIBIS-II (the Cardiac Insufficiency Bisoprolol Study II)²³ investigated the effects of beta-blockers on survival and morbidity. CIBIS-II included 2,647 NYHA class III or IV patients with a left ventricular ejection fraction less than 35% on background medical therapy that included diuretics and ACE inhibitors. This trial was also terminated early, after demonstrating a significant survival benefit with bisoprolol.

MERIT-HF (the Metoprolol Extended Release Randomized Intervention Trial in Congestive Heart Failure)²⁴ evaluated if once-daily metoprolol would lower mortality rates  in patients with symptomatic heart failure. The study enrolled 3,991 NYHA class II–IV patients with chronic heart failure and a left ventricular ejection fraction of 40% or less. Like the previous two beta-blocker trials, MERIT-HF was terminated early, as it demonstrated a 34% reduction in all-cause mortality (7.2% risk of death per patient-year vs 11.0%, P = .00009).

The beta-blocker trials have shown that when added to background therapy, beta-blockers improve survival and reduce hospitalizations. However, when prescribing a beta-blocker, it is important to understand that not all beta-blockers are equal in the treatment of heart failure.

COMET (the Carvedilol or Metoprolol European Trial)²⁵ was the only head-to-head randomized control trial evaluating clinical outcomes in patients receiving carvedilol or metoprolol tartrate (not metoprolol succinate). In COMET, 1,511 patients with NYHA class II, III, or IV heart failure with a left ventricular ejection fraction of 35% or less were randomized to carvedilol or metoprolol tartrate. The primary end point of all-cause mortality occurred in 34% of the carvedilol group and 40% of the metoprolol tartrate group (P = .0017). There was no significant difference with regard to the composite end point of mortality and all-cause admissions.

Recommendations. The 2013 guidelines give a class IA recommendation for starting a beta-blocker (carvedilol, bisoprolol, or metoprolol succinate, Table 6) in patients with current or prior symptoms of heart failure.¹ Beta-blockers should be initiated with caution or avoided in patients with acutely decompensated heart failure with evidence of fluid overload.

Brain-type natriuretic peptide

Brain-type natriuretic peptide (BNP) or its amino-terminal cleavage product (NT-proBNP) originates in cardiomyocytes and is released by several triggers, most commonly cardiomyocyte stretch in the setting of volume or pressure overload.²⁶ The biologic significance of BNP includes natriuresis and vasodilation, renin-angiotensin system inhibition, and sympathetic nervous system modulation.²⁶

TIME-CHF (the Trial of Intensified vs. Standard Medical Therapy in Elderly Patients With Congestive HF)²⁷ investigated whether 18-month outcomes would be better if treatment were guided by N-terminal BNP levels rather than by symptoms. The BNP-guided strategy was not associated with a reduction in hospitalization or a survival benefit.

BATTLESCARRED (the NT-proBNP-Assisted Treatment to Lessen Serial Cardiac Readmissions and Death trial)²⁸ in 2009 showed that a BNP-guided management strategy significantly reduced mortality rates in patients under age 75 compared with standard medical therapy.

PROTECT (the Use of NT-proBNP Testing to Guide HF Therapy in the Outpatient Setting study)²⁹ also showed that a BNP-guided strategy was superior to usual care and was associated with reduced cardiovascular events and improved quality of life.²⁹

GUIDE IT-HF (the Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure study), currently ongoing, is designed to assess the safety, efficacy and cost-effectiveness of a biomarker-guided strategy in 1,100 high-risk patients with heart failure with reduced ejection fraction. 

Recommendations. The 2013 ACC/AHA guidelines give a class IA recommendation for the use of BNP to support clinical decision-making, particularly in cases of clinical uncertainty.¹ BNP can also be used to establish prognosis or disease severity in chronic heart failure and to achieve optimal dosage of goal-directed medical therapy for euvolemic patients followed in a structured heart failure program.¹

Heart failure clinics

Continuity of care upon discharge from the hospital is currently in a state of evolution. Those diagnosed with heart failure can now experience more comprehensive posthospital care by virtue of disease management clinics. The name may vary by institution, but whether it is called a “diuresis clinic,” “bridge clinic,” or “heart failure clinic,” the goal is to improve guideline-driven care, educate the patient, and reduce heart failure hospitalizations. Heart failure clinics are designed to provide a smooth transition from inpatient to outpatient care and to encourage patient self-accountability in health maintenance thereafter.

Studies have shown that heart failure clinics are associated with better medication dosing, fewer hospitalizations, and lower healthcare costs.^30–32

Chronotropy: I_f inhibition

An elevated resting heart rate has been shown to be associated with increased cardiovascular morbidity and mortality.³³ Studies have shown that slowing the heart rate improves myocardial contraction and energy supply and reduces energy expenditure.³⁴ Ivabradine, a selective I_f (the f is for “funny”) channel inhibitor, slows the heart rate without other known cardiovascular effects.

SHIFT (the Systolic Heart Failure Treatment With the I_f Inhibitor Ivabradine Trial)³⁵ investigated whether isolated heart rate reduction with ivabradine would reduce adverse clinical outcomes in patients with symptomatic heart failure. SHIFT randomized 6,505 patients with a left ventricular ejection fraction of 35% or less, in sinus rhythm, with a heart rate of at least 70 beats per minute, on optimal medical therapy, and hospitalized within 12 months of enrollment to receive ivabradine or placebo. The primary end point was a composite of cardiovascular mortality and hospital admission for worsening heart failure. Outcomes varied by heart rates achieved, with the best outcomes in those with the lowest heart rates at trial conclusion.

Ivabradine (Table 7) is indicated for patients with symptomatic heart failure with a left ventricular ejection fraction less than 35%, in sinus rhythm, with a resting heart rate of at least 70 beats per minute, and either on a maximally tolerated beta-blocker or with a contraindication to beta-blockers.

Ivabradine should be avoided in patients who are in acute decompensated heart failure or are hypotensive (blood pressure < 90/50 mm Hg), as well as in patients with a significant conduction abnormality (sick sinus syndrome, sinoatrial block, third-degree atrioventricular block), hepatic impairment, or bradycardia (resting heart rate < 60 beats per minute).

Digoxin

Digoxin has been used in treating systolic heart failure for more than 70 years.^36,37

DIG (Digoxin Investigative Group trial)³⁸ evaluated the long-term effect of digoxin on rates of mortality and hospitalization for heart failure over a 3-year period. In patients with  a left ventricular ejection fraction less than 45%, digoxin had no effect on overall mortality when combined with diuretics and ACE inhibitors. However, the risk of hospitalization for worsening heart failure was significantly reduced with digoxin treatment.³⁸

Recommendations. Digoxin should be considered when patients are on guideline-recommended therapy but heart failure symptoms persist. It is commonly initiated at a dose of 0.125 to 0.25 mg. The target therapeutic range for digoxin is 0.5 to 0.9 ng/mL.¹ Digoxin toxicity can occur in patients with renal impairment, hypokalemia, hypomagnesemia, and hypothyroidism.

The 2013 ACC/AHA guidelines give a class IIA recommendation (treatment is “reasonable”) for digoxin in patients with heart failure with reduced ejection fraction unless contraindicated, to decrease hospitalizations for heart failure.¹

Diuretics

Clinical manifestations of volume overload in patients with heart failure are from excess salt and water retention leading to inappropriate volume expansion in both the vascular and extravascular space. Diuretics (Table 8) are the foundation of heart failure treatment. Most patients are first initiated on a combination of a loop diuretic and a low-sodium diet to improve symptoms.

The 2013 ACC/AHA guidelines give a class I recommendation for diuretics in patients with heart failure with reduced ejection fraction who have evidence of fluid retention, unless contraindicated, to improve symptoms.¹

Devices: ICDs

Patients with heart failure are at increased risk of sudden death and ventricular arrhythmias.³⁹ Previously, antiarrhythmic drugs were considered the standard of care for nonsustained ventricular tachycardia after myocardial infarction.

MADIT (the Multicenter Automatic Defibrillator Implantation Trial) investigated whether prophylactic implantation of an internal cardiac defibrillator would improve 5-year survival rates in patients with heart failure. Eligible patients had had a Q-wave or enzyme-positive myocardial infarction within 3 weeks of study entry. They also had had an episode of asymptomatic nonsustained ventricular tachycardia unrelated to an acute myocardial infarction. Additionally, the patients had a left ventricular ejection fraction less than 35%, and inducible, sustained, nonsuppressible ventricular tachyarrhythmia on electrophysiologic testing.⁴⁰

During the study, 15 patients in the defibrillator group died vs 39 in the conventional therapy group (P = .009).⁴⁰

MADIT II evaluated the potential survival benefit of a prophylactically implanted defibrillator in the absence of electrophysiologic testing to induce arrhythmias.⁴¹ MADIT II included 1,232 patients with prior myocardial infarctions and a left ventricular ejection fracton of 30% or less. Patients were randomized to receive an implanted cardioverter-defibrillator or conventional medical therapy. The primary end point was death from any cause.⁴¹

The mortality rate was 19.8% in the conventional therapy group vs 14.2% in the defibrillator group (hazard ratio 0.69, P = .016).⁴¹ Thus, MADIT-II confirmed the benefits of prophylactic implantable cardioverter-defibrillator therapy seen in the original MADIT, and additionally eliminated the need for an electrophysiology test prior to device implantation.

SCD-HeFT (the Sudden Cardiac Death in Heart Failure Trial) evaluated whether amiodarone or a conservatively programmed shock-only, single-lead implanted cardioverter-defibrillator would decrease the risk of death (all-cause) in a population with mild to moderate heart failure with ischemic and nonischemic causes.⁴² In this trial, 2,521 patients with an ejection fraction of 35% or less, in NYHA class II or III, and with stable heart failure were randomized to receive a single-chamber implantable cardioverter-defibrillator,  amiodarone, or placebo.

There were 244 deaths in the placebo group, 240 deaths in the amiodarone group (P = .53 compared with placebo), and 182 deaths in the defibrillator group (P = .007 compared with placebo).⁴²

Recommendations. The 2013 ACC/AHA guideline¹ gives implantable defibrillator therapy a class IA recommendation for the primary prevention of sudden cardiac death in selected patients with nonischemic cardiomyopathy or ischemic cardiomyopathy at least 40 days after a myocardial infarction and 90 days after percutaneous coronary intervention or coronary artery bypass grafting; with a left ventricular ejection fraction of 35% or less; and NYHA class II or III symptoms on chronic goal-directed medical management.

This therapy receives a class IB recommendation for primary prevention of sudden cardiac death to reduce total mortality in selected patients at least 40 days after myocardial infarction with a left ventricular ejection fraction of 30% or less and NYHA class I symptoms while receiving goal-directed medical therapy.

Implantable cardioverter-defibrillators are not recommended in patients who otherwise have a life expectancy of less than 1 year.

Devices: Cardiac resynchronization therapy

From 25% to 30% of heart failure patients have an intraventricular conduction abnormality,^43,44 which can result in abnormalities of systolic and diastolic function. Biventricular pacing, in which a pacing lead is placed in the coronary sinus in addition to the right atrium and right ventricle, optimizes synchronization of ventricular contraction.^43,44

MUSTIC (the Multisite Stimulation in Cardiomyopathies study) was a randomized trial designed to assess the efficacy of biventricular pacing (also known as cardiac resynchronization therapy) in heart failure patients.⁴⁴ Entry criteria included NYHA class III heart failure for at least 1 month, left ventricular ejection fraction less than 35%, left ventricular end-diastolic diameter greater than 60 mm, and QRS duration longer than 150 ms. Patients were followed up at 9 and 12 months with 6-minute walking distance, peak oxygen consumption, changes in NYHA class, and left ventricular systolic function by echocardiography or radionuclide testing. Quality of life was assessed by the Minnesota Living With Heart Failure Questionnaire.

At 12 months, patients could walk significantly farther in 6 minutes, and their peak oxygen consumption had increased. They also reported significant improvement in quality of life, and NYHA class improved by 25%. MUSTIC was the first study to show a benefit in exercise tolerance, quality of life, improvement in cardiac performance, and reduction in heart failure symptoms with the use of biventricular pacing at 1 year.

MIRACLE (the Multicenter InSync Randomized Clinical Evaluation) validated the findings seen in MUSTIC by using a larger population size and a double-blinded method.⁴⁵ Compared with a control group, patients who underwent cardiac resynchronization therapy could walk farther in 6 minutes and scored better in NYHA class, quality of life, and left ventricular ejection fraction.⁴⁵

Recommendations. The 2013 ACC/AHA guidelines¹ give cardiac resynchronization therapy a class IA/B indication for NYHA class II, III, or IV patients on goal-directed medical therapy in sinus rhythm with left ventricular ejection fraction 35% or less, left bundle branch block, and QRS duration of 150 ms or more.¹

Devices: Implantable sensors

The future of ambulatory heart failure management may include implantable pulmonary artery pressure sensors.

The CardioMEMS is a permanently implantable pressure measurement system designed to provide daily pulmonary artery pressure measurements in an ambulatory setting with a goal of reducing heart failure-related hospitalizations. Through a transvenous delivery system, an implantable, battery-free sensor is positioned in the distal pulmonary artery.^46,47

CHAMPION (the CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Patients trial) was one of the first major trials to assess the safety and efficacy of implantable pulmonary artery pressure monitoring systems.⁴⁶ The study device was associated with a significant reduction in mean pulmonary artery pressures, fewer heart failure hospitalizations, and better quality of life. The length of stay for heart failure-related hospitalizations was also significantly shorter in the CardioMEMs group.⁴⁶

Exercise

Patients with heart failure routinely experience a decline in functional capacity. This decline manifests as reduced exercise tolerance and poor quality of life, usually resulting in a physician recommendation to rest and paradoxical deconditioning and possible progression of symptoms.

Several studies have shown that cardiac rehabilitation has improved outcomes in heart failure patients.⁴⁸ Cardiac rehabilitation is a supervised program that helps patients with exercise training, healthy living, education, and psychosocial counseling.

HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) is the largest randomized trial performed to determine whether aerobic exercise training reduces all-cause mortality or all-cause hospitalization and improves quality of life in patients with stable heart failure.⁴⁹ Although the reduction in end points was initially not statistically significant, after adjusting for highly prognostic predictors of poor outcomes (cardiopulmonary exercise time, left ventricular ejection fraction, atrial fibrillation, and depression), exercise training was found to reduce the incidence of all-cause mortality or all-cause hospitalization by 11% (P = .03).⁴⁹

Recommendations. Based on the results of HF-ACTION and several smaller studies, the ACC/AHA guidelines give exercise training a class IA recommendation as a safe and effective activity for patients with heart failure who are able to participate, to improve functional status.¹ A class IIA recommendation is given to cardiac rehabilitation for the improvement of functional capacity, exercise duration, quality of life, and mortality rates.¹

End-stage heart failure: Recognition

Despite adequate titration of goal-directed medical therapy, a portion of patients with heart failure with reduced ejection fraction ultimately progress to stage D, also termed “advanced” heart failure. The 5-year survival rate for patients with heart failure overall is 50%, but the 1-year mortality rate for those with advanced heart failure exceeds 50%.⁵⁰

Because the high rates of morbidity and mortality can potentially be lowered, recognition of heart failure disease progression is imperative so that patients can be promptly referred for therapies such as inotropic infusion, mechanical circulatory support, and cardiac transplant, as well as end-of-life care such as hospice.¹

The ACC/AHA¹ have published clinical events and findings useful in identifying patients with advanced heart failure:

• Two or more hospitalizations or emergency department visits for heart failure in the past year
• Progressive deterioration in renal function (eg, elevation in creatinine or blood urea nitrogen)
• Weight loss without other cause
• Intolerance to ACE inhibitors due to hypotension or worsening renal function
• Inability to tolerate beta-blockers due to worsening heart failure or hypotension
• Systolic blood pressure often below 90 mm Hg
• Persistent dyspnea with dressing or bathing requiring rest
• Inability to walk one block on level ground due to dyspnea or fatigue
• Recent need to escalate diuretics to maintain volume status, often reaching daily dose equivalent to furosemide more than 160 mg/day or use of supplemental metolazone
• Progressive decline in serum sodium, usually to below 133 mmol/L
• Frequent shocks from implanted cardiac defibrillator.

End-stage heart failure: Left ventricular assist devices

For patients with refractory heart failure despite optimal medical management, advanced therapies such as heart transplant or ventricular assist devices have been proven to be durable options. These mechanical circulatory support devices “unload” the diseased ventricle and maintain cardiac output to vital organs.⁵¹ They were initially designed as temporary support to allow ventricular recovery or as a bridge to cardiac transplant. However, they have also evolved into permanent (“destination”) therapy.⁵²

REMATCH (the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive HF trial) was the landmark study that showed that left ventricular assist device implantation resulted in a survival benefit and an improved quality of life in patients with advanced heart failure ineligible for cardiac transplant, compared with medical management.⁵⁰ Implantation of a left ventricular assist device was associated with a 27% absolute reduction in the 1-year mortality rate.⁵⁰

Since the National Institutes of Health’s artificial heart program was launched in 1964, there has been tremendous progress in the development of mechanical circulatory devices.⁵⁰ The results of REMATCH were promising, but the 2-year survival rate was still only 23%, leaving a lot to be desired.

The HeartMate II (Thoratec) trial compared an axial continuous-flow device vs the previously established pulsatile left ventricular assist device, and noted a 2-year survival of 58% with the continuous flow device vs  24% with the pulsatile device (P = .008).⁵³

ADVANCE (Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure) showed similar efficacy of the HVAD (Heartware), a centrifugal continuous-flow LVAD currently in use.⁵⁴

The next generation of continuous-flow left ventricular assist devices are currently in clinical trials in the United States and include the axial flow MVAD (Heartware) and centrifugal flow Heartmate III (Thoratec).

We emphasize the importance of early identification of patients with advanced disease who may qualify for and benefit from such therapies.

The management of heart failure is evolving. In the 1960s, the standard heart failure medical regimen included digoxin, diuretics, and the recommendation of rest. This contrasts with the current era, in which medical regimens include neurohormonal blockade, diuretics, and the promotion of physical activity.⁵⁵ Since the publication of the 2013 heart failure guidelines, new medical and device options have emerged that have been proven to either improve survival or reduce hospitalizations. The development of clinical guidelines promotes evidence-based practice and overcomes the inertia of practice patterns based on anecdotal evidence.

Several approaches to the management of heart failure have been recommended. A major effort should be made to identify those at risk for heart failure (stage A) and to implement risk factor modification. Treatment of hypertension, diabetes mellitus, and dyslipidemia decreases the risk of heart failure.¹

For patients with evidence of structural heart disease with and without symptoms, Figure 1 summarizes a guideline approach to the management of heart failure. It should be stressed that guidelines are meant to guide management, but do not serve as a substitute for sound clinical judgment.

Heart failure is the common final pathway of all cardiac pathology, and understanding the neurohormonal response and maladaptive physiology has led to the development of novel therapeutics and devices. At present, the field of cardiology may not be able to remove the “failure” from heart failure, but we can make every effort to prevent failure of treatment delivery and reduce resource utilization and morbidity associated with this syndrome.

Acknowledgments: We would like to thank Chankya Dahagam and Cynthia Obenwa for their valuable contribution in the preparation of this manuscript.

Managing heart failure is a challenge. To aid clinicians in this task, the American College of Cardiology Foundation (ACC) and the American Heart Association (AHA) publish evidence-based guidelines, most recently in 2013.¹ Since then, new drugs and devices have been shown to improve survival and reduce hospitalizations.

See related editorial

This paper reviews the ABCs of outpatient management of systolic heart failure (or heart failure with reduced ejection fraction), including the results of major trials and recommendations.

A common and serious condition

Heart failure is a debilitating syndrome that takes a significant physical and mental toll on those affected.

And it is common. An American age 40 or older faces a 20% lifetime risk of heart failure.¹ An estimated 5.1 million Americans have clinical signs and symptoms of heart failure, and 900,000 new cases are diagnosed each year.² By 2030 the prevalence of heart failure is projected to increase by 46%, and 9 million Americans will have been diagnosed with it.²

The severity of heart failure can be described using either the functional classification devised by the New York Heart Association (NYHA; Table 1) or the stages defined by the ACC and AHA.^1,3 Though survival rates have improved, there is a direct correlation between worsening symptoms and death.⁴

Heart failure is the leading cause of hospitalizations annually. It accounts for $30 billion in healthcare costs, with direct medical costs accounting for 68% and another $1.8 billion associated with clinic visits, most often with primary care providers. By 2030, the cost is projected to increase by 127% to $69.7 billion—$244 per person in the United States.²

ACE inhibitors

The renin-angiotensin-aldosterone system has been studied for over 100 years.⁵

In heart failure with reduced ejection fraction, this system is upregulated as an adaptive mechanism to maintain hemodynamic homeostasis.^6–8 However, prolonged activation of the renin-angiotensin-aldosterone system can lead to deleterious cardiovascular effects such as myocyte hypertrophy, myocardial fibrosis, sodium conservation, and fluid overload.^8,9 Angiotensin II is a potent vasoconstrictor and plays a role in cardiovascular remodeling, leading to worsening progression of heart failure.⁶

CONSENSUS (the Cooperative North Scandinavian Enalapril Survival Study) examined the effect of the angiotensin-converting enzyme (ACE) inhibitor enalapril on survival in 253 patients with NYHA class IV heart failure. Participants were randomized to receive either enalapril or placebo. At 6 months, the mortality rate was 26% in the enalapril group vs 44% in the placebo group, an 18% absolute risk reduction and a 41% relative risk reduction (P = .002). At 12 months, the relative risk reduction in mortality was 30% (P = .001).¹⁰

SOLVD (the Study of Left Ventricular Dysfunction) extended the use of ACE inhibitors to all patients with heart failure, not just those in NYHA class IV. It randomized 1,284 patients with heart failure of any NYHA class and an ejection fraction less than 35% to receive either enalapril or placebo, and demonstrated a 16% relative risk reduction in mortality in the enalapril group, with mortality rates of 36% vs 39.7% (P = .0036).¹¹

Recommendations. The benefits of ACE inhibition have been demonstrated in patients with mild, moderate, and severe heart failure. Thus, the guidelines recommend ACE inhibitors (Table 2) for all patients with heart failure with reduced ejection fraction.¹

Angiotensin II receptor blockers

Angiotensin II receptor blockers (ARBs) (Table 3) have been proven to be suitable alternatives for patients with heart failure with reduced ejection fraction who cannot tolerate ACE inhibitors.

Val-HefT (the Valsartan HF Trial)¹² randomized 5,010 patients in a double-blind fashion to receive either valsartan or placebo, with background therapy that included beta-blockers, digoxin, diuretics, and ACE inhibitors. There was a 13% reduction of the combined primary end point of mortality and morbidity and a 24% reduction in heart failure hospitalizations in the valsartan group.¹²

Subgroup analysis compared patients on the basis of use of ACE inhibitors and beta-blockers at study entry. Valsartan had a favorable effect in the subgroups using beta-blockers alone, ACE inhibitors alone, and neither drug. However, when patients received all three (a beta-blocker, an ACE inhibitor, and valsartan), the mortality rate was significantly increased (P = .009).¹² This finding conflicted with those of other studies, which found a small benefit of combining an ACE inhibitor and an ARB.

CHARM-Added (the Candesartan in HF Assessment of Reduction in Mortality and Morbidity trial)¹³ investigated whether adding the ARB candesartan to an ACE inhibitor would improve clinical outcomes. In the study, 2,548 patients in NYHA class II, III, or IV with a left ventricular ejection fraction of less than 40% who were receiving ACE inhibitors were randomized to either candesartan or placebo. The addition of candesartan resulted in a significant reduction in cardiovascular mortality and heart failure hospitalizations, but with the downside of higher rates of hyperkalemia and serum creatinine elevation.¹³

Recommendations. The 2013 guidelines recommend that ARBs be used in patients who cannot tolerate an ACE inhibitor due to cough. However, routine combined use of ARBs, ACE inhibitors, and aldosterone antagonists is not recommended and may cause harm.¹

Aldosterone receptor antagonists

Elevated levels of aldosterone lead to fluid retention, loss of magnesium and potassium, and myocardial fibrosis.

RALES (the Randomized Aldactone Evaluation Study)¹⁴ tested the hypothesis that the aldosterone receptor antagonist spironolactone (25 mg daily) would reduce deaths from all causes in patients with severe heart failure receiving standard medications including an ACE inhibitor. RALES included 1,663 patients in NYHA class III or IV with a left ventricular ejection fraction of 35% or less, randomized to receive 25 mg of spironolactone or matching placebo. This study found a 30% relative risk reduction and an 11% absolute risk reduction in all-cause mortality, a 31% relative risk reduction and a 10% absolute risk reduction in cardiac mortality, and 30% fewer cardiac-related hospitalizations in the spironolactone group.¹⁴

Eplerenone, an aldosterone receptor antagonist that lacks the antiandrogenic side effects of spironolactone, has also been shown to be beneficial. Its efficacy in patients with left ventricular systolic dysfunction was first established in postmyocardial infarction patients.¹⁵

EMPHASIS-HF (the Eplerenone in Mild Patients Hospitalized and Survival Study in Heart Failure)¹⁶ broadened the application of eplerenone (and aldosterone antagonists in general), investigating the effects of eplerenone in 2,737 NYHA class II patients, regardless of ischemic etiology. The composite end point of cardiovascular death or heart failure hospitalization occurred in 18.3% of the eplerenone group vs 25.9% of the placebo group (P < .001). A total of 12.5% of patients in the eplerenone group died, compared with 15.5% in the placebo group (P = .008). Hospitalizations were also fewer in the eplerenone group.

Recommendations. The 2013 guidelines recommend aldosterone receptor antagonists (Table 4) for patients with NYHA class II, III, or IV heart failure who have an ejection fraction of 35% or less, to reduce morbidity and mortality (class IA recommendation).¹ The guidelines also recommend that these agents not be used in patients with renal insufficiency (serum creatinine > 2.5 mg/dL in men or > 2.0 mg/dL in women; an estimated glomerular filtration rate < 30 mL/min/1.73 m²); or a serum potassium level above 5 mmol/L.¹

Angiotensin-neprilysin inhibitor (the future)

Research has identified neprilysin as another potential target in the treatment of heart failure and has sought to combine inhibition of angiotensin and neprilysin.

Neprilysin, a neutral endopeptidase, is associated with degradation of several natural vasoactive peptides such as natriuretic peptide, bradykinin, and adrenomedullin. Neprilysin inhibition increases these substances and counters the neurohormonal overactivation that leads to vasoconstriction, sodium retention, and cardiac remodeling.¹⁷

The ARB valsartan has been combined with the neprilysin inhibitor sacubitril to create the first angiotensin-neprilysin inhibitor (ARNI) (Table 5). The combination was selected to minimize the potential for angioedema.

PARADIGM-HF (the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure trial)¹⁷ examined whether combined angiotensin-neprilysin inhibition was superior to ACE inhibition alone with enalapril in patients with chronic heart failure.

In PARADIGM-HF, 10,521 patients with NYHA class II, III, or IV heart failure were randomized to receive either sacubitril-valsartan or enalapril. The group receiving sacubitril-valsartan had significantly fewer deaths from cardiovascular causes and heart failure hospitalizations.¹⁷ An improvement in quality of life and NYHA functional class was also observed in the sacubitril-valsartan group.¹⁷

Sacubitril-valsartan underwent priority review by the US Food and Drug Administration and has been approved. Currently, it is indicated for the treatment of heart failure with reduced ejection fraction and NYHA class II, III, or IV symptoms. It should be avoided in patients who have previously experienced angioedema with an ACE inhibitor or ARB, in patients receiving aliskiren for diabetes, and in patients with hypersensitivity reactions to either of its components. Simultaneous use of sacubitril-valsartan and an ACE inhibitor should be avoided, and a washout period is recommended when transitioning from an ACE inhibitor to this combined agent.

Beta-blockers

In heart failure, there is increased sympathetic activation and associated elevations in norepinephrine levels, which may lead to deleterious long-term effects on cardiac function and structure. Beta-adrenergic receptor blockade is now known to be cardioprotective, but it was not always so; beta-blockers used to be contraindicated in patients with heart failure.

An early experience using beta-blockers in heart failure was described in 1975.^18,19 The first study to report a survival benefit of treating systolic heart failure with a beta-blocker was published in 1979.²⁰ Later, small controlled trials demonstrated a reduction in heart failure symptoms and improvement in left ventricular function and in NYHA functional class.²¹ Larger clinical trials have demonstrated a tremendous survival benefit with beta-blockers in heart failure, specifically carvedilol, extended-release metoprolol, and bisoprolol.

The US Carvedilol Heart Failure Study Group trial²² evaluated whether beta-blocker use in heart failure patients would reduce the rates of morbidity and mortality.²² The trial included 1,094 patients with symptomatic heart failure for at least 3 months and a left ventricular ejection fraction of 35% or less on background therapy including vasodilators, ACE inhibitors, and digoxin. Patients were randomized to receive either carvedilol or placebo. Carvedilol use was associated with a dramatic 65% risk reduction in mortality (7.8% with placebo vs 3.2% with carvedilol, P < .001) and a 27% risk reduction in hospitalizations (19.6% vs 14.1%, P = .036), leading to early trial termination.

CIBIS-II (the Cardiac Insufficiency Bisoprolol Study II)²³ investigated the effects of beta-blockers on survival and morbidity. CIBIS-II included 2,647 NYHA class III or IV patients with a left ventricular ejection fraction less than 35% on background medical therapy that included diuretics and ACE inhibitors. This trial was also terminated early, after demonstrating a significant survival benefit with bisoprolol.

MERIT-HF (the Metoprolol Extended Release Randomized Intervention Trial in Congestive Heart Failure)²⁴ evaluated if once-daily metoprolol would lower mortality rates  in patients with symptomatic heart failure. The study enrolled 3,991 NYHA class II–IV patients with chronic heart failure and a left ventricular ejection fraction of 40% or less. Like the previous two beta-blocker trials, MERIT-HF was terminated early, as it demonstrated a 34% reduction in all-cause mortality (7.2% risk of death per patient-year vs 11.0%, P = .00009).

The beta-blocker trials have shown that when added to background therapy, beta-blockers improve survival and reduce hospitalizations. However, when prescribing a beta-blocker, it is important to understand that not all beta-blockers are equal in the treatment of heart failure.

COMET (the Carvedilol or Metoprolol European Trial)²⁵ was the only head-to-head randomized control trial evaluating clinical outcomes in patients receiving carvedilol or metoprolol tartrate (not metoprolol succinate). In COMET, 1,511 patients with NYHA class II, III, or IV heart failure with a left ventricular ejection fraction of 35% or less were randomized to carvedilol or metoprolol tartrate. The primary end point of all-cause mortality occurred in 34% of the carvedilol group and 40% of the metoprolol tartrate group (P = .0017). There was no significant difference with regard to the composite end point of mortality and all-cause admissions.

Recommendations. The 2013 guidelines give a class IA recommendation for starting a beta-blocker (carvedilol, bisoprolol, or metoprolol succinate, Table 6) in patients with current or prior symptoms of heart failure.¹ Beta-blockers should be initiated with caution or avoided in patients with acutely decompensated heart failure with evidence of fluid overload.

Brain-type natriuretic peptide

Brain-type natriuretic peptide (BNP) or its amino-terminal cleavage product (NT-proBNP) originates in cardiomyocytes and is released by several triggers, most commonly cardiomyocyte stretch in the setting of volume or pressure overload.²⁶ The biologic significance of BNP includes natriuresis and vasodilation, renin-angiotensin system inhibition, and sympathetic nervous system modulation.²⁶

TIME-CHF (the Trial of Intensified vs. Standard Medical Therapy in Elderly Patients With Congestive HF)²⁷ investigated whether 18-month outcomes would be better if treatment were guided by N-terminal BNP levels rather than by symptoms. The BNP-guided strategy was not associated with a reduction in hospitalization or a survival benefit.

BATTLESCARRED (the NT-proBNP-Assisted Treatment to Lessen Serial Cardiac Readmissions and Death trial)²⁸ in 2009 showed that a BNP-guided management strategy significantly reduced mortality rates in patients under age 75 compared with standard medical therapy.

PROTECT (the Use of NT-proBNP Testing to Guide HF Therapy in the Outpatient Setting study)²⁹ also showed that a BNP-guided strategy was superior to usual care and was associated with reduced cardiovascular events and improved quality of life.²⁹

GUIDE IT-HF (the Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure study), currently ongoing, is designed to assess the safety, efficacy and cost-effectiveness of a biomarker-guided strategy in 1,100 high-risk patients with heart failure with reduced ejection fraction. 

Recommendations. The 2013 ACC/AHA guidelines give a class IA recommendation for the use of BNP to support clinical decision-making, particularly in cases of clinical uncertainty.¹ BNP can also be used to establish prognosis or disease severity in chronic heart failure and to achieve optimal dosage of goal-directed medical therapy for euvolemic patients followed in a structured heart failure program.¹

Heart failure clinics

Continuity of care upon discharge from the hospital is currently in a state of evolution. Those diagnosed with heart failure can now experience more comprehensive posthospital care by virtue of disease management clinics. The name may vary by institution, but whether it is called a “diuresis clinic,” “bridge clinic,” or “heart failure clinic,” the goal is to improve guideline-driven care, educate the patient, and reduce heart failure hospitalizations. Heart failure clinics are designed to provide a smooth transition from inpatient to outpatient care and to encourage patient self-accountability in health maintenance thereafter.

Studies have shown that heart failure clinics are associated with better medication dosing, fewer hospitalizations, and lower healthcare costs.^30–32

Chronotropy: I_f inhibition

An elevated resting heart rate has been shown to be associated with increased cardiovascular morbidity and mortality.³³ Studies have shown that slowing the heart rate improves myocardial contraction and energy supply and reduces energy expenditure.³⁴ Ivabradine, a selective I_f (the f is for “funny”) channel inhibitor, slows the heart rate without other known cardiovascular effects.

SHIFT (the Systolic Heart Failure Treatment With the I_f Inhibitor Ivabradine Trial)³⁵ investigated whether isolated heart rate reduction with ivabradine would reduce adverse clinical outcomes in patients with symptomatic heart failure. SHIFT randomized 6,505 patients with a left ventricular ejection fraction of 35% or less, in sinus rhythm, with a heart rate of at least 70 beats per minute, on optimal medical therapy, and hospitalized within 12 months of enrollment to receive ivabradine or placebo. The primary end point was a composite of cardiovascular mortality and hospital admission for worsening heart failure. Outcomes varied by heart rates achieved, with the best outcomes in those with the lowest heart rates at trial conclusion.

Ivabradine (Table 7) is indicated for patients with symptomatic heart failure with a left ventricular ejection fraction less than 35%, in sinus rhythm, with a resting heart rate of at least 70 beats per minute, and either on a maximally tolerated beta-blocker or with a contraindication to beta-blockers.

Ivabradine should be avoided in patients who are in acute decompensated heart failure or are hypotensive (blood pressure < 90/50 mm Hg), as well as in patients with a significant conduction abnormality (sick sinus syndrome, sinoatrial block, third-degree atrioventricular block), hepatic impairment, or bradycardia (resting heart rate < 60 beats per minute).

Digoxin

Digoxin has been used in treating systolic heart failure for more than 70 years.^36,37

DIG (Digoxin Investigative Group trial)³⁸ evaluated the long-term effect of digoxin on rates of mortality and hospitalization for heart failure over a 3-year period. In patients with  a left ventricular ejection fraction less than 45%, digoxin had no effect on overall mortality when combined with diuretics and ACE inhibitors. However, the risk of hospitalization for worsening heart failure was significantly reduced with digoxin treatment.³⁸

Recommendations. Digoxin should be considered when patients are on guideline-recommended therapy but heart failure symptoms persist. It is commonly initiated at a dose of 0.125 to 0.25 mg. The target therapeutic range for digoxin is 0.5 to 0.9 ng/mL.¹ Digoxin toxicity can occur in patients with renal impairment, hypokalemia, hypomagnesemia, and hypothyroidism.

The 2013 ACC/AHA guidelines give a class IIA recommendation (treatment is “reasonable”) for digoxin in patients with heart failure with reduced ejection fraction unless contraindicated, to decrease hospitalizations for heart failure.¹

Diuretics

Clinical manifestations of volume overload in patients with heart failure are from excess salt and water retention leading to inappropriate volume expansion in both the vascular and extravascular space. Diuretics (Table 8) are the foundation of heart failure treatment. Most patients are first initiated on a combination of a loop diuretic and a low-sodium diet to improve symptoms.

The 2013 ACC/AHA guidelines give a class I recommendation for diuretics in patients with heart failure with reduced ejection fraction who have evidence of fluid retention, unless contraindicated, to improve symptoms.¹

Devices: ICDs

Patients with heart failure are at increased risk of sudden death and ventricular arrhythmias.³⁹ Previously, antiarrhythmic drugs were considered the standard of care for nonsustained ventricular tachycardia after myocardial infarction.

MADIT (the Multicenter Automatic Defibrillator Implantation Trial) investigated whether prophylactic implantation of an internal cardiac defibrillator would improve 5-year survival rates in patients with heart failure. Eligible patients had had a Q-wave or enzyme-positive myocardial infarction within 3 weeks of study entry. They also had had an episode of asymptomatic nonsustained ventricular tachycardia unrelated to an acute myocardial infarction. Additionally, the patients had a left ventricular ejection fraction less than 35%, and inducible, sustained, nonsuppressible ventricular tachyarrhythmia on electrophysiologic testing.⁴⁰

During the study, 15 patients in the defibrillator group died vs 39 in the conventional therapy group (P = .009).⁴⁰

MADIT II evaluated the potential survival benefit of a prophylactically implanted defibrillator in the absence of electrophysiologic testing to induce arrhythmias.⁴¹ MADIT II included 1,232 patients with prior myocardial infarctions and a left ventricular ejection fracton of 30% or less. Patients were randomized to receive an implanted cardioverter-defibrillator or conventional medical therapy. The primary end point was death from any cause.⁴¹

The mortality rate was 19.8% in the conventional therapy group vs 14.2% in the defibrillator group (hazard ratio 0.69, P = .016).⁴¹ Thus, MADIT-II confirmed the benefits of prophylactic implantable cardioverter-defibrillator therapy seen in the original MADIT, and additionally eliminated the need for an electrophysiology test prior to device implantation.

SCD-HeFT (the Sudden Cardiac Death in Heart Failure Trial) evaluated whether amiodarone or a conservatively programmed shock-only, single-lead implanted cardioverter-defibrillator would decrease the risk of death (all-cause) in a population with mild to moderate heart failure with ischemic and nonischemic causes.⁴² In this trial, 2,521 patients with an ejection fraction of 35% or less, in NYHA class II or III, and with stable heart failure were randomized to receive a single-chamber implantable cardioverter-defibrillator,  amiodarone, or placebo.

There were 244 deaths in the placebo group, 240 deaths in the amiodarone group (P = .53 compared with placebo), and 182 deaths in the defibrillator group (P = .007 compared with placebo).⁴²

Recommendations. The 2013 ACC/AHA guideline¹ gives implantable defibrillator therapy a class IA recommendation for the primary prevention of sudden cardiac death in selected patients with nonischemic cardiomyopathy or ischemic cardiomyopathy at least 40 days after a myocardial infarction and 90 days after percutaneous coronary intervention or coronary artery bypass grafting; with a left ventricular ejection fraction of 35% or less; and NYHA class II or III symptoms on chronic goal-directed medical management.

This therapy receives a class IB recommendation for primary prevention of sudden cardiac death to reduce total mortality in selected patients at least 40 days after myocardial infarction with a left ventricular ejection fraction of 30% or less and NYHA class I symptoms while receiving goal-directed medical therapy.

Implantable cardioverter-defibrillators are not recommended in patients who otherwise have a life expectancy of less than 1 year.

Devices: Cardiac resynchronization therapy

From 25% to 30% of heart failure patients have an intraventricular conduction abnormality,^43,44 which can result in abnormalities of systolic and diastolic function. Biventricular pacing, in which a pacing lead is placed in the coronary sinus in addition to the right atrium and right ventricle, optimizes synchronization of ventricular contraction.^43,44

MUSTIC (the Multisite Stimulation in Cardiomyopathies study) was a randomized trial designed to assess the efficacy of biventricular pacing (also known as cardiac resynchronization therapy) in heart failure patients.⁴⁴ Entry criteria included NYHA class III heart failure for at least 1 month, left ventricular ejection fraction less than 35%, left ventricular end-diastolic diameter greater than 60 mm, and QRS duration longer than 150 ms. Patients were followed up at 9 and 12 months with 6-minute walking distance, peak oxygen consumption, changes in NYHA class, and left ventricular systolic function by echocardiography or radionuclide testing. Quality of life was assessed by the Minnesota Living With Heart Failure Questionnaire.

At 12 months, patients could walk significantly farther in 6 minutes, and their peak oxygen consumption had increased. They also reported significant improvement in quality of life, and NYHA class improved by 25%. MUSTIC was the first study to show a benefit in exercise tolerance, quality of life, improvement in cardiac performance, and reduction in heart failure symptoms with the use of biventricular pacing at 1 year.

MIRACLE (the Multicenter InSync Randomized Clinical Evaluation) validated the findings seen in MUSTIC by using a larger population size and a double-blinded method.⁴⁵ Compared with a control group, patients who underwent cardiac resynchronization therapy could walk farther in 6 minutes and scored better in NYHA class, quality of life, and left ventricular ejection fraction.⁴⁵

Recommendations. The 2013 ACC/AHA guidelines¹ give cardiac resynchronization therapy a class IA/B indication for NYHA class II, III, or IV patients on goal-directed medical therapy in sinus rhythm with left ventricular ejection fraction 35% or less, left bundle branch block, and QRS duration of 150 ms or more.¹

Devices: Implantable sensors

The future of ambulatory heart failure management may include implantable pulmonary artery pressure sensors.

The CardioMEMS is a permanently implantable pressure measurement system designed to provide daily pulmonary artery pressure measurements in an ambulatory setting with a goal of reducing heart failure-related hospitalizations. Through a transvenous delivery system, an implantable, battery-free sensor is positioned in the distal pulmonary artery.^46,47

CHAMPION (the CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Patients trial) was one of the first major trials to assess the safety and efficacy of implantable pulmonary artery pressure monitoring systems.⁴⁶ The study device was associated with a significant reduction in mean pulmonary artery pressures, fewer heart failure hospitalizations, and better quality of life. The length of stay for heart failure-related hospitalizations was also significantly shorter in the CardioMEMs group.⁴⁶

Exercise

Patients with heart failure routinely experience a decline in functional capacity. This decline manifests as reduced exercise tolerance and poor quality of life, usually resulting in a physician recommendation to rest and paradoxical deconditioning and possible progression of symptoms.

Several studies have shown that cardiac rehabilitation has improved outcomes in heart failure patients.⁴⁸ Cardiac rehabilitation is a supervised program that helps patients with exercise training, healthy living, education, and psychosocial counseling.

HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) is the largest randomized trial performed to determine whether aerobic exercise training reduces all-cause mortality or all-cause hospitalization and improves quality of life in patients with stable heart failure.⁴⁹ Although the reduction in end points was initially not statistically significant, after adjusting for highly prognostic predictors of poor outcomes (cardiopulmonary exercise time, left ventricular ejection fraction, atrial fibrillation, and depression), exercise training was found to reduce the incidence of all-cause mortality or all-cause hospitalization by 11% (P = .03).⁴⁹

Recommendations. Based on the results of HF-ACTION and several smaller studies, the ACC/AHA guidelines give exercise training a class IA recommendation as a safe and effective activity for patients with heart failure who are able to participate, to improve functional status.¹ A class IIA recommendation is given to cardiac rehabilitation for the improvement of functional capacity, exercise duration, quality of life, and mortality rates.¹

End-stage heart failure: Recognition

Despite adequate titration of goal-directed medical therapy, a portion of patients with heart failure with reduced ejection fraction ultimately progress to stage D, also termed “advanced” heart failure. The 5-year survival rate for patients with heart failure overall is 50%, but the 1-year mortality rate for those with advanced heart failure exceeds 50%.⁵⁰

Because the high rates of morbidity and mortality can potentially be lowered, recognition of heart failure disease progression is imperative so that patients can be promptly referred for therapies such as inotropic infusion, mechanical circulatory support, and cardiac transplant, as well as end-of-life care such as hospice.¹

The ACC/AHA¹ have published clinical events and findings useful in identifying patients with advanced heart failure:

• Two or more hospitalizations or emergency department visits for heart failure in the past year
• Progressive deterioration in renal function (eg, elevation in creatinine or blood urea nitrogen)
• Weight loss without other cause
• Intolerance to ACE inhibitors due to hypotension or worsening renal function
• Inability to tolerate beta-blockers due to worsening heart failure or hypotension
• Systolic blood pressure often below 90 mm Hg
• Persistent dyspnea with dressing or bathing requiring rest
• Inability to walk one block on level ground due to dyspnea or fatigue
• Recent need to escalate diuretics to maintain volume status, often reaching daily dose equivalent to furosemide more than 160 mg/day or use of supplemental metolazone
• Progressive decline in serum sodium, usually to below 133 mmol/L
• Frequent shocks from implanted cardiac defibrillator.

End-stage heart failure: Left ventricular assist devices

For patients with refractory heart failure despite optimal medical management, advanced therapies such as heart transplant or ventricular assist devices have been proven to be durable options. These mechanical circulatory support devices “unload” the diseased ventricle and maintain cardiac output to vital organs.⁵¹ They were initially designed as temporary support to allow ventricular recovery or as a bridge to cardiac transplant. However, they have also evolved into permanent (“destination”) therapy.⁵²

REMATCH (the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive HF trial) was the landmark study that showed that left ventricular assist device implantation resulted in a survival benefit and an improved quality of life in patients with advanced heart failure ineligible for cardiac transplant, compared with medical management.⁵⁰ Implantation of a left ventricular assist device was associated with a 27% absolute reduction in the 1-year mortality rate.⁵⁰

Since the National Institutes of Health’s artificial heart program was launched in 1964, there has been tremendous progress in the development of mechanical circulatory devices.⁵⁰ The results of REMATCH were promising, but the 2-year survival rate was still only 23%, leaving a lot to be desired.

The HeartMate II (Thoratec) trial compared an axial continuous-flow device vs the previously established pulsatile left ventricular assist device, and noted a 2-year survival of 58% with the continuous flow device vs  24% with the pulsatile device (P = .008).⁵³

ADVANCE (Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure) showed similar efficacy of the HVAD (Heartware), a centrifugal continuous-flow LVAD currently in use.⁵⁴

The next generation of continuous-flow left ventricular assist devices are currently in clinical trials in the United States and include the axial flow MVAD (Heartware) and centrifugal flow Heartmate III (Thoratec).

We emphasize the importance of early identification of patients with advanced disease who may qualify for and benefit from such therapies.

The management of heart failure is evolving. In the 1960s, the standard heart failure medical regimen included digoxin, diuretics, and the recommendation of rest. This contrasts with the current era, in which medical regimens include neurohormonal blockade, diuretics, and the promotion of physical activity.⁵⁵ Since the publication of the 2013 heart failure guidelines, new medical and device options have emerged that have been proven to either improve survival or reduce hospitalizations. The development of clinical guidelines promotes evidence-based practice and overcomes the inertia of practice patterns based on anecdotal evidence.

Several approaches to the management of heart failure have been recommended. A major effort should be made to identify those at risk for heart failure (stage A) and to implement risk factor modification. Treatment of hypertension, diabetes mellitus, and dyslipidemia decreases the risk of heart failure.¹

For patients with evidence of structural heart disease with and without symptoms, Figure 1 summarizes a guideline approach to the management of heart failure. It should be stressed that guidelines are meant to guide management, but do not serve as a substitute for sound clinical judgment.

Heart failure is the common final pathway of all cardiac pathology, and understanding the neurohormonal response and maladaptive physiology has led to the development of novel therapeutics and devices. At present, the field of cardiology may not be able to remove the “failure” from heart failure, but we can make every effort to prevent failure of treatment delivery and reduce resource utilization and morbidity associated with this syndrome.

Acknowledgments: We would like to thank Chankya Dahagam and Cynthia Obenwa for their valuable contribution in the preparation of this manuscript.

The woods are lovely, dark and deep,
But I have promises to keep,
And miles to go before I sleep,
And miles to go before I sleep.

—Robert Frost, “Stopping by Woods on a Snowy Evening”¹

Frost's words are simple yet elegant. They can be interpreted many ways. I see the allegory of life as a journey in this poem. The passage, like the woods, is beautiful, but there is a long, long way to go.

See related article

And so it is with the treatment of heart failure. There is beauty in our understanding of the syndrome’s physiologic complexities and natural history, and of effective treatments uncovered. Still, we’ve a monstrous climb ahead to get to the summit of this clinical challenge in order to start a real descent.

THE PAST, PRESENT, AND FUTURE OF HEART FAILURE THERAPY

Okwuosa et al,² in this issue of the Journal, have capably summarized the ABCs of treating heart failure with reduced ejection fraction (also called systolic heart failure), approaching the subject from a perspective on past, present, and future therapies. They summarize heart failure interventions with a guideline-based philosophy, pointing out that these care paths are supposed to be evidence-based. They observe that in the 1960s the standard of care was digitalis, diuretics (furosemide first became available in 1967), and rest. That was about all we had for this problem.

There are now many drugs, devices, and operations that help patients with heart failure. But they never really cure the disease or, more aptly, the syndrome—and therapies are supposed to cure. This limitation of present therapies is important, given the disturbing epidemiology of heart failure, its economic cost, and the suffering of patients. That burden is well detailed.

In addition to curing, the overarching goals of treatment generally are to ameliorate distressing symptoms and to prevent comorbidities. In heart failure with reduced ejection fraction, we want to prevent premature death, stroke, myocardial infarction, congestive states, hospitalization, renal insufficiency, renal failure, cachexia, inanition, feebleness, and respiratory distress, among others.

The ABC mnemonic of Okwuosa et al will help caregivers remember the basics. It is important, however, to put algorithms into proper perspective and to look toward the future.

PROBLEMS WITH EVIDENCE-BASED MEDICINE

Several problems with our current heart failure treatments are rooted in how we perform clinical trials, arguably the premier method of determining truth in clinical practice and the foundation of evidence-based medicine.^3,4

Do the trials represent real-world practice?

Were the clinical trials that led to regulatory approval and professional society endorsement of the therapies that we prescribe in our offices done in the same sorts of patients as those in our waiting rooms asking for help? Perhaps, for the most part, they have been. And thus, Okwuosa et al have crafted a work relevant to all of us and every patient.

But I believe there are major gaps in the types of participants enrolled in trials, eg, underrepresentation of certain racial and ethnic groups, not to mention the relative paucity of women. The very elderly (a rapidly growing population) have largely been ignored as well, and participants with significant renal insufficiency, anemia, and diabetes mellitus seem far fewer than what we deal with in a busy clinic.

In addition, Okwuosa et al focus only on patients with reduced left ventricular ejection fraction, a group that makes up only about half of the heart failure crowd.

What about quality of life and other important outcomes?

Clinical trials in heart failure with reduced ejection fraction have generally focused on major clinical end points (primarily, but not exclusively, mortality), to the exclusion of quality of life. Though sometimes included in trials, quality-of-life metrics generally get relegated to second-class seats or ‘tween-deck steerage. Perhaps that is because measuring quality of life can be time-consuming and difficult.

Yet, in the words of sociologist William Bruce Cameron, not everything that counts can be counted, and not everything that can be counted counts. That goes for quality of life.

Lies, damned lies, and P values

Quandaries in data management and analysis include what to do about trial dropouts, study power, precision of statistical analysis, intention-to-treat principles, and choice of the P value that defines significance (or not) for any end point observation. Of course, there are myriad sophisticated mathematical and statistical reasons to justify why we don’t simply count on-treatment participants or allow imputation of results when patients or results drop out, forcing us to worship at the altar of P < .05.

A review of the P value concept⁵ recently appeared with an accompanying editorial by Kyriacou⁶ that concluded that “the automatic application of dichotomized hypothesis testing based on prearranged levels of statistical significance should be substituted with a more complex process using effect estimates, confidence intervals, and even P values, thereby permitting scientists, statisticians, and clinicians to use their own inferential capabilities to assign scientific significance.”⁶

How many great treatments have we tossed out because of rigid reliance on old-fashioned approaches to determining therapeutic evidence? Many treatments studied have had great results in a minority of patients in clinical trials but did not have a major positive (or negative) impact on the overall cohort (with lack of primary end point statistical significance). And what to do when the primary end point is a neutral or negative one but secondary end points are positive? Why not focus more attention on those patients benefiting from an intervention despite the overall results of any trial?

Dilemmas of trials

Other issues are that clinical trials cost too much, and that recruitment and follow-up take too long. Intercurrent therapies (and guidelines) can emerge that jeopardize the trial itself or make observations untimely. The dilemma of stacking therapies one on top of another, often making patient compliance impossible, is another problem with clinical trials. Yet this is how we get to the ABCs.

A NEW WAY TO DO TRIALS

The information provided by Okwuosa et al is useful and encouraging, but too many gaps exist in our heart failure therapies to permit us to celebrate with exuberance. Too many patients still suffer, too many die too young, and the costs are still too great.

Perhaps the future of therapeutic development should embrace different and better ways to demonstrate real value (relying on the equation of value equals outcomes meaningful to patients, divided by cost) of therapies, including the old, the new, the trashed and the underdeveloped. More creative data analysis to reexamine the current tools on the shelf and the ones tried but discarded is essential.

A position paper from the Cardiovascular Round Table of the European Society of Cardiology concluded that “a coordinated effort involving academia, regulators, industry and payors will help to foster better and more effective conduct of clinical cardiovascular trials, supporting earlier availability of innovative therapies and better management of cardiovascular diseases.”⁷

Lauer and D’Agostino,⁸ also in an editorial, argued for innovative methods of doing clinical trials and discovering truth about therapies that are applicable to the future of developing treatments for heart failure with reduced ejection fraction. They noted that “the randomized registry trial represents a disruptive technology” and wondered if it will be “given serious consideration as a way to resolve the recognized limitations of current clinical-trial design.”⁸

Indeed, conducting megatrials with existing megadatabases using a registry format could help. Registries emerging from early adaptive trial design efforts, particularly when Bayesian analysis theory is applied, might help inform clinical experience faster and more efficiently. Bayesian analysis is a statistical approach that attempts to estimate parameters of an underlying distribution of events in an ongoing fashion based on the observed distribution. A clinical trial of stem cell therapies could, at the end of the trial, be turned into a multicenter registry that would continue to inform us about the more real-world application of newer treatment approaches.

Though the therapeutic cupboard for heart failure is certainly not bare, as Okwuosa et al point out, it is wanting. Let’s look for new therapeutic ABCs differently. We should be attacking the real challenge—curing the disease processes that cause the syndrome. Yes, there are miles to go before we sleep.

The woods are lovely, dark and deep,
But I have promises to keep,
And miles to go before I sleep,
And miles to go before I sleep.

—Robert Frost, “Stopping by Woods on a Snowy Evening”¹

Frost's words are simple yet elegant. They can be interpreted many ways. I see the allegory of life as a journey in this poem. The passage, like the woods, is beautiful, but there is a long, long way to go.

See related article

And so it is with the treatment of heart failure. There is beauty in our understanding of the syndrome’s physiologic complexities and natural history, and of effective treatments uncovered. Still, we’ve a monstrous climb ahead to get to the summit of this clinical challenge in order to start a real descent.

THE PAST, PRESENT, AND FUTURE OF HEART FAILURE THERAPY

Okwuosa et al,² in this issue of the Journal, have capably summarized the ABCs of treating heart failure with reduced ejection fraction (also called systolic heart failure), approaching the subject from a perspective on past, present, and future therapies. They summarize heart failure interventions with a guideline-based philosophy, pointing out that these care paths are supposed to be evidence-based. They observe that in the 1960s the standard of care was digitalis, diuretics (furosemide first became available in 1967), and rest. That was about all we had for this problem.

There are now many drugs, devices, and operations that help patients with heart failure. But they never really cure the disease or, more aptly, the syndrome—and therapies are supposed to cure. This limitation of present therapies is important, given the disturbing epidemiology of heart failure, its economic cost, and the suffering of patients. That burden is well detailed.

In addition to curing, the overarching goals of treatment generally are to ameliorate distressing symptoms and to prevent comorbidities. In heart failure with reduced ejection fraction, we want to prevent premature death, stroke, myocardial infarction, congestive states, hospitalization, renal insufficiency, renal failure, cachexia, inanition, feebleness, and respiratory distress, among others.

The ABC mnemonic of Okwuosa et al will help caregivers remember the basics. It is important, however, to put algorithms into proper perspective and to look toward the future.

PROBLEMS WITH EVIDENCE-BASED MEDICINE

Several problems with our current heart failure treatments are rooted in how we perform clinical trials, arguably the premier method of determining truth in clinical practice and the foundation of evidence-based medicine.^3,4

Do the trials represent real-world practice?

Were the clinical trials that led to regulatory approval and professional society endorsement of the therapies that we prescribe in our offices done in the same sorts of patients as those in our waiting rooms asking for help? Perhaps, for the most part, they have been. And thus, Okwuosa et al have crafted a work relevant to all of us and every patient.

But I believe there are major gaps in the types of participants enrolled in trials, eg, underrepresentation of certain racial and ethnic groups, not to mention the relative paucity of women. The very elderly (a rapidly growing population) have largely been ignored as well, and participants with significant renal insufficiency, anemia, and diabetes mellitus seem far fewer than what we deal with in a busy clinic.

In addition, Okwuosa et al focus only on patients with reduced left ventricular ejection fraction, a group that makes up only about half of the heart failure crowd.

What about quality of life and other important outcomes?

Clinical trials in heart failure with reduced ejection fraction have generally focused on major clinical end points (primarily, but not exclusively, mortality), to the exclusion of quality of life. Though sometimes included in trials, quality-of-life metrics generally get relegated to second-class seats or ‘tween-deck steerage. Perhaps that is because measuring quality of life can be time-consuming and difficult.

Yet, in the words of sociologist William Bruce Cameron, not everything that counts can be counted, and not everything that can be counted counts. That goes for quality of life.

Lies, damned lies, and P values

Quandaries in data management and analysis include what to do about trial dropouts, study power, precision of statistical analysis, intention-to-treat principles, and choice of the P value that defines significance (or not) for any end point observation. Of course, there are myriad sophisticated mathematical and statistical reasons to justify why we don’t simply count on-treatment participants or allow imputation of results when patients or results drop out, forcing us to worship at the altar of P < .05.

A review of the P value concept⁵ recently appeared with an accompanying editorial by Kyriacou⁶ that concluded that “the automatic application of dichotomized hypothesis testing based on prearranged levels of statistical significance should be substituted with a more complex process using effect estimates, confidence intervals, and even P values, thereby permitting scientists, statisticians, and clinicians to use their own inferential capabilities to assign scientific significance.”⁶

How many great treatments have we tossed out because of rigid reliance on old-fashioned approaches to determining therapeutic evidence? Many treatments studied have had great results in a minority of patients in clinical trials but did not have a major positive (or negative) impact on the overall cohort (with lack of primary end point statistical significance). And what to do when the primary end point is a neutral or negative one but secondary end points are positive? Why not focus more attention on those patients benefiting from an intervention despite the overall results of any trial?

Dilemmas of trials

Other issues are that clinical trials cost too much, and that recruitment and follow-up take too long. Intercurrent therapies (and guidelines) can emerge that jeopardize the trial itself or make observations untimely. The dilemma of stacking therapies one on top of another, often making patient compliance impossible, is another problem with clinical trials. Yet this is how we get to the ABCs.

A NEW WAY TO DO TRIALS

The information provided by Okwuosa et al is useful and encouraging, but too many gaps exist in our heart failure therapies to permit us to celebrate with exuberance. Too many patients still suffer, too many die too young, and the costs are still too great.

Perhaps the future of therapeutic development should embrace different and better ways to demonstrate real value (relying on the equation of value equals outcomes meaningful to patients, divided by cost) of therapies, including the old, the new, the trashed and the underdeveloped. More creative data analysis to reexamine the current tools on the shelf and the ones tried but discarded is essential.

A position paper from the Cardiovascular Round Table of the European Society of Cardiology concluded that “a coordinated effort involving academia, regulators, industry and payors will help to foster better and more effective conduct of clinical cardiovascular trials, supporting earlier availability of innovative therapies and better management of cardiovascular diseases.”⁷

Lauer and D’Agostino,⁸ also in an editorial, argued for innovative methods of doing clinical trials and discovering truth about therapies that are applicable to the future of developing treatments for heart failure with reduced ejection fraction. They noted that “the randomized registry trial represents a disruptive technology” and wondered if it will be “given serious consideration as a way to resolve the recognized limitations of current clinical-trial design.”⁸

Indeed, conducting megatrials with existing megadatabases using a registry format could help. Registries emerging from early adaptive trial design efforts, particularly when Bayesian analysis theory is applied, might help inform clinical experience faster and more efficiently. Bayesian analysis is a statistical approach that attempts to estimate parameters of an underlying distribution of events in an ongoing fashion based on the observed distribution. A clinical trial of stem cell therapies could, at the end of the trial, be turned into a multicenter registry that would continue to inform us about the more real-world application of newer treatment approaches.

Though the therapeutic cupboard for heart failure is certainly not bare, as Okwuosa et al point out, it is wanting. Let’s look for new therapeutic ABCs differently. We should be attacking the real challenge—curing the disease processes that cause the syndrome. Yes, there are miles to go before we sleep.

The woods are lovely, dark and deep,
But I have promises to keep,
And miles to go before I sleep,
And miles to go before I sleep.

—Robert Frost, “Stopping by Woods on a Snowy Evening”¹

Frost's words are simple yet elegant. They can be interpreted many ways. I see the allegory of life as a journey in this poem. The passage, like the woods, is beautiful, but there is a long, long way to go.

See related article

And so it is with the treatment of heart failure. There is beauty in our understanding of the syndrome’s physiologic complexities and natural history, and of effective treatments uncovered. Still, we’ve a monstrous climb ahead to get to the summit of this clinical challenge in order to start a real descent.

THE PAST, PRESENT, AND FUTURE OF HEART FAILURE THERAPY

Okwuosa et al,² in this issue of the Journal, have capably summarized the ABCs of treating heart failure with reduced ejection fraction (also called systolic heart failure), approaching the subject from a perspective on past, present, and future therapies. They summarize heart failure interventions with a guideline-based philosophy, pointing out that these care paths are supposed to be evidence-based. They observe that in the 1960s the standard of care was digitalis, diuretics (furosemide first became available in 1967), and rest. That was about all we had for this problem.

There are now many drugs, devices, and operations that help patients with heart failure. But they never really cure the disease or, more aptly, the syndrome—and therapies are supposed to cure. This limitation of present therapies is important, given the disturbing epidemiology of heart failure, its economic cost, and the suffering of patients. That burden is well detailed.

In addition to curing, the overarching goals of treatment generally are to ameliorate distressing symptoms and to prevent comorbidities. In heart failure with reduced ejection fraction, we want to prevent premature death, stroke, myocardial infarction, congestive states, hospitalization, renal insufficiency, renal failure, cachexia, inanition, feebleness, and respiratory distress, among others.

The ABC mnemonic of Okwuosa et al will help caregivers remember the basics. It is important, however, to put algorithms into proper perspective and to look toward the future.

PROBLEMS WITH EVIDENCE-BASED MEDICINE

Several problems with our current heart failure treatments are rooted in how we perform clinical trials, arguably the premier method of determining truth in clinical practice and the foundation of evidence-based medicine.^3,4

Do the trials represent real-world practice?

Were the clinical trials that led to regulatory approval and professional society endorsement of the therapies that we prescribe in our offices done in the same sorts of patients as those in our waiting rooms asking for help? Perhaps, for the most part, they have been. And thus, Okwuosa et al have crafted a work relevant to all of us and every patient.

But I believe there are major gaps in the types of participants enrolled in trials, eg, underrepresentation of certain racial and ethnic groups, not to mention the relative paucity of women. The very elderly (a rapidly growing population) have largely been ignored as well, and participants with significant renal insufficiency, anemia, and diabetes mellitus seem far fewer than what we deal with in a busy clinic.

In addition, Okwuosa et al focus only on patients with reduced left ventricular ejection fraction, a group that makes up only about half of the heart failure crowd.

What about quality of life and other important outcomes?

Clinical trials in heart failure with reduced ejection fraction have generally focused on major clinical end points (primarily, but not exclusively, mortality), to the exclusion of quality of life. Though sometimes included in trials, quality-of-life metrics generally get relegated to second-class seats or ‘tween-deck steerage. Perhaps that is because measuring quality of life can be time-consuming and difficult.

Yet, in the words of sociologist William Bruce Cameron, not everything that counts can be counted, and not everything that can be counted counts. That goes for quality of life.

Lies, damned lies, and P values

Quandaries in data management and analysis include what to do about trial dropouts, study power, precision of statistical analysis, intention-to-treat principles, and choice of the P value that defines significance (or not) for any end point observation. Of course, there are myriad sophisticated mathematical and statistical reasons to justify why we don’t simply count on-treatment participants or allow imputation of results when patients or results drop out, forcing us to worship at the altar of P < .05.

A review of the P value concept⁵ recently appeared with an accompanying editorial by Kyriacou⁶ that concluded that “the automatic application of dichotomized hypothesis testing based on prearranged levels of statistical significance should be substituted with a more complex process using effect estimates, confidence intervals, and even P values, thereby permitting scientists, statisticians, and clinicians to use their own inferential capabilities to assign scientific significance.”⁶

How many great treatments have we tossed out because of rigid reliance on old-fashioned approaches to determining therapeutic evidence? Many treatments studied have had great results in a minority of patients in clinical trials but did not have a major positive (or negative) impact on the overall cohort (with lack of primary end point statistical significance). And what to do when the primary end point is a neutral or negative one but secondary end points are positive? Why not focus more attention on those patients benefiting from an intervention despite the overall results of any trial?

Dilemmas of trials

Other issues are that clinical trials cost too much, and that recruitment and follow-up take too long. Intercurrent therapies (and guidelines) can emerge that jeopardize the trial itself or make observations untimely. The dilemma of stacking therapies one on top of another, often making patient compliance impossible, is another problem with clinical trials. Yet this is how we get to the ABCs.

A NEW WAY TO DO TRIALS

The information provided by Okwuosa et al is useful and encouraging, but too many gaps exist in our heart failure therapies to permit us to celebrate with exuberance. Too many patients still suffer, too many die too young, and the costs are still too great.

Perhaps the future of therapeutic development should embrace different and better ways to demonstrate real value (relying on the equation of value equals outcomes meaningful to patients, divided by cost) of therapies, including the old, the new, the trashed and the underdeveloped. More creative data analysis to reexamine the current tools on the shelf and the ones tried but discarded is essential.

A position paper from the Cardiovascular Round Table of the European Society of Cardiology concluded that “a coordinated effort involving academia, regulators, industry and payors will help to foster better and more effective conduct of clinical cardiovascular trials, supporting earlier availability of innovative therapies and better management of cardiovascular diseases.”⁷

Lauer and D’Agostino,⁸ also in an editorial, argued for innovative methods of doing clinical trials and discovering truth about therapies that are applicable to the future of developing treatments for heart failure with reduced ejection fraction. They noted that “the randomized registry trial represents a disruptive technology” and wondered if it will be “given serious consideration as a way to resolve the recognized limitations of current clinical-trial design.”⁸

Indeed, conducting megatrials with existing megadatabases using a registry format could help. Registries emerging from early adaptive trial design efforts, particularly when Bayesian analysis theory is applied, might help inform clinical experience faster and more efficiently. Bayesian analysis is a statistical approach that attempts to estimate parameters of an underlying distribution of events in an ongoing fashion based on the observed distribution. A clinical trial of stem cell therapies could, at the end of the trial, be turned into a multicenter registry that would continue to inform us about the more real-world application of newer treatment approaches.

Though the therapeutic cupboard for heart failure is certainly not bare, as Okwuosa et al point out, it is wanting. Let’s look for new therapeutic ABCs differently. We should be attacking the real challenge—curing the disease processes that cause the syndrome. Yes, there are miles to go before we sleep.

WAIKOLOA, HAWAII – The FRAIL scale questionnaire predicts functional status and mortality at 1 year among geriatric trauma patients and is a useful tool for bedside screening by clinicians, results from a single-center study demonstrated.

“Over the past 2 years, the implications of frailty among the geriatric trauma population have gained much attention in the trauma community,” Cathy A. Maxwell, PhD, RN, said in an interview in advance of the annual meeting of the American Association for the Surgery of Trauma. “This work highlights the clinical utility of the FRAIL scale for screening injured older patients who are admitted to trauma centers and other acute care hospitals. Hopefully, it will encourage trauma care providers to use the instrument to identify older patients’ pre-injury/baseline status and to obtain a frailty risk adjustment measure for quality improvement efforts.”

Developed by the International Association of Nutrition and Aging, the validated five-item FRAIL scale requires answers to questions about fatigue, resistance, ambulation, illnesses, and loss of weight (J Nutr Health Aging. 2012;16[7]:601-8). In an effort to examine the influence of pre-injury physical frailty (as measured by FRAIL) on 1-year outcomes, Dr. Maxwell, of the Vanderbilt University, Nashville, Tenn., and her associates evaluated injured patients aged 65 and older who were admitted through the ED between October 2013 and March 2014 and who participated in a prior study (J Trauma Acute Care Surg. 2016;80[2]:195-203). The researchers identified the five items of the FRAIL instrument from that study and created a pre-injury FRAIL score for each patient.

Dr. Maxwell reported results from 188 patients with a median age of 77, a median Injury Severity Score of 10, and a median comorbidity index of 3. Upon admission to the ED, 63 patients (34%) screened as frail (defined as a FRAIL score of 3 or greater), 71 (38%) screened as pre-frail (defined as a FRAIL score of 1-2), and 54 (29%) screened as non-frail (defined as a FRAIL score of zero). Frequencies for components of the FRAIL score were as follows: fatigue (65%), resistance (32%), ambulation (40%), illnesses (27%), and loss of weight (6%).

After the researchers controlled for age, comorbidities, injury severity, and cognitive status via the Ascertain Dementia 8-item Informant Questionnaire (AD8), they found that pre-injury FRAIL scores explained about 13% of the variability in physical function as measured by the Barthel Index (P less than .001). A total of 47 patients (26%) died within 1 year of admission. Logistic regression analysis revealed that after adjustment for these same variables, the higher the pre-injury FRAIL score, the greater the likelihood of mortality within 1 year (odds ratio, 1.74; P = .001).

“The FRAIL scale predicts functional decline and mortality in geriatric trauma patients and is a useful tool for clinicians,” Dr. Maxwell concluded. “Bedside nurses in our trauma unit at Vanderbilt University Medical Center are currently using this instrument to screen our older patients. We have seen an increase in earlier geriatric palliative care consultations as a result of our screening efforts.”

She acknowledged certain limitations of the study, including the fact that it was a secondary analysis. “We created FRAIL scale scores for 188 patients from six different data sources, thus, the created scores may not accurately represent actual prospectively collected FRAIL scores,” Dr. Maxwell said. “That being said, we compared the frailty frequencies from this study with actual FRAIL scale scores (from current bedside FRAIL screens) and we are seeing similar percentages of patients in non-frail, pre-frail and frail categories. This strengthens the findings of this study.”

She reported having no financial disclosures.

dbrunk@frontlinemedcom.com

WAIKOLOA, HAWAII – The FRAIL scale questionnaire predicts functional status and mortality at 1 year among geriatric trauma patients and is a useful tool for bedside screening by clinicians, results from a single-center study demonstrated.

“Over the past 2 years, the implications of frailty among the geriatric trauma population have gained much attention in the trauma community,” Cathy A. Maxwell, PhD, RN, said in an interview in advance of the annual meeting of the American Association for the Surgery of Trauma. “This work highlights the clinical utility of the FRAIL scale for screening injured older patients who are admitted to trauma centers and other acute care hospitals. Hopefully, it will encourage trauma care providers to use the instrument to identify older patients’ pre-injury/baseline status and to obtain a frailty risk adjustment measure for quality improvement efforts.”

Developed by the International Association of Nutrition and Aging, the validated five-item FRAIL scale requires answers to questions about fatigue, resistance, ambulation, illnesses, and loss of weight (J Nutr Health Aging. 2012;16[7]:601-8). In an effort to examine the influence of pre-injury physical frailty (as measured by FRAIL) on 1-year outcomes, Dr. Maxwell, of the Vanderbilt University, Nashville, Tenn., and her associates evaluated injured patients aged 65 and older who were admitted through the ED between October 2013 and March 2014 and who participated in a prior study (J Trauma Acute Care Surg. 2016;80[2]:195-203). The researchers identified the five items of the FRAIL instrument from that study and created a pre-injury FRAIL score for each patient.

Dr. Maxwell reported results from 188 patients with a median age of 77, a median Injury Severity Score of 10, and a median comorbidity index of 3. Upon admission to the ED, 63 patients (34%) screened as frail (defined as a FRAIL score of 3 or greater), 71 (38%) screened as pre-frail (defined as a FRAIL score of 1-2), and 54 (29%) screened as non-frail (defined as a FRAIL score of zero). Frequencies for components of the FRAIL score were as follows: fatigue (65%), resistance (32%), ambulation (40%), illnesses (27%), and loss of weight (6%).

After the researchers controlled for age, comorbidities, injury severity, and cognitive status via the Ascertain Dementia 8-item Informant Questionnaire (AD8), they found that pre-injury FRAIL scores explained about 13% of the variability in physical function as measured by the Barthel Index (P less than .001). A total of 47 patients (26%) died within 1 year of admission. Logistic regression analysis revealed that after adjustment for these same variables, the higher the pre-injury FRAIL score, the greater the likelihood of mortality within 1 year (odds ratio, 1.74; P = .001).

“The FRAIL scale predicts functional decline and mortality in geriatric trauma patients and is a useful tool for clinicians,” Dr. Maxwell concluded. “Bedside nurses in our trauma unit at Vanderbilt University Medical Center are currently using this instrument to screen our older patients. We have seen an increase in earlier geriatric palliative care consultations as a result of our screening efforts.”

She acknowledged certain limitations of the study, including the fact that it was a secondary analysis. “We created FRAIL scale scores for 188 patients from six different data sources, thus, the created scores may not accurately represent actual prospectively collected FRAIL scores,” Dr. Maxwell said. “That being said, we compared the frailty frequencies from this study with actual FRAIL scale scores (from current bedside FRAIL screens) and we are seeing similar percentages of patients in non-frail, pre-frail and frail categories. This strengthens the findings of this study.”

She reported having no financial disclosures.

dbrunk@frontlinemedcom.com

WAIKOLOA, HAWAII – The FRAIL scale questionnaire predicts functional status and mortality at 1 year among geriatric trauma patients and is a useful tool for bedside screening by clinicians, results from a single-center study demonstrated.

“Over the past 2 years, the implications of frailty among the geriatric trauma population have gained much attention in the trauma community,” Cathy A. Maxwell, PhD, RN, said in an interview in advance of the annual meeting of the American Association for the Surgery of Trauma. “This work highlights the clinical utility of the FRAIL scale for screening injured older patients who are admitted to trauma centers and other acute care hospitals. Hopefully, it will encourage trauma care providers to use the instrument to identify older patients’ pre-injury/baseline status and to obtain a frailty risk adjustment measure for quality improvement efforts.”

Developed by the International Association of Nutrition and Aging, the validated five-item FRAIL scale requires answers to questions about fatigue, resistance, ambulation, illnesses, and loss of weight (J Nutr Health Aging. 2012;16[7]:601-8). In an effort to examine the influence of pre-injury physical frailty (as measured by FRAIL) on 1-year outcomes, Dr. Maxwell, of the Vanderbilt University, Nashville, Tenn., and her associates evaluated injured patients aged 65 and older who were admitted through the ED between October 2013 and March 2014 and who participated in a prior study (J Trauma Acute Care Surg. 2016;80[2]:195-203). The researchers identified the five items of the FRAIL instrument from that study and created a pre-injury FRAIL score for each patient.

Dr. Maxwell reported results from 188 patients with a median age of 77, a median Injury Severity Score of 10, and a median comorbidity index of 3. Upon admission to the ED, 63 patients (34%) screened as frail (defined as a FRAIL score of 3 or greater), 71 (38%) screened as pre-frail (defined as a FRAIL score of 1-2), and 54 (29%) screened as non-frail (defined as a FRAIL score of zero). Frequencies for components of the FRAIL score were as follows: fatigue (65%), resistance (32%), ambulation (40%), illnesses (27%), and loss of weight (6%).

After the researchers controlled for age, comorbidities, injury severity, and cognitive status via the Ascertain Dementia 8-item Informant Questionnaire (AD8), they found that pre-injury FRAIL scores explained about 13% of the variability in physical function as measured by the Barthel Index (P less than .001). A total of 47 patients (26%) died within 1 year of admission. Logistic regression analysis revealed that after adjustment for these same variables, the higher the pre-injury FRAIL score, the greater the likelihood of mortality within 1 year (odds ratio, 1.74; P = .001).

“The FRAIL scale predicts functional decline and mortality in geriatric trauma patients and is a useful tool for clinicians,” Dr. Maxwell concluded. “Bedside nurses in our trauma unit at Vanderbilt University Medical Center are currently using this instrument to screen our older patients. We have seen an increase in earlier geriatric palliative care consultations as a result of our screening efforts.”

She acknowledged certain limitations of the study, including the fact that it was a secondary analysis. “We created FRAIL scale scores for 188 patients from six different data sources, thus, the created scores may not accurately represent actual prospectively collected FRAIL scores,” Dr. Maxwell said. “That being said, we compared the frailty frequencies from this study with actual FRAIL scale scores (from current bedside FRAIL screens) and we are seeing similar percentages of patients in non-frail, pre-frail and frail categories. This strengthens the findings of this study.”

She reported having no financial disclosures.

dbrunk@frontlinemedcom.com

There is increased anxiety and depression among family caregivers who do not take care of themselves, according to a study to be presented at the 2016 ASCO Palliative Care in Oncology Symposium.

Nearly a quarter of 294 caregivers of Medicare patients with advanced cancer reported high depression scores (23%) and 34% reported borderline or high anxiety scores. Worse caregiver anxiety, depression, and mental health–related quality of life scores were significantly associated with lower scores in every self-care measure (P less than .05 for all). Lower self-care behavior scores were associated with longer durations, higher hours, and more days/week of caregiving and with fair or poor patient health.

The cross-sectional survey was conducted in community settings of eight cancer centers in Alabama, Florida, and Tennessee. The family caregivers of Medicare beneficiaries diagnosed with pancreatic, lung, brain, ovarian, head & neck, hematologic, or stage IV cancer completed measures of self-care behaviors, including health responsibility, physical activity, nutrition, spiritual growth, interpersonal relations, stress management, and sleep. Caregivers averaged 66 years and were mostly female (72.8%), white (91.2%), Protestant (76.2%), retired (54.4%), and patients’ spouse/partner (60.2%). Approximately half were rural dwellers (46.9%) and had incomes less than $50,000 (53.8%). The majority provided support 6-7 days per week (71%) for greater than 1 year (68%).

“This research serves as an important call to action for the oncology community to implement support networks and services that care for the caregiver,” ASCO representative Andrew Epstein, MD, of Memorial Sloan Kettering Cancer Center, New York, said in a written statement ahead of the symposium.

“We hope our research rallies the oncology palliative care communities to develop assessment tools and services that support caregivers,” lead author James Nicholas Dionne-Odom, PhD, RN, of the University of Alabama at Birmingham, said in the statement.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

There is increased anxiety and depression among family caregivers who do not take care of themselves, according to a study to be presented at the 2016 ASCO Palliative Care in Oncology Symposium.

Nearly a quarter of 294 caregivers of Medicare patients with advanced cancer reported high depression scores (23%) and 34% reported borderline or high anxiety scores. Worse caregiver anxiety, depression, and mental health–related quality of life scores were significantly associated with lower scores in every self-care measure (P less than .05 for all). Lower self-care behavior scores were associated with longer durations, higher hours, and more days/week of caregiving and with fair or poor patient health.

The cross-sectional survey was conducted in community settings of eight cancer centers in Alabama, Florida, and Tennessee. The family caregivers of Medicare beneficiaries diagnosed with pancreatic, lung, brain, ovarian, head & neck, hematologic, or stage IV cancer completed measures of self-care behaviors, including health responsibility, physical activity, nutrition, spiritual growth, interpersonal relations, stress management, and sleep. Caregivers averaged 66 years and were mostly female (72.8%), white (91.2%), Protestant (76.2%), retired (54.4%), and patients’ spouse/partner (60.2%). Approximately half were rural dwellers (46.9%) and had incomes less than $50,000 (53.8%). The majority provided support 6-7 days per week (71%) for greater than 1 year (68%).

“This research serves as an important call to action for the oncology community to implement support networks and services that care for the caregiver,” ASCO representative Andrew Epstein, MD, of Memorial Sloan Kettering Cancer Center, New York, said in a written statement ahead of the symposium.

“We hope our research rallies the oncology palliative care communities to develop assessment tools and services that support caregivers,” lead author James Nicholas Dionne-Odom, PhD, RN, of the University of Alabama at Birmingham, said in the statement.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

There is increased anxiety and depression among family caregivers who do not take care of themselves, according to a study to be presented at the 2016 ASCO Palliative Care in Oncology Symposium.

Nearly a quarter of 294 caregivers of Medicare patients with advanced cancer reported high depression scores (23%) and 34% reported borderline or high anxiety scores. Worse caregiver anxiety, depression, and mental health–related quality of life scores were significantly associated with lower scores in every self-care measure (P less than .05 for all). Lower self-care behavior scores were associated with longer durations, higher hours, and more days/week of caregiving and with fair or poor patient health.

The cross-sectional survey was conducted in community settings of eight cancer centers in Alabama, Florida, and Tennessee. The family caregivers of Medicare beneficiaries diagnosed with pancreatic, lung, brain, ovarian, head & neck, hematologic, or stage IV cancer completed measures of self-care behaviors, including health responsibility, physical activity, nutrition, spiritual growth, interpersonal relations, stress management, and sleep. Caregivers averaged 66 years and were mostly female (72.8%), white (91.2%), Protestant (76.2%), retired (54.4%), and patients’ spouse/partner (60.2%). Approximately half were rural dwellers (46.9%) and had incomes less than $50,000 (53.8%). The majority provided support 6-7 days per week (71%) for greater than 1 year (68%).

“This research serves as an important call to action for the oncology community to implement support networks and services that care for the caregiver,” ASCO representative Andrew Epstein, MD, of Memorial Sloan Kettering Cancer Center, New York, said in a written statement ahead of the symposium.

“We hope our research rallies the oncology palliative care communities to develop assessment tools and services that support caregivers,” lead author James Nicholas Dionne-Odom, PhD, RN, of the University of Alabama at Birmingham, said in the statement.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

Nearly one-third of hospital newborn nurseries and neonatal ICUs do not have an antibiotic stewardship program, according to a survey of 146 hospital nursery centers across all 50 states.

Researchers randomly selected a level III NICU in each state using the 2014 American Hospital Association annual survey, then selected a level I and level II nursery in the same city. They collected data on the hospital, nursery, and antibiotic stewardship program characteristics and interviewed staff pharmacists and infectious diseases physicians (J Pediatric Infect Dis Soc. 2016 Jul 15. doi: 10.1093/jpids/piw040).

©luchschen/Thinkstock

A total of 104 (71%) of responding hospitals had an antibiotic stewardship program in place for their nurseries. Hospitals with a nursery-based antibiotic stewardship programs tended to be larger, have more full-time equivalent staff dedicated to the antibiotic stewardship program, have higher level nurses, and be affiliated with a university, according to Joseph B. Cantey, MD, and his colleagues from the Texas A&M Health Science Center in Temple.

Geographic region and core stewardship strategies did not influence the likelihood of a nursery-based antibiotic stewardship program in place.

From the interviews, the researchers identified several barriers to implementation of antibiotic stewardship programs, and themes such as unwanted coverage, unnecessary coverage, and need for communication.

“Many [antibiotic stewardship program] and nursery representatives stated that nursery [antibiotic stewardship program] coverage was not important, either because antibiotic consumption was perceived as low (theme 1), narrow-spectrum (theme 2), or both,” the authors wrote.

Some nursery providers also argued that participating in stewardship programs was time consuming and not valuable, which the authors said was often related to a lack of pediatric expertise in the program providers. Some of those interviewed also spoke of issues relating to jurisdiction and responsibility for the programs, and there was also a common perception that antibiotic stewardship programs were more concerned with cost savings than patient care.

“Barriers to effective nursery stewardship are exacerbated by lack of communication between stewardship providers and their nursery counterparts,” the authors reported.

No conflicts of interest were declared.

Nearly one-third of hospital newborn nurseries and neonatal ICUs do not have an antibiotic stewardship program, according to a survey of 146 hospital nursery centers across all 50 states.

Researchers randomly selected a level III NICU in each state using the 2014 American Hospital Association annual survey, then selected a level I and level II nursery in the same city. They collected data on the hospital, nursery, and antibiotic stewardship program characteristics and interviewed staff pharmacists and infectious diseases physicians (J Pediatric Infect Dis Soc. 2016 Jul 15. doi: 10.1093/jpids/piw040).

©luchschen/Thinkstock

A total of 104 (71%) of responding hospitals had an antibiotic stewardship program in place for their nurseries. Hospitals with a nursery-based antibiotic stewardship programs tended to be larger, have more full-time equivalent staff dedicated to the antibiotic stewardship program, have higher level nurses, and be affiliated with a university, according to Joseph B. Cantey, MD, and his colleagues from the Texas A&M Health Science Center in Temple.

Geographic region and core stewardship strategies did not influence the likelihood of a nursery-based antibiotic stewardship program in place.

From the interviews, the researchers identified several barriers to implementation of antibiotic stewardship programs, and themes such as unwanted coverage, unnecessary coverage, and need for communication.

“Many [antibiotic stewardship program] and nursery representatives stated that nursery [antibiotic stewardship program] coverage was not important, either because antibiotic consumption was perceived as low (theme 1), narrow-spectrum (theme 2), or both,” the authors wrote.

Some nursery providers also argued that participating in stewardship programs was time consuming and not valuable, which the authors said was often related to a lack of pediatric expertise in the program providers. Some of those interviewed also spoke of issues relating to jurisdiction and responsibility for the programs, and there was also a common perception that antibiotic stewardship programs were more concerned with cost savings than patient care.

“Barriers to effective nursery stewardship are exacerbated by lack of communication between stewardship providers and their nursery counterparts,” the authors reported.

No conflicts of interest were declared.

Nearly one-third of hospital newborn nurseries and neonatal ICUs do not have an antibiotic stewardship program, according to a survey of 146 hospital nursery centers across all 50 states.

Researchers randomly selected a level III NICU in each state using the 2014 American Hospital Association annual survey, then selected a level I and level II nursery in the same city. They collected data on the hospital, nursery, and antibiotic stewardship program characteristics and interviewed staff pharmacists and infectious diseases physicians (J Pediatric Infect Dis Soc. 2016 Jul 15. doi: 10.1093/jpids/piw040).

©luchschen/Thinkstock

A total of 104 (71%) of responding hospitals had an antibiotic stewardship program in place for their nurseries. Hospitals with a nursery-based antibiotic stewardship programs tended to be larger, have more full-time equivalent staff dedicated to the antibiotic stewardship program, have higher level nurses, and be affiliated with a university, according to Joseph B. Cantey, MD, and his colleagues from the Texas A&M Health Science Center in Temple.

Geographic region and core stewardship strategies did not influence the likelihood of a nursery-based antibiotic stewardship program in place.

From the interviews, the researchers identified several barriers to implementation of antibiotic stewardship programs, and themes such as unwanted coverage, unnecessary coverage, and need for communication.

“Many [antibiotic stewardship program] and nursery representatives stated that nursery [antibiotic stewardship program] coverage was not important, either because antibiotic consumption was perceived as low (theme 1), narrow-spectrum (theme 2), or both,” the authors wrote.

Some nursery providers also argued that participating in stewardship programs was time consuming and not valuable, which the authors said was often related to a lack of pediatric expertise in the program providers. Some of those interviewed also spoke of issues relating to jurisdiction and responsibility for the programs, and there was also a common perception that antibiotic stewardship programs were more concerned with cost savings than patient care.

“Barriers to effective nursery stewardship are exacerbated by lack of communication between stewardship providers and their nursery counterparts,” the authors reported.

No conflicts of interest were declared.

Purpose: This literature review was performed to better understand how to facilitate the integration of palliative care and oncology care at the onset of treatment for patients at a VAMC facility.

Background: Palliative care is defined by the World Health Organization (WHO) as an approach to care aimed at improving the quality of life of patients and their families who are facing obstacles associated with a serious or terminal illness (WHO). The intention of palliative care is not curative; it does however address the prevention, early identification and treatment of pain, and problems which may be physical, psychosocial and spiritual. Palliative care should be integrated early in the course of the disease and in conjunction with life-saving treatments (Greer et al, 2013).

Methods: A search of databases included Google Scholar, PubMed, Ovid, and CINAHL identified randomized clinical trials, systematic reviews and expert reviews regarding the integration of palliative care at the initial diagnosis and when cancer treatment begins.

Results: Several interventions for integration of palliative care with standard cancer were identified as well as increase patient outcomes. The National Comprehensive Care Network,(NCCN), the American Society of Clinical Oncology, (ASCO), and the Institute of Medicine (IOM), all advocate for the initiation of palliative care at the onset of treatment. Guidelines for screening, assessments, and interventions are available to begin the process of integration. There are several barriers, however, affecting the integration of palliative care with comprehensive oncology care. These barriers include inadequate staffing, inadequate training, standardized assessment and screening tools. The process also requires the cooperation and support of facility leadership and administration.

Implications: There is strong evidence for the integration of palliative and oncology care for Veterans receiving cancer care at VAMC facilities. Oncology would continue to focus on the treatment of disease with the primary assessment of pain, other symptom management, and goals of care. Palliative care would be able to assist the patient with the more complicated symptomatology, psychosocial support, advance care planning and easier transitions into hospice care. Each discipline has a role in the improved outcomes and improved quality of life for patients.

Purpose: This literature review was performed to better understand how to facilitate the integration of palliative care and oncology care at the onset of treatment for patients at a VAMC facility.

Background: Palliative care is defined by the World Health Organization (WHO) as an approach to care aimed at improving the quality of life of patients and their families who are facing obstacles associated with a serious or terminal illness (WHO). The intention of palliative care is not curative; it does however address the prevention, early identification and treatment of pain, and problems which may be physical, psychosocial and spiritual. Palliative care should be integrated early in the course of the disease and in conjunction with life-saving treatments (Greer et al, 2013).

Methods: A search of databases included Google Scholar, PubMed, Ovid, and CINAHL identified randomized clinical trials, systematic reviews and expert reviews regarding the integration of palliative care at the initial diagnosis and when cancer treatment begins.

Results: Several interventions for integration of palliative care with standard cancer were identified as well as increase patient outcomes. The National Comprehensive Care Network,(NCCN), the American Society of Clinical Oncology, (ASCO), and the Institute of Medicine (IOM), all advocate for the initiation of palliative care at the onset of treatment. Guidelines for screening, assessments, and interventions are available to begin the process of integration. There are several barriers, however, affecting the integration of palliative care with comprehensive oncology care. These barriers include inadequate staffing, inadequate training, standardized assessment and screening tools. The process also requires the cooperation and support of facility leadership and administration.

Implications: There is strong evidence for the integration of palliative and oncology care for Veterans receiving cancer care at VAMC facilities. Oncology would continue to focus on the treatment of disease with the primary assessment of pain, other symptom management, and goals of care. Palliative care would be able to assist the patient with the more complicated symptomatology, psychosocial support, advance care planning and easier transitions into hospice care. Each discipline has a role in the improved outcomes and improved quality of life for patients.

Purpose: This literature review was performed to better understand how to facilitate the integration of palliative care and oncology care at the onset of treatment for patients at a VAMC facility.

Background: Palliative care is defined by the World Health Organization (WHO) as an approach to care aimed at improving the quality of life of patients and their families who are facing obstacles associated with a serious or terminal illness (WHO). The intention of palliative care is not curative; it does however address the prevention, early identification and treatment of pain, and problems which may be physical, psychosocial and spiritual. Palliative care should be integrated early in the course of the disease and in conjunction with life-saving treatments (Greer et al, 2013).

Methods: A search of databases included Google Scholar, PubMed, Ovid, and CINAHL identified randomized clinical trials, systematic reviews and expert reviews regarding the integration of palliative care at the initial diagnosis and when cancer treatment begins.

Results: Several interventions for integration of palliative care with standard cancer were identified as well as increase patient outcomes. The National Comprehensive Care Network,(NCCN), the American Society of Clinical Oncology, (ASCO), and the Institute of Medicine (IOM), all advocate for the initiation of palliative care at the onset of treatment. Guidelines for screening, assessments, and interventions are available to begin the process of integration. There are several barriers, however, affecting the integration of palliative care with comprehensive oncology care. These barriers include inadequate staffing, inadequate training, standardized assessment and screening tools. The process also requires the cooperation and support of facility leadership and administration.

Implications: There is strong evidence for the integration of palliative and oncology care for Veterans receiving cancer care at VAMC facilities. Oncology would continue to focus on the treatment of disease with the primary assessment of pain, other symptom management, and goals of care. Palliative care would be able to assist the patient with the more complicated symptomatology, psychosocial support, advance care planning and easier transitions into hospice care. Each discipline has a role in the improved outcomes and improved quality of life for patients.

Labeling for prescription opioid pain or cough medicines and benzodiazepines will now carry the strongest available warning regarding serious side effects and death associated with their combined use, according to the Food and Drug Administration.

The new boxed warnings urge health care professionals to limit prescribing opioid pain medicines with benzodiazepines or other central nervous system depressants only to patients for whom alternative treatment options are inadequate, and to limit dosages and treatment duration to the minimum possible while achieving the desired clinical effect.

“First, the FDA is requiring companies to update their product labeling for ... benzodiazepines and opioids to include possible harms when they are used together. Second, we are requiring new or updated medication guides for these drugs reflecting those same warnings,” said Doug Throckmorton, MD, deputy director of the FDA’s Center for Drug Evaluation and Research, during a telebriefing.

Opioids will include a warning regarding prescribing with benzodiazepines and other central nervous system depressants, including alcohol. Benzodiazepines will include a warning regarding prescribing with opioids.

In addition, the FDA has issued a safety communication to “warn the public about the serious risk of taking these products together to help make doctors more cautious and patients better informed,” Dr. Throckmorton said.

The action comes amid ongoing efforts to address an epidemic of opioid addiction across the United States, and in response to a first-of-its-kind “citizen petition” calling for the boxed warnings.

A coalition of health officials from multiple cities, states, and U.S. territories initiated that petition in February, and thousands of concerned community members started an additional online petition. Those petitions were in response to both the increasing combined use of opioids and benzodiazepines and a concomitant increase in the risk of serious side effects and deaths associated with their combined use, according to Baltimore City Health Commissioner Leana Wen, MD.

As an emergency physician, Dr. Wen said that she has seen firsthand the alarming trends; one in three unintentional overdose deaths from prescribed opioids also involve benzodiazepines, she noted.

“In my state of Maryland in 2014, benzodiazepines were associated with 19% of prescription opioid deaths, and 59% of benzodiazepine-associated deaths involved prescription opioids. We also noted the growing biological evidence that combining these medications caused sleepiness and slowed breathing, increasing the likelihood of a fatal overdose,” she said.

Dr. Throckmorton further noted that emergency department visits and deaths involving patients prescribed both opioids and benzodiazepines have increased significantly over time. From 2004 to 2011, the rate of nonmedical use–related emergency department visits increased significantly each year, and overdose deaths involving both drug classes during that period nearly tripled on an annual basis.

“Communities have been seeing this trend for some time, but ultimately we needed data in order to act today,” FDA Commissioner Robert Califf, MD, said during the telebriefing.

The current action is just “one part of a larger effort to address this epidemic.

“We remain focused and deeply committed to contributing to the comprehensive effort to address the opioid epidemic,” Dr. Califf said. The FDA “will continue to monitor these products carefully and take additional actions as needed, and will share updates with the public as necessary as we work to address this public health crisis.”

Dr. Califf noted that the current action is part of the FDA’s Opioids Action Plan, which is “importantly not meant just to cover illicit or abusive use of opioids.”

“So, you’ll be hearing a lot more from us, because this is a national crisis that is not going away. We’re making progress on the prescribing, and we’re seeing a reduction in the use of opioids now,” he noted. “But we’re still seeing many overdoses.

“This is a continuum, and we’ll continue to try to do everything we can to address the epidemic,” Dr. Califf concluded.

sworcester@frontlinemedcom.com

Labeling for prescription opioid pain or cough medicines and benzodiazepines will now carry the strongest available warning regarding serious side effects and death associated with their combined use, according to the Food and Drug Administration.

The new boxed warnings urge health care professionals to limit prescribing opioid pain medicines with benzodiazepines or other central nervous system depressants only to patients for whom alternative treatment options are inadequate, and to limit dosages and treatment duration to the minimum possible while achieving the desired clinical effect.

“First, the FDA is requiring companies to update their product labeling for ... benzodiazepines and opioids to include possible harms when they are used together. Second, we are requiring new or updated medication guides for these drugs reflecting those same warnings,” said Doug Throckmorton, MD, deputy director of the FDA’s Center for Drug Evaluation and Research, during a telebriefing.

Opioids will include a warning regarding prescribing with benzodiazepines and other central nervous system depressants, including alcohol. Benzodiazepines will include a warning regarding prescribing with opioids.

In addition, the FDA has issued a safety communication to “warn the public about the serious risk of taking these products together to help make doctors more cautious and patients better informed,” Dr. Throckmorton said.

The action comes amid ongoing efforts to address an epidemic of opioid addiction across the United States, and in response to a first-of-its-kind “citizen petition” calling for the boxed warnings.

A coalition of health officials from multiple cities, states, and U.S. territories initiated that petition in February, and thousands of concerned community members started an additional online petition. Those petitions were in response to both the increasing combined use of opioids and benzodiazepines and a concomitant increase in the risk of serious side effects and deaths associated with their combined use, according to Baltimore City Health Commissioner Leana Wen, MD.

As an emergency physician, Dr. Wen said that she has seen firsthand the alarming trends; one in three unintentional overdose deaths from prescribed opioids also involve benzodiazepines, she noted.

“In my state of Maryland in 2014, benzodiazepines were associated with 19% of prescription opioid deaths, and 59% of benzodiazepine-associated deaths involved prescription opioids. We also noted the growing biological evidence that combining these medications caused sleepiness and slowed breathing, increasing the likelihood of a fatal overdose,” she said.

Dr. Throckmorton further noted that emergency department visits and deaths involving patients prescribed both opioids and benzodiazepines have increased significantly over time. From 2004 to 2011, the rate of nonmedical use–related emergency department visits increased significantly each year, and overdose deaths involving both drug classes during that period nearly tripled on an annual basis.

“Communities have been seeing this trend for some time, but ultimately we needed data in order to act today,” FDA Commissioner Robert Califf, MD, said during the telebriefing.

The current action is just “one part of a larger effort to address this epidemic.

“We remain focused and deeply committed to contributing to the comprehensive effort to address the opioid epidemic,” Dr. Califf said. The FDA “will continue to monitor these products carefully and take additional actions as needed, and will share updates with the public as necessary as we work to address this public health crisis.”

Dr. Califf noted that the current action is part of the FDA’s Opioids Action Plan, which is “importantly not meant just to cover illicit or abusive use of opioids.”

“So, you’ll be hearing a lot more from us, because this is a national crisis that is not going away. We’re making progress on the prescribing, and we’re seeing a reduction in the use of opioids now,” he noted. “But we’re still seeing many overdoses.

“This is a continuum, and we’ll continue to try to do everything we can to address the epidemic,” Dr. Califf concluded.

sworcester@frontlinemedcom.com

Labeling for prescription opioid pain or cough medicines and benzodiazepines will now carry the strongest available warning regarding serious side effects and death associated with their combined use, according to the Food and Drug Administration.

The new boxed warnings urge health care professionals to limit prescribing opioid pain medicines with benzodiazepines or other central nervous system depressants only to patients for whom alternative treatment options are inadequate, and to limit dosages and treatment duration to the minimum possible while achieving the desired clinical effect.

“First, the FDA is requiring companies to update their product labeling for ... benzodiazepines and opioids to include possible harms when they are used together. Second, we are requiring new or updated medication guides for these drugs reflecting those same warnings,” said Doug Throckmorton, MD, deputy director of the FDA’s Center for Drug Evaluation and Research, during a telebriefing.

Opioids will include a warning regarding prescribing with benzodiazepines and other central nervous system depressants, including alcohol. Benzodiazepines will include a warning regarding prescribing with opioids.

In addition, the FDA has issued a safety communication to “warn the public about the serious risk of taking these products together to help make doctors more cautious and patients better informed,” Dr. Throckmorton said.

The action comes amid ongoing efforts to address an epidemic of opioid addiction across the United States, and in response to a first-of-its-kind “citizen petition” calling for the boxed warnings.

A coalition of health officials from multiple cities, states, and U.S. territories initiated that petition in February, and thousands of concerned community members started an additional online petition. Those petitions were in response to both the increasing combined use of opioids and benzodiazepines and a concomitant increase in the risk of serious side effects and deaths associated with their combined use, according to Baltimore City Health Commissioner Leana Wen, MD.

As an emergency physician, Dr. Wen said that she has seen firsthand the alarming trends; one in three unintentional overdose deaths from prescribed opioids also involve benzodiazepines, she noted.

“In my state of Maryland in 2014, benzodiazepines were associated with 19% of prescription opioid deaths, and 59% of benzodiazepine-associated deaths involved prescription opioids. We also noted the growing biological evidence that combining these medications caused sleepiness and slowed breathing, increasing the likelihood of a fatal overdose,” she said.

Dr. Throckmorton further noted that emergency department visits and deaths involving patients prescribed both opioids and benzodiazepines have increased significantly over time. From 2004 to 2011, the rate of nonmedical use–related emergency department visits increased significantly each year, and overdose deaths involving both drug classes during that period nearly tripled on an annual basis.

“Communities have been seeing this trend for some time, but ultimately we needed data in order to act today,” FDA Commissioner Robert Califf, MD, said during the telebriefing.

The current action is just “one part of a larger effort to address this epidemic.

“We remain focused and deeply committed to contributing to the comprehensive effort to address the opioid epidemic,” Dr. Califf said. The FDA “will continue to monitor these products carefully and take additional actions as needed, and will share updates with the public as necessary as we work to address this public health crisis.”

Dr. Califf noted that the current action is part of the FDA’s Opioids Action Plan, which is “importantly not meant just to cover illicit or abusive use of opioids.”

“So, you’ll be hearing a lot more from us, because this is a national crisis that is not going away. We’re making progress on the prescribing, and we’re seeing a reduction in the use of opioids now,” he noted. “But we’re still seeing many overdoses.

“This is a continuum, and we’ll continue to try to do everything we can to address the epidemic,” Dr. Califf concluded.

sworcester@frontlinemedcom.com

Clinicians outside of the surgical specialties may consider surgeons primarily providers of technical services, but those of us who provide surgical care fully appreciate that communicating with patients and families is a large component of routine surgical practice. Typical communications in surgical practice include obtaining a history of present illness, which is a key element in the ultimate decision to offer a surgical intervention, or not; discussing the risks, benefits, and alternatives of any operation being considered; and the numerous discussions held following any surgical procedure. What many surgeons may not fully appreciate, however, is how these routine communication events can fall under the general category of advance care planning (ACP).

ACP is defined as a process in which physicians (and other health care providers) discuss a patient’s goals, values, and beliefs and determine how these inform a patient’s desire for current or future medical care. Hickman et al. (Hastings Center Report Special Report 35, no. 6 (2005):S26-S30) note that ACP should focus on defining “good” care for each patient. Furthermore, changes in a patient’s medical condition represent an opportune time to revisit a patient’s hopes and goals. Consideration of surgical intervention often represents a major change in a patient’s medical condition and therefore is an excellent opportunity to engage a patient in an ACP discussion.

Given that ACP discussions are likely occurring in surgical practices on a regular basis, surgeons need to be aware of a recent change in the Physician Fee Schedule that took effect Jan. 1, 2016. Effective this date, Current Procedural Terminology (CPT) codes 99497 and 99498 now allow for billing for ACP services. CPT code 99497 includes ACP “including the explanation and discussion of advance directives such as standard forms (with the completion of such forms, when performed), by the physician or other qualified health care professional; first 30 minutes, face-to-face with patient, family member(s) and/or surrogate.” CPT code 99498 is used for each additional 30 minutes spent in such face-to-face ACP counseling.

The nuts and bolts of how these ACP CPT codes work:

How many times can these code(s) be used? There are no limits on the number of times ACP can be reported for a given beneficiary in a given time period. For example, if an ACP discussion was held with a patient and/or family member and/or surrogate prior to a major elective procedure and again in the postoperative period, the above CPT codes could be used twice. In each instance, the ACP discussion must be documented, along with any relevant change in the patient’s clinical status that prompted another ACP discussion.

Can a patient or their family member/surrogate refuse ACP services? ACP services are voluntary; therefore, a patient or their family member/surrogate can refuse ACP services. These CPT codes only can be used if a patient or family member/surrogate consents for ACP services.

What must be documented in ACP services? Physicians should consult their Medicare Administrative Contractors for documentation requirements. Examples of elements to be included in the documentation are a brief description of the discussion with the patient or family/surrogate regarding the voluntary nature of ACP services, an explanation of advance directives and documentation if an advance directive is completed, who was present during the discussion, and time spent in the face-to-face encounter.

Does an advance directive have to be completed to bill the service? No. If an advance directive is completed, this should be documented (see above), but completion of the directive is not a requirement for billing the service.

Can ACP be reported in addition to an evaluation and management (E/M) service (such as an office visit)? Yes. CPT codes 99497 and 99498 may be billed on the same day or a different day as most other E/M services. They may be billed within the global surgical period.

Is a specific diagnosis required to use the ACP CPT codes? No, a specific diagnosis is not required for the ACP codes to be billed.

According to the 2016 Medicare Physician Fee Schedule, the reimbursement is $85.99 for CPT 99497 and $74.88 for CPT 99498. For comparison, the reimbursement for E/M CPT 99203 (30-minute initial evaluation) = $108.85, CPT 99204 (45-minute initial evaluation) = $166.13, and CPT 99205 (60-minute initial evaluation) = $208.38. Far more important than the financial remuneration for these discussions, however, is the critical need for surgeons to have and document their ACP discussions with their patients and/or their family member/surrogate. As surgeons, we are often called to see patients when they are facing a significant change in their health – whether that is a new diagnosis of cancer or after a traumatic injury. Understanding a patient’s values, hopes, and concerns is an essential component to ensuring that our patients receive the best care, as defined by them.

Dr. Fahy is associate professor of surgery and internal medicine at the University of New Mexico, Albuquerque. She is a surgical oncologist who is also board certified in hospice and palliative medicine. Dr. Fahy does not have any relevant conflicts of interest to disclose.

Clinicians outside of the surgical specialties may consider surgeons primarily providers of technical services, but those of us who provide surgical care fully appreciate that communicating with patients and families is a large component of routine surgical practice. Typical communications in surgical practice include obtaining a history of present illness, which is a key element in the ultimate decision to offer a surgical intervention, or not; discussing the risks, benefits, and alternatives of any operation being considered; and the numerous discussions held following any surgical procedure. What many surgeons may not fully appreciate, however, is how these routine communication events can fall under the general category of advance care planning (ACP).

ACP is defined as a process in which physicians (and other health care providers) discuss a patient’s goals, values, and beliefs and determine how these inform a patient’s desire for current or future medical care. Hickman et al. (Hastings Center Report Special Report 35, no. 6 (2005):S26-S30) note that ACP should focus on defining “good” care for each patient. Furthermore, changes in a patient’s medical condition represent an opportune time to revisit a patient’s hopes and goals. Consideration of surgical intervention often represents a major change in a patient’s medical condition and therefore is an excellent opportunity to engage a patient in an ACP discussion.

Given that ACP discussions are likely occurring in surgical practices on a regular basis, surgeons need to be aware of a recent change in the Physician Fee Schedule that took effect Jan. 1, 2016. Effective this date, Current Procedural Terminology (CPT) codes 99497 and 99498 now allow for billing for ACP services. CPT code 99497 includes ACP “including the explanation and discussion of advance directives such as standard forms (with the completion of such forms, when performed), by the physician or other qualified health care professional; first 30 minutes, face-to-face with patient, family member(s) and/or surrogate.” CPT code 99498 is used for each additional 30 minutes spent in such face-to-face ACP counseling.

The nuts and bolts of how these ACP CPT codes work:

How many times can these code(s) be used? There are no limits on the number of times ACP can be reported for a given beneficiary in a given time period. For example, if an ACP discussion was held with a patient and/or family member and/or surrogate prior to a major elective procedure and again in the postoperative period, the above CPT codes could be used twice. In each instance, the ACP discussion must be documented, along with any relevant change in the patient’s clinical status that prompted another ACP discussion.

Can a patient or their family member/surrogate refuse ACP services? ACP services are voluntary; therefore, a patient or their family member/surrogate can refuse ACP services. These CPT codes only can be used if a patient or family member/surrogate consents for ACP services.

What must be documented in ACP services? Physicians should consult their Medicare Administrative Contractors for documentation requirements. Examples of elements to be included in the documentation are a brief description of the discussion with the patient or family/surrogate regarding the voluntary nature of ACP services, an explanation of advance directives and documentation if an advance directive is completed, who was present during the discussion, and time spent in the face-to-face encounter.

Does an advance directive have to be completed to bill the service? No. If an advance directive is completed, this should be documented (see above), but completion of the directive is not a requirement for billing the service.

Can ACP be reported in addition to an evaluation and management (E/M) service (such as an office visit)? Yes. CPT codes 99497 and 99498 may be billed on the same day or a different day as most other E/M services. They may be billed within the global surgical period.

Is a specific diagnosis required to use the ACP CPT codes? No, a specific diagnosis is not required for the ACP codes to be billed.

According to the 2016 Medicare Physician Fee Schedule, the reimbursement is $85.99 for CPT 99497 and $74.88 for CPT 99498. For comparison, the reimbursement for E/M CPT 99203 (30-minute initial evaluation) = $108.85, CPT 99204 (45-minute initial evaluation) = $166.13, and CPT 99205 (60-minute initial evaluation) = $208.38. Far more important than the financial remuneration for these discussions, however, is the critical need for surgeons to have and document their ACP discussions with their patients and/or their family member/surrogate. As surgeons, we are often called to see patients when they are facing a significant change in their health – whether that is a new diagnosis of cancer or after a traumatic injury. Understanding a patient’s values, hopes, and concerns is an essential component to ensuring that our patients receive the best care, as defined by them.

Dr. Fahy is associate professor of surgery and internal medicine at the University of New Mexico, Albuquerque. She is a surgical oncologist who is also board certified in hospice and palliative medicine. Dr. Fahy does not have any relevant conflicts of interest to disclose.

Clinicians outside of the surgical specialties may consider surgeons primarily providers of technical services, but those of us who provide surgical care fully appreciate that communicating with patients and families is a large component of routine surgical practice. Typical communications in surgical practice include obtaining a history of present illness, which is a key element in the ultimate decision to offer a surgical intervention, or not; discussing the risks, benefits, and alternatives of any operation being considered; and the numerous discussions held following any surgical procedure. What many surgeons may not fully appreciate, however, is how these routine communication events can fall under the general category of advance care planning (ACP).

ACP is defined as a process in which physicians (and other health care providers) discuss a patient’s goals, values, and beliefs and determine how these inform a patient’s desire for current or future medical care. Hickman et al. (Hastings Center Report Special Report 35, no. 6 (2005):S26-S30) note that ACP should focus on defining “good” care for each patient. Furthermore, changes in a patient’s medical condition represent an opportune time to revisit a patient’s hopes and goals. Consideration of surgical intervention often represents a major change in a patient’s medical condition and therefore is an excellent opportunity to engage a patient in an ACP discussion.

Given that ACP discussions are likely occurring in surgical practices on a regular basis, surgeons need to be aware of a recent change in the Physician Fee Schedule that took effect Jan. 1, 2016. Effective this date, Current Procedural Terminology (CPT) codes 99497 and 99498 now allow for billing for ACP services. CPT code 99497 includes ACP “including the explanation and discussion of advance directives such as standard forms (with the completion of such forms, when performed), by the physician or other qualified health care professional; first 30 minutes, face-to-face with patient, family member(s) and/or surrogate.” CPT code 99498 is used for each additional 30 minutes spent in such face-to-face ACP counseling.

The nuts and bolts of how these ACP CPT codes work:

How many times can these code(s) be used? There are no limits on the number of times ACP can be reported for a given beneficiary in a given time period. For example, if an ACP discussion was held with a patient and/or family member and/or surrogate prior to a major elective procedure and again in the postoperative period, the above CPT codes could be used twice. In each instance, the ACP discussion must be documented, along with any relevant change in the patient’s clinical status that prompted another ACP discussion.

Can a patient or their family member/surrogate refuse ACP services? ACP services are voluntary; therefore, a patient or their family member/surrogate can refuse ACP services. These CPT codes only can be used if a patient or family member/surrogate consents for ACP services.

What must be documented in ACP services? Physicians should consult their Medicare Administrative Contractors for documentation requirements. Examples of elements to be included in the documentation are a brief description of the discussion with the patient or family/surrogate regarding the voluntary nature of ACP services, an explanation of advance directives and documentation if an advance directive is completed, who was present during the discussion, and time spent in the face-to-face encounter.

Does an advance directive have to be completed to bill the service? No. If an advance directive is completed, this should be documented (see above), but completion of the directive is not a requirement for billing the service.

Can ACP be reported in addition to an evaluation and management (E/M) service (such as an office visit)? Yes. CPT codes 99497 and 99498 may be billed on the same day or a different day as most other E/M services. They may be billed within the global surgical period.

Is a specific diagnosis required to use the ACP CPT codes? No, a specific diagnosis is not required for the ACP codes to be billed.

According to the 2016 Medicare Physician Fee Schedule, the reimbursement is $85.99 for CPT 99497 and $74.88 for CPT 99498. For comparison, the reimbursement for E/M CPT 99203 (30-minute initial evaluation) = $108.85, CPT 99204 (45-minute initial evaluation) = $166.13, and CPT 99205 (60-minute initial evaluation) = $208.38. Far more important than the financial remuneration for these discussions, however, is the critical need for surgeons to have and document their ACP discussions with their patients and/or their family member/surrogate. As surgeons, we are often called to see patients when they are facing a significant change in their health – whether that is a new diagnosis of cancer or after a traumatic injury. Understanding a patient’s values, hopes, and concerns is an essential component to ensuring that our patients receive the best care, as defined by them.

Dr. Fahy is associate professor of surgery and internal medicine at the University of New Mexico, Albuquerque. She is a surgical oncologist who is also board certified in hospice and palliative medicine. Dr. Fahy does not have any relevant conflicts of interest to disclose.

Although effective palliative care has always been a must-have for patients and caregivers facing serious illness, it hasn’t always been readily available. With the emergence of value-based healthcare models—and their potent incentives to reduce avoidable readmissions—there is renewed hope that such care will be accessible to those who need it.

Palliative and end-of-life care have long been promoted as core skills for hospitalists. The topic has regularly been included at SHM annual meetings and other prominent hospital medicine conferences, in the American Board of Internal Medicine blueprint for recognition of focused practice in hospital medicine, and in a number of influential references for hospitalists. Still, as I look at hospitalist programs around the country, there is a clear need to improve hospitalists’ delivery of palliative and end-of-life care.

Care of patients with chronic illness in their last two years of life accounts for a third of all Medicare spending.1 As hospitalists, we encounter many of these patients as they are hospitalized—and often re-hospitalized. Palliative care, which can improve quality of life and decrease costs for patients while leading to increased satisfaction and better outcomes for caregivers, can help alleviate unneeded and unwanted aggressive interventions like hospitalization.2,3

In its 2014 report, Dying in America, the Institute of Medicine (IOM) identified several areas for improvement, including better advance care planning and payment systems supporting high quality end-of-life care.4 As I write this column in mid 2016, there are two notable achievements since the IOM report: two E&M codes for advance care planning and a substantial and growing number of hospitalist patients in alternative payment models like bundled payments or ACOs.5 I believe we are entering a time when the availability of good palliative care will be accelerated due to broader forces in healthcare that for the first time align incentives between patients’ wishes and how care is paid for.

Palliative Care Skills for Hospitalists

The following are key actions for physicians in addressing palliative care for the hospitalized patient. At the risk of oversimplifying the discipline, I offer a few key actions for hospitalists to keep in mind.

Identify patients who would benefit from palliative care. The surprise question—“Would I be surprised if this patient died in the next year?”—has the ability to predict which patients would benefit from palliative care. In one observation from a group of patients with cancer, a “no” answer identified 60% of patients who died within a year.6 The surprise question has previously been shown to be predictive in other cancer and non-cancer populations.7,8

Weisman and Meier suggest using the following in a checklist at the time of hospital admission as “primary criteria to screen for unmet palliative care needs”:9

• The surprise question
• Frequent admissions
• Admission prompted by difficult-to-control physical or psychological symptoms
• Complex care requirements
• Decline in function, feeding intolerance, or unintended decline in weight

Hold a “goals of care” meeting. A notable step forward for supporting conversations between physicians and patients occurred on Jan. 1, when the Centers for Medicare & Medicaid Services (CMS) announced the Advance Care Planning E&M codes. These are CPT codes 99497 and 99498. They can be used on the same day as other E&M codes and cover discussions regarding advance care planning issues including discussing advance directives, appointing a healthcare proxy or durable power of attorney, discussing a living will, or addressing orders for life-sustaining treatment like the role of hydration or future hospitalizations. (For more information on how to use them, visit the CMS website and search for the FAQ.)

What should hospitalists concentrate on when having “goals of care” conversations with patients and caregivers? Ariadne Labs, a Harvard-affiliated health innovation group, offers the following as elements of a serious illness conversation:10

• Patients’ understanding of their illness
• Patients’ preferences for information and for family involvement
• Personal life goals, fears, and anxieties
• Trade-offs they are willing to accept

For hospitalists, an important area to pay particular attention to is the role of future hospitalizations in patients’ wishes for care, as some patients, if offered appropriate symptom control, would prefer to remain at home.

Two other crucial elements of inpatient palliative care—offer psychosocial support and symptom relief and hand off patient to effective post-hospital palliative care—are outside the scope of this article. However, they should be kept in mind and, of course, applied.

Understand the role of the palliative care consultation. Busy hospitalists might reasonably think, “I simply don’t have time to address palliative care in patients who aren’t likely to die during this hospitalization or soon after.” The palliative care consult service, if available, should be accessed when patients are identified as palliative care candidates but the primary hospitalist does not have the time or resources—including specialized knowledge in some cases—to deliver adequate palliative care. Palliative care specialists can also help bridge the gap between inpatient and outpatient palliative care resources.

In sum, the move to value-based payment models and the new advance care planning E&M codes provide a renewed focus—with more aligned incentives—and the opportunity to provide good palliative care to all who need it.

For hospitalists, identifying those who would benefit from palliative care and working with the healthcare team to ensure the care is delivered are at the heart of our professional mission. TH

References

1. End-of-life care. The Darmouth Atlas of Health Care website. Accessed June 23, 2016.
2. Gade G, Venohr I, Conner D, et al. Impact of an inpatient palliative care team: a randomized control trial. J Palliat Med. 2008;11(2):180-190.
3. Morrison RS, Penrod JD, Cassel JB, et al. Cost savings associated with US hospital palliative care consultation programs. Arch Int Med. 2008;168(16):1783-1790.
4. Institute of Medicine. Dying in America: Improving Quality and Honoring Individual Preferences near the End of Life. 2014.
5. BPCI Model 2: Retrospective acute & post acute care episode. Centers for Medicare & Medicaid Services website. Accessed June 24, 2016.
6. Vick JB, Pertsch N, Hutchings M, et al. The utility of the surprise question in identifying patients most at risk of death. J Clin Oncol. 2015;33(suppl):8.
7. Moss AH, Ganjoo J, Sharma S, et al. Utility of the “surprise” question to identify dialysis patients with high mortality. Clin J Am Soc Nephrol. 2008;3:1379-1384.
8. Moss AH, Lunney JR, Culp S, et al. Prognostic significance of the “surprise” question in cancer patients. J Palliat Med. 2010;13(7):837-840.
9. Weissman D, Meier C. Identifying patients in need of a palliative care assessment in the hospital setting: a consensus report from the Center to Advance Palliative Care. J Palliat Med. 2011;14(1):17-23.
10. Serious illness care resources. Ariadne Labs website. Accessed June 24, 2016.

Although effective palliative care has always been a must-have for patients and caregivers facing serious illness, it hasn’t always been readily available. With the emergence of value-based healthcare models—and their potent incentives to reduce avoidable readmissions—there is renewed hope that such care will be accessible to those who need it.

Palliative and end-of-life care have long been promoted as core skills for hospitalists. The topic has regularly been included at SHM annual meetings and other prominent hospital medicine conferences, in the American Board of Internal Medicine blueprint for recognition of focused practice in hospital medicine, and in a number of influential references for hospitalists. Still, as I look at hospitalist programs around the country, there is a clear need to improve hospitalists’ delivery of palliative and end-of-life care.

Care of patients with chronic illness in their last two years of life accounts for a third of all Medicare spending.1 As hospitalists, we encounter many of these patients as they are hospitalized—and often re-hospitalized. Palliative care, which can improve quality of life and decrease costs for patients while leading to increased satisfaction and better outcomes for caregivers, can help alleviate unneeded and unwanted aggressive interventions like hospitalization.2,3

In its 2014 report, Dying in America, the Institute of Medicine (IOM) identified several areas for improvement, including better advance care planning and payment systems supporting high quality end-of-life care.4 As I write this column in mid 2016, there are two notable achievements since the IOM report: two E&M codes for advance care planning and a substantial and growing number of hospitalist patients in alternative payment models like bundled payments or ACOs.5 I believe we are entering a time when the availability of good palliative care will be accelerated due to broader forces in healthcare that for the first time align incentives between patients’ wishes and how care is paid for.

Palliative Care Skills for Hospitalists

The following are key actions for physicians in addressing palliative care for the hospitalized patient. At the risk of oversimplifying the discipline, I offer a few key actions for hospitalists to keep in mind.

Identify patients who would benefit from palliative care. The surprise question—“Would I be surprised if this patient died in the next year?”—has the ability to predict which patients would benefit from palliative care. In one observation from a group of patients with cancer, a “no” answer identified 60% of patients who died within a year.6 The surprise question has previously been shown to be predictive in other cancer and non-cancer populations.7,8

Weisman and Meier suggest using the following in a checklist at the time of hospital admission as “primary criteria to screen for unmet palliative care needs”:9

• The surprise question
• Frequent admissions
• Admission prompted by difficult-to-control physical or psychological symptoms
• Complex care requirements
• Decline in function, feeding intolerance, or unintended decline in weight

Hold a “goals of care” meeting. A notable step forward for supporting conversations between physicians and patients occurred on Jan. 1, when the Centers for Medicare & Medicaid Services (CMS) announced the Advance Care Planning E&M codes. These are CPT codes 99497 and 99498. They can be used on the same day as other E&M codes and cover discussions regarding advance care planning issues including discussing advance directives, appointing a healthcare proxy or durable power of attorney, discussing a living will, or addressing orders for life-sustaining treatment like the role of hydration or future hospitalizations. (For more information on how to use them, visit the CMS website and search for the FAQ.)

What should hospitalists concentrate on when having “goals of care” conversations with patients and caregivers? Ariadne Labs, a Harvard-affiliated health innovation group, offers the following as elements of a serious illness conversation:10

• Patients’ understanding of their illness
• Patients’ preferences for information and for family involvement
• Personal life goals, fears, and anxieties
• Trade-offs they are willing to accept

For hospitalists, an important area to pay particular attention to is the role of future hospitalizations in patients’ wishes for care, as some patients, if offered appropriate symptom control, would prefer to remain at home.

Two other crucial elements of inpatient palliative care—offer psychosocial support and symptom relief and hand off patient to effective post-hospital palliative care—are outside the scope of this article. However, they should be kept in mind and, of course, applied.

Understand the role of the palliative care consultation. Busy hospitalists might reasonably think, “I simply don’t have time to address palliative care in patients who aren’t likely to die during this hospitalization or soon after.” The palliative care consult service, if available, should be accessed when patients are identified as palliative care candidates but the primary hospitalist does not have the time or resources—including specialized knowledge in some cases—to deliver adequate palliative care. Palliative care specialists can also help bridge the gap between inpatient and outpatient palliative care resources.

In sum, the move to value-based payment models and the new advance care planning E&M codes provide a renewed focus—with more aligned incentives—and the opportunity to provide good palliative care to all who need it.

For hospitalists, identifying those who would benefit from palliative care and working with the healthcare team to ensure the care is delivered are at the heart of our professional mission. TH

References

1. End-of-life care. The Darmouth Atlas of Health Care website. Accessed June 23, 2016.
2. Gade G, Venohr I, Conner D, et al. Impact of an inpatient palliative care team: a randomized control trial. J Palliat Med. 2008;11(2):180-190.
3. Morrison RS, Penrod JD, Cassel JB, et al. Cost savings associated with US hospital palliative care consultation programs. Arch Int Med. 2008;168(16):1783-1790.
4. Institute of Medicine. Dying in America: Improving Quality and Honoring Individual Preferences near the End of Life. 2014.
5. BPCI Model 2: Retrospective acute & post acute care episode. Centers for Medicare & Medicaid Services website. Accessed June 24, 2016.
6. Vick JB, Pertsch N, Hutchings M, et al. The utility of the surprise question in identifying patients most at risk of death. J Clin Oncol. 2015;33(suppl):8.
7. Moss AH, Ganjoo J, Sharma S, et al. Utility of the “surprise” question to identify dialysis patients with high mortality. Clin J Am Soc Nephrol. 2008;3:1379-1384.
8. Moss AH, Lunney JR, Culp S, et al. Prognostic significance of the “surprise” question in cancer patients. J Palliat Med. 2010;13(7):837-840.
9. Weissman D, Meier C. Identifying patients in need of a palliative care assessment in the hospital setting: a consensus report from the Center to Advance Palliative Care. J Palliat Med. 2011;14(1):17-23.
10. Serious illness care resources. Ariadne Labs website. Accessed June 24, 2016.

Although effective palliative care has always been a must-have for patients and caregivers facing serious illness, it hasn’t always been readily available. With the emergence of value-based healthcare models—and their potent incentives to reduce avoidable readmissions—there is renewed hope that such care will be accessible to those who need it.

Palliative and end-of-life care have long been promoted as core skills for hospitalists. The topic has regularly been included at SHM annual meetings and other prominent hospital medicine conferences, in the American Board of Internal Medicine blueprint for recognition of focused practice in hospital medicine, and in a number of influential references for hospitalists. Still, as I look at hospitalist programs around the country, there is a clear need to improve hospitalists’ delivery of palliative and end-of-life care.

Care of patients with chronic illness in their last two years of life accounts for a third of all Medicare spending.1 As hospitalists, we encounter many of these patients as they are hospitalized—and often re-hospitalized. Palliative care, which can improve quality of life and decrease costs for patients while leading to increased satisfaction and better outcomes for caregivers, can help alleviate unneeded and unwanted aggressive interventions like hospitalization.2,3

In its 2014 report, Dying in America, the Institute of Medicine (IOM) identified several areas for improvement, including better advance care planning and payment systems supporting high quality end-of-life care.4 As I write this column in mid 2016, there are two notable achievements since the IOM report: two E&M codes for advance care planning and a substantial and growing number of hospitalist patients in alternative payment models like bundled payments or ACOs.5 I believe we are entering a time when the availability of good palliative care will be accelerated due to broader forces in healthcare that for the first time align incentives between patients’ wishes and how care is paid for.

Palliative Care Skills for Hospitalists

The following are key actions for physicians in addressing palliative care for the hospitalized patient. At the risk of oversimplifying the discipline, I offer a few key actions for hospitalists to keep in mind.

Identify patients who would benefit from palliative care. The surprise question—“Would I be surprised if this patient died in the next year?”—has the ability to predict which patients would benefit from palliative care. In one observation from a group of patients with cancer, a “no” answer identified 60% of patients who died within a year.6 The surprise question has previously been shown to be predictive in other cancer and non-cancer populations.7,8

Weisman and Meier suggest using the following in a checklist at the time of hospital admission as “primary criteria to screen for unmet palliative care needs”:9

• The surprise question
• Frequent admissions
• Admission prompted by difficult-to-control physical or psychological symptoms
• Complex care requirements
• Decline in function, feeding intolerance, or unintended decline in weight

Hold a “goals of care” meeting. A notable step forward for supporting conversations between physicians and patients occurred on Jan. 1, when the Centers for Medicare & Medicaid Services (CMS) announced the Advance Care Planning E&M codes. These are CPT codes 99497 and 99498. They can be used on the same day as other E&M codes and cover discussions regarding advance care planning issues including discussing advance directives, appointing a healthcare proxy or durable power of attorney, discussing a living will, or addressing orders for life-sustaining treatment like the role of hydration or future hospitalizations. (For more information on how to use them, visit the CMS website and search for the FAQ.)

What should hospitalists concentrate on when having “goals of care” conversations with patients and caregivers? Ariadne Labs, a Harvard-affiliated health innovation group, offers the following as elements of a serious illness conversation:10

• Patients’ understanding of their illness
• Patients’ preferences for information and for family involvement
• Personal life goals, fears, and anxieties
• Trade-offs they are willing to accept

For hospitalists, an important area to pay particular attention to is the role of future hospitalizations in patients’ wishes for care, as some patients, if offered appropriate symptom control, would prefer to remain at home.

Two other crucial elements of inpatient palliative care—offer psychosocial support and symptom relief and hand off patient to effective post-hospital palliative care—are outside the scope of this article. However, they should be kept in mind and, of course, applied.

Understand the role of the palliative care consultation. Busy hospitalists might reasonably think, “I simply don’t have time to address palliative care in patients who aren’t likely to die during this hospitalization or soon after.” The palliative care consult service, if available, should be accessed when patients are identified as palliative care candidates but the primary hospitalist does not have the time or resources—including specialized knowledge in some cases—to deliver adequate palliative care. Palliative care specialists can also help bridge the gap between inpatient and outpatient palliative care resources.

In sum, the move to value-based payment models and the new advance care planning E&M codes provide a renewed focus—with more aligned incentives—and the opportunity to provide good palliative care to all who need it.

For hospitalists, identifying those who would benefit from palliative care and working with the healthcare team to ensure the care is delivered are at the heart of our professional mission. TH

References

1. End-of-life care. The Darmouth Atlas of Health Care website. Accessed June 23, 2016.
2. Gade G, Venohr I, Conner D, et al. Impact of an inpatient palliative care team: a randomized control trial. J Palliat Med. 2008;11(2):180-190.
3. Morrison RS, Penrod JD, Cassel JB, et al. Cost savings associated with US hospital palliative care consultation programs. Arch Int Med. 2008;168(16):1783-1790.
4. Institute of Medicine. Dying in America: Improving Quality and Honoring Individual Preferences near the End of Life. 2014.
5. BPCI Model 2: Retrospective acute & post acute care episode. Centers for Medicare & Medicaid Services website. Accessed June 24, 2016.
6. Vick JB, Pertsch N, Hutchings M, et al. The utility of the surprise question in identifying patients most at risk of death. J Clin Oncol. 2015;33(suppl):8.
7. Moss AH, Ganjoo J, Sharma S, et al. Utility of the “surprise” question to identify dialysis patients with high mortality. Clin J Am Soc Nephrol. 2008;3:1379-1384.
8. Moss AH, Lunney JR, Culp S, et al. Prognostic significance of the “surprise” question in cancer patients. J Palliat Med. 2010;13(7):837-840.
9. Weissman D, Meier C. Identifying patients in need of a palliative care assessment in the hospital setting: a consensus report from the Center to Advance Palliative Care. J Palliat Med. 2011;14(1):17-23.
10. Serious illness care resources. Ariadne Labs website. Accessed June 24, 2016.

Purpose: Describe symptom burden and distress among Veteran cancer survivors.

Background: Survivorship is an important component of cancer care as patients transition from treatment to surveillance and cope with long-term effects of therapy. Veterans receiving care at the VA are quite different from those described in existing survivorship literature, with lower income and health literacy, poorer physical andmental health, and more comorbidities compared to the general population. Survivorship needs have not been well defined in this population.

Methods: Veterans are referred or recruited to survivorship clinic after completing definitive therapy. An NCCN distress thermometer (DT) is completed in survivorship clinic as part of routine clinical care.

Data Analysis: This analysis was restricted to cancer survivors meeting Commission on Cancer guidance for survivorship care eligibility. Descriptive statistics summarized findings from the DT. To place symptom burden in context, a comparison group was selected consisting of Veterans with comparable cancer site and stage who completed a DT at their first treatment appointment. Reported symptoms were compared to those from survivors with chi-square analysis.

Results: The DT was completed by 47 lung, colorectal, anal, and head and neck cancer survivors between February 2015 and April 2016. Most were white males, with an average age of 66. Of 39 practical, family, emotional, and physical problems included on the DT, survivors reported an average of 9.2 issues (range 0-22). The most common problems were dyspnea (64%), fatigue (60%), pain (57%), sleep (45%), worry (43%), and depression (40%). The average distress score was 3.6 (range 0-9).

The comparison group contained 147 Veterans; they reported an average of 7.4 issues as sources of distress.

Survivors were significantly more likely to report difficulty with breathing, constipation, depression, anhedonia, sadness, sleep concerns, and tingling in the hands and feet. The only issues more common in patients at the start of treatment compared to survivors were nervousness and transportation concerns. There was no difference in concerns regarding treatment decisions, pain, or finances.

Implications: Veteran cancer survivors reported significant symptom burden, particularly concerning mental health and side effects of treatment. Cancer survivorship clinic can play an important role in identifying and addressing the significant symptom burden. A multidisciplinary approach, particularly one including mental health services, is very important.

Purpose: Describe symptom burden and distress among Veteran cancer survivors.

Background: Survivorship is an important component of cancer care as patients transition from treatment to surveillance and cope with long-term effects of therapy. Veterans receiving care at the VA are quite different from those described in existing survivorship literature, with lower income and health literacy, poorer physical andmental health, and more comorbidities compared to the general population. Survivorship needs have not been well defined in this population.

Methods: Veterans are referred or recruited to survivorship clinic after completing definitive therapy. An NCCN distress thermometer (DT) is completed in survivorship clinic as part of routine clinical care.

Data Analysis: This analysis was restricted to cancer survivors meeting Commission on Cancer guidance for survivorship care eligibility. Descriptive statistics summarized findings from the DT. To place symptom burden in context, a comparison group was selected consisting of Veterans with comparable cancer site and stage who completed a DT at their first treatment appointment. Reported symptoms were compared to those from survivors with chi-square analysis.

Results: The DT was completed by 47 lung, colorectal, anal, and head and neck cancer survivors between February 2015 and April 2016. Most were white males, with an average age of 66. Of 39 practical, family, emotional, and physical problems included on the DT, survivors reported an average of 9.2 issues (range 0-22). The most common problems were dyspnea (64%), fatigue (60%), pain (57%), sleep (45%), worry (43%), and depression (40%). The average distress score was 3.6 (range 0-9).

The comparison group contained 147 Veterans; they reported an average of 7.4 issues as sources of distress.

Survivors were significantly more likely to report difficulty with breathing, constipation, depression, anhedonia, sadness, sleep concerns, and tingling in the hands and feet. The only issues more common in patients at the start of treatment compared to survivors were nervousness and transportation concerns. There was no difference in concerns regarding treatment decisions, pain, or finances.

Implications: Veteran cancer survivors reported significant symptom burden, particularly concerning mental health and side effects of treatment. Cancer survivorship clinic can play an important role in identifying and addressing the significant symptom burden. A multidisciplinary approach, particularly one including mental health services, is very important.

Purpose: Describe symptom burden and distress among Veteran cancer survivors.

Background: Survivorship is an important component of cancer care as patients transition from treatment to surveillance and cope with long-term effects of therapy. Veterans receiving care at the VA are quite different from those described in existing survivorship literature, with lower income and health literacy, poorer physical andmental health, and more comorbidities compared to the general population. Survivorship needs have not been well defined in this population.

Methods: Veterans are referred or recruited to survivorship clinic after completing definitive therapy. An NCCN distress thermometer (DT) is completed in survivorship clinic as part of routine clinical care.

Data Analysis: This analysis was restricted to cancer survivors meeting Commission on Cancer guidance for survivorship care eligibility. Descriptive statistics summarized findings from the DT. To place symptom burden in context, a comparison group was selected consisting of Veterans with comparable cancer site and stage who completed a DT at their first treatment appointment. Reported symptoms were compared to those from survivors with chi-square analysis.

Results: The DT was completed by 47 lung, colorectal, anal, and head and neck cancer survivors between February 2015 and April 2016. Most were white males, with an average age of 66. Of 39 practical, family, emotional, and physical problems included on the DT, survivors reported an average of 9.2 issues (range 0-22). The most common problems were dyspnea (64%), fatigue (60%), pain (57%), sleep (45%), worry (43%), and depression (40%). The average distress score was 3.6 (range 0-9).

The comparison group contained 147 Veterans; they reported an average of 7.4 issues as sources of distress.

Survivors were significantly more likely to report difficulty with breathing, constipation, depression, anhedonia, sadness, sleep concerns, and tingling in the hands and feet. The only issues more common in patients at the start of treatment compared to survivors were nervousness and transportation concerns. There was no difference in concerns regarding treatment decisions, pain, or finances.

Implications: Veteran cancer survivors reported significant symptom burden, particularly concerning mental health and side effects of treatment. Cancer survivorship clinic can play an important role in identifying and addressing the significant symptom burden. A multidisciplinary approach, particularly one including mental health services, is very important.