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Gait speed hones risk stratification of elderly heart failure patients
Gait speed was independently associated with hospitalization and death and aided in risk stratification of elderly patients with heart failure in a study reported online March 9 in JACC Heart Failure.
Optimal clinical management of heart failure is dependent on accurate prognostic stratification, Dr. Giovanni Pulignano and his coinvestigators wrote. Geriatric conditions such as frailty, cognitive impairment, and disability impact prognosis along with comorbidities and cardiac disease. Further, gait speed is a marker of frailty and is predictive of adverse health events in older patients, including mortality. However, there is limited research on the impact of geriatric conditions in heart failure studies.
Dr. Pulignano of San Camillo Hospital in Rome and colleagues sought to examine the relationship between gait speed in older patients with heart failure and the risk of hospitalization and death.
The investigators calculated the predicted all-cause mortality using the Cardiac and Comorbid Conditions Heart Failure (3C-HF) score. Variables included in the 3C-HF score are left ventricular ejection fraction of less than 20%, New York Heart Association class III-IV heart failure, no renin-angiotensin inhibitor treatment, no beta-blocker treatment, severe valvular heart disease, diabetes with macro- or microangiopathy, atrial fibrillation, hypertension, anemia, renal dysfunction, and older age.
Participants were at least 70 years old, with clinically stable heart failure with normal or reduced left ventricular ejection fraction and a previous hospitalization necessitating intravenous inotropes, diuretics, and/or vasodilators for heart failure.
Exclusion criteria included a condition that would decrease their walking speed, valvular heart disease with surgery planned, long-term intravenous inotrope treatment, or living in a nursing home.
Gait speed was assessed over 4 meters and grouped into groups of slow walkers (up to 0.65 m/s), intermediate walkers (0.66-0.99 m/s), and fast walkers (at least 1.0 m/s). Participants were allowed to use a walker or cane as a walking aid.
Data were analyzed on 331 patients (mean age 78 years, 43% women) with clinically stable and optimized chronic heart failure (mean NYHA class 2.7, mean left ventricular ejection fraction 35%). The mean 3C-HF score was 19.7 points.
The mean gait speed was 0.74 m/s, with 35% (115 patients) demonstrating severely reduced (less than or equal to 0.65 m/s) gait speed.
After 1 year of follow-up, they found a significant association between the measured gait speed and 1-year mortality, with 9.1%, 21.9%, and 38.3% for the high, intermediate, and low tertiles, respectively (P less than .001). A similar relationship was found for gait speed and heart failure–related hospitalization (26.6%, 58.6%, and 71.3%, respectively; P = .002) and all-cause hospitalization (26.6%, 58.6%, and 71.3%, respectively; P = .002).
Multivariate analysis revealed an independent association between gait speed and lower risk of all-cause death (hazard ratio, 0.62; P = .008). Gait speed was also associated with a lower risk for all-cause hospitalizations (HR, 0.74; P = .002) and heart failure–related hospitalizations (HR, 0.69; P = .004).
Finally, when gait speed was included in the 3C-HF risk score, accuracy of risk stratification for all-cause death (net reclassification improvement, 0.49; P less than .001) and heart failure admissions (NRI, 0.37; P less than .001) was improved (JCHF. 2016 Mar 9. doi:10.1016/j.jchf.2015.12.017).
“Gait speed, in combination with a validated clinical risk score, improves prognosis prediction in older HF patients,” the investigators concluded. “Frailty assessment using gait speed is simple and inexpensive and suggests new strategies for intervention. Its measurement should be incorporated in the routine clinical evaluation of older patients with HF.”
The study was supported by the ADRIANO-Italian Association for Research on Cardiac Disease in Older Patients. The authors had no disclosures.
Gait speed was independently associated with hospitalization and death and aided in risk stratification of elderly patients with heart failure in a study reported online March 9 in JACC Heart Failure.
Optimal clinical management of heart failure is dependent on accurate prognostic stratification, Dr. Giovanni Pulignano and his coinvestigators wrote. Geriatric conditions such as frailty, cognitive impairment, and disability impact prognosis along with comorbidities and cardiac disease. Further, gait speed is a marker of frailty and is predictive of adverse health events in older patients, including mortality. However, there is limited research on the impact of geriatric conditions in heart failure studies.
Dr. Pulignano of San Camillo Hospital in Rome and colleagues sought to examine the relationship between gait speed in older patients with heart failure and the risk of hospitalization and death.
The investigators calculated the predicted all-cause mortality using the Cardiac and Comorbid Conditions Heart Failure (3C-HF) score. Variables included in the 3C-HF score are left ventricular ejection fraction of less than 20%, New York Heart Association class III-IV heart failure, no renin-angiotensin inhibitor treatment, no beta-blocker treatment, severe valvular heart disease, diabetes with macro- or microangiopathy, atrial fibrillation, hypertension, anemia, renal dysfunction, and older age.
Participants were at least 70 years old, with clinically stable heart failure with normal or reduced left ventricular ejection fraction and a previous hospitalization necessitating intravenous inotropes, diuretics, and/or vasodilators for heart failure.
Exclusion criteria included a condition that would decrease their walking speed, valvular heart disease with surgery planned, long-term intravenous inotrope treatment, or living in a nursing home.
Gait speed was assessed over 4 meters and grouped into groups of slow walkers (up to 0.65 m/s), intermediate walkers (0.66-0.99 m/s), and fast walkers (at least 1.0 m/s). Participants were allowed to use a walker or cane as a walking aid.
Data were analyzed on 331 patients (mean age 78 years, 43% women) with clinically stable and optimized chronic heart failure (mean NYHA class 2.7, mean left ventricular ejection fraction 35%). The mean 3C-HF score was 19.7 points.
The mean gait speed was 0.74 m/s, with 35% (115 patients) demonstrating severely reduced (less than or equal to 0.65 m/s) gait speed.
After 1 year of follow-up, they found a significant association between the measured gait speed and 1-year mortality, with 9.1%, 21.9%, and 38.3% for the high, intermediate, and low tertiles, respectively (P less than .001). A similar relationship was found for gait speed and heart failure–related hospitalization (26.6%, 58.6%, and 71.3%, respectively; P = .002) and all-cause hospitalization (26.6%, 58.6%, and 71.3%, respectively; P = .002).
Multivariate analysis revealed an independent association between gait speed and lower risk of all-cause death (hazard ratio, 0.62; P = .008). Gait speed was also associated with a lower risk for all-cause hospitalizations (HR, 0.74; P = .002) and heart failure–related hospitalizations (HR, 0.69; P = .004).
Finally, when gait speed was included in the 3C-HF risk score, accuracy of risk stratification for all-cause death (net reclassification improvement, 0.49; P less than .001) and heart failure admissions (NRI, 0.37; P less than .001) was improved (JCHF. 2016 Mar 9. doi:10.1016/j.jchf.2015.12.017).
“Gait speed, in combination with a validated clinical risk score, improves prognosis prediction in older HF patients,” the investigators concluded. “Frailty assessment using gait speed is simple and inexpensive and suggests new strategies for intervention. Its measurement should be incorporated in the routine clinical evaluation of older patients with HF.”
The study was supported by the ADRIANO-Italian Association for Research on Cardiac Disease in Older Patients. The authors had no disclosures.
Gait speed was independently associated with hospitalization and death and aided in risk stratification of elderly patients with heart failure in a study reported online March 9 in JACC Heart Failure.
Optimal clinical management of heart failure is dependent on accurate prognostic stratification, Dr. Giovanni Pulignano and his coinvestigators wrote. Geriatric conditions such as frailty, cognitive impairment, and disability impact prognosis along with comorbidities and cardiac disease. Further, gait speed is a marker of frailty and is predictive of adverse health events in older patients, including mortality. However, there is limited research on the impact of geriatric conditions in heart failure studies.
Dr. Pulignano of San Camillo Hospital in Rome and colleagues sought to examine the relationship between gait speed in older patients with heart failure and the risk of hospitalization and death.
The investigators calculated the predicted all-cause mortality using the Cardiac and Comorbid Conditions Heart Failure (3C-HF) score. Variables included in the 3C-HF score are left ventricular ejection fraction of less than 20%, New York Heart Association class III-IV heart failure, no renin-angiotensin inhibitor treatment, no beta-blocker treatment, severe valvular heart disease, diabetes with macro- or microangiopathy, atrial fibrillation, hypertension, anemia, renal dysfunction, and older age.
Participants were at least 70 years old, with clinically stable heart failure with normal or reduced left ventricular ejection fraction and a previous hospitalization necessitating intravenous inotropes, diuretics, and/or vasodilators for heart failure.
Exclusion criteria included a condition that would decrease their walking speed, valvular heart disease with surgery planned, long-term intravenous inotrope treatment, or living in a nursing home.
Gait speed was assessed over 4 meters and grouped into groups of slow walkers (up to 0.65 m/s), intermediate walkers (0.66-0.99 m/s), and fast walkers (at least 1.0 m/s). Participants were allowed to use a walker or cane as a walking aid.
Data were analyzed on 331 patients (mean age 78 years, 43% women) with clinically stable and optimized chronic heart failure (mean NYHA class 2.7, mean left ventricular ejection fraction 35%). The mean 3C-HF score was 19.7 points.
The mean gait speed was 0.74 m/s, with 35% (115 patients) demonstrating severely reduced (less than or equal to 0.65 m/s) gait speed.
After 1 year of follow-up, they found a significant association between the measured gait speed and 1-year mortality, with 9.1%, 21.9%, and 38.3% for the high, intermediate, and low tertiles, respectively (P less than .001). A similar relationship was found for gait speed and heart failure–related hospitalization (26.6%, 58.6%, and 71.3%, respectively; P = .002) and all-cause hospitalization (26.6%, 58.6%, and 71.3%, respectively; P = .002).
Multivariate analysis revealed an independent association between gait speed and lower risk of all-cause death (hazard ratio, 0.62; P = .008). Gait speed was also associated with a lower risk for all-cause hospitalizations (HR, 0.74; P = .002) and heart failure–related hospitalizations (HR, 0.69; P = .004).
Finally, when gait speed was included in the 3C-HF risk score, accuracy of risk stratification for all-cause death (net reclassification improvement, 0.49; P less than .001) and heart failure admissions (NRI, 0.37; P less than .001) was improved (JCHF. 2016 Mar 9. doi:10.1016/j.jchf.2015.12.017).
“Gait speed, in combination with a validated clinical risk score, improves prognosis prediction in older HF patients,” the investigators concluded. “Frailty assessment using gait speed is simple and inexpensive and suggests new strategies for intervention. Its measurement should be incorporated in the routine clinical evaluation of older patients with HF.”
The study was supported by the ADRIANO-Italian Association for Research on Cardiac Disease in Older Patients. The authors had no disclosures.
JACC HEART FAILURE
Key clinical point: Gait speed was independently associated with hospitalization and death, and aided in risk stratification of elderly patients with heart failure.
Major finding: When gait speed was included in the 3C-HF risk score, accuracy of risk stratification for all-cause death (net reclassification improvement, 0.49) and heart failure admissions (NRI, 0.37) was improved significantly.
Data source: Gait speed was tested in 331 elderly patients with clinically stable heart failure who were prospectively followed for 1 year to assess mortality and hospitalization rate.
Disclosures: The study was supported by the ADRIANO-Italian Association for Research on Cardiac Disease in Older Patients. The authors report no disclosures.
No LIGHT shed on CV safety of naltrexone-bupropion
The cardiovascular risks of the weight-loss combination drug naltrexone-bupropion are still uncertain, because the FDA-mandated safety trial, LIGHT, was terminated prematurely due to the sponsoring drug company’s breach of confidentiality. Other irregularities also were discovered, according to a report published online March 8 in JAMA.
Orexigen violated its agreement with FDA not to disclose the findings of an interim analysis performed after only 25% of expected CV events accrued. These findings appeared highly favorable for the drug, prompting the sponsor to publicly, and prematurely, claim naltrexone-bupropion reduced CV risk by 41% independently of its weight-loss effect. This favorable outcome was later found to be “driven almost exclusively by a 12-to-1 imbalance in death favoring naltrexone-bupropion among patients who were no longer taking the study drug,” said Dr. Steven E. Nissen of the Cleveland Clinic Center for Cardiovascular Research and his associates.
They now report the results of a second interim analysis of LIGHT (Cardiovascular Outcomes Study of Naltrexone SR/Bupropion SR in Overweight and Obese Subjects With Cardiovascular Risk Factors) performed after 50% of expected CV events accrued, as well as those of a final analysis performed when the trial was halted and 64% of expected CV events accrued. These findings are much less favorable, showing no significant difference between naltrexone-bupropion and placebo in the rate of major adverse cardiovascular events (MACE). In addition, extremely poor adherence to both active treatment and placebo over time, together with the complex statistical issues involved, call into question any interpretation of the results and preclude “any reliable conclusions about the long-term safety of naltrexone-bupropion,” the investigators said.
“The cardiovascular safety of this treatment remains uncertain and will require evaluation in a new, adequately powered outcome trial.” The results of such a study, should it be undertaken, wouldn’t be available for at least 3-4 years, they noted.
In their report, the investigators described in detail why the FDA required a CV safety study even though the agency had already approved naltrexone-bupropion as a weight-loss treatment.
The study was a phase IIIb randomized, double-blind, placebo-controlled trial involving 8,910 overweight/obese patients aged 45 or older (mean age, 61 years) who were at risk of adverse CV outcomes due to preexisting CV disease; exercise-induced angina; an unfavorable ankle/brachial index; stenosis of coronary, carotid, or lower extremity arteries; type 2 diabetes; hypertension; dyslipidemia; or smoking. These participants received daily tablets of either 32 mg naltrexone plus 360 mg bupropion or a matching placebo and were to be followed for 4 years at 266 U.S. medical centers.
The analysis performed after 50% of expected CV events accrued showed that MACE – the primary safety outcome – occurred in 2.0% of the naltrexone-bupropion group and 2.3% of the placebo group, a nonsignificant difference. Differences between the two study groups also were nonsignificant for the individual components of the primary outcome, including cardiovascular death (0.4% vs. 0.8%), nonfatal stroke (0.5% vs. 0.4%), and nonfatal MI (1.2% vs. 1.2%). These results were confirmed in a sensitivity analysis based on the final data collection, when 64% of expected CV events accrued: MACE occurred in 2.7% of the naltrexone-bupropion group and 2.8% of the placebo group, another nonsignificant difference.
The active treatment also was no better than placebo regarding all secondary outcomes, including all-cause mortality, CV hospitalization, and coronary revascularization, Dr. Nissen and his associates said (JAMA. 2016 Mar 8. doi: 10.1001/jama.2016.1558). Treatment adherence was low. At 16 weeks, only 64% of the naltrexone-bupropion group and 72% of the placebo group were still taking the study treatment. By 2 years, only 27% of the naltrexone-bupropion group and 17% of the placebo group were. The mean duration of treatment was only 18.4 weeks for naltrexone-bupropion and 16.3 weeks for placebo. Most treatment discontinuations were due to a failure to lose weight, but a substantial proportion occurred because of treatment-related increases in blood pressure or heart rate.
The active treatment’s ability to reduce body weight was deemed “modest.” When the trial was halted, the mean decrease in weight was 3.9 kg with naltrexone-bupropion, representing a 3.6% reduction in total weight, and was 1.2 kg with placebo, representing a 1.1% reduction.
Adverse effects developed in 28.1% of patients taking naltrexone-bupropion, which was a significantly greater proportion than the 8.7% rate in the placebo group. The most common adverse events leading to discontinuation of the study drug affected the gastrointestinal system (nausea, constipation, vomiting), the CNS (tremor, dizziness, headache), and mental/emotional problems (insomnia, anxiety, hallucinations, depression).
The sponsor of this trial, Orexigen Therapeutics, disregarded the multiple harms caused by breaches of confidentiality, treated the academic investigators unfairly, ignored the trial’s data monitoring committee, and defied the FDA. Their statements about the naltrexone-bupropion’s cardiovascular efficacy were highly misleading, and there were obvious signs that the supporting data were not reliable. For example, nearly all of the CV mortality in the first interim analysis occurred well after participants had stopped taking their medication.
Yet the drug company was not sanctioned, and the naltrexone-bupropion retains FDA approval. At a minimum, the FDA should withhold approval until a viable replacement study is conducted, or it should require Risk Evaluation and Mitigation Strategies to counter the misinformation disseminated by the study sponsor, or it should restrict use of the drug outright.
Clinicians should be aware of these research improprieties and should know that the purported weight-loss benefit of naltrexone-bupropion is only 2.7 kg more than that achieved with placebo. How does this modest benefit balance against an unknown cardiovascular risk? In addition, the drug’s lack of efficacy clearly contributed to the very poor adherence rate in this trial: At 1 year, only 37.5% were still taking naltrexone-bupropion and 26.3% were still taking placebo.
Dr. Joshua M. Sharfstein is in the department of health policy and management at Johns Hopkins Bloomberg School of Public Health, Baltimore. Dr. Bruce M. Psaty is in the Cardiovascular Health Research Unit and the departments of medicine, epidemiology, and health services at the University of Washington, Seattle. They reported that this work was supported by the National Heart, Lung, and Blood Institute. Dr. Sharfstein reported serving as principal deputy commissioner of the FDA in 2009-2011. Dr. Psaty reported serving on the data monitoring committee of a clinical trial funded by Zoll LifeCor, on the steering committee of the Yale Open Data Access Project funded by Johnson & Johnson, and on the FDA Science Board. Dr. Sharfstein and Dr. Psaty made these remarks in an editorial accompanying Dr. Nissen’s report (JAMA. 2016;315:984-6).
The sponsor of this trial, Orexigen Therapeutics, disregarded the multiple harms caused by breaches of confidentiality, treated the academic investigators unfairly, ignored the trial’s data monitoring committee, and defied the FDA. Their statements about the naltrexone-bupropion’s cardiovascular efficacy were highly misleading, and there were obvious signs that the supporting data were not reliable. For example, nearly all of the CV mortality in the first interim analysis occurred well after participants had stopped taking their medication.
Yet the drug company was not sanctioned, and the naltrexone-bupropion retains FDA approval. At a minimum, the FDA should withhold approval until a viable replacement study is conducted, or it should require Risk Evaluation and Mitigation Strategies to counter the misinformation disseminated by the study sponsor, or it should restrict use of the drug outright.
Clinicians should be aware of these research improprieties and should know that the purported weight-loss benefit of naltrexone-bupropion is only 2.7 kg more than that achieved with placebo. How does this modest benefit balance against an unknown cardiovascular risk? In addition, the drug’s lack of efficacy clearly contributed to the very poor adherence rate in this trial: At 1 year, only 37.5% were still taking naltrexone-bupropion and 26.3% were still taking placebo.
Dr. Joshua M. Sharfstein is in the department of health policy and management at Johns Hopkins Bloomberg School of Public Health, Baltimore. Dr. Bruce M. Psaty is in the Cardiovascular Health Research Unit and the departments of medicine, epidemiology, and health services at the University of Washington, Seattle. They reported that this work was supported by the National Heart, Lung, and Blood Institute. Dr. Sharfstein reported serving as principal deputy commissioner of the FDA in 2009-2011. Dr. Psaty reported serving on the data monitoring committee of a clinical trial funded by Zoll LifeCor, on the steering committee of the Yale Open Data Access Project funded by Johnson & Johnson, and on the FDA Science Board. Dr. Sharfstein and Dr. Psaty made these remarks in an editorial accompanying Dr. Nissen’s report (JAMA. 2016;315:984-6).
The sponsor of this trial, Orexigen Therapeutics, disregarded the multiple harms caused by breaches of confidentiality, treated the academic investigators unfairly, ignored the trial’s data monitoring committee, and defied the FDA. Their statements about the naltrexone-bupropion’s cardiovascular efficacy were highly misleading, and there were obvious signs that the supporting data were not reliable. For example, nearly all of the CV mortality in the first interim analysis occurred well after participants had stopped taking their medication.
Yet the drug company was not sanctioned, and the naltrexone-bupropion retains FDA approval. At a minimum, the FDA should withhold approval until a viable replacement study is conducted, or it should require Risk Evaluation and Mitigation Strategies to counter the misinformation disseminated by the study sponsor, or it should restrict use of the drug outright.
Clinicians should be aware of these research improprieties and should know that the purported weight-loss benefit of naltrexone-bupropion is only 2.7 kg more than that achieved with placebo. How does this modest benefit balance against an unknown cardiovascular risk? In addition, the drug’s lack of efficacy clearly contributed to the very poor adherence rate in this trial: At 1 year, only 37.5% were still taking naltrexone-bupropion and 26.3% were still taking placebo.
Dr. Joshua M. Sharfstein is in the department of health policy and management at Johns Hopkins Bloomberg School of Public Health, Baltimore. Dr. Bruce M. Psaty is in the Cardiovascular Health Research Unit and the departments of medicine, epidemiology, and health services at the University of Washington, Seattle. They reported that this work was supported by the National Heart, Lung, and Blood Institute. Dr. Sharfstein reported serving as principal deputy commissioner of the FDA in 2009-2011. Dr. Psaty reported serving on the data monitoring committee of a clinical trial funded by Zoll LifeCor, on the steering committee of the Yale Open Data Access Project funded by Johnson & Johnson, and on the FDA Science Board. Dr. Sharfstein and Dr. Psaty made these remarks in an editorial accompanying Dr. Nissen’s report (JAMA. 2016;315:984-6).
The cardiovascular risks of the weight-loss combination drug naltrexone-bupropion are still uncertain, because the FDA-mandated safety trial, LIGHT, was terminated prematurely due to the sponsoring drug company’s breach of confidentiality. Other irregularities also were discovered, according to a report published online March 8 in JAMA.
Orexigen violated its agreement with FDA not to disclose the findings of an interim analysis performed after only 25% of expected CV events accrued. These findings appeared highly favorable for the drug, prompting the sponsor to publicly, and prematurely, claim naltrexone-bupropion reduced CV risk by 41% independently of its weight-loss effect. This favorable outcome was later found to be “driven almost exclusively by a 12-to-1 imbalance in death favoring naltrexone-bupropion among patients who were no longer taking the study drug,” said Dr. Steven E. Nissen of the Cleveland Clinic Center for Cardiovascular Research and his associates.
They now report the results of a second interim analysis of LIGHT (Cardiovascular Outcomes Study of Naltrexone SR/Bupropion SR in Overweight and Obese Subjects With Cardiovascular Risk Factors) performed after 50% of expected CV events accrued, as well as those of a final analysis performed when the trial was halted and 64% of expected CV events accrued. These findings are much less favorable, showing no significant difference between naltrexone-bupropion and placebo in the rate of major adverse cardiovascular events (MACE). In addition, extremely poor adherence to both active treatment and placebo over time, together with the complex statistical issues involved, call into question any interpretation of the results and preclude “any reliable conclusions about the long-term safety of naltrexone-bupropion,” the investigators said.
“The cardiovascular safety of this treatment remains uncertain and will require evaluation in a new, adequately powered outcome trial.” The results of such a study, should it be undertaken, wouldn’t be available for at least 3-4 years, they noted.
In their report, the investigators described in detail why the FDA required a CV safety study even though the agency had already approved naltrexone-bupropion as a weight-loss treatment.
The study was a phase IIIb randomized, double-blind, placebo-controlled trial involving 8,910 overweight/obese patients aged 45 or older (mean age, 61 years) who were at risk of adverse CV outcomes due to preexisting CV disease; exercise-induced angina; an unfavorable ankle/brachial index; stenosis of coronary, carotid, or lower extremity arteries; type 2 diabetes; hypertension; dyslipidemia; or smoking. These participants received daily tablets of either 32 mg naltrexone plus 360 mg bupropion or a matching placebo and were to be followed for 4 years at 266 U.S. medical centers.
The analysis performed after 50% of expected CV events accrued showed that MACE – the primary safety outcome – occurred in 2.0% of the naltrexone-bupropion group and 2.3% of the placebo group, a nonsignificant difference. Differences between the two study groups also were nonsignificant for the individual components of the primary outcome, including cardiovascular death (0.4% vs. 0.8%), nonfatal stroke (0.5% vs. 0.4%), and nonfatal MI (1.2% vs. 1.2%). These results were confirmed in a sensitivity analysis based on the final data collection, when 64% of expected CV events accrued: MACE occurred in 2.7% of the naltrexone-bupropion group and 2.8% of the placebo group, another nonsignificant difference.
The active treatment also was no better than placebo regarding all secondary outcomes, including all-cause mortality, CV hospitalization, and coronary revascularization, Dr. Nissen and his associates said (JAMA. 2016 Mar 8. doi: 10.1001/jama.2016.1558). Treatment adherence was low. At 16 weeks, only 64% of the naltrexone-bupropion group and 72% of the placebo group were still taking the study treatment. By 2 years, only 27% of the naltrexone-bupropion group and 17% of the placebo group were. The mean duration of treatment was only 18.4 weeks for naltrexone-bupropion and 16.3 weeks for placebo. Most treatment discontinuations were due to a failure to lose weight, but a substantial proportion occurred because of treatment-related increases in blood pressure or heart rate.
The active treatment’s ability to reduce body weight was deemed “modest.” When the trial was halted, the mean decrease in weight was 3.9 kg with naltrexone-bupropion, representing a 3.6% reduction in total weight, and was 1.2 kg with placebo, representing a 1.1% reduction.
Adverse effects developed in 28.1% of patients taking naltrexone-bupropion, which was a significantly greater proportion than the 8.7% rate in the placebo group. The most common adverse events leading to discontinuation of the study drug affected the gastrointestinal system (nausea, constipation, vomiting), the CNS (tremor, dizziness, headache), and mental/emotional problems (insomnia, anxiety, hallucinations, depression).
The cardiovascular risks of the weight-loss combination drug naltrexone-bupropion are still uncertain, because the FDA-mandated safety trial, LIGHT, was terminated prematurely due to the sponsoring drug company’s breach of confidentiality. Other irregularities also were discovered, according to a report published online March 8 in JAMA.
Orexigen violated its agreement with FDA not to disclose the findings of an interim analysis performed after only 25% of expected CV events accrued. These findings appeared highly favorable for the drug, prompting the sponsor to publicly, and prematurely, claim naltrexone-bupropion reduced CV risk by 41% independently of its weight-loss effect. This favorable outcome was later found to be “driven almost exclusively by a 12-to-1 imbalance in death favoring naltrexone-bupropion among patients who were no longer taking the study drug,” said Dr. Steven E. Nissen of the Cleveland Clinic Center for Cardiovascular Research and his associates.
They now report the results of a second interim analysis of LIGHT (Cardiovascular Outcomes Study of Naltrexone SR/Bupropion SR in Overweight and Obese Subjects With Cardiovascular Risk Factors) performed after 50% of expected CV events accrued, as well as those of a final analysis performed when the trial was halted and 64% of expected CV events accrued. These findings are much less favorable, showing no significant difference between naltrexone-bupropion and placebo in the rate of major adverse cardiovascular events (MACE). In addition, extremely poor adherence to both active treatment and placebo over time, together with the complex statistical issues involved, call into question any interpretation of the results and preclude “any reliable conclusions about the long-term safety of naltrexone-bupropion,” the investigators said.
“The cardiovascular safety of this treatment remains uncertain and will require evaluation in a new, adequately powered outcome trial.” The results of such a study, should it be undertaken, wouldn’t be available for at least 3-4 years, they noted.
In their report, the investigators described in detail why the FDA required a CV safety study even though the agency had already approved naltrexone-bupropion as a weight-loss treatment.
The study was a phase IIIb randomized, double-blind, placebo-controlled trial involving 8,910 overweight/obese patients aged 45 or older (mean age, 61 years) who were at risk of adverse CV outcomes due to preexisting CV disease; exercise-induced angina; an unfavorable ankle/brachial index; stenosis of coronary, carotid, or lower extremity arteries; type 2 diabetes; hypertension; dyslipidemia; or smoking. These participants received daily tablets of either 32 mg naltrexone plus 360 mg bupropion or a matching placebo and were to be followed for 4 years at 266 U.S. medical centers.
The analysis performed after 50% of expected CV events accrued showed that MACE – the primary safety outcome – occurred in 2.0% of the naltrexone-bupropion group and 2.3% of the placebo group, a nonsignificant difference. Differences between the two study groups also were nonsignificant for the individual components of the primary outcome, including cardiovascular death (0.4% vs. 0.8%), nonfatal stroke (0.5% vs. 0.4%), and nonfatal MI (1.2% vs. 1.2%). These results were confirmed in a sensitivity analysis based on the final data collection, when 64% of expected CV events accrued: MACE occurred in 2.7% of the naltrexone-bupropion group and 2.8% of the placebo group, another nonsignificant difference.
The active treatment also was no better than placebo regarding all secondary outcomes, including all-cause mortality, CV hospitalization, and coronary revascularization, Dr. Nissen and his associates said (JAMA. 2016 Mar 8. doi: 10.1001/jama.2016.1558). Treatment adherence was low. At 16 weeks, only 64% of the naltrexone-bupropion group and 72% of the placebo group were still taking the study treatment. By 2 years, only 27% of the naltrexone-bupropion group and 17% of the placebo group were. The mean duration of treatment was only 18.4 weeks for naltrexone-bupropion and 16.3 weeks for placebo. Most treatment discontinuations were due to a failure to lose weight, but a substantial proportion occurred because of treatment-related increases in blood pressure or heart rate.
The active treatment’s ability to reduce body weight was deemed “modest.” When the trial was halted, the mean decrease in weight was 3.9 kg with naltrexone-bupropion, representing a 3.6% reduction in total weight, and was 1.2 kg with placebo, representing a 1.1% reduction.
Adverse effects developed in 28.1% of patients taking naltrexone-bupropion, which was a significantly greater proportion than the 8.7% rate in the placebo group. The most common adverse events leading to discontinuation of the study drug affected the gastrointestinal system (nausea, constipation, vomiting), the CNS (tremor, dizziness, headache), and mental/emotional problems (insomnia, anxiety, hallucinations, depression).
FROM JAMA
Key clinical point: The cardiovascular risks of the weight-loss combination drug naltrexone-bupropion are still uncertain.
Major finding: The primary safety outcome, major adverse cardiovascular events, occurred in 2.0% of the naltrexone-bupropion group and 2.3% of the placebo group, a nonsignificant difference.
Data source: LIGHT, a multicenter randomized placebo-controlled double-blind noninferiority trial involving 8,910 overweight/obese patients.
Disclosures: This trial was sponsored by Orexigen Therapeutics and Takeda Pharmaceuticals. Dr. Nissen reported receiving grants from The Medicines Company, Amgen, Pfizer, AstraZeneca, Esperion Therapeutics, Eli Lilly, and Cerenis, and consulting for numerous drug companies that pay his fees directly to charities. His associates reported ties to numerous industry sources.
Two new drugs
Two new drugs have arrived to challenge our prescription pad or electronic record, depending on which you use. Empagliflozin (Jardiance), a drug used to modify glucose metabolism in type 2 diabetes in patients with preexisting cardiovascular disease, demonstrated a decrease in cardiovascular mortality. The other drug, Entresto, appears to provide an added benefit in heart failure therapy and was compared with a standard ACE inhibitor.
The results of EMPA-REG OUTCOME, reported at the European Association for the Study of Diabetes meeting in Stockholm, showed empagliflozin to be the first drug to decrease the mortality and morbidity of cardiovascular disease in diabetes. It is one of a group of new sodium-glucose cotransporter 2 (SGLT-2) blockers being tested in type 2 diabetes with established cardiovascular disease. Patients were randomized to placebo or empagliflozin while receiving standard medical and cardiovascular medications. After 3 years of follow-up, patients receiving the drug experienced a lower cardiovascular mortality rate, compared with placebo patients (3.7% vs. 5.9%, a 38% reduction) in addition to a decrease in hospitalization for heart failure and death from any cause. No effect was observed on the incidence of myocardial infarction or stroke. In addition, the drug also lowered blood glucose and blood pressure and led to some significant weight loss. The drug also was shown to decrease vascular resistance and albuminuria (N Engl J Med. 2015. 373:2117-2).
Furthermore, an analysis of EMPA-REG OUTCOME presented in November at the American Society of Nephrology meeting in San Diego, showed a profound benefit on the new onset and progression of chronic renal disease in diabetes patients. The importance of these results needs emphasis. Up until recently, the Food and Drug Administration has given a pass to diabetes drugs in regard to cardiovascular endpoints; approval has been based on their primary effect on lowering blood glucose. Some drugs in the past, such as rosiglitazone, actually have shown an increase in mortality in some diabetes patients. At long last, FDA approval for diabetes drugs hinges on acceptable outcomes in cardiovascular endpoints. The addition of a drug that can actually affect cardiovascular mortality and morbidity, the major risk factor of diabetes, provides an important addition to therapy.
The other drug that provides a choice of drugs for the treatment of heart failure is Entresto, a combination of sacubitril, a neprilysin inhibitor, and the angiotensin receptor inhibitor valsartan, approved in July 2015. In PARADIGM-HF, the compound was compared to enalapril in the treatment of patients with class II, III, and IV heart failure who were also receiving beta-blockers. Entresto-treated patients reported a 21.8% incidence of the primary outcome measure, cardiovascular death and hospitalization for heart failure, compared with the enalapril alone incidence of 26.5% (P less than .001) (N Engl J Med. 2014;371:993-1004). Investigators initially excluded 11.4% of the recruited patients from the study who could not tolerate Entresto or enalapril therapy. The drugs were well tolerated without any adverse reactions during therapy. Entresto was more effective than enalapril in regards to the occurrence of heart failure and death from any cause over a 27-month average follow-up.
The observations in this study emphasize how much the mortality of heart failure has decreased over the last decade. Cardiovascular deaths have decreased to roughly 7% per year and rehospitalization occurs in about 8% in the first year. Both drugs provide an important incremental benefit in heart failure patients.
Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.
Two new drugs have arrived to challenge our prescription pad or electronic record, depending on which you use. Empagliflozin (Jardiance), a drug used to modify glucose metabolism in type 2 diabetes in patients with preexisting cardiovascular disease, demonstrated a decrease in cardiovascular mortality. The other drug, Entresto, appears to provide an added benefit in heart failure therapy and was compared with a standard ACE inhibitor.
The results of EMPA-REG OUTCOME, reported at the European Association for the Study of Diabetes meeting in Stockholm, showed empagliflozin to be the first drug to decrease the mortality and morbidity of cardiovascular disease in diabetes. It is one of a group of new sodium-glucose cotransporter 2 (SGLT-2) blockers being tested in type 2 diabetes with established cardiovascular disease. Patients were randomized to placebo or empagliflozin while receiving standard medical and cardiovascular medications. After 3 years of follow-up, patients receiving the drug experienced a lower cardiovascular mortality rate, compared with placebo patients (3.7% vs. 5.9%, a 38% reduction) in addition to a decrease in hospitalization for heart failure and death from any cause. No effect was observed on the incidence of myocardial infarction or stroke. In addition, the drug also lowered blood glucose and blood pressure and led to some significant weight loss. The drug also was shown to decrease vascular resistance and albuminuria (N Engl J Med. 2015. 373:2117-2).
Furthermore, an analysis of EMPA-REG OUTCOME presented in November at the American Society of Nephrology meeting in San Diego, showed a profound benefit on the new onset and progression of chronic renal disease in diabetes patients. The importance of these results needs emphasis. Up until recently, the Food and Drug Administration has given a pass to diabetes drugs in regard to cardiovascular endpoints; approval has been based on their primary effect on lowering blood glucose. Some drugs in the past, such as rosiglitazone, actually have shown an increase in mortality in some diabetes patients. At long last, FDA approval for diabetes drugs hinges on acceptable outcomes in cardiovascular endpoints. The addition of a drug that can actually affect cardiovascular mortality and morbidity, the major risk factor of diabetes, provides an important addition to therapy.
The other drug that provides a choice of drugs for the treatment of heart failure is Entresto, a combination of sacubitril, a neprilysin inhibitor, and the angiotensin receptor inhibitor valsartan, approved in July 2015. In PARADIGM-HF, the compound was compared to enalapril in the treatment of patients with class II, III, and IV heart failure who were also receiving beta-blockers. Entresto-treated patients reported a 21.8% incidence of the primary outcome measure, cardiovascular death and hospitalization for heart failure, compared with the enalapril alone incidence of 26.5% (P less than .001) (N Engl J Med. 2014;371:993-1004). Investigators initially excluded 11.4% of the recruited patients from the study who could not tolerate Entresto or enalapril therapy. The drugs were well tolerated without any adverse reactions during therapy. Entresto was more effective than enalapril in regards to the occurrence of heart failure and death from any cause over a 27-month average follow-up.
The observations in this study emphasize how much the mortality of heart failure has decreased over the last decade. Cardiovascular deaths have decreased to roughly 7% per year and rehospitalization occurs in about 8% in the first year. Both drugs provide an important incremental benefit in heart failure patients.
Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.
Two new drugs have arrived to challenge our prescription pad or electronic record, depending on which you use. Empagliflozin (Jardiance), a drug used to modify glucose metabolism in type 2 diabetes in patients with preexisting cardiovascular disease, demonstrated a decrease in cardiovascular mortality. The other drug, Entresto, appears to provide an added benefit in heart failure therapy and was compared with a standard ACE inhibitor.
The results of EMPA-REG OUTCOME, reported at the European Association for the Study of Diabetes meeting in Stockholm, showed empagliflozin to be the first drug to decrease the mortality and morbidity of cardiovascular disease in diabetes. It is one of a group of new sodium-glucose cotransporter 2 (SGLT-2) blockers being tested in type 2 diabetes with established cardiovascular disease. Patients were randomized to placebo or empagliflozin while receiving standard medical and cardiovascular medications. After 3 years of follow-up, patients receiving the drug experienced a lower cardiovascular mortality rate, compared with placebo patients (3.7% vs. 5.9%, a 38% reduction) in addition to a decrease in hospitalization for heart failure and death from any cause. No effect was observed on the incidence of myocardial infarction or stroke. In addition, the drug also lowered blood glucose and blood pressure and led to some significant weight loss. The drug also was shown to decrease vascular resistance and albuminuria (N Engl J Med. 2015. 373:2117-2).
Furthermore, an analysis of EMPA-REG OUTCOME presented in November at the American Society of Nephrology meeting in San Diego, showed a profound benefit on the new onset and progression of chronic renal disease in diabetes patients. The importance of these results needs emphasis. Up until recently, the Food and Drug Administration has given a pass to diabetes drugs in regard to cardiovascular endpoints; approval has been based on their primary effect on lowering blood glucose. Some drugs in the past, such as rosiglitazone, actually have shown an increase in mortality in some diabetes patients. At long last, FDA approval for diabetes drugs hinges on acceptable outcomes in cardiovascular endpoints. The addition of a drug that can actually affect cardiovascular mortality and morbidity, the major risk factor of diabetes, provides an important addition to therapy.
The other drug that provides a choice of drugs for the treatment of heart failure is Entresto, a combination of sacubitril, a neprilysin inhibitor, and the angiotensin receptor inhibitor valsartan, approved in July 2015. In PARADIGM-HF, the compound was compared to enalapril in the treatment of patients with class II, III, and IV heart failure who were also receiving beta-blockers. Entresto-treated patients reported a 21.8% incidence of the primary outcome measure, cardiovascular death and hospitalization for heart failure, compared with the enalapril alone incidence of 26.5% (P less than .001) (N Engl J Med. 2014;371:993-1004). Investigators initially excluded 11.4% of the recruited patients from the study who could not tolerate Entresto or enalapril therapy. The drugs were well tolerated without any adverse reactions during therapy. Entresto was more effective than enalapril in regards to the occurrence of heart failure and death from any cause over a 27-month average follow-up.
The observations in this study emphasize how much the mortality of heart failure has decreased over the last decade. Cardiovascular deaths have decreased to roughly 7% per year and rehospitalization occurs in about 8% in the first year. Both drugs provide an important incremental benefit in heart failure patients.
Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.
Pro basketball players’ hearts: LV keeps growing, aortic root doesn’t
For the first time, cardiologists have characterized the adaptive cardiac remodeling in a large cohort of National Basketball Association players, which establishes a normative database and allows physicians to distinguish it from occult pathologic changes that may precipitate sudden cardiac death, according to an imaging study.
“We hope that the present data will help to focus decision making and improve clinical acumen for the purpose of primary prevention of cardiac emergencies in U.S. basketball players and in the athletic community at large,” said Dr. David J. Engel and his associates of Columbia University, New York.
Until now, most of the literature concerning the structural features of the athletic heart has been based on European studies, where comprehensive cardiac screening of all elite athletes is mandatory. The typical sports activities and the demographics of athletes in the U.S. are different, and their cardiologic profiles have not been well studied because detailed cardiac examinations are not compulsory. But the NBA recently mandated that all athletes undergo annual preseason medical evaluations including stress echocardiograms, and allowed the division of cardiology at Columbia to assess the results each year.
“A detailed understanding of normal and expected cardiac remodeling in U.S. basketball players has significant clinical importance given that the incidence of sports-related sudden cardiac death in the U.S. is highest among basketball players and that the most common cause ... in this population is hypertrophic cardiomyopathy,” the investigators noted.
Their analysis of all 526 ECGs performed on NBA players during a 1-year period “will provide an invaluable frame of reference to enhance player safety for the large group of U.S. basketball players in training at all skill levels, and in the athletic community at large,” they said.
The study participants were aged 18-39 years (mean age, 25.7 years). Roughly 77% were African American, 20% were white, 2% were Hispanic, and 1% were Asian or other ethnicities. The mean height was 200.2 cm (6’7”).
Left ventricular cavity size was larger than that in the general population, but LV size was proportional to the athletes’ large body size. “Scaling LV size to body size is vitally important in the cardiac evaluation of basketball players, whose heights extend to 218 cm and body surface areas to 2.8 m2,” Dr. Engel and his associates said (JAMA Cardiol. 2016 Feb 24. doi: 10.1001/jamacardio.2015.0252).
Left ventricular hypertrophy (LVH) was identified in only 27% of the athletes. African Americans had increased indices of LVH, compared with whites, and had a higher incidence of nondilated concentric hypertrophy, while whites showed predominantly eccentric dilated hypertrophy. These findings should help clinicians recognize genuine hypertrophic cardiomyopathy, which is a contraindication to participating in all but the most low-intensity competitive sports.
Most of the participants had a normal left ventricular ejection fraction, and all showed normal augmentation of LV systolic function with exercise.
Aortic root diameter was larger than that in the general population but similar to that in other elite athletes. Surprisingly, aortic root diameter increased with increasing body size only to a certain point, reaching a plateau at 31-35 mm. Fewer than 5% of the participants had an aortic root diameter of 40 mm or more, and the maximal diameter was 42 mm. “These data have important implications in the evaluation of exceptionally large athletes and question the applicability in individuals with significantly increased biometrics of the traditional formula to estimate aortic root diameter that assumes a linear association between [it] and body surface area,” they noted.
“We hope that the results of this study will assist recognition of cardiac pathologic change and provide a framework to help avoid unnecessary exclusions of athletes from competition. We believe that these data have additional applicability to other sports that preselect for athletes with height, such as volleyball, rowing, and track and field,” Dr. Engel and his associates added.
This study was supported by the National Basketball Association as part of a medical services agreement with Columbia University. Dr. Engel and his associates reported having no relevant financial disclosures.
The most interesting finding of this study was that despite the immense body size of the athletes, aortic root diameter exceeded 40 mm in less than 5%, and when dilation did occur it was of a very small magnitude, with a maximal diameter of 42 mm.
This important finding confirms that only mild aortic dilation should be considered physiologic among athletes, and that even athletes at the extreme end of the height spectrum should not be expected to show proportionally extreme aortic dilation.
Unlike ventricular size, which increases proportionally with body size, aortic dilation has an upper limit. Athletes with aortic dimensions that exceed this limit should be considered at risk for aortopathy and either prohibited from competitive sports or closely monitored if they do participate.
Dr. Aaron L. Baggish of the Cardiovascular Performance Program at Massachusetts General Hospital, Boston, made these remarks in an accompanying editorial (JAMA Cardiol. 2016 Feb 24. doi: 10.1001/jamacardio.2015.0289). He reported having no relevant financial conflicts of interest.
The most interesting finding of this study was that despite the immense body size of the athletes, aortic root diameter exceeded 40 mm in less than 5%, and when dilation did occur it was of a very small magnitude, with a maximal diameter of 42 mm.
This important finding confirms that only mild aortic dilation should be considered physiologic among athletes, and that even athletes at the extreme end of the height spectrum should not be expected to show proportionally extreme aortic dilation.
Unlike ventricular size, which increases proportionally with body size, aortic dilation has an upper limit. Athletes with aortic dimensions that exceed this limit should be considered at risk for aortopathy and either prohibited from competitive sports or closely monitored if they do participate.
Dr. Aaron L. Baggish of the Cardiovascular Performance Program at Massachusetts General Hospital, Boston, made these remarks in an accompanying editorial (JAMA Cardiol. 2016 Feb 24. doi: 10.1001/jamacardio.2015.0289). He reported having no relevant financial conflicts of interest.
The most interesting finding of this study was that despite the immense body size of the athletes, aortic root diameter exceeded 40 mm in less than 5%, and when dilation did occur it was of a very small magnitude, with a maximal diameter of 42 mm.
This important finding confirms that only mild aortic dilation should be considered physiologic among athletes, and that even athletes at the extreme end of the height spectrum should not be expected to show proportionally extreme aortic dilation.
Unlike ventricular size, which increases proportionally with body size, aortic dilation has an upper limit. Athletes with aortic dimensions that exceed this limit should be considered at risk for aortopathy and either prohibited from competitive sports or closely monitored if they do participate.
Dr. Aaron L. Baggish of the Cardiovascular Performance Program at Massachusetts General Hospital, Boston, made these remarks in an accompanying editorial (JAMA Cardiol. 2016 Feb 24. doi: 10.1001/jamacardio.2015.0289). He reported having no relevant financial conflicts of interest.
For the first time, cardiologists have characterized the adaptive cardiac remodeling in a large cohort of National Basketball Association players, which establishes a normative database and allows physicians to distinguish it from occult pathologic changes that may precipitate sudden cardiac death, according to an imaging study.
“We hope that the present data will help to focus decision making and improve clinical acumen for the purpose of primary prevention of cardiac emergencies in U.S. basketball players and in the athletic community at large,” said Dr. David J. Engel and his associates of Columbia University, New York.
Until now, most of the literature concerning the structural features of the athletic heart has been based on European studies, where comprehensive cardiac screening of all elite athletes is mandatory. The typical sports activities and the demographics of athletes in the U.S. are different, and their cardiologic profiles have not been well studied because detailed cardiac examinations are not compulsory. But the NBA recently mandated that all athletes undergo annual preseason medical evaluations including stress echocardiograms, and allowed the division of cardiology at Columbia to assess the results each year.
“A detailed understanding of normal and expected cardiac remodeling in U.S. basketball players has significant clinical importance given that the incidence of sports-related sudden cardiac death in the U.S. is highest among basketball players and that the most common cause ... in this population is hypertrophic cardiomyopathy,” the investigators noted.
Their analysis of all 526 ECGs performed on NBA players during a 1-year period “will provide an invaluable frame of reference to enhance player safety for the large group of U.S. basketball players in training at all skill levels, and in the athletic community at large,” they said.
The study participants were aged 18-39 years (mean age, 25.7 years). Roughly 77% were African American, 20% were white, 2% were Hispanic, and 1% were Asian or other ethnicities. The mean height was 200.2 cm (6’7”).
Left ventricular cavity size was larger than that in the general population, but LV size was proportional to the athletes’ large body size. “Scaling LV size to body size is vitally important in the cardiac evaluation of basketball players, whose heights extend to 218 cm and body surface areas to 2.8 m2,” Dr. Engel and his associates said (JAMA Cardiol. 2016 Feb 24. doi: 10.1001/jamacardio.2015.0252).
Left ventricular hypertrophy (LVH) was identified in only 27% of the athletes. African Americans had increased indices of LVH, compared with whites, and had a higher incidence of nondilated concentric hypertrophy, while whites showed predominantly eccentric dilated hypertrophy. These findings should help clinicians recognize genuine hypertrophic cardiomyopathy, which is a contraindication to participating in all but the most low-intensity competitive sports.
Most of the participants had a normal left ventricular ejection fraction, and all showed normal augmentation of LV systolic function with exercise.
Aortic root diameter was larger than that in the general population but similar to that in other elite athletes. Surprisingly, aortic root diameter increased with increasing body size only to a certain point, reaching a plateau at 31-35 mm. Fewer than 5% of the participants had an aortic root diameter of 40 mm or more, and the maximal diameter was 42 mm. “These data have important implications in the evaluation of exceptionally large athletes and question the applicability in individuals with significantly increased biometrics of the traditional formula to estimate aortic root diameter that assumes a linear association between [it] and body surface area,” they noted.
“We hope that the results of this study will assist recognition of cardiac pathologic change and provide a framework to help avoid unnecessary exclusions of athletes from competition. We believe that these data have additional applicability to other sports that preselect for athletes with height, such as volleyball, rowing, and track and field,” Dr. Engel and his associates added.
This study was supported by the National Basketball Association as part of a medical services agreement with Columbia University. Dr. Engel and his associates reported having no relevant financial disclosures.
For the first time, cardiologists have characterized the adaptive cardiac remodeling in a large cohort of National Basketball Association players, which establishes a normative database and allows physicians to distinguish it from occult pathologic changes that may precipitate sudden cardiac death, according to an imaging study.
“We hope that the present data will help to focus decision making and improve clinical acumen for the purpose of primary prevention of cardiac emergencies in U.S. basketball players and in the athletic community at large,” said Dr. David J. Engel and his associates of Columbia University, New York.
Until now, most of the literature concerning the structural features of the athletic heart has been based on European studies, where comprehensive cardiac screening of all elite athletes is mandatory. The typical sports activities and the demographics of athletes in the U.S. are different, and their cardiologic profiles have not been well studied because detailed cardiac examinations are not compulsory. But the NBA recently mandated that all athletes undergo annual preseason medical evaluations including stress echocardiograms, and allowed the division of cardiology at Columbia to assess the results each year.
“A detailed understanding of normal and expected cardiac remodeling in U.S. basketball players has significant clinical importance given that the incidence of sports-related sudden cardiac death in the U.S. is highest among basketball players and that the most common cause ... in this population is hypertrophic cardiomyopathy,” the investigators noted.
Their analysis of all 526 ECGs performed on NBA players during a 1-year period “will provide an invaluable frame of reference to enhance player safety for the large group of U.S. basketball players in training at all skill levels, and in the athletic community at large,” they said.
The study participants were aged 18-39 years (mean age, 25.7 years). Roughly 77% were African American, 20% were white, 2% were Hispanic, and 1% were Asian or other ethnicities. The mean height was 200.2 cm (6’7”).
Left ventricular cavity size was larger than that in the general population, but LV size was proportional to the athletes’ large body size. “Scaling LV size to body size is vitally important in the cardiac evaluation of basketball players, whose heights extend to 218 cm and body surface areas to 2.8 m2,” Dr. Engel and his associates said (JAMA Cardiol. 2016 Feb 24. doi: 10.1001/jamacardio.2015.0252).
Left ventricular hypertrophy (LVH) was identified in only 27% of the athletes. African Americans had increased indices of LVH, compared with whites, and had a higher incidence of nondilated concentric hypertrophy, while whites showed predominantly eccentric dilated hypertrophy. These findings should help clinicians recognize genuine hypertrophic cardiomyopathy, which is a contraindication to participating in all but the most low-intensity competitive sports.
Most of the participants had a normal left ventricular ejection fraction, and all showed normal augmentation of LV systolic function with exercise.
Aortic root diameter was larger than that in the general population but similar to that in other elite athletes. Surprisingly, aortic root diameter increased with increasing body size only to a certain point, reaching a plateau at 31-35 mm. Fewer than 5% of the participants had an aortic root diameter of 40 mm or more, and the maximal diameter was 42 mm. “These data have important implications in the evaluation of exceptionally large athletes and question the applicability in individuals with significantly increased biometrics of the traditional formula to estimate aortic root diameter that assumes a linear association between [it] and body surface area,” they noted.
“We hope that the results of this study will assist recognition of cardiac pathologic change and provide a framework to help avoid unnecessary exclusions of athletes from competition. We believe that these data have additional applicability to other sports that preselect for athletes with height, such as volleyball, rowing, and track and field,” Dr. Engel and his associates added.
This study was supported by the National Basketball Association as part of a medical services agreement with Columbia University. Dr. Engel and his associates reported having no relevant financial disclosures.
FROM JAMA CARDIOLOGY
Key clinical point: Cardiologists characterized normal, adaptive cardiac remodeling in NBA players, allowing physicians to distinguish it from occult pathologic changes that may precipitate sudden cardiac death.
Major finding: Aortic root diameter increased with increasing body size only to a certain point, reaching a plateau at 31-35 mm.
Data source: An observational cohort study in which echocardiograms of 526 professional athletes were analyzed.
Disclosures: This study was supported by the National Basketball Association as part of a medical services agreement with Columbia University. Dr. Engel and his associates reported having no relevant financial disclosures.
ACA accelerated hospital readmission reduction efforts
Hospital readmissions have declined in recent years for three conditions targeted under the Affordable Care Act, with smaller declines for other conditions, according to new research.
The study, published online Feb. 24 in the New England Journal of Medicine, found that 30-day readmission rates declined quickly after the passage of the ACA in 2010 and then slowed at the end of 2012. The researchers also analyzed trends in the use of observation units during the same period and concluded that the drop in readmissions was not being masked by a similar uptick in patients being seen under observation status (N Engl J Med. 2016 Feb 24. doi: 10.1056/NEJMsa1513024).
Under the ACA’s Hospital Readmissions Reduction Program, hospitals are financially penalized if they have higher-than-expected readmission rates for acute myocardial infarction, heart failure, and pneumonia.
The researchers, led by Rachael B. Zuckerman, M.P.H., of the Department of Health & Human Services, examined Medicare data from 3,387 hospitals from October 2007 through May 2015. Overall readmissions for acute myocardial infarction, heart failure, and pneumonia – the three conditions targeted in the readmissions reduction program – dropped from 21.5% to 17.8% during this time period. Readmissions for nontargeted conditions also dropped from 15.3% to 13.1%.
The researchers reported that readmissions for the targeted conditions were already declining before the ACA implementation (slope of monthly rate, –0.017), accelerating between April 2010 and October 2010 (–0.103), then leveling off through 2015 (–0.05). A similar pattern was seen with readmissions for conditions not targeted under the health law, though the declines were less pronounced.
Observation rates for the targeted conditions increased from 2.6% to 4.7% during the study period, while rates for nontargeted conditions rose from 2.5% to 4.2%. The researchers did not observe any significant associations increases in observation-unit stays – which were steady throughout the study period – and the implementation of the ACA.
“It seems likely that the upward trend in observation-service use may be attributable to factors that are largely unrelated to the Hospital Readmissions Reduction Program, such as confusion over whether an inpatient stay would be deemed inappropriate by Medicare recovery audit contractors,” the researchers wrote.
Though the observational design of the study could not confirm a causal link between the ACA penalties and the drop in readmissions, the findings suggest that the declines are not solely a response to the ACA.
The health law likely “catalyzed behavioral change by many hospitals” that was already underway, possibly because of broader concern about readmissions and to earlier Medicare initiatives designed to reduce them. Also, the investigators noted, hospitals may have been helped by other government efforts on the readmission front, including the dissemination of best practices by the Centers for Medicare & Medicaid Services.
The study was funded by HHS and the researchers were agency employees. They reported having no other financial disclosures.
Hospital readmissions have declined in recent years for three conditions targeted under the Affordable Care Act, with smaller declines for other conditions, according to new research.
The study, published online Feb. 24 in the New England Journal of Medicine, found that 30-day readmission rates declined quickly after the passage of the ACA in 2010 and then slowed at the end of 2012. The researchers also analyzed trends in the use of observation units during the same period and concluded that the drop in readmissions was not being masked by a similar uptick in patients being seen under observation status (N Engl J Med. 2016 Feb 24. doi: 10.1056/NEJMsa1513024).
Under the ACA’s Hospital Readmissions Reduction Program, hospitals are financially penalized if they have higher-than-expected readmission rates for acute myocardial infarction, heart failure, and pneumonia.
The researchers, led by Rachael B. Zuckerman, M.P.H., of the Department of Health & Human Services, examined Medicare data from 3,387 hospitals from October 2007 through May 2015. Overall readmissions for acute myocardial infarction, heart failure, and pneumonia – the three conditions targeted in the readmissions reduction program – dropped from 21.5% to 17.8% during this time period. Readmissions for nontargeted conditions also dropped from 15.3% to 13.1%.
The researchers reported that readmissions for the targeted conditions were already declining before the ACA implementation (slope of monthly rate, –0.017), accelerating between April 2010 and October 2010 (–0.103), then leveling off through 2015 (–0.05). A similar pattern was seen with readmissions for conditions not targeted under the health law, though the declines were less pronounced.
Observation rates for the targeted conditions increased from 2.6% to 4.7% during the study period, while rates for nontargeted conditions rose from 2.5% to 4.2%. The researchers did not observe any significant associations increases in observation-unit stays – which were steady throughout the study period – and the implementation of the ACA.
“It seems likely that the upward trend in observation-service use may be attributable to factors that are largely unrelated to the Hospital Readmissions Reduction Program, such as confusion over whether an inpatient stay would be deemed inappropriate by Medicare recovery audit contractors,” the researchers wrote.
Though the observational design of the study could not confirm a causal link between the ACA penalties and the drop in readmissions, the findings suggest that the declines are not solely a response to the ACA.
The health law likely “catalyzed behavioral change by many hospitals” that was already underway, possibly because of broader concern about readmissions and to earlier Medicare initiatives designed to reduce them. Also, the investigators noted, hospitals may have been helped by other government efforts on the readmission front, including the dissemination of best practices by the Centers for Medicare & Medicaid Services.
The study was funded by HHS and the researchers were agency employees. They reported having no other financial disclosures.
Hospital readmissions have declined in recent years for three conditions targeted under the Affordable Care Act, with smaller declines for other conditions, according to new research.
The study, published online Feb. 24 in the New England Journal of Medicine, found that 30-day readmission rates declined quickly after the passage of the ACA in 2010 and then slowed at the end of 2012. The researchers also analyzed trends in the use of observation units during the same period and concluded that the drop in readmissions was not being masked by a similar uptick in patients being seen under observation status (N Engl J Med. 2016 Feb 24. doi: 10.1056/NEJMsa1513024).
Under the ACA’s Hospital Readmissions Reduction Program, hospitals are financially penalized if they have higher-than-expected readmission rates for acute myocardial infarction, heart failure, and pneumonia.
The researchers, led by Rachael B. Zuckerman, M.P.H., of the Department of Health & Human Services, examined Medicare data from 3,387 hospitals from October 2007 through May 2015. Overall readmissions for acute myocardial infarction, heart failure, and pneumonia – the three conditions targeted in the readmissions reduction program – dropped from 21.5% to 17.8% during this time period. Readmissions for nontargeted conditions also dropped from 15.3% to 13.1%.
The researchers reported that readmissions for the targeted conditions were already declining before the ACA implementation (slope of monthly rate, –0.017), accelerating between April 2010 and October 2010 (–0.103), then leveling off through 2015 (–0.05). A similar pattern was seen with readmissions for conditions not targeted under the health law, though the declines were less pronounced.
Observation rates for the targeted conditions increased from 2.6% to 4.7% during the study period, while rates for nontargeted conditions rose from 2.5% to 4.2%. The researchers did not observe any significant associations increases in observation-unit stays – which were steady throughout the study period – and the implementation of the ACA.
“It seems likely that the upward trend in observation-service use may be attributable to factors that are largely unrelated to the Hospital Readmissions Reduction Program, such as confusion over whether an inpatient stay would be deemed inappropriate by Medicare recovery audit contractors,” the researchers wrote.
Though the observational design of the study could not confirm a causal link between the ACA penalties and the drop in readmissions, the findings suggest that the declines are not solely a response to the ACA.
The health law likely “catalyzed behavioral change by many hospitals” that was already underway, possibly because of broader concern about readmissions and to earlier Medicare initiatives designed to reduce them. Also, the investigators noted, hospitals may have been helped by other government efforts on the readmission front, including the dissemination of best practices by the Centers for Medicare & Medicaid Services.
The study was funded by HHS and the researchers were agency employees. They reported having no other financial disclosures.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Hospital readmission rates declined following ACA enactment in 2010, but increased use of observation units did not account for the change.
Major finding: During 2007-2015, 30-day hospital readmissions for three targeted conditions dropped from 21.5% to 17.8%.
Data source: An interrupted time-series analysis of readmission and observation unit stay data of elderly Medicare beneficiaries from nearly 3,400 hospitals from 2007-2015.
Disclosures: The Health and Human Services department funded the study and the researchers were agency employees. They reported having no other financial disclosures.
STS: Lactate dehydrogenase of 1,150 IU/L flags LVAD thrombosis
PHOENIX – A blood lactate dehydrogenase level of at least 1,150 IU/L may be the best cutoff for identifying pump thrombosis in patients who have received a left ventricular assist device based on findings from a combined series of 502 pump recipients.
Using this cutoff correlated with a positive predictive value of 74% and a negative predictive value of 92%, Dr. Vikram Sood said at the annual meeting of the Society of Thoracic Surgeons.
Results from several prior studies had established an elevated blood level of lactate dehydrogenase (LDH) as perhaps the best early flag of significant thrombus inside of a left ventricular assist device (LVAD), a condition called pump thrombosis. But prior studies had not identified a specific cutoff value to use that could confidently diagnose pump thrombosis. A level of 1,150 IU/L is about five times the upper limit of normal, noted Dr. Francis D. Pagani, professor of surgery and surgical director of adult heart transplantation at the University of Michigan, Ann Arbor, and a senior author on this report.
Dr. Sood and his associates reviewed records for 502 patients who received a HeartMate II LVAD at either the University of Michigan or at the Mayo Clinic in Rochester, Minn., during 2004-2014. During that time, 58 of the patients required a total of 70 LVAD explants. Fifty-two of the explants were for suspected pump thrombosis, 12 for infection, and 6 for lead fracture. The average time from LVAD placement to explant was 12 months.
Among the 52 LVADs explanted for suspected pump thrombosis, 47 actually had thrombosis. In addition, six of the LVADs that were explanted for other reasons also had a significant amount of thrombus, resulting in 53 total explanted LVAD with confirmed pump thrombosis.
The researchers analyzed blood levels of LDH during the 6 months prior to explant. Among the patients with the 53 LVADs explanted with confirmed pump thrombosis, the median of all LDH levels during the period was 1,061 IU/L and the median maximum LDH level for each patient was 1,940 IU/L, reported Dr. Sood, a cardiac surgeon at the University of Michigan. In contrast, among the patients who had a total of 17 LVADs explanted without pump thrombosis, the median value for all LDH measures during the 6 months prior to explant was 533 IU/L, and their medium maximum level was 504 IU/L.
Analysis of LDH levels prior to explant and subsequent confirmation of pump thrombosis identified a cut off of 1,150 IU/L as able to identify pump thrombosis with a sensitivity of 78% and a specificity of 90%, Dr. Sood reported.
On Twitter @mitchelzoler
PHOENIX – A blood lactate dehydrogenase level of at least 1,150 IU/L may be the best cutoff for identifying pump thrombosis in patients who have received a left ventricular assist device based on findings from a combined series of 502 pump recipients.
Using this cutoff correlated with a positive predictive value of 74% and a negative predictive value of 92%, Dr. Vikram Sood said at the annual meeting of the Society of Thoracic Surgeons.
Results from several prior studies had established an elevated blood level of lactate dehydrogenase (LDH) as perhaps the best early flag of significant thrombus inside of a left ventricular assist device (LVAD), a condition called pump thrombosis. But prior studies had not identified a specific cutoff value to use that could confidently diagnose pump thrombosis. A level of 1,150 IU/L is about five times the upper limit of normal, noted Dr. Francis D. Pagani, professor of surgery and surgical director of adult heart transplantation at the University of Michigan, Ann Arbor, and a senior author on this report.
Dr. Sood and his associates reviewed records for 502 patients who received a HeartMate II LVAD at either the University of Michigan or at the Mayo Clinic in Rochester, Minn., during 2004-2014. During that time, 58 of the patients required a total of 70 LVAD explants. Fifty-two of the explants were for suspected pump thrombosis, 12 for infection, and 6 for lead fracture. The average time from LVAD placement to explant was 12 months.
Among the 52 LVADs explanted for suspected pump thrombosis, 47 actually had thrombosis. In addition, six of the LVADs that were explanted for other reasons also had a significant amount of thrombus, resulting in 53 total explanted LVAD with confirmed pump thrombosis.
The researchers analyzed blood levels of LDH during the 6 months prior to explant. Among the patients with the 53 LVADs explanted with confirmed pump thrombosis, the median of all LDH levels during the period was 1,061 IU/L and the median maximum LDH level for each patient was 1,940 IU/L, reported Dr. Sood, a cardiac surgeon at the University of Michigan. In contrast, among the patients who had a total of 17 LVADs explanted without pump thrombosis, the median value for all LDH measures during the 6 months prior to explant was 533 IU/L, and their medium maximum level was 504 IU/L.
Analysis of LDH levels prior to explant and subsequent confirmation of pump thrombosis identified a cut off of 1,150 IU/L as able to identify pump thrombosis with a sensitivity of 78% and a specificity of 90%, Dr. Sood reported.
On Twitter @mitchelzoler
PHOENIX – A blood lactate dehydrogenase level of at least 1,150 IU/L may be the best cutoff for identifying pump thrombosis in patients who have received a left ventricular assist device based on findings from a combined series of 502 pump recipients.
Using this cutoff correlated with a positive predictive value of 74% and a negative predictive value of 92%, Dr. Vikram Sood said at the annual meeting of the Society of Thoracic Surgeons.
Results from several prior studies had established an elevated blood level of lactate dehydrogenase (LDH) as perhaps the best early flag of significant thrombus inside of a left ventricular assist device (LVAD), a condition called pump thrombosis. But prior studies had not identified a specific cutoff value to use that could confidently diagnose pump thrombosis. A level of 1,150 IU/L is about five times the upper limit of normal, noted Dr. Francis D. Pagani, professor of surgery and surgical director of adult heart transplantation at the University of Michigan, Ann Arbor, and a senior author on this report.
Dr. Sood and his associates reviewed records for 502 patients who received a HeartMate II LVAD at either the University of Michigan or at the Mayo Clinic in Rochester, Minn., during 2004-2014. During that time, 58 of the patients required a total of 70 LVAD explants. Fifty-two of the explants were for suspected pump thrombosis, 12 for infection, and 6 for lead fracture. The average time from LVAD placement to explant was 12 months.
Among the 52 LVADs explanted for suspected pump thrombosis, 47 actually had thrombosis. In addition, six of the LVADs that were explanted for other reasons also had a significant amount of thrombus, resulting in 53 total explanted LVAD with confirmed pump thrombosis.
The researchers analyzed blood levels of LDH during the 6 months prior to explant. Among the patients with the 53 LVADs explanted with confirmed pump thrombosis, the median of all LDH levels during the period was 1,061 IU/L and the median maximum LDH level for each patient was 1,940 IU/L, reported Dr. Sood, a cardiac surgeon at the University of Michigan. In contrast, among the patients who had a total of 17 LVADs explanted without pump thrombosis, the median value for all LDH measures during the 6 months prior to explant was 533 IU/L, and their medium maximum level was 504 IU/L.
Analysis of LDH levels prior to explant and subsequent confirmation of pump thrombosis identified a cut off of 1,150 IU/L as able to identify pump thrombosis with a sensitivity of 78% and a specificity of 90%, Dr. Sood reported.
On Twitter @mitchelzoler
AT THE STS ANNUAL MEETING
Key clinical point: In patients who have received a left ventricular assist device, a blood level of lactate dehydrogenase of at least 1,150 IU/L had a good positive and negative predictive value for pump thrombosis.
Major finding: A 1,150 IU/L cutoff for LDH had a positive predictive value of 74% and a negative predictive value of 92%.
Data source: Retrospective review of 502 patients who received a HeartMate II LVAD at either of two U.S. centers during 2004-2014.
Disclosures: Dr. Sood and Dr. Pagani had no disclosures.
STS: Minimizing LVAD pump thrombosis poses new challenges
PHOENIX – Cardiothoracic surgeons who implant left ventricular assist devices in patients with failing hearts remain at a loss to fully explain why they started seeing a sharp increase in thrombus clogging in these devices in 2012, but nevertheless they are gaining a better sense of how to minimize the risk.
Three key principles for minimizing thrombosis risk are selecting the right patients to receive left ventricular assist devices (LVAD), applying optimal management strategies once patients receive a LVAD, and maintaining adequate flow of blood through the pump, Dr. Francis D. Pagani said in a talk at a session devoted to pump thrombosis at the annual meeting of the Society of Thoracic Surgeons.
Other critical aspects include optimal implantation technique, quick work-up of patients to rule out reversible LVAD inflow or outflow problems once pump thrombosis is suspected, and ceasing medical therapy of the thrombosis if it proves ineffective and instead progress to surgical pump exchange, pump explantation, or heart transplant when necessary, said Dr. Ahmet Kilic, a cardiothoracic surgeon at the Ohio State University, Columbus.
Another key issue is that, now that the pump thrombosis incidence is averaging about 10% of LVAD recipients, with an incidence rate during 2-year follow-up as high as 24% reported from one series, surgeons and physicians who care for LVAD patients must have a high index of suspicion and routinely screen LVAD recipients for early signs of pump thrombosis. The best way to catch pump thrombosis early seems to be by regularly measuring patients’ serum level of lactate dehydrogenase (LDH), said Dr. Robert L. Kormos, professor of surgery and director of the artificial heart program at the University of Pittsburgh.
“We measure LDH on most clinic visits, whether or not the patient has an indication of pump thrombosis. We need to screen [LDH levels] much more routinely than we used to,” he said during the session. “Elevated LDH is probably the first and most reliable early sign, but you need to also assess LDH isoenzymes because we’ve had patients with an elevation but no sign of pump thrombosis, and their isoenzymes showed that the increased LDH was coming from their liver,” Dr. Kormos said in an interview.
Although serial measurements and isoenzyme analysis can establish a sharp rise in heart-specific LDH in an individual patient, a report at the meeting documented that in a series of 53 patients with pump thrombosis treated at either of two U.S. centers, an LDH level of at least 1,155 IU/L flagged pump thrombosis with a fairly high sensitivity and specificity. This LDH level is roughly five times the upper limit of normal, noted Dr. Pagani, professor of surgery and surgical director of adult heart transplantation at the University of Michigan, Ann Arbor, and a senior author on this report.
But prior to this report Dr. Kormos said that he regarded a LDH level of 600-800 IU/L as enough of an elevation above normal to prompt concern and investigation. And he criticized some LVAD programs that allow LDH levels to rise much higher.
“I know of clinicians who see a LDH of 1,500-2,000 IU/L but the patient seems okay and they wonder if they should change out the pump. For me, it’s a no brainer. Others try to list a patient like this for a heart transplant so they can avoid doing a pump exchange. I think that’s dangerous; it risks liver failure or renal failure. I would not sit on any LVAD that is starting to produce signs of hemolysis syndrome, but some places do this,” Dr. Kormos said in an interview.
“Pump thrombosis probably did not get addressed in as timely a fashion as it should have been” when it was first seen on the rise in 2012, noted Dr. James K. Kirklin, professor of surgery and director of cardiothoracic surgery at the University of Alabama, Birmingham. “It is now being addressed, and we realize that this is not just a pump problem but also involves patient factors and management factors that we need to learn more about. We are quite ignorant of the patient factors and understanding their contributions to bleeding and thrombosis,” said Dr. Kirklin. He also acknowledged that whatever role the current generation of LVAD pumps play in causing thrombosis will not quickly resolve.
“I’m looking forward to a new generation of pumps, but the pumps we have today will probably remain for another 3-5 years.”
The issue of LVAD pump thrombosis first came into clear focus with publication at the start of 2014 of a report that tracked its incidence from 2004 to mid-2013 at three U.S. centers that had placed a total of 895 LVADs in 837 patients. The annual rate of new episodes of pump thrombosis jumped from about 1%-2% of LVAD recipients throughout the first part of the study period through the end of 2011, to an annual rate of about 10% by mid 2013 (N Engl J Med. 2014 Jan 2;370[1]:33-40).
“The inflection occurred in about 2012,” noted Dr. Nicholas G. Smedira, a cardiothoracic surgeon at the Cleveland Clinic. “No one has figured out why” the incidence suddenly spiked starting in 2012 and intensified in 2013, he said. This epidemic of pump thrombosis has produced “devastating complications” that have led to multiple readmissions and reduced cost-effectiveness of LVADs and has affected how the heart transplant community allocates hearts, Dr. Smedira said during his talk at the session. He noted that once the surge in pump thrombosis started, the timing of the appearance of significant thrombus shifted earlier, often occurring within 2-3 months after LVAD placement. There now is “increasing device-related pessimism” and increasing demoralization among clinicians because of this recurring complication, he said.
More recent data show the trend toward increasingly higher rates of pump thrombosis continuing through the end of 2013, with the situation during 2014 a bit less clear. Late last year, data from 9,808 U.S. patients who received an LVAD and entered the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) showed that the incidence of pump thrombosis during the first 6 months following an implant rose from 1% in 2008 to 2% in 2009 and in 2010, 4% in 2011, 7% in 2012, 8% in 2013, and then eased back to 5% in the first half of 2014 (J Heart Lung Transplant. 2015 Dec;34[12]:1515-26). The annual rate rose from 2% in 2008 to a peak of 11% in 2013, with 12-month data from 2014 not yet available at the time of this report.
“The modest reduction of observed pump thrombosis at 6 months during 2014 has occurred in a milieu of heightened intensity of anti-coagulation management, greater surgical awareness of optimal pump implantation and positioning and pump speed management. Thus, one may speculate that current thrombosis risk-mitigation strategies have contributed to reducing but not eliminating the increased thrombosis risk observed since 2011,” concluded the authors of the report.
Surgeons and cardiologists must now have a high index of suspicion for pump thrombosis in LVAD recipients, and be especially on the lookout for four key flags of a problem, said Dr. Kormos. The first is a rising LDH level, but additional flags include an isolated power elevation that doesn’t correlate with anything else, evidence of hemolysis, and new-onset heart failure symptoms. These can occur individually or in some combination. He recommended following a diagnostic algorithm first presented in 2013 that remains very valid today (J Heart Lung Transplant. 2013 July;32[7]:667-70).
Dr. Kormos also highlighted that the presentation of pump thrombosis can differ between the two LVADs most commonly used in U.S. practice, the HeartMate II and the HeartWare devices. A LDH elevation is primarily an indicator for HeartMate II, while both that model and the HeartWare device show sustained, isolated power elevations when thrombosis occurs.
Dr. Pagani, Dr. Kirklin, and Dr. Smedira had no disclosures. Dr. Kormos has received travel support from HeartWare. Dr. Kilic has been a consultant to Thoratec and a speaker on behalf of Baxter International.
On Twitter @mitchelzoler
Dr. Hossein Almassi, FCCP, comments: With improvements in technology and development of rotary pumps, there has been a significant growth in the use of mechanical circulatory support (MCS) for treatment of end stage heart failure with a parallel improvement in patients’ survival and the quality of life.
|
| Dr. Hossein Almassi |
The authors of this report presented at the 2016 annual meeting of the STS, are authorities in the field of MCS outlining the observed increase in pump thrombosis noted in 2012. The sharp increase in the thrombosis rate is different from the lower incidence seen in the preapproval stage of the pump trial.
It should be noted that the report is related mainly to the HeatMate II left ventricular assist device (LVAD) and not the more recently implanted HeartWare device.
The diagnostic algorithm outlined in the accompanying reference (J Heart Lung Transplant. 2013 July;32[7]:667-70) regarding the diagnosis and management of suspected pump thrombosis is worth reading with the main criteria heralding a potential pump thrombosis being 1)sustained pump power elevation, 2) elevation of cardiac LDH or plasma-free hemoglobin, 3) hemolysis, and 4) symptoms of heart failure.
With further refinements in technology, the field of MCS is awaiting the development of newer LVAD devices that would mitigate the serious problem of pump thrombosis.
Dr. Hossein Almassi, FCCP, comments: With improvements in technology and development of rotary pumps, there has been a significant growth in the use of mechanical circulatory support (MCS) for treatment of end stage heart failure with a parallel improvement in patients’ survival and the quality of life.
|
|
| Dr. Hossein Almassi |
The authors of this report presented at the 2016 annual meeting of the STS, are authorities in the field of MCS outlining the observed increase in pump thrombosis noted in 2012. The sharp increase in the thrombosis rate is different from the lower incidence seen in the preapproval stage of the pump trial.
It should be noted that the report is related mainly to the HeatMate II left ventricular assist device (LVAD) and not the more recently implanted HeartWare device.
The diagnostic algorithm outlined in the accompanying reference (J Heart Lung Transplant. 2013 July;32[7]:667-70) regarding the diagnosis and management of suspected pump thrombosis is worth reading with the main criteria heralding a potential pump thrombosis being 1)sustained pump power elevation, 2) elevation of cardiac LDH or plasma-free hemoglobin, 3) hemolysis, and 4) symptoms of heart failure.
With further refinements in technology, the field of MCS is awaiting the development of newer LVAD devices that would mitigate the serious problem of pump thrombosis.
Dr. Hossein Almassi, FCCP, comments: With improvements in technology and development of rotary pumps, there has been a significant growth in the use of mechanical circulatory support (MCS) for treatment of end stage heart failure with a parallel improvement in patients’ survival and the quality of life.
|
|
| Dr. Hossein Almassi |
The authors of this report presented at the 2016 annual meeting of the STS, are authorities in the field of MCS outlining the observed increase in pump thrombosis noted in 2012. The sharp increase in the thrombosis rate is different from the lower incidence seen in the preapproval stage of the pump trial.
It should be noted that the report is related mainly to the HeatMate II left ventricular assist device (LVAD) and not the more recently implanted HeartWare device.
The diagnostic algorithm outlined in the accompanying reference (J Heart Lung Transplant. 2013 July;32[7]:667-70) regarding the diagnosis and management of suspected pump thrombosis is worth reading with the main criteria heralding a potential pump thrombosis being 1)sustained pump power elevation, 2) elevation of cardiac LDH or plasma-free hemoglobin, 3) hemolysis, and 4) symptoms of heart failure.
With further refinements in technology, the field of MCS is awaiting the development of newer LVAD devices that would mitigate the serious problem of pump thrombosis.
PHOENIX – Cardiothoracic surgeons who implant left ventricular assist devices in patients with failing hearts remain at a loss to fully explain why they started seeing a sharp increase in thrombus clogging in these devices in 2012, but nevertheless they are gaining a better sense of how to minimize the risk.
Three key principles for minimizing thrombosis risk are selecting the right patients to receive left ventricular assist devices (LVAD), applying optimal management strategies once patients receive a LVAD, and maintaining adequate flow of blood through the pump, Dr. Francis D. Pagani said in a talk at a session devoted to pump thrombosis at the annual meeting of the Society of Thoracic Surgeons.
Other critical aspects include optimal implantation technique, quick work-up of patients to rule out reversible LVAD inflow or outflow problems once pump thrombosis is suspected, and ceasing medical therapy of the thrombosis if it proves ineffective and instead progress to surgical pump exchange, pump explantation, or heart transplant when necessary, said Dr. Ahmet Kilic, a cardiothoracic surgeon at the Ohio State University, Columbus.
Another key issue is that, now that the pump thrombosis incidence is averaging about 10% of LVAD recipients, with an incidence rate during 2-year follow-up as high as 24% reported from one series, surgeons and physicians who care for LVAD patients must have a high index of suspicion and routinely screen LVAD recipients for early signs of pump thrombosis. The best way to catch pump thrombosis early seems to be by regularly measuring patients’ serum level of lactate dehydrogenase (LDH), said Dr. Robert L. Kormos, professor of surgery and director of the artificial heart program at the University of Pittsburgh.
“We measure LDH on most clinic visits, whether or not the patient has an indication of pump thrombosis. We need to screen [LDH levels] much more routinely than we used to,” he said during the session. “Elevated LDH is probably the first and most reliable early sign, but you need to also assess LDH isoenzymes because we’ve had patients with an elevation but no sign of pump thrombosis, and their isoenzymes showed that the increased LDH was coming from their liver,” Dr. Kormos said in an interview.
Although serial measurements and isoenzyme analysis can establish a sharp rise in heart-specific LDH in an individual patient, a report at the meeting documented that in a series of 53 patients with pump thrombosis treated at either of two U.S. centers, an LDH level of at least 1,155 IU/L flagged pump thrombosis with a fairly high sensitivity and specificity. This LDH level is roughly five times the upper limit of normal, noted Dr. Pagani, professor of surgery and surgical director of adult heart transplantation at the University of Michigan, Ann Arbor, and a senior author on this report.
But prior to this report Dr. Kormos said that he regarded a LDH level of 600-800 IU/L as enough of an elevation above normal to prompt concern and investigation. And he criticized some LVAD programs that allow LDH levels to rise much higher.
“I know of clinicians who see a LDH of 1,500-2,000 IU/L but the patient seems okay and they wonder if they should change out the pump. For me, it’s a no brainer. Others try to list a patient like this for a heart transplant so they can avoid doing a pump exchange. I think that’s dangerous; it risks liver failure or renal failure. I would not sit on any LVAD that is starting to produce signs of hemolysis syndrome, but some places do this,” Dr. Kormos said in an interview.
“Pump thrombosis probably did not get addressed in as timely a fashion as it should have been” when it was first seen on the rise in 2012, noted Dr. James K. Kirklin, professor of surgery and director of cardiothoracic surgery at the University of Alabama, Birmingham. “It is now being addressed, and we realize that this is not just a pump problem but also involves patient factors and management factors that we need to learn more about. We are quite ignorant of the patient factors and understanding their contributions to bleeding and thrombosis,” said Dr. Kirklin. He also acknowledged that whatever role the current generation of LVAD pumps play in causing thrombosis will not quickly resolve.
“I’m looking forward to a new generation of pumps, but the pumps we have today will probably remain for another 3-5 years.”
The issue of LVAD pump thrombosis first came into clear focus with publication at the start of 2014 of a report that tracked its incidence from 2004 to mid-2013 at three U.S. centers that had placed a total of 895 LVADs in 837 patients. The annual rate of new episodes of pump thrombosis jumped from about 1%-2% of LVAD recipients throughout the first part of the study period through the end of 2011, to an annual rate of about 10% by mid 2013 (N Engl J Med. 2014 Jan 2;370[1]:33-40).
“The inflection occurred in about 2012,” noted Dr. Nicholas G. Smedira, a cardiothoracic surgeon at the Cleveland Clinic. “No one has figured out why” the incidence suddenly spiked starting in 2012 and intensified in 2013, he said. This epidemic of pump thrombosis has produced “devastating complications” that have led to multiple readmissions and reduced cost-effectiveness of LVADs and has affected how the heart transplant community allocates hearts, Dr. Smedira said during his talk at the session. He noted that once the surge in pump thrombosis started, the timing of the appearance of significant thrombus shifted earlier, often occurring within 2-3 months after LVAD placement. There now is “increasing device-related pessimism” and increasing demoralization among clinicians because of this recurring complication, he said.
More recent data show the trend toward increasingly higher rates of pump thrombosis continuing through the end of 2013, with the situation during 2014 a bit less clear. Late last year, data from 9,808 U.S. patients who received an LVAD and entered the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) showed that the incidence of pump thrombosis during the first 6 months following an implant rose from 1% in 2008 to 2% in 2009 and in 2010, 4% in 2011, 7% in 2012, 8% in 2013, and then eased back to 5% in the first half of 2014 (J Heart Lung Transplant. 2015 Dec;34[12]:1515-26). The annual rate rose from 2% in 2008 to a peak of 11% in 2013, with 12-month data from 2014 not yet available at the time of this report.
“The modest reduction of observed pump thrombosis at 6 months during 2014 has occurred in a milieu of heightened intensity of anti-coagulation management, greater surgical awareness of optimal pump implantation and positioning and pump speed management. Thus, one may speculate that current thrombosis risk-mitigation strategies have contributed to reducing but not eliminating the increased thrombosis risk observed since 2011,” concluded the authors of the report.
Surgeons and cardiologists must now have a high index of suspicion for pump thrombosis in LVAD recipients, and be especially on the lookout for four key flags of a problem, said Dr. Kormos. The first is a rising LDH level, but additional flags include an isolated power elevation that doesn’t correlate with anything else, evidence of hemolysis, and new-onset heart failure symptoms. These can occur individually or in some combination. He recommended following a diagnostic algorithm first presented in 2013 that remains very valid today (J Heart Lung Transplant. 2013 July;32[7]:667-70).
Dr. Kormos also highlighted that the presentation of pump thrombosis can differ between the two LVADs most commonly used in U.S. practice, the HeartMate II and the HeartWare devices. A LDH elevation is primarily an indicator for HeartMate II, while both that model and the HeartWare device show sustained, isolated power elevations when thrombosis occurs.
Dr. Pagani, Dr. Kirklin, and Dr. Smedira had no disclosures. Dr. Kormos has received travel support from HeartWare. Dr. Kilic has been a consultant to Thoratec and a speaker on behalf of Baxter International.
On Twitter @mitchelzoler
PHOENIX – Cardiothoracic surgeons who implant left ventricular assist devices in patients with failing hearts remain at a loss to fully explain why they started seeing a sharp increase in thrombus clogging in these devices in 2012, but nevertheless they are gaining a better sense of how to minimize the risk.
Three key principles for minimizing thrombosis risk are selecting the right patients to receive left ventricular assist devices (LVAD), applying optimal management strategies once patients receive a LVAD, and maintaining adequate flow of blood through the pump, Dr. Francis D. Pagani said in a talk at a session devoted to pump thrombosis at the annual meeting of the Society of Thoracic Surgeons.
Other critical aspects include optimal implantation technique, quick work-up of patients to rule out reversible LVAD inflow or outflow problems once pump thrombosis is suspected, and ceasing medical therapy of the thrombosis if it proves ineffective and instead progress to surgical pump exchange, pump explantation, or heart transplant when necessary, said Dr. Ahmet Kilic, a cardiothoracic surgeon at the Ohio State University, Columbus.
Another key issue is that, now that the pump thrombosis incidence is averaging about 10% of LVAD recipients, with an incidence rate during 2-year follow-up as high as 24% reported from one series, surgeons and physicians who care for LVAD patients must have a high index of suspicion and routinely screen LVAD recipients for early signs of pump thrombosis. The best way to catch pump thrombosis early seems to be by regularly measuring patients’ serum level of lactate dehydrogenase (LDH), said Dr. Robert L. Kormos, professor of surgery and director of the artificial heart program at the University of Pittsburgh.
“We measure LDH on most clinic visits, whether or not the patient has an indication of pump thrombosis. We need to screen [LDH levels] much more routinely than we used to,” he said during the session. “Elevated LDH is probably the first and most reliable early sign, but you need to also assess LDH isoenzymes because we’ve had patients with an elevation but no sign of pump thrombosis, and their isoenzymes showed that the increased LDH was coming from their liver,” Dr. Kormos said in an interview.
Although serial measurements and isoenzyme analysis can establish a sharp rise in heart-specific LDH in an individual patient, a report at the meeting documented that in a series of 53 patients with pump thrombosis treated at either of two U.S. centers, an LDH level of at least 1,155 IU/L flagged pump thrombosis with a fairly high sensitivity and specificity. This LDH level is roughly five times the upper limit of normal, noted Dr. Pagani, professor of surgery and surgical director of adult heart transplantation at the University of Michigan, Ann Arbor, and a senior author on this report.
But prior to this report Dr. Kormos said that he regarded a LDH level of 600-800 IU/L as enough of an elevation above normal to prompt concern and investigation. And he criticized some LVAD programs that allow LDH levels to rise much higher.
“I know of clinicians who see a LDH of 1,500-2,000 IU/L but the patient seems okay and they wonder if they should change out the pump. For me, it’s a no brainer. Others try to list a patient like this for a heart transplant so they can avoid doing a pump exchange. I think that’s dangerous; it risks liver failure or renal failure. I would not sit on any LVAD that is starting to produce signs of hemolysis syndrome, but some places do this,” Dr. Kormos said in an interview.
“Pump thrombosis probably did not get addressed in as timely a fashion as it should have been” when it was first seen on the rise in 2012, noted Dr. James K. Kirklin, professor of surgery and director of cardiothoracic surgery at the University of Alabama, Birmingham. “It is now being addressed, and we realize that this is not just a pump problem but also involves patient factors and management factors that we need to learn more about. We are quite ignorant of the patient factors and understanding their contributions to bleeding and thrombosis,” said Dr. Kirklin. He also acknowledged that whatever role the current generation of LVAD pumps play in causing thrombosis will not quickly resolve.
“I’m looking forward to a new generation of pumps, but the pumps we have today will probably remain for another 3-5 years.”
The issue of LVAD pump thrombosis first came into clear focus with publication at the start of 2014 of a report that tracked its incidence from 2004 to mid-2013 at three U.S. centers that had placed a total of 895 LVADs in 837 patients. The annual rate of new episodes of pump thrombosis jumped from about 1%-2% of LVAD recipients throughout the first part of the study period through the end of 2011, to an annual rate of about 10% by mid 2013 (N Engl J Med. 2014 Jan 2;370[1]:33-40).
“The inflection occurred in about 2012,” noted Dr. Nicholas G. Smedira, a cardiothoracic surgeon at the Cleveland Clinic. “No one has figured out why” the incidence suddenly spiked starting in 2012 and intensified in 2013, he said. This epidemic of pump thrombosis has produced “devastating complications” that have led to multiple readmissions and reduced cost-effectiveness of LVADs and has affected how the heart transplant community allocates hearts, Dr. Smedira said during his talk at the session. He noted that once the surge in pump thrombosis started, the timing of the appearance of significant thrombus shifted earlier, often occurring within 2-3 months after LVAD placement. There now is “increasing device-related pessimism” and increasing demoralization among clinicians because of this recurring complication, he said.
More recent data show the trend toward increasingly higher rates of pump thrombosis continuing through the end of 2013, with the situation during 2014 a bit less clear. Late last year, data from 9,808 U.S. patients who received an LVAD and entered the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) showed that the incidence of pump thrombosis during the first 6 months following an implant rose from 1% in 2008 to 2% in 2009 and in 2010, 4% in 2011, 7% in 2012, 8% in 2013, and then eased back to 5% in the first half of 2014 (J Heart Lung Transplant. 2015 Dec;34[12]:1515-26). The annual rate rose from 2% in 2008 to a peak of 11% in 2013, with 12-month data from 2014 not yet available at the time of this report.
“The modest reduction of observed pump thrombosis at 6 months during 2014 has occurred in a milieu of heightened intensity of anti-coagulation management, greater surgical awareness of optimal pump implantation and positioning and pump speed management. Thus, one may speculate that current thrombosis risk-mitigation strategies have contributed to reducing but not eliminating the increased thrombosis risk observed since 2011,” concluded the authors of the report.
Surgeons and cardiologists must now have a high index of suspicion for pump thrombosis in LVAD recipients, and be especially on the lookout for four key flags of a problem, said Dr. Kormos. The first is a rising LDH level, but additional flags include an isolated power elevation that doesn’t correlate with anything else, evidence of hemolysis, and new-onset heart failure symptoms. These can occur individually or in some combination. He recommended following a diagnostic algorithm first presented in 2013 that remains very valid today (J Heart Lung Transplant. 2013 July;32[7]:667-70).
Dr. Kormos also highlighted that the presentation of pump thrombosis can differ between the two LVADs most commonly used in U.S. practice, the HeartMate II and the HeartWare devices. A LDH elevation is primarily an indicator for HeartMate II, while both that model and the HeartWare device show sustained, isolated power elevations when thrombosis occurs.
Dr. Pagani, Dr. Kirklin, and Dr. Smedira had no disclosures. Dr. Kormos has received travel support from HeartWare. Dr. Kilic has been a consultant to Thoratec and a speaker on behalf of Baxter International.
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM THE STS ANNUAL MEETING
Putting a lid on precious bodily fluids
An old and true chestnut is that people are roughly 60% water and that we evolved in a lineage of land-based life selected to have complex and finely tuned mechanisms to maintain proper internal levels of salts and fluids. When the processes that regulate these are out of whack, bad things happen.
As I recently reported, surgeons at Johns Hopkins Hospital, Baltimore, have documented that excess fluid retention in patients who have just undergone heart surgery was the most common factor driving these patients back to the hospital during the 30 days after their index discharge. Dr. John V. Conte Jr., a Johns Hopkins cardiac surgeon, told me that patients often retain 5-10 pounds of excess fluid during the weeks immediately following heart surgery, and if they have trouble voiding this tsunami that can accumulate in their chest from pleural effusions, they develop acute problems, most notably difficulty breathing.
As a consequence, heart surgery patients with the highest risk for complications from fluid overload following their operation include those with severe chronic lung disease and those who develop acute renal failure postoperatively.
Problems with postsurgical fluid balance that lead to rehospitalization sound remarkably like the fluid-balance issue that also drives rehospitalization in patients with hard-to-control heart failure. Acute decompensation episodes in heart failure patients are triggered by fluid overload that manifests as severe dyspnea (and peripheral edema) that sends patients to the hospital. Patients with kidney dysfunction in addition to heart failure are particularly vulnerable to decompensation events.
“Fluid is an issue for both heart failure and heart surgery patients. Fluid is the common pathway to readmissions,” Dr. Conte noted when I spoke with him recently.
The parallels between the two disorders run deeper. To combat fluid overload, both types of patients need aggressive diuresis. Results from at least some studies also suggest that heart failure patients benefit clinically and also need fewer hospitalizations when they are closely monitored at home to provide early warning of incipient fluid overload that can be nipped by prompt treatment. The same approach may also help cut rehospitalization rates in recent heart surgery patients; Dr. Conte plans to soon test this strategy in a formal study.
Another parallel is that improved fluid management in these patients when they are at home may also help the hospitals that initially treat them by reducing the hospitals’ risk from financial penalties imposed by the Centers for Medicare & Medicaid Services. In fiscal year 2017, which starts in July 2016, CMS adds 30-day rehospitalization following coronary artery bypass grafting to its short list of hospital readmission types that can generate a monetary penalty from the agency’s Readmissions Reduction Program when a hospital’s numbers exceed national norms.
The CMS plans to soon start penalizing for seven types of excess rehospitalizations and the fact that two of the seven result in large part from deranged fluid balance shows just how important successful fluid management is these days, both to patients and to the hospitals and clinicians that treat them.
On Twitter @mitchelzoler
An old and true chestnut is that people are roughly 60% water and that we evolved in a lineage of land-based life selected to have complex and finely tuned mechanisms to maintain proper internal levels of salts and fluids. When the processes that regulate these are out of whack, bad things happen.
As I recently reported, surgeons at Johns Hopkins Hospital, Baltimore, have documented that excess fluid retention in patients who have just undergone heart surgery was the most common factor driving these patients back to the hospital during the 30 days after their index discharge. Dr. John V. Conte Jr., a Johns Hopkins cardiac surgeon, told me that patients often retain 5-10 pounds of excess fluid during the weeks immediately following heart surgery, and if they have trouble voiding this tsunami that can accumulate in their chest from pleural effusions, they develop acute problems, most notably difficulty breathing.
As a consequence, heart surgery patients with the highest risk for complications from fluid overload following their operation include those with severe chronic lung disease and those who develop acute renal failure postoperatively.
Problems with postsurgical fluid balance that lead to rehospitalization sound remarkably like the fluid-balance issue that also drives rehospitalization in patients with hard-to-control heart failure. Acute decompensation episodes in heart failure patients are triggered by fluid overload that manifests as severe dyspnea (and peripheral edema) that sends patients to the hospital. Patients with kidney dysfunction in addition to heart failure are particularly vulnerable to decompensation events.
“Fluid is an issue for both heart failure and heart surgery patients. Fluid is the common pathway to readmissions,” Dr. Conte noted when I spoke with him recently.
The parallels between the two disorders run deeper. To combat fluid overload, both types of patients need aggressive diuresis. Results from at least some studies also suggest that heart failure patients benefit clinically and also need fewer hospitalizations when they are closely monitored at home to provide early warning of incipient fluid overload that can be nipped by prompt treatment. The same approach may also help cut rehospitalization rates in recent heart surgery patients; Dr. Conte plans to soon test this strategy in a formal study.
Another parallel is that improved fluid management in these patients when they are at home may also help the hospitals that initially treat them by reducing the hospitals’ risk from financial penalties imposed by the Centers for Medicare & Medicaid Services. In fiscal year 2017, which starts in July 2016, CMS adds 30-day rehospitalization following coronary artery bypass grafting to its short list of hospital readmission types that can generate a monetary penalty from the agency’s Readmissions Reduction Program when a hospital’s numbers exceed national norms.
The CMS plans to soon start penalizing for seven types of excess rehospitalizations and the fact that two of the seven result in large part from deranged fluid balance shows just how important successful fluid management is these days, both to patients and to the hospitals and clinicians that treat them.
On Twitter @mitchelzoler
An old and true chestnut is that people are roughly 60% water and that we evolved in a lineage of land-based life selected to have complex and finely tuned mechanisms to maintain proper internal levels of salts and fluids. When the processes that regulate these are out of whack, bad things happen.
As I recently reported, surgeons at Johns Hopkins Hospital, Baltimore, have documented that excess fluid retention in patients who have just undergone heart surgery was the most common factor driving these patients back to the hospital during the 30 days after their index discharge. Dr. John V. Conte Jr., a Johns Hopkins cardiac surgeon, told me that patients often retain 5-10 pounds of excess fluid during the weeks immediately following heart surgery, and if they have trouble voiding this tsunami that can accumulate in their chest from pleural effusions, they develop acute problems, most notably difficulty breathing.
As a consequence, heart surgery patients with the highest risk for complications from fluid overload following their operation include those with severe chronic lung disease and those who develop acute renal failure postoperatively.
Problems with postsurgical fluid balance that lead to rehospitalization sound remarkably like the fluid-balance issue that also drives rehospitalization in patients with hard-to-control heart failure. Acute decompensation episodes in heart failure patients are triggered by fluid overload that manifests as severe dyspnea (and peripheral edema) that sends patients to the hospital. Patients with kidney dysfunction in addition to heart failure are particularly vulnerable to decompensation events.
“Fluid is an issue for both heart failure and heart surgery patients. Fluid is the common pathway to readmissions,” Dr. Conte noted when I spoke with him recently.
The parallels between the two disorders run deeper. To combat fluid overload, both types of patients need aggressive diuresis. Results from at least some studies also suggest that heart failure patients benefit clinically and also need fewer hospitalizations when they are closely monitored at home to provide early warning of incipient fluid overload that can be nipped by prompt treatment. The same approach may also help cut rehospitalization rates in recent heart surgery patients; Dr. Conte plans to soon test this strategy in a formal study.
Another parallel is that improved fluid management in these patients when they are at home may also help the hospitals that initially treat them by reducing the hospitals’ risk from financial penalties imposed by the Centers for Medicare & Medicaid Services. In fiscal year 2017, which starts in July 2016, CMS adds 30-day rehospitalization following coronary artery bypass grafting to its short list of hospital readmission types that can generate a monetary penalty from the agency’s Readmissions Reduction Program when a hospital’s numbers exceed national norms.
The CMS plans to soon start penalizing for seven types of excess rehospitalizations and the fact that two of the seven result in large part from deranged fluid balance shows just how important successful fluid management is these days, both to patients and to the hospitals and clinicians that treat them.
On Twitter @mitchelzoler
Acute heart failure: What works, what doesn’t
SNOWMASS, COLO. – The primary treatment goal in patients hospitalized for acute decompensated heart failure is aggressive decongestion to get them feeling better and out of the hospital quicker – and the best way to achieve that is with high-dose loop diuretics administered intravenously at a dose equivalent to 2.5 times the previous oral dose, Dr. Akshay S. Desai said at the Annual Cardiovascular Conference at Snowmass.
This was the key lesson of the Diuretic Optimization Strategies Evaluation (DOSE) trial, a prospective double-blind randomized trial that provides physicians with the best available data on how to decongest patients with acute decompensated heart failure (ADHF), according to Dr. Desai, a coinvestigator. The study was conducted by the National Heart, Lung, and Blood Institute Heart Failure Clinical Research Network.
The DOSE trial showed that it really doesn’t matter whether the diuretic is administered intravenously by continuous infusion or a bolus every 12 hours. The important thing is the high-dose strategy. It proved to be safe and was associated with accelerated decongestion as manifest in greater relief of dyspnea, greater weight loss and fluid loss, and a larger reduction in serum brain natriuretic peptide at 72 hours than low-dose therapy equivalent to the patient’s previous oral dose (N Engl J Med. 2011 Mar 3;364[9]:797-805).
“The message for you in practice is that the route of diuretic administration is probably not important as long as you give an adequate dose. I would consider giving the higher dose of diuretic because it’s associated with more effective decongestion and perhaps shorter length of stay,” said Dr. Desai, director of heart failure disease management at Brigham and Women’s Hospital in Boston.
There is a trade-off in ADHF between effective decongestion and worsening renal function as reflected in increased serum creatinine levels. Transient worsening of renal function occurred more frequently with the high-dose strategy in the DOSE trial, but it had no impact on clinical outcomes at 60 days follow-up. This finding is consistent with the results of an important Italian study showing that worsening renal function alone isn’t independently associated with increased risk of death or ADHF readmission; the problems arise in patients with worsening renal function and persistent congestion (Circ Heart Fail. 2012 Jan;5[1]:54-62).
Worsening congestion drives most hospitalizations for heart failure. And patients who are still congested at discharge are at dramatically increased risk for death or readmission in the ensuing 6 months. Yet the limitations of current therapy mean that even in expert hands, a substantial proportion of patients are discharged with clinically significant congestion. For example, in a retrospective analysis of nearly 500 patients enrolled in ADHF studies conducted by physicians in the NHLBI Heart Failure Clinical Research Network, only 52% were discharged free of congestion (Circ Heart Fail. 2015 Jul;8[4]:741-8).
Beyond aggressive treatment with loop diuretics, what else is useful in achieving the goal of hospital discharge with normalized filling pressures? Not much, according to a considerable body of research on the topic.
“The data tell us more about what not to do than what to do,” according to Dr. Desai.
For example, even though aggressive salt and fluid restriction is often forced upon patients hospitalized for ADHF on the rationale that this strategy may make it easier for diuretics to work, it’s not an evidence-based practice. Indeed, in a randomized clinical trial with blinded outcome assessments, an in-hospital diet restricted to a maximum intake of 800 mg of sodium and 800 mL of fluid daily had no effect on weight loss or a clinical congestion score (JAMA Intern Med. 2013 June 24;173[12]:1058-64).
“What it did very effectively was make patients thirsty. There are probably some patients where restriction of sodium and fluid intake is important, but routine use of tight restrictions is probably more harmful than helpful,” he observed.
The list of failed once-promising alternatives to diuretics in the setting of ADHF is impressive. It includes milrinone, tolvaptan, nesiritide, levosimendan, tezosentan, low-dose dopamine, and ultrafiltration. All had a sound mechanistic basis for the belief that they might improve outcomes, but in clinical trials none of them did.
Although routine use of pulmonary artery catheters to guide decongestion therapy in ADHF isn’t warranted because it has not been shown to be better than clinical assessment, there are certain situations where it is extremely helpful. For example, in the patient who isn’t responding to adequate doses of loop diuretics, it becomes important to understand the hemodynamics, which may involve systemic vascular resistance or a cardiac output problem.
Other situations where it’s worthwhile to consider placement of a pulmonary artery catheter include the patient of uncertain fluid status where it’s not possible to confidently estimate cardiac output at the bedside or markedly worsening renal function with empiric therapy.
Dr. Desai reported receiving research funding from Novartis and St. Jude Medical and serving as a paid consultant to Merck, Relypsa, and St. Jude Medical.
SNOWMASS, COLO. – The primary treatment goal in patients hospitalized for acute decompensated heart failure is aggressive decongestion to get them feeling better and out of the hospital quicker – and the best way to achieve that is with high-dose loop diuretics administered intravenously at a dose equivalent to 2.5 times the previous oral dose, Dr. Akshay S. Desai said at the Annual Cardiovascular Conference at Snowmass.
This was the key lesson of the Diuretic Optimization Strategies Evaluation (DOSE) trial, a prospective double-blind randomized trial that provides physicians with the best available data on how to decongest patients with acute decompensated heart failure (ADHF), according to Dr. Desai, a coinvestigator. The study was conducted by the National Heart, Lung, and Blood Institute Heart Failure Clinical Research Network.
The DOSE trial showed that it really doesn’t matter whether the diuretic is administered intravenously by continuous infusion or a bolus every 12 hours. The important thing is the high-dose strategy. It proved to be safe and was associated with accelerated decongestion as manifest in greater relief of dyspnea, greater weight loss and fluid loss, and a larger reduction in serum brain natriuretic peptide at 72 hours than low-dose therapy equivalent to the patient’s previous oral dose (N Engl J Med. 2011 Mar 3;364[9]:797-805).
“The message for you in practice is that the route of diuretic administration is probably not important as long as you give an adequate dose. I would consider giving the higher dose of diuretic because it’s associated with more effective decongestion and perhaps shorter length of stay,” said Dr. Desai, director of heart failure disease management at Brigham and Women’s Hospital in Boston.
There is a trade-off in ADHF between effective decongestion and worsening renal function as reflected in increased serum creatinine levels. Transient worsening of renal function occurred more frequently with the high-dose strategy in the DOSE trial, but it had no impact on clinical outcomes at 60 days follow-up. This finding is consistent with the results of an important Italian study showing that worsening renal function alone isn’t independently associated with increased risk of death or ADHF readmission; the problems arise in patients with worsening renal function and persistent congestion (Circ Heart Fail. 2012 Jan;5[1]:54-62).
Worsening congestion drives most hospitalizations for heart failure. And patients who are still congested at discharge are at dramatically increased risk for death or readmission in the ensuing 6 months. Yet the limitations of current therapy mean that even in expert hands, a substantial proportion of patients are discharged with clinically significant congestion. For example, in a retrospective analysis of nearly 500 patients enrolled in ADHF studies conducted by physicians in the NHLBI Heart Failure Clinical Research Network, only 52% were discharged free of congestion (Circ Heart Fail. 2015 Jul;8[4]:741-8).
Beyond aggressive treatment with loop diuretics, what else is useful in achieving the goal of hospital discharge with normalized filling pressures? Not much, according to a considerable body of research on the topic.
“The data tell us more about what not to do than what to do,” according to Dr. Desai.
For example, even though aggressive salt and fluid restriction is often forced upon patients hospitalized for ADHF on the rationale that this strategy may make it easier for diuretics to work, it’s not an evidence-based practice. Indeed, in a randomized clinical trial with blinded outcome assessments, an in-hospital diet restricted to a maximum intake of 800 mg of sodium and 800 mL of fluid daily had no effect on weight loss or a clinical congestion score (JAMA Intern Med. 2013 June 24;173[12]:1058-64).
“What it did very effectively was make patients thirsty. There are probably some patients where restriction of sodium and fluid intake is important, but routine use of tight restrictions is probably more harmful than helpful,” he observed.
The list of failed once-promising alternatives to diuretics in the setting of ADHF is impressive. It includes milrinone, tolvaptan, nesiritide, levosimendan, tezosentan, low-dose dopamine, and ultrafiltration. All had a sound mechanistic basis for the belief that they might improve outcomes, but in clinical trials none of them did.
Although routine use of pulmonary artery catheters to guide decongestion therapy in ADHF isn’t warranted because it has not been shown to be better than clinical assessment, there are certain situations where it is extremely helpful. For example, in the patient who isn’t responding to adequate doses of loop diuretics, it becomes important to understand the hemodynamics, which may involve systemic vascular resistance or a cardiac output problem.
Other situations where it’s worthwhile to consider placement of a pulmonary artery catheter include the patient of uncertain fluid status where it’s not possible to confidently estimate cardiac output at the bedside or markedly worsening renal function with empiric therapy.
Dr. Desai reported receiving research funding from Novartis and St. Jude Medical and serving as a paid consultant to Merck, Relypsa, and St. Jude Medical.
SNOWMASS, COLO. – The primary treatment goal in patients hospitalized for acute decompensated heart failure is aggressive decongestion to get them feeling better and out of the hospital quicker – and the best way to achieve that is with high-dose loop diuretics administered intravenously at a dose equivalent to 2.5 times the previous oral dose, Dr. Akshay S. Desai said at the Annual Cardiovascular Conference at Snowmass.
This was the key lesson of the Diuretic Optimization Strategies Evaluation (DOSE) trial, a prospective double-blind randomized trial that provides physicians with the best available data on how to decongest patients with acute decompensated heart failure (ADHF), according to Dr. Desai, a coinvestigator. The study was conducted by the National Heart, Lung, and Blood Institute Heart Failure Clinical Research Network.
The DOSE trial showed that it really doesn’t matter whether the diuretic is administered intravenously by continuous infusion or a bolus every 12 hours. The important thing is the high-dose strategy. It proved to be safe and was associated with accelerated decongestion as manifest in greater relief of dyspnea, greater weight loss and fluid loss, and a larger reduction in serum brain natriuretic peptide at 72 hours than low-dose therapy equivalent to the patient’s previous oral dose (N Engl J Med. 2011 Mar 3;364[9]:797-805).
“The message for you in practice is that the route of diuretic administration is probably not important as long as you give an adequate dose. I would consider giving the higher dose of diuretic because it’s associated with more effective decongestion and perhaps shorter length of stay,” said Dr. Desai, director of heart failure disease management at Brigham and Women’s Hospital in Boston.
There is a trade-off in ADHF between effective decongestion and worsening renal function as reflected in increased serum creatinine levels. Transient worsening of renal function occurred more frequently with the high-dose strategy in the DOSE trial, but it had no impact on clinical outcomes at 60 days follow-up. This finding is consistent with the results of an important Italian study showing that worsening renal function alone isn’t independently associated with increased risk of death or ADHF readmission; the problems arise in patients with worsening renal function and persistent congestion (Circ Heart Fail. 2012 Jan;5[1]:54-62).
Worsening congestion drives most hospitalizations for heart failure. And patients who are still congested at discharge are at dramatically increased risk for death or readmission in the ensuing 6 months. Yet the limitations of current therapy mean that even in expert hands, a substantial proportion of patients are discharged with clinically significant congestion. For example, in a retrospective analysis of nearly 500 patients enrolled in ADHF studies conducted by physicians in the NHLBI Heart Failure Clinical Research Network, only 52% were discharged free of congestion (Circ Heart Fail. 2015 Jul;8[4]:741-8).
Beyond aggressive treatment with loop diuretics, what else is useful in achieving the goal of hospital discharge with normalized filling pressures? Not much, according to a considerable body of research on the topic.
“The data tell us more about what not to do than what to do,” according to Dr. Desai.
For example, even though aggressive salt and fluid restriction is often forced upon patients hospitalized for ADHF on the rationale that this strategy may make it easier for diuretics to work, it’s not an evidence-based practice. Indeed, in a randomized clinical trial with blinded outcome assessments, an in-hospital diet restricted to a maximum intake of 800 mg of sodium and 800 mL of fluid daily had no effect on weight loss or a clinical congestion score (JAMA Intern Med. 2013 June 24;173[12]:1058-64).
“What it did very effectively was make patients thirsty. There are probably some patients where restriction of sodium and fluid intake is important, but routine use of tight restrictions is probably more harmful than helpful,” he observed.
The list of failed once-promising alternatives to diuretics in the setting of ADHF is impressive. It includes milrinone, tolvaptan, nesiritide, levosimendan, tezosentan, low-dose dopamine, and ultrafiltration. All had a sound mechanistic basis for the belief that they might improve outcomes, but in clinical trials none of them did.
Although routine use of pulmonary artery catheters to guide decongestion therapy in ADHF isn’t warranted because it has not been shown to be better than clinical assessment, there are certain situations where it is extremely helpful. For example, in the patient who isn’t responding to adequate doses of loop diuretics, it becomes important to understand the hemodynamics, which may involve systemic vascular resistance or a cardiac output problem.
Other situations where it’s worthwhile to consider placement of a pulmonary artery catheter include the patient of uncertain fluid status where it’s not possible to confidently estimate cardiac output at the bedside or markedly worsening renal function with empiric therapy.
Dr. Desai reported receiving research funding from Novartis and St. Jude Medical and serving as a paid consultant to Merck, Relypsa, and St. Jude Medical.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
STS: Risk score predicts rehospitalization after heart surgery
PHOENIX – A simple, five-element formula can help identify the patients undergoing heart surgery who face the greatest risk for a hospital readmission within 30 days following discharge from their index hospitalization.
The surgeons who developed this formula hope to use it in an investigational program that will target intensified management resources in postsurgical patients who face the highest readmission risk, to cut rehospitalizations and better improve their clinical status and quality of life.
The analysis that produced this formula also documented that the worst offender for triggering rehospitalizations following heart surgery is fluid overload, the proximate readmission cause for 23% of postsurgical patients, Dr. Arman Kilic said at the annual meeting of the Society of Thoracic Surgeons. The next most common cause was infection, which led to 20% of readmissions, followed by arrhythmias, responsible for 8% of readmissions, said Dr. Kilic, a thoracic surgeon at the University of Pennsylvania in Philadelphia.
Because fluid overload, often in the form of pleural effusion, is such an important driver of rehospitalizations, a more targeted management program would include better titration of diuretic treatment to patients following heart surgery, thoracentesis, and closer monitoring of clinical features that flag fluid overload such as weight.
“The volume overload issue is where the money is. If we can reduce that, it could really impact readmissions,” Dr. Kilic said in an interview.
An investigational program to target rehospitalization risk in heart surgery patients is planned at Johns Hopkins Hospital in Baltimore, where Dr. Kilic worked when he performed this analysis. Surgeons at Johns Hopkins are now in the process of getting funding for this pilot program, said Dr. John V. Conte Jr., professor of surgery and director of mechanical circulatory support at Johns Hopkins and a collaborator with Dr. Kilic on developing the risk formula.
“We’ll tailor postoperative follow-up. We’ll get high-risk patients back to the clinic sooner, and we’ll send nurse practitioners to see them to make sure they’re taking their medications and are getting weighed daily,” Dr. Conte said in an interview. “When a patient has heart surgery, they typically retain about 5-10 pounds of fluid. Patients with good renal function give up that fluid easily, but others are difficult to diurese. Many patients go home before they have been fully diuresed, and we need to follow these patients and transition them better to out-of-hospital care.”
He noted that other situations also come up that unnecessarily drive patients back to the hospital when an alternative and less expensive intervention might be equally effective. For example, some patients return to the hospital out of concern for how their chest wound is healing. Instead of being rehospitalized, such patients could be reassured by having them send a nurse a photo of their wound or by coming to an outpatient clinic.
“We need to engage more often with recently discharged patients,” Dr. Conte said in an interview. “Discharging them doesn’t mean separating them from the health care system; it should mean interacting with patients in a different way” that produces better outcomes and patient satisfaction for less money. Developing improved ways to manage recent heart surgery patients following discharge becomes even more critical later this year when, in July, the Centers for Medicare & Medicaid Services adds 30-day readmissions following coronary artery bypass grafting (CABG) to its list of procedures that can generate a penalty to hospitals if they exceed U.S. norms for readmission rates.
The risk model developed by Dr. Kilic, Dr. Conte, and their associates used data collected from 5,360 heart surgery patients treated at Johns Hopkins during 2008-2013. Nearly half the patients underwent isolated CABG, and 20% had isolated valve surgery. Overall, 585 patients (11%) had a hospital readmission within 30 days of their index discharge. One limitation of the analysis was it used data only on readmissions back to Johns Hopkins Hospital.
The researchers used data from three-quarters of the database to derive the risk formula, and from the remaining 25% of the database to validate the formula. A multivariate analysis of demographic and clinical characteristics that significantly linked with an elevated risk for readmissions identified five factors that independently made a significant contribution to readmission risk. The researchers assigned each of these five factors points depending on its relative contribution to readmission risk in the adjusted model: Severe chronic lung disease received 6 points; placement of a ventricular assist device received 5 points, while other types of heart surgery that was not CABG or valve surgery received 4 points (isolated CABG, isolated valve, or combined CABG and valve surgery received 0 points); development of acute renal failure postoperatively but before index discharge received 4 points; an index length of stay beyond 7 days received 4 points; and African American race received 3 points. The maximum number of points a patient could receive was 22.
Patients with a score of 0 had a 6% rate of a 30-day readmission; those with a score of 22 had a 63% readmission rate. For simplicity, Dr. Kilic suggested dividing patients into three categories based on their readmission risk score: Low-risk patients with a score of 0 had a readmission risk of 6%, medium-risk patients with a score of 1-10 had a readmission risk of 12%, and high-risk patients with a score of 11 or more had a readmission risk of 31%. The researchers found a 96% correlation when comparing these predicted readmission risk rates based on the derivation-subgroup analysis with the actual readmission rates seen in the validation subgroup of their database. The targeted risk-management program planned by Dr. Conte would primarily focus on high-risk patients.
Dr. Kilic and Dr. Conte said they had no relevant financial disclosures.
On Twitter@mitchelzoler
Identifying the factors that determine whether a patient will need rehospitalization following discharge after heart surgery is a huge and unresolved problem. Risk models for the rate of hospital readmission following cardiothoracic surgery have historically performed poorly. Perhaps that’s because the models often fail to include factors with the strongest impact on readmissions. Most of the factors that appear to drive readmissions seem to be out of the direct control of hospital staffs, such as a lack of support for patients once they leave the hospital. Socioeconomic factors like this have usually not been included in risk models.
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Dr. David M. Shahian |
The C statistic (area under the receiver operating characteristic curve) for the model reported by Dr. Kilic was 0.66, very close to the 0.648 that my colleagues and I reported in 2014 for a risk model of 30-day hospital readmission following isolated coronary artery bypass grafting that used data from more than 162,000 Medicare patients who underwent surgery during 2008-2010 (Circulation. 2014 July 29;130[5]:399-409). This means that both models accounted for roughly two-thirds of the variability in readmission rates, which makes our model as well as Dr. Kilic’s model marginal in its ability to identify patients at greatest risk. Similar limitations exist for the other reported models for assessing the readmission risk following heart surgery.
One strength of the model reported by Dr. Kilic was its inclusion of patient factors that developed following the start of the index admission, such as postoperative acute renal failure.
Dr. David M. Shahian is a professor of surgery at Harvard Medical School and associate director of the Codman Center for Clinical Effectiveness in Surgery at the Massachusetts General Hospital, both in Boston. He made these comments during the discussion of Dr. Kilic’s report. Dr. Shahian had no relevant financial disclosures.
Identifying the factors that determine whether a patient will need rehospitalization following discharge after heart surgery is a huge and unresolved problem. Risk models for the rate of hospital readmission following cardiothoracic surgery have historically performed poorly. Perhaps that’s because the models often fail to include factors with the strongest impact on readmissions. Most of the factors that appear to drive readmissions seem to be out of the direct control of hospital staffs, such as a lack of support for patients once they leave the hospital. Socioeconomic factors like this have usually not been included in risk models.
|
|
Dr. David M. Shahian |
The C statistic (area under the receiver operating characteristic curve) for the model reported by Dr. Kilic was 0.66, very close to the 0.648 that my colleagues and I reported in 2014 for a risk model of 30-day hospital readmission following isolated coronary artery bypass grafting that used data from more than 162,000 Medicare patients who underwent surgery during 2008-2010 (Circulation. 2014 July 29;130[5]:399-409). This means that both models accounted for roughly two-thirds of the variability in readmission rates, which makes our model as well as Dr. Kilic’s model marginal in its ability to identify patients at greatest risk. Similar limitations exist for the other reported models for assessing the readmission risk following heart surgery.
One strength of the model reported by Dr. Kilic was its inclusion of patient factors that developed following the start of the index admission, such as postoperative acute renal failure.
Dr. David M. Shahian is a professor of surgery at Harvard Medical School and associate director of the Codman Center for Clinical Effectiveness in Surgery at the Massachusetts General Hospital, both in Boston. He made these comments during the discussion of Dr. Kilic’s report. Dr. Shahian had no relevant financial disclosures.
Identifying the factors that determine whether a patient will need rehospitalization following discharge after heart surgery is a huge and unresolved problem. Risk models for the rate of hospital readmission following cardiothoracic surgery have historically performed poorly. Perhaps that’s because the models often fail to include factors with the strongest impact on readmissions. Most of the factors that appear to drive readmissions seem to be out of the direct control of hospital staffs, such as a lack of support for patients once they leave the hospital. Socioeconomic factors like this have usually not been included in risk models.
|
|
Dr. David M. Shahian |
The C statistic (area under the receiver operating characteristic curve) for the model reported by Dr. Kilic was 0.66, very close to the 0.648 that my colleagues and I reported in 2014 for a risk model of 30-day hospital readmission following isolated coronary artery bypass grafting that used data from more than 162,000 Medicare patients who underwent surgery during 2008-2010 (Circulation. 2014 July 29;130[5]:399-409). This means that both models accounted for roughly two-thirds of the variability in readmission rates, which makes our model as well as Dr. Kilic’s model marginal in its ability to identify patients at greatest risk. Similar limitations exist for the other reported models for assessing the readmission risk following heart surgery.
One strength of the model reported by Dr. Kilic was its inclusion of patient factors that developed following the start of the index admission, such as postoperative acute renal failure.
Dr. David M. Shahian is a professor of surgery at Harvard Medical School and associate director of the Codman Center for Clinical Effectiveness in Surgery at the Massachusetts General Hospital, both in Boston. He made these comments during the discussion of Dr. Kilic’s report. Dr. Shahian had no relevant financial disclosures.
PHOENIX – A simple, five-element formula can help identify the patients undergoing heart surgery who face the greatest risk for a hospital readmission within 30 days following discharge from their index hospitalization.
The surgeons who developed this formula hope to use it in an investigational program that will target intensified management resources in postsurgical patients who face the highest readmission risk, to cut rehospitalizations and better improve their clinical status and quality of life.
The analysis that produced this formula also documented that the worst offender for triggering rehospitalizations following heart surgery is fluid overload, the proximate readmission cause for 23% of postsurgical patients, Dr. Arman Kilic said at the annual meeting of the Society of Thoracic Surgeons. The next most common cause was infection, which led to 20% of readmissions, followed by arrhythmias, responsible for 8% of readmissions, said Dr. Kilic, a thoracic surgeon at the University of Pennsylvania in Philadelphia.
Because fluid overload, often in the form of pleural effusion, is such an important driver of rehospitalizations, a more targeted management program would include better titration of diuretic treatment to patients following heart surgery, thoracentesis, and closer monitoring of clinical features that flag fluid overload such as weight.
“The volume overload issue is where the money is. If we can reduce that, it could really impact readmissions,” Dr. Kilic said in an interview.
An investigational program to target rehospitalization risk in heart surgery patients is planned at Johns Hopkins Hospital in Baltimore, where Dr. Kilic worked when he performed this analysis. Surgeons at Johns Hopkins are now in the process of getting funding for this pilot program, said Dr. John V. Conte Jr., professor of surgery and director of mechanical circulatory support at Johns Hopkins and a collaborator with Dr. Kilic on developing the risk formula.
“We’ll tailor postoperative follow-up. We’ll get high-risk patients back to the clinic sooner, and we’ll send nurse practitioners to see them to make sure they’re taking their medications and are getting weighed daily,” Dr. Conte said in an interview. “When a patient has heart surgery, they typically retain about 5-10 pounds of fluid. Patients with good renal function give up that fluid easily, but others are difficult to diurese. Many patients go home before they have been fully diuresed, and we need to follow these patients and transition them better to out-of-hospital care.”
He noted that other situations also come up that unnecessarily drive patients back to the hospital when an alternative and less expensive intervention might be equally effective. For example, some patients return to the hospital out of concern for how their chest wound is healing. Instead of being rehospitalized, such patients could be reassured by having them send a nurse a photo of their wound or by coming to an outpatient clinic.
“We need to engage more often with recently discharged patients,” Dr. Conte said in an interview. “Discharging them doesn’t mean separating them from the health care system; it should mean interacting with patients in a different way” that produces better outcomes and patient satisfaction for less money. Developing improved ways to manage recent heart surgery patients following discharge becomes even more critical later this year when, in July, the Centers for Medicare & Medicaid Services adds 30-day readmissions following coronary artery bypass grafting (CABG) to its list of procedures that can generate a penalty to hospitals if they exceed U.S. norms for readmission rates.
The risk model developed by Dr. Kilic, Dr. Conte, and their associates used data collected from 5,360 heart surgery patients treated at Johns Hopkins during 2008-2013. Nearly half the patients underwent isolated CABG, and 20% had isolated valve surgery. Overall, 585 patients (11%) had a hospital readmission within 30 days of their index discharge. One limitation of the analysis was it used data only on readmissions back to Johns Hopkins Hospital.
The researchers used data from three-quarters of the database to derive the risk formula, and from the remaining 25% of the database to validate the formula. A multivariate analysis of demographic and clinical characteristics that significantly linked with an elevated risk for readmissions identified five factors that independently made a significant contribution to readmission risk. The researchers assigned each of these five factors points depending on its relative contribution to readmission risk in the adjusted model: Severe chronic lung disease received 6 points; placement of a ventricular assist device received 5 points, while other types of heart surgery that was not CABG or valve surgery received 4 points (isolated CABG, isolated valve, or combined CABG and valve surgery received 0 points); development of acute renal failure postoperatively but before index discharge received 4 points; an index length of stay beyond 7 days received 4 points; and African American race received 3 points. The maximum number of points a patient could receive was 22.
Patients with a score of 0 had a 6% rate of a 30-day readmission; those with a score of 22 had a 63% readmission rate. For simplicity, Dr. Kilic suggested dividing patients into three categories based on their readmission risk score: Low-risk patients with a score of 0 had a readmission risk of 6%, medium-risk patients with a score of 1-10 had a readmission risk of 12%, and high-risk patients with a score of 11 or more had a readmission risk of 31%. The researchers found a 96% correlation when comparing these predicted readmission risk rates based on the derivation-subgroup analysis with the actual readmission rates seen in the validation subgroup of their database. The targeted risk-management program planned by Dr. Conte would primarily focus on high-risk patients.
Dr. Kilic and Dr. Conte said they had no relevant financial disclosures.
On Twitter@mitchelzoler
PHOENIX – A simple, five-element formula can help identify the patients undergoing heart surgery who face the greatest risk for a hospital readmission within 30 days following discharge from their index hospitalization.
The surgeons who developed this formula hope to use it in an investigational program that will target intensified management resources in postsurgical patients who face the highest readmission risk, to cut rehospitalizations and better improve their clinical status and quality of life.
The analysis that produced this formula also documented that the worst offender for triggering rehospitalizations following heart surgery is fluid overload, the proximate readmission cause for 23% of postsurgical patients, Dr. Arman Kilic said at the annual meeting of the Society of Thoracic Surgeons. The next most common cause was infection, which led to 20% of readmissions, followed by arrhythmias, responsible for 8% of readmissions, said Dr. Kilic, a thoracic surgeon at the University of Pennsylvania in Philadelphia.
Because fluid overload, often in the form of pleural effusion, is such an important driver of rehospitalizations, a more targeted management program would include better titration of diuretic treatment to patients following heart surgery, thoracentesis, and closer monitoring of clinical features that flag fluid overload such as weight.
“The volume overload issue is where the money is. If we can reduce that, it could really impact readmissions,” Dr. Kilic said in an interview.
An investigational program to target rehospitalization risk in heart surgery patients is planned at Johns Hopkins Hospital in Baltimore, where Dr. Kilic worked when he performed this analysis. Surgeons at Johns Hopkins are now in the process of getting funding for this pilot program, said Dr. John V. Conte Jr., professor of surgery and director of mechanical circulatory support at Johns Hopkins and a collaborator with Dr. Kilic on developing the risk formula.
“We’ll tailor postoperative follow-up. We’ll get high-risk patients back to the clinic sooner, and we’ll send nurse practitioners to see them to make sure they’re taking their medications and are getting weighed daily,” Dr. Conte said in an interview. “When a patient has heart surgery, they typically retain about 5-10 pounds of fluid. Patients with good renal function give up that fluid easily, but others are difficult to diurese. Many patients go home before they have been fully diuresed, and we need to follow these patients and transition them better to out-of-hospital care.”
He noted that other situations also come up that unnecessarily drive patients back to the hospital when an alternative and less expensive intervention might be equally effective. For example, some patients return to the hospital out of concern for how their chest wound is healing. Instead of being rehospitalized, such patients could be reassured by having them send a nurse a photo of their wound or by coming to an outpatient clinic.
“We need to engage more often with recently discharged patients,” Dr. Conte said in an interview. “Discharging them doesn’t mean separating them from the health care system; it should mean interacting with patients in a different way” that produces better outcomes and patient satisfaction for less money. Developing improved ways to manage recent heart surgery patients following discharge becomes even more critical later this year when, in July, the Centers for Medicare & Medicaid Services adds 30-day readmissions following coronary artery bypass grafting (CABG) to its list of procedures that can generate a penalty to hospitals if they exceed U.S. norms for readmission rates.
The risk model developed by Dr. Kilic, Dr. Conte, and their associates used data collected from 5,360 heart surgery patients treated at Johns Hopkins during 2008-2013. Nearly half the patients underwent isolated CABG, and 20% had isolated valve surgery. Overall, 585 patients (11%) had a hospital readmission within 30 days of their index discharge. One limitation of the analysis was it used data only on readmissions back to Johns Hopkins Hospital.
The researchers used data from three-quarters of the database to derive the risk formula, and from the remaining 25% of the database to validate the formula. A multivariate analysis of demographic and clinical characteristics that significantly linked with an elevated risk for readmissions identified five factors that independently made a significant contribution to readmission risk. The researchers assigned each of these five factors points depending on its relative contribution to readmission risk in the adjusted model: Severe chronic lung disease received 6 points; placement of a ventricular assist device received 5 points, while other types of heart surgery that was not CABG or valve surgery received 4 points (isolated CABG, isolated valve, or combined CABG and valve surgery received 0 points); development of acute renal failure postoperatively but before index discharge received 4 points; an index length of stay beyond 7 days received 4 points; and African American race received 3 points. The maximum number of points a patient could receive was 22.
Patients with a score of 0 had a 6% rate of a 30-day readmission; those with a score of 22 had a 63% readmission rate. For simplicity, Dr. Kilic suggested dividing patients into three categories based on their readmission risk score: Low-risk patients with a score of 0 had a readmission risk of 6%, medium-risk patients with a score of 1-10 had a readmission risk of 12%, and high-risk patients with a score of 11 or more had a readmission risk of 31%. The researchers found a 96% correlation when comparing these predicted readmission risk rates based on the derivation-subgroup analysis with the actual readmission rates seen in the validation subgroup of their database. The targeted risk-management program planned by Dr. Conte would primarily focus on high-risk patients.
Dr. Kilic and Dr. Conte said they had no relevant financial disclosures.
On Twitter@mitchelzoler
AT THE STS ANNUAL MEETING
Key clinical point: A risk score predicted which heart surgery patients faced the greatest risk for hospital readmission within 30 days of their index discharge.
Major finding: Patients with a 0 score had a 6% 30-day readmission rate; a high score of 22 linked with a 63% rate.
Data source: A review of 5,360 heart surgery patients treated at one U.S. center.
Disclosures: Dr. Kilic and Dr. Conte said they had no relevant financial disclosures.
