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Framingham: Exercise lessens cardiometabolic risk of poor diet
PHILADELPHIA – Engaging in at least 150 minutes of moderate to vigorous physical activity per week as recommended in national guidelines appears to mitigate the cardiometabolic risks associated with poor diet quality in middle-aged and older adults, according to an analysis of Framingham Heart Study data.
“Our findings suggest adherence to physical activity guidelines may have a protective effect on cardiometabolic health regardless of diet quality,” Joowon Lee, PhD, declared at the American Heart Association scientific sessions.
He presented separate cross-sectional analyses of the risks of metabolic syndrome in 2,379 middle-aged participants in the National Heart, Lung, and Blood Institute–sponsored Framingham (Mass.) Third Generation Study and 1,180 older participants in the Framingham Offspring Study.
The two analyses showed the same thing across a broad age spectrum: The highest prevalence of metabolic syndrome as defined by Adult Treatment Panel III criteria was present among those individuals who got less than 150 minutes of physical activity per week and were also in the lowest tertile in terms of diet quality, while the lowest prevalence of metabolic syndrome occurred in participants in the top tertile for diet quality who engaged in at least 150 minutes per week of moderate to vigorous physical activity in accord with the Department of Health & Human Services 2018 Physical Activity Guidelines for Americans.
In both the middle-aged and older populations, optimal physical activity – that is, at least 150 minutes per week – appeared to override the adverse impact of suboptimal diet quality. Physically active individuals with moderate or even poor diet quality had a significantly lower prevalence of metabolic syndrome than did the reference group constituted by participants with poor diet quality who didn’t exercise for 150 minutes per week.
But the converse didn’t hold true: Individuals with optimal diet quality who didn’t reach the physical activity threshold had no reduction in metabolic syndrome, compared with the reference group, according to Dr. Lee of Boston University.
For example, among the Framingham Offspring Study participants, whose mean age was 69 years at the time of their ninth formal examination in 2014, the prevalence of metabolic syndrome was 59% in those who got less than 150 minutes of moderate to vigorous physical activity weekly as assessed by accelerometer and who were also in the lowest tertile for diet quality as self-reported on the DGAI-2010 (Dietary Guidelines Adherence Index) semiquantitative food frequency questionnaire. The relative risk of metabolic syndrome was reduced by 61% in participants with both optimal physical activity and diet quality, by 49% in those with at least 150 minutes of physical activity but only moderate diet quality, and by 39% in those with optimal exercise and poor diet quality. In contrast, individuals in the top or middle tertiles for diet quality who didn’t meet the physical activity standard had a metabolic syndrome rate that wasn’t significantly lower than the reference group.
Dr. Lee observed that his analyses are best viewed as hypothesis generating. Their cross-sectional format precludes firm conclusions as to causality.
His findings prompted session comoderator Satyam Sarma, MD, of the University of Texas, Dallas, to make one of the most memorable comments heard at AHA 2019: that the Framingham findings suggest it may be possible to outrun a bad diet.
Dr. Lee reported having no financial conflicts regarding his study, supported by Boston University.
SOURCE: Lee J. AHA 2019, Abstract RF244.
PHILADELPHIA – Engaging in at least 150 minutes of moderate to vigorous physical activity per week as recommended in national guidelines appears to mitigate the cardiometabolic risks associated with poor diet quality in middle-aged and older adults, according to an analysis of Framingham Heart Study data.
“Our findings suggest adherence to physical activity guidelines may have a protective effect on cardiometabolic health regardless of diet quality,” Joowon Lee, PhD, declared at the American Heart Association scientific sessions.
He presented separate cross-sectional analyses of the risks of metabolic syndrome in 2,379 middle-aged participants in the National Heart, Lung, and Blood Institute–sponsored Framingham (Mass.) Third Generation Study and 1,180 older participants in the Framingham Offspring Study.
The two analyses showed the same thing across a broad age spectrum: The highest prevalence of metabolic syndrome as defined by Adult Treatment Panel III criteria was present among those individuals who got less than 150 minutes of physical activity per week and were also in the lowest tertile in terms of diet quality, while the lowest prevalence of metabolic syndrome occurred in participants in the top tertile for diet quality who engaged in at least 150 minutes per week of moderate to vigorous physical activity in accord with the Department of Health & Human Services 2018 Physical Activity Guidelines for Americans.
In both the middle-aged and older populations, optimal physical activity – that is, at least 150 minutes per week – appeared to override the adverse impact of suboptimal diet quality. Physically active individuals with moderate or even poor diet quality had a significantly lower prevalence of metabolic syndrome than did the reference group constituted by participants with poor diet quality who didn’t exercise for 150 minutes per week.
But the converse didn’t hold true: Individuals with optimal diet quality who didn’t reach the physical activity threshold had no reduction in metabolic syndrome, compared with the reference group, according to Dr. Lee of Boston University.
For example, among the Framingham Offspring Study participants, whose mean age was 69 years at the time of their ninth formal examination in 2014, the prevalence of metabolic syndrome was 59% in those who got less than 150 minutes of moderate to vigorous physical activity weekly as assessed by accelerometer and who were also in the lowest tertile for diet quality as self-reported on the DGAI-2010 (Dietary Guidelines Adherence Index) semiquantitative food frequency questionnaire. The relative risk of metabolic syndrome was reduced by 61% in participants with both optimal physical activity and diet quality, by 49% in those with at least 150 minutes of physical activity but only moderate diet quality, and by 39% in those with optimal exercise and poor diet quality. In contrast, individuals in the top or middle tertiles for diet quality who didn’t meet the physical activity standard had a metabolic syndrome rate that wasn’t significantly lower than the reference group.
Dr. Lee observed that his analyses are best viewed as hypothesis generating. Their cross-sectional format precludes firm conclusions as to causality.
His findings prompted session comoderator Satyam Sarma, MD, of the University of Texas, Dallas, to make one of the most memorable comments heard at AHA 2019: that the Framingham findings suggest it may be possible to outrun a bad diet.
Dr. Lee reported having no financial conflicts regarding his study, supported by Boston University.
SOURCE: Lee J. AHA 2019, Abstract RF244.
PHILADELPHIA – Engaging in at least 150 minutes of moderate to vigorous physical activity per week as recommended in national guidelines appears to mitigate the cardiometabolic risks associated with poor diet quality in middle-aged and older adults, according to an analysis of Framingham Heart Study data.
“Our findings suggest adherence to physical activity guidelines may have a protective effect on cardiometabolic health regardless of diet quality,” Joowon Lee, PhD, declared at the American Heart Association scientific sessions.
He presented separate cross-sectional analyses of the risks of metabolic syndrome in 2,379 middle-aged participants in the National Heart, Lung, and Blood Institute–sponsored Framingham (Mass.) Third Generation Study and 1,180 older participants in the Framingham Offspring Study.
The two analyses showed the same thing across a broad age spectrum: The highest prevalence of metabolic syndrome as defined by Adult Treatment Panel III criteria was present among those individuals who got less than 150 minutes of physical activity per week and were also in the lowest tertile in terms of diet quality, while the lowest prevalence of metabolic syndrome occurred in participants in the top tertile for diet quality who engaged in at least 150 minutes per week of moderate to vigorous physical activity in accord with the Department of Health & Human Services 2018 Physical Activity Guidelines for Americans.
In both the middle-aged and older populations, optimal physical activity – that is, at least 150 minutes per week – appeared to override the adverse impact of suboptimal diet quality. Physically active individuals with moderate or even poor diet quality had a significantly lower prevalence of metabolic syndrome than did the reference group constituted by participants with poor diet quality who didn’t exercise for 150 minutes per week.
But the converse didn’t hold true: Individuals with optimal diet quality who didn’t reach the physical activity threshold had no reduction in metabolic syndrome, compared with the reference group, according to Dr. Lee of Boston University.
For example, among the Framingham Offspring Study participants, whose mean age was 69 years at the time of their ninth formal examination in 2014, the prevalence of metabolic syndrome was 59% in those who got less than 150 minutes of moderate to vigorous physical activity weekly as assessed by accelerometer and who were also in the lowest tertile for diet quality as self-reported on the DGAI-2010 (Dietary Guidelines Adherence Index) semiquantitative food frequency questionnaire. The relative risk of metabolic syndrome was reduced by 61% in participants with both optimal physical activity and diet quality, by 49% in those with at least 150 minutes of physical activity but only moderate diet quality, and by 39% in those with optimal exercise and poor diet quality. In contrast, individuals in the top or middle tertiles for diet quality who didn’t meet the physical activity standard had a metabolic syndrome rate that wasn’t significantly lower than the reference group.
Dr. Lee observed that his analyses are best viewed as hypothesis generating. Their cross-sectional format precludes firm conclusions as to causality.
His findings prompted session comoderator Satyam Sarma, MD, of the University of Texas, Dallas, to make one of the most memorable comments heard at AHA 2019: that the Framingham findings suggest it may be possible to outrun a bad diet.
Dr. Lee reported having no financial conflicts regarding his study, supported by Boston University.
SOURCE: Lee J. AHA 2019, Abstract RF244.
REPORTING FROM AHA 2019
Testosterone gel increases LV mass in older men
PHILADELPHIA – Testosterone gel for treatment of hypogonadism in older men boosted their left ventricular mass by 3.5% in a single year in the multicenter, double-blind, placebo-controlled Testosterone Cardiovascular Trial, although the clinical implications of this impressive increase remain unclear, Elizabeth Hutchins, MD, reported at the American Heart Association scientific sessions.
“I do think these results should be considered as part of the safety profile for testosterone gel and also represent an interesting and understudied area for future research,” said Dr. Hutchins, a hospitalist affiliated with the Los Angeles Biomedical Research Center at Harbor-UCLA Medical Center.
The Testosterone Cardiovascular Trial was one of seven coordinated placebo-controlled, double-blind clinical trials of the impact of raising serum testosterone levels in older men with low testosterone. Some results of what are known as the TTrials have previously been reported (Endocr Rev. 2018 Jun 1;39[3]:369-86).
Dr. Hutchins presented new findings on the effect of treatment with 1% topical testosterone gel on body surface area–indexed left ventricular mass. The trial utilized a widely prescribed, commercially available product known as AndroGel. The study included 123 men over age 65 with low serum testosterone and coronary CT angiography images obtained at baseline and again after 1 year of double-blind testosterone gel or placebo. More than 80% of the men were above age 75, half were obese, more than two-thirds had hypertension, and 30% had diabetes.
The men initially applied 5 g of the testosterone gel daily, providing 15 mg/day of testosterone, with subsequent dosing adjustments as needed based on serum testosterone levels measured at a central laboratory. Participants were evaluated in office visits with serum testosterone measurements every 3 months. Testosterone levels in the men assigned to active treatment quickly rose to normal range and stayed there for the full 12 months, while the placebo-treated controls continued to have below-normal testosterone throughout the trial.
The key study finding was that LV mass indexed to body surface area rose significantly in the testosterone gel group, from an average of 71.5 g/m2 at baseline to 74.8 g/m2 at 1 year. That’s a statistically significant 3.5% increase. In contrast, LV mass remained flat across the year in controls: 73.8 g/m2 at baseline and 73.3 g/m2 at 12 months.
There was, however, no change over time in left or right atrial or ventricular chamber volumes in the testosterone gel recipients, nor in the controls.
Session comoderator Eric D. Peterson, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C., said that “this is a very important topic,” then posed a provocative question to Dr. Hutchins: “If the intervention had been running instead of testosterone gel, would the results have looked similar, and would you be concluding that there should be a warning around the use of running?”
Dr. Hutchins replied that she’s given that question much thought.
“Of course, exercise leads to LV hypertrophy and we consider that to be good muscle, and high blood pressure leads to LV hypertrophy and we consider that bad muscle. So which one is it in this case? From what I can find in the literature, it seems that incremental increases in LV mass in the absence of being an athlete are deleterious. But I think we would need outcomes-based research to really answer that question,” she said.
Dr. Hutchins noted that this was the first-ever randomized controlled trial to measure the effect of testosterone therapy on LV mass in humans. The documented increase achieved with 1 year of testosterone gel doesn’t come close to reaching the threshold of LV hypertrophy, which is about 125 g/m2 for men. But evidence from animal and observational human studies suggests that even in the absence of LV hypertrophy, increases in LV mass are associated with increased mortality, she added.
She reported having no financial conflicts regarding her study, sponsored by the National Institutes of Health.
SOURCE: Hutchins E. AHA 2019, Session FS.AOS.04.
PHILADELPHIA – Testosterone gel for treatment of hypogonadism in older men boosted their left ventricular mass by 3.5% in a single year in the multicenter, double-blind, placebo-controlled Testosterone Cardiovascular Trial, although the clinical implications of this impressive increase remain unclear, Elizabeth Hutchins, MD, reported at the American Heart Association scientific sessions.
“I do think these results should be considered as part of the safety profile for testosterone gel and also represent an interesting and understudied area for future research,” said Dr. Hutchins, a hospitalist affiliated with the Los Angeles Biomedical Research Center at Harbor-UCLA Medical Center.
The Testosterone Cardiovascular Trial was one of seven coordinated placebo-controlled, double-blind clinical trials of the impact of raising serum testosterone levels in older men with low testosterone. Some results of what are known as the TTrials have previously been reported (Endocr Rev. 2018 Jun 1;39[3]:369-86).
Dr. Hutchins presented new findings on the effect of treatment with 1% topical testosterone gel on body surface area–indexed left ventricular mass. The trial utilized a widely prescribed, commercially available product known as AndroGel. The study included 123 men over age 65 with low serum testosterone and coronary CT angiography images obtained at baseline and again after 1 year of double-blind testosterone gel or placebo. More than 80% of the men were above age 75, half were obese, more than two-thirds had hypertension, and 30% had diabetes.
The men initially applied 5 g of the testosterone gel daily, providing 15 mg/day of testosterone, with subsequent dosing adjustments as needed based on serum testosterone levels measured at a central laboratory. Participants were evaluated in office visits with serum testosterone measurements every 3 months. Testosterone levels in the men assigned to active treatment quickly rose to normal range and stayed there for the full 12 months, while the placebo-treated controls continued to have below-normal testosterone throughout the trial.
The key study finding was that LV mass indexed to body surface area rose significantly in the testosterone gel group, from an average of 71.5 g/m2 at baseline to 74.8 g/m2 at 1 year. That’s a statistically significant 3.5% increase. In contrast, LV mass remained flat across the year in controls: 73.8 g/m2 at baseline and 73.3 g/m2 at 12 months.
There was, however, no change over time in left or right atrial or ventricular chamber volumes in the testosterone gel recipients, nor in the controls.
Session comoderator Eric D. Peterson, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C., said that “this is a very important topic,” then posed a provocative question to Dr. Hutchins: “If the intervention had been running instead of testosterone gel, would the results have looked similar, and would you be concluding that there should be a warning around the use of running?”
Dr. Hutchins replied that she’s given that question much thought.
“Of course, exercise leads to LV hypertrophy and we consider that to be good muscle, and high blood pressure leads to LV hypertrophy and we consider that bad muscle. So which one is it in this case? From what I can find in the literature, it seems that incremental increases in LV mass in the absence of being an athlete are deleterious. But I think we would need outcomes-based research to really answer that question,” she said.
Dr. Hutchins noted that this was the first-ever randomized controlled trial to measure the effect of testosterone therapy on LV mass in humans. The documented increase achieved with 1 year of testosterone gel doesn’t come close to reaching the threshold of LV hypertrophy, which is about 125 g/m2 for men. But evidence from animal and observational human studies suggests that even in the absence of LV hypertrophy, increases in LV mass are associated with increased mortality, she added.
She reported having no financial conflicts regarding her study, sponsored by the National Institutes of Health.
SOURCE: Hutchins E. AHA 2019, Session FS.AOS.04.
PHILADELPHIA – Testosterone gel for treatment of hypogonadism in older men boosted their left ventricular mass by 3.5% in a single year in the multicenter, double-blind, placebo-controlled Testosterone Cardiovascular Trial, although the clinical implications of this impressive increase remain unclear, Elizabeth Hutchins, MD, reported at the American Heart Association scientific sessions.
“I do think these results should be considered as part of the safety profile for testosterone gel and also represent an interesting and understudied area for future research,” said Dr. Hutchins, a hospitalist affiliated with the Los Angeles Biomedical Research Center at Harbor-UCLA Medical Center.
The Testosterone Cardiovascular Trial was one of seven coordinated placebo-controlled, double-blind clinical trials of the impact of raising serum testosterone levels in older men with low testosterone. Some results of what are known as the TTrials have previously been reported (Endocr Rev. 2018 Jun 1;39[3]:369-86).
Dr. Hutchins presented new findings on the effect of treatment with 1% topical testosterone gel on body surface area–indexed left ventricular mass. The trial utilized a widely prescribed, commercially available product known as AndroGel. The study included 123 men over age 65 with low serum testosterone and coronary CT angiography images obtained at baseline and again after 1 year of double-blind testosterone gel or placebo. More than 80% of the men were above age 75, half were obese, more than two-thirds had hypertension, and 30% had diabetes.
The men initially applied 5 g of the testosterone gel daily, providing 15 mg/day of testosterone, with subsequent dosing adjustments as needed based on serum testosterone levels measured at a central laboratory. Participants were evaluated in office visits with serum testosterone measurements every 3 months. Testosterone levels in the men assigned to active treatment quickly rose to normal range and stayed there for the full 12 months, while the placebo-treated controls continued to have below-normal testosterone throughout the trial.
The key study finding was that LV mass indexed to body surface area rose significantly in the testosterone gel group, from an average of 71.5 g/m2 at baseline to 74.8 g/m2 at 1 year. That’s a statistically significant 3.5% increase. In contrast, LV mass remained flat across the year in controls: 73.8 g/m2 at baseline and 73.3 g/m2 at 12 months.
There was, however, no change over time in left or right atrial or ventricular chamber volumes in the testosterone gel recipients, nor in the controls.
Session comoderator Eric D. Peterson, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C., said that “this is a very important topic,” then posed a provocative question to Dr. Hutchins: “If the intervention had been running instead of testosterone gel, would the results have looked similar, and would you be concluding that there should be a warning around the use of running?”
Dr. Hutchins replied that she’s given that question much thought.
“Of course, exercise leads to LV hypertrophy and we consider that to be good muscle, and high blood pressure leads to LV hypertrophy and we consider that bad muscle. So which one is it in this case? From what I can find in the literature, it seems that incremental increases in LV mass in the absence of being an athlete are deleterious. But I think we would need outcomes-based research to really answer that question,” she said.
Dr. Hutchins noted that this was the first-ever randomized controlled trial to measure the effect of testosterone therapy on LV mass in humans. The documented increase achieved with 1 year of testosterone gel doesn’t come close to reaching the threshold of LV hypertrophy, which is about 125 g/m2 for men. But evidence from animal and observational human studies suggests that even in the absence of LV hypertrophy, increases in LV mass are associated with increased mortality, she added.
She reported having no financial conflicts regarding her study, sponsored by the National Institutes of Health.
SOURCE: Hutchins E. AHA 2019, Session FS.AOS.04.
REPORTING FROM AHA 2019
Coronary function testing during angiography boosts 1-year angina outcomes
PHILADELPHIA – Longer and more extensive follow-up of the positive CorMicA trial confirmed that clinicians who receive added information on the presence or absence of microvascular coronary disease or coronary vasospasm in patients with chronic, stable angina but without detectable coronary obstruction adjust patient treatment in ways that produce better outcomes.
For example, expanded 1-year follow-up of the 151-patient, multicenter, CorMicA randomized study showed that stable angina patients without coronary obstruction treated by clinicians aware of microvascular or vasospastic coronary disease had blood pressures that averaged about 12/5 mm Hg lower than those of patients in the control arm, in which this information was kept blinded.
Clinicians in the study who received information about diagnoses of microvascular angina, vasospastic angina, both, or neither, generally better tailored the treatments they gave these patients, were more likely to prescribe cardiac rehabilitation to these patients, and successfully capped increases in blood pressure that occurred in the control patients, Colin Berry, MD, said at the American Heart Association scientific sessions. The investigators made the diagnoses of microvascular and vasospastic angina using an “invasive diagnostic procedure” that involved placing a wire with pressure and temperature sensors in a selected coronary artery and measuring flow patterns that resulted from a systemic infusion of adenosine and from incremental, intracoronary infusions of acetylcholine.
The CorMicA results “tell us that, if we use existing drugs and nonpharmacologic treatments, we can improve patients’ quality of life,” said Dr. Berry, co-lead investigator of the study and professor of cardiology and imaging at the University of Glasgow. “There were probably two drivers of change in treatment” between the intervention arm where clinicians learned whether their patients had microvascular angina or vasospasm, and the control arm where this information was kept blinded. Some patients reclassified as having microvascular disease or vasospasm were restarted on standard agents for treatment of coronary artery disease such as statins and ACE inhibitors that had previously been stopped, noted Dr. Berry. The identification of a specific type of vascular disorder also helped guide treatment. For example, patients identified as having vasospasm were taken off of beta-blockers, which are contraindicated in these patients, and instead began treatment with a calcium channel antagonist, he said.
“CorMicA was a landmark trial. The interventional cardiologists at my center believe that the testing [for microvascular and vasospastic angina] should be used routinely, based on the reported data,” said Harmony R. Reynolds, MD, a cardiologist at NYU Langone Health in New York.
The CorMicA (Coronary Microvascular Angina) trial enrolled 391 patients at either of two hospitals in Scotland during November 2016–November 2017. All patients were scheduled for clinically indicated, elective diagnostic angiography for suspected stable angina. Clinicians identified a coronary obstruction in 206 patients that excluded them from the main CorMicA analysis. They focused on the 181 without coronary obstruction visible by angiography, and specifically the 151 of these patients who underwent the invasive diagnostic procedure, with 76 randomized to have their diagnostic-procedure results relayed to their treating physicians and 75 patients whose diagnostic results remained blinded. The study’s primary endpoint was the mean difference in angina severity at 6 months after treatment assessed by the Seattle Angina Questionnaire (SAQ) summary score. After 6 months, the between-group difference in average SAQ summary scores was 11.7 units, a statistically significant as well as clinically meaningful benefit that linked with knowledge of the coronary function of patients based on invasive testing (J Am Coll Cardiol. 2018 Dec 11;72[23 Part A]:2841-55).
The prespecified 1-year follow-up with another SAQ took place for 142 of the 151 randomized patients, and showed ongoing separation of SAQ scores between the intervention and control patients, reaching a statistically significant mean difference of 13.6 units, Dr. Berry reported. Other benefits that linked with dissemination of results from the invasive diagnostic procedure included maintenance of the quality-of-life benefit seen after 6 months, an incremental further reduction in illness perception from 6 to 12 months, and a substantial further improvement in global treatment satisfaction, which grew from a 30% higher level in the intervention group compared with controls at 6 months to a 44% between-group difference after 12 months. Concurrently with Dr. Berry’s report, the results appeared online (JACC: Cardiovasc Interv. 2020 Jan 13;13[1] 33-45).
Additional findings for various clinical measures that were not part of the 6-month findings provided further insight into the impact that clinician knowledge about microvascular disease or vasospasm had on patients. These metrics suggested that the benefits in the intervention patients may have largely resulted from their avoiding elevations in risk markers that occurred among controls who received routine care.
For example, after 12 months, average 12/5 mm Hg differences in systolic and diastolic blood pressures between the two arms was nearly all because of pressure increases from baseline in the control patients with only very small drops in pressure from baseline among the intervention patients. Weight measurements after 1 year showed that the control patients were on average 1.3 kg heavier than the intervention patients, again mostly because of weight increases among the controls. Enrollment in a cardiac rehabilitation program at 12 months had occurred for 40% of the intervention patients and 16% of the controls, a 73% relative increase in the intervention arm, Dr. Berry reported.
The invasive, coronary, physiological assessments used in CorMicA led to stratified medical therapy and created an opportunity for better long-term angina treatment in patients without obstructive coronary disease, Dr. Berry concluded. He stressed the need to further test this hypothesis in larger, prospective studies, and to assess its cost effectiveness. But the proof-of-concept demonstrated by the CorMicA results indicate a role for more thorough investigation of coronary dysfunction when obstructive disease is absent, with the opportunity to use this information to better tailor treatment. The findings also highlight the potential for new drug development that can address nonobstructive microvascular or vasospastic coronary disease, he said.
Dr. Berry has been a speaker on behalf of Abbott Vascular, and he has received research funding from AstraZeneca, GlaxoSmithKline, HeartFlow, Novartis, and Siemens Healthcare. Dr. Reynolds had no disclosures.
SOURCE: Ford TJ. AHA 2019, session FS.AOS.03 abstract.
PHILADELPHIA – Longer and more extensive follow-up of the positive CorMicA trial confirmed that clinicians who receive added information on the presence or absence of microvascular coronary disease or coronary vasospasm in patients with chronic, stable angina but without detectable coronary obstruction adjust patient treatment in ways that produce better outcomes.
For example, expanded 1-year follow-up of the 151-patient, multicenter, CorMicA randomized study showed that stable angina patients without coronary obstruction treated by clinicians aware of microvascular or vasospastic coronary disease had blood pressures that averaged about 12/5 mm Hg lower than those of patients in the control arm, in which this information was kept blinded.
Clinicians in the study who received information about diagnoses of microvascular angina, vasospastic angina, both, or neither, generally better tailored the treatments they gave these patients, were more likely to prescribe cardiac rehabilitation to these patients, and successfully capped increases in blood pressure that occurred in the control patients, Colin Berry, MD, said at the American Heart Association scientific sessions. The investigators made the diagnoses of microvascular and vasospastic angina using an “invasive diagnostic procedure” that involved placing a wire with pressure and temperature sensors in a selected coronary artery and measuring flow patterns that resulted from a systemic infusion of adenosine and from incremental, intracoronary infusions of acetylcholine.
The CorMicA results “tell us that, if we use existing drugs and nonpharmacologic treatments, we can improve patients’ quality of life,” said Dr. Berry, co-lead investigator of the study and professor of cardiology and imaging at the University of Glasgow. “There were probably two drivers of change in treatment” between the intervention arm where clinicians learned whether their patients had microvascular angina or vasospasm, and the control arm where this information was kept blinded. Some patients reclassified as having microvascular disease or vasospasm were restarted on standard agents for treatment of coronary artery disease such as statins and ACE inhibitors that had previously been stopped, noted Dr. Berry. The identification of a specific type of vascular disorder also helped guide treatment. For example, patients identified as having vasospasm were taken off of beta-blockers, which are contraindicated in these patients, and instead began treatment with a calcium channel antagonist, he said.
“CorMicA was a landmark trial. The interventional cardiologists at my center believe that the testing [for microvascular and vasospastic angina] should be used routinely, based on the reported data,” said Harmony R. Reynolds, MD, a cardiologist at NYU Langone Health in New York.
The CorMicA (Coronary Microvascular Angina) trial enrolled 391 patients at either of two hospitals in Scotland during November 2016–November 2017. All patients were scheduled for clinically indicated, elective diagnostic angiography for suspected stable angina. Clinicians identified a coronary obstruction in 206 patients that excluded them from the main CorMicA analysis. They focused on the 181 without coronary obstruction visible by angiography, and specifically the 151 of these patients who underwent the invasive diagnostic procedure, with 76 randomized to have their diagnostic-procedure results relayed to their treating physicians and 75 patients whose diagnostic results remained blinded. The study’s primary endpoint was the mean difference in angina severity at 6 months after treatment assessed by the Seattle Angina Questionnaire (SAQ) summary score. After 6 months, the between-group difference in average SAQ summary scores was 11.7 units, a statistically significant as well as clinically meaningful benefit that linked with knowledge of the coronary function of patients based on invasive testing (J Am Coll Cardiol. 2018 Dec 11;72[23 Part A]:2841-55).
The prespecified 1-year follow-up with another SAQ took place for 142 of the 151 randomized patients, and showed ongoing separation of SAQ scores between the intervention and control patients, reaching a statistically significant mean difference of 13.6 units, Dr. Berry reported. Other benefits that linked with dissemination of results from the invasive diagnostic procedure included maintenance of the quality-of-life benefit seen after 6 months, an incremental further reduction in illness perception from 6 to 12 months, and a substantial further improvement in global treatment satisfaction, which grew from a 30% higher level in the intervention group compared with controls at 6 months to a 44% between-group difference after 12 months. Concurrently with Dr. Berry’s report, the results appeared online (JACC: Cardiovasc Interv. 2020 Jan 13;13[1] 33-45).
Additional findings for various clinical measures that were not part of the 6-month findings provided further insight into the impact that clinician knowledge about microvascular disease or vasospasm had on patients. These metrics suggested that the benefits in the intervention patients may have largely resulted from their avoiding elevations in risk markers that occurred among controls who received routine care.
For example, after 12 months, average 12/5 mm Hg differences in systolic and diastolic blood pressures between the two arms was nearly all because of pressure increases from baseline in the control patients with only very small drops in pressure from baseline among the intervention patients. Weight measurements after 1 year showed that the control patients were on average 1.3 kg heavier than the intervention patients, again mostly because of weight increases among the controls. Enrollment in a cardiac rehabilitation program at 12 months had occurred for 40% of the intervention patients and 16% of the controls, a 73% relative increase in the intervention arm, Dr. Berry reported.
The invasive, coronary, physiological assessments used in CorMicA led to stratified medical therapy and created an opportunity for better long-term angina treatment in patients without obstructive coronary disease, Dr. Berry concluded. He stressed the need to further test this hypothesis in larger, prospective studies, and to assess its cost effectiveness. But the proof-of-concept demonstrated by the CorMicA results indicate a role for more thorough investigation of coronary dysfunction when obstructive disease is absent, with the opportunity to use this information to better tailor treatment. The findings also highlight the potential for new drug development that can address nonobstructive microvascular or vasospastic coronary disease, he said.
Dr. Berry has been a speaker on behalf of Abbott Vascular, and he has received research funding from AstraZeneca, GlaxoSmithKline, HeartFlow, Novartis, and Siemens Healthcare. Dr. Reynolds had no disclosures.
SOURCE: Ford TJ. AHA 2019, session FS.AOS.03 abstract.
PHILADELPHIA – Longer and more extensive follow-up of the positive CorMicA trial confirmed that clinicians who receive added information on the presence or absence of microvascular coronary disease or coronary vasospasm in patients with chronic, stable angina but without detectable coronary obstruction adjust patient treatment in ways that produce better outcomes.
For example, expanded 1-year follow-up of the 151-patient, multicenter, CorMicA randomized study showed that stable angina patients without coronary obstruction treated by clinicians aware of microvascular or vasospastic coronary disease had blood pressures that averaged about 12/5 mm Hg lower than those of patients in the control arm, in which this information was kept blinded.
Clinicians in the study who received information about diagnoses of microvascular angina, vasospastic angina, both, or neither, generally better tailored the treatments they gave these patients, were more likely to prescribe cardiac rehabilitation to these patients, and successfully capped increases in blood pressure that occurred in the control patients, Colin Berry, MD, said at the American Heart Association scientific sessions. The investigators made the diagnoses of microvascular and vasospastic angina using an “invasive diagnostic procedure” that involved placing a wire with pressure and temperature sensors in a selected coronary artery and measuring flow patterns that resulted from a systemic infusion of adenosine and from incremental, intracoronary infusions of acetylcholine.
The CorMicA results “tell us that, if we use existing drugs and nonpharmacologic treatments, we can improve patients’ quality of life,” said Dr. Berry, co-lead investigator of the study and professor of cardiology and imaging at the University of Glasgow. “There were probably two drivers of change in treatment” between the intervention arm where clinicians learned whether their patients had microvascular angina or vasospasm, and the control arm where this information was kept blinded. Some patients reclassified as having microvascular disease or vasospasm were restarted on standard agents for treatment of coronary artery disease such as statins and ACE inhibitors that had previously been stopped, noted Dr. Berry. The identification of a specific type of vascular disorder also helped guide treatment. For example, patients identified as having vasospasm were taken off of beta-blockers, which are contraindicated in these patients, and instead began treatment with a calcium channel antagonist, he said.
“CorMicA was a landmark trial. The interventional cardiologists at my center believe that the testing [for microvascular and vasospastic angina] should be used routinely, based on the reported data,” said Harmony R. Reynolds, MD, a cardiologist at NYU Langone Health in New York.
The CorMicA (Coronary Microvascular Angina) trial enrolled 391 patients at either of two hospitals in Scotland during November 2016–November 2017. All patients were scheduled for clinically indicated, elective diagnostic angiography for suspected stable angina. Clinicians identified a coronary obstruction in 206 patients that excluded them from the main CorMicA analysis. They focused on the 181 without coronary obstruction visible by angiography, and specifically the 151 of these patients who underwent the invasive diagnostic procedure, with 76 randomized to have their diagnostic-procedure results relayed to their treating physicians and 75 patients whose diagnostic results remained blinded. The study’s primary endpoint was the mean difference in angina severity at 6 months after treatment assessed by the Seattle Angina Questionnaire (SAQ) summary score. After 6 months, the between-group difference in average SAQ summary scores was 11.7 units, a statistically significant as well as clinically meaningful benefit that linked with knowledge of the coronary function of patients based on invasive testing (J Am Coll Cardiol. 2018 Dec 11;72[23 Part A]:2841-55).
The prespecified 1-year follow-up with another SAQ took place for 142 of the 151 randomized patients, and showed ongoing separation of SAQ scores between the intervention and control patients, reaching a statistically significant mean difference of 13.6 units, Dr. Berry reported. Other benefits that linked with dissemination of results from the invasive diagnostic procedure included maintenance of the quality-of-life benefit seen after 6 months, an incremental further reduction in illness perception from 6 to 12 months, and a substantial further improvement in global treatment satisfaction, which grew from a 30% higher level in the intervention group compared with controls at 6 months to a 44% between-group difference after 12 months. Concurrently with Dr. Berry’s report, the results appeared online (JACC: Cardiovasc Interv. 2020 Jan 13;13[1] 33-45).
Additional findings for various clinical measures that were not part of the 6-month findings provided further insight into the impact that clinician knowledge about microvascular disease or vasospasm had on patients. These metrics suggested that the benefits in the intervention patients may have largely resulted from their avoiding elevations in risk markers that occurred among controls who received routine care.
For example, after 12 months, average 12/5 mm Hg differences in systolic and diastolic blood pressures between the two arms was nearly all because of pressure increases from baseline in the control patients with only very small drops in pressure from baseline among the intervention patients. Weight measurements after 1 year showed that the control patients were on average 1.3 kg heavier than the intervention patients, again mostly because of weight increases among the controls. Enrollment in a cardiac rehabilitation program at 12 months had occurred for 40% of the intervention patients and 16% of the controls, a 73% relative increase in the intervention arm, Dr. Berry reported.
The invasive, coronary, physiological assessments used in CorMicA led to stratified medical therapy and created an opportunity for better long-term angina treatment in patients without obstructive coronary disease, Dr. Berry concluded. He stressed the need to further test this hypothesis in larger, prospective studies, and to assess its cost effectiveness. But the proof-of-concept demonstrated by the CorMicA results indicate a role for more thorough investigation of coronary dysfunction when obstructive disease is absent, with the opportunity to use this information to better tailor treatment. The findings also highlight the potential for new drug development that can address nonobstructive microvascular or vasospastic coronary disease, he said.
Dr. Berry has been a speaker on behalf of Abbott Vascular, and he has received research funding from AstraZeneca, GlaxoSmithKline, HeartFlow, Novartis, and Siemens Healthcare. Dr. Reynolds had no disclosures.
SOURCE: Ford TJ. AHA 2019, session FS.AOS.03 abstract.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
SPRINT-type BP control provides up to 3 years of additional life
PHILADELPHIA – in age-dependent fashion, compared with the older target standard BP, according to a novel analysis of data from the landmark SPRINT trial.
SPRINT randomized 9,361 hypertensive patients aged 50 years or older with at least one additional cardiovascular risk factor to intensive control with a target systolic BP of less than 120 mm Hg or to the then-standard target of less than 140 mm Hg. The trial was stopped early for ethical reasons when an interim analysis showed intensive control was associated with a 27% reduction in mortality. But that 27% reduction in mortality risk is a tough concept for many patients to interpret in practical terms, Muthiah Vaduganathan, MD, observed at the American Heart Association scientific sessions.
So he and his coinvestigators sliced and diced the mountainous SPRINT data in a novel way, using an actuarial statistical analysis.
“These actuarial data from SPRINT support the survival benefits of intensive blood pressure control, especially when initiated in middle-aged, high-risk adults. Our analysis really reaffirms the original SPRINT trial results [N Engl J Med. 2015 Nov 26;373(22):2103-16] and helps present them in an alternative format that can potentially be more easily communicated to clinicians, patients, and the public at large,” explained Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital and Harvard Medical School, both in Boston.
The impact of intensive BP control on residual survival was magnified in patients who were younger, since they intrinsically have a longer expected survival and will apply the antihypertensive regimen over a longer period. For example, the actuarial analysis concluded that the mean survival benefit of starting intensive BP lowering, rather than settling for a target systolic BP of less than 140 mm Hg starting at age 50 years, was 3 additional years of life, as compared with 1.1 additional years in 65-year-olds and 0.5 years in patients aged 85 years or older. The same approach can be applied to patients at any individual age from 50 to 95 years at the time of enrollment.
“This is very helpful in conveying messages to individual patients. Often if you tell a patient: ‘Your risk is going to go down by 27%,’ it’s tough for them to recognize what the baseline is and if that actually applied to them. So this may personalize that decision-making conversation,” according to the cardiologist.
One audience member commented that this SPRINT analysis might actually underestimate the true survival advantage of intensive BP lowering. He noted that SPRINT, which was halted after an average of 3.3 years, didn’t show a significant benefit for intensive BP lowering in terms of stroke reduction, whereas the ACCORD trial did, but that benefit didn’t occur until after 3 years into the study (Hypertension. 2018 Aug;72[2]:323-30).
Dr. Vaduganathan conceded that’s a limitation of his analysis.
“The assumption we’ve used is that long-term cardiovascular benefits are going to be as seen in the trial, but since SPRINT was stopped early, some benefits may be exaggerated and some may not have been observed yet,” he agreed.
Another audience member observed, “I think a lot of patients will think: ‘Okay, you’re tacking on a year at the end, when I’m going to be 89 and demented.’ The National Institute on Aging is focusing a lot more now on nondisabled life expectancy or healthy life expectancy.’”
Dr. Vaduganathan offered a degree of reassurance on this score. Because of time limitations, he said, he only presented the life expectancy results. But he and his coworkers have performed the same actuarial analysis of the SPRINT data for other endpoints related to freedom from various forms of disease or disability and found a consistent effect: Intensive BP control was associated with a longer time to onset of morbidity.
SPRINT was sponsored primarily by the National Heart, Lung, and Blood Institute. Dr. Vaduganathan reported that he receives research support from/and or serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer, Boehringer Ingelheim, and Relypsa.
SOURCE: Vaduganathan M et al. AHA 2019, Abstract MDP233.
PHILADELPHIA – in age-dependent fashion, compared with the older target standard BP, according to a novel analysis of data from the landmark SPRINT trial.
SPRINT randomized 9,361 hypertensive patients aged 50 years or older with at least one additional cardiovascular risk factor to intensive control with a target systolic BP of less than 120 mm Hg or to the then-standard target of less than 140 mm Hg. The trial was stopped early for ethical reasons when an interim analysis showed intensive control was associated with a 27% reduction in mortality. But that 27% reduction in mortality risk is a tough concept for many patients to interpret in practical terms, Muthiah Vaduganathan, MD, observed at the American Heart Association scientific sessions.
So he and his coinvestigators sliced and diced the mountainous SPRINT data in a novel way, using an actuarial statistical analysis.
“These actuarial data from SPRINT support the survival benefits of intensive blood pressure control, especially when initiated in middle-aged, high-risk adults. Our analysis really reaffirms the original SPRINT trial results [N Engl J Med. 2015 Nov 26;373(22):2103-16] and helps present them in an alternative format that can potentially be more easily communicated to clinicians, patients, and the public at large,” explained Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital and Harvard Medical School, both in Boston.
The impact of intensive BP control on residual survival was magnified in patients who were younger, since they intrinsically have a longer expected survival and will apply the antihypertensive regimen over a longer period. For example, the actuarial analysis concluded that the mean survival benefit of starting intensive BP lowering, rather than settling for a target systolic BP of less than 140 mm Hg starting at age 50 years, was 3 additional years of life, as compared with 1.1 additional years in 65-year-olds and 0.5 years in patients aged 85 years or older. The same approach can be applied to patients at any individual age from 50 to 95 years at the time of enrollment.
“This is very helpful in conveying messages to individual patients. Often if you tell a patient: ‘Your risk is going to go down by 27%,’ it’s tough for them to recognize what the baseline is and if that actually applied to them. So this may personalize that decision-making conversation,” according to the cardiologist.
One audience member commented that this SPRINT analysis might actually underestimate the true survival advantage of intensive BP lowering. He noted that SPRINT, which was halted after an average of 3.3 years, didn’t show a significant benefit for intensive BP lowering in terms of stroke reduction, whereas the ACCORD trial did, but that benefit didn’t occur until after 3 years into the study (Hypertension. 2018 Aug;72[2]:323-30).
Dr. Vaduganathan conceded that’s a limitation of his analysis.
“The assumption we’ve used is that long-term cardiovascular benefits are going to be as seen in the trial, but since SPRINT was stopped early, some benefits may be exaggerated and some may not have been observed yet,” he agreed.
Another audience member observed, “I think a lot of patients will think: ‘Okay, you’re tacking on a year at the end, when I’m going to be 89 and demented.’ The National Institute on Aging is focusing a lot more now on nondisabled life expectancy or healthy life expectancy.’”
Dr. Vaduganathan offered a degree of reassurance on this score. Because of time limitations, he said, he only presented the life expectancy results. But he and his coworkers have performed the same actuarial analysis of the SPRINT data for other endpoints related to freedom from various forms of disease or disability and found a consistent effect: Intensive BP control was associated with a longer time to onset of morbidity.
SPRINT was sponsored primarily by the National Heart, Lung, and Blood Institute. Dr. Vaduganathan reported that he receives research support from/and or serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer, Boehringer Ingelheim, and Relypsa.
SOURCE: Vaduganathan M et al. AHA 2019, Abstract MDP233.
PHILADELPHIA – in age-dependent fashion, compared with the older target standard BP, according to a novel analysis of data from the landmark SPRINT trial.
SPRINT randomized 9,361 hypertensive patients aged 50 years or older with at least one additional cardiovascular risk factor to intensive control with a target systolic BP of less than 120 mm Hg or to the then-standard target of less than 140 mm Hg. The trial was stopped early for ethical reasons when an interim analysis showed intensive control was associated with a 27% reduction in mortality. But that 27% reduction in mortality risk is a tough concept for many patients to interpret in practical terms, Muthiah Vaduganathan, MD, observed at the American Heart Association scientific sessions.
So he and his coinvestigators sliced and diced the mountainous SPRINT data in a novel way, using an actuarial statistical analysis.
“These actuarial data from SPRINT support the survival benefits of intensive blood pressure control, especially when initiated in middle-aged, high-risk adults. Our analysis really reaffirms the original SPRINT trial results [N Engl J Med. 2015 Nov 26;373(22):2103-16] and helps present them in an alternative format that can potentially be more easily communicated to clinicians, patients, and the public at large,” explained Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital and Harvard Medical School, both in Boston.
The impact of intensive BP control on residual survival was magnified in patients who were younger, since they intrinsically have a longer expected survival and will apply the antihypertensive regimen over a longer period. For example, the actuarial analysis concluded that the mean survival benefit of starting intensive BP lowering, rather than settling for a target systolic BP of less than 140 mm Hg starting at age 50 years, was 3 additional years of life, as compared with 1.1 additional years in 65-year-olds and 0.5 years in patients aged 85 years or older. The same approach can be applied to patients at any individual age from 50 to 95 years at the time of enrollment.
“This is very helpful in conveying messages to individual patients. Often if you tell a patient: ‘Your risk is going to go down by 27%,’ it’s tough for them to recognize what the baseline is and if that actually applied to them. So this may personalize that decision-making conversation,” according to the cardiologist.
One audience member commented that this SPRINT analysis might actually underestimate the true survival advantage of intensive BP lowering. He noted that SPRINT, which was halted after an average of 3.3 years, didn’t show a significant benefit for intensive BP lowering in terms of stroke reduction, whereas the ACCORD trial did, but that benefit didn’t occur until after 3 years into the study (Hypertension. 2018 Aug;72[2]:323-30).
Dr. Vaduganathan conceded that’s a limitation of his analysis.
“The assumption we’ve used is that long-term cardiovascular benefits are going to be as seen in the trial, but since SPRINT was stopped early, some benefits may be exaggerated and some may not have been observed yet,” he agreed.
Another audience member observed, “I think a lot of patients will think: ‘Okay, you’re tacking on a year at the end, when I’m going to be 89 and demented.’ The National Institute on Aging is focusing a lot more now on nondisabled life expectancy or healthy life expectancy.’”
Dr. Vaduganathan offered a degree of reassurance on this score. Because of time limitations, he said, he only presented the life expectancy results. But he and his coworkers have performed the same actuarial analysis of the SPRINT data for other endpoints related to freedom from various forms of disease or disability and found a consistent effect: Intensive BP control was associated with a longer time to onset of morbidity.
SPRINT was sponsored primarily by the National Heart, Lung, and Blood Institute. Dr. Vaduganathan reported that he receives research support from/and or serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer, Boehringer Ingelheim, and Relypsa.
SOURCE: Vaduganathan M et al. AHA 2019, Abstract MDP233.
REPORTING FROM AHA 2019
COACT: No benefit of immediate PCI for non–ST-elevation cardiac arrest at 1 year
PHILADELPHIA – Immediate coronary angiography following restoration of spontaneous circulation after out-of-hospital cardiac arrest without ST-elevation MI (STEMI) offered no survival benefit at 1 year, compared with a strategy of delaying angiography until after neurologic recovery, in the landmark COACT trial, Jorrit Lemkes, MD, reported at the American Heart Association scientific sessions.
Nor was immediate coronary angiography advantageous in terms of any of the numerous secondary long-term endpoints, including rates of MI, revascularization, hospitalization for heart failure, implantable cardioverter defibrillator (ICD) shocks, or quality of life measures (see graphic), according to Dr. Lemkes, an interventional cardiologist at Amsterdam University Medical Center.
COACT, a 552-patient randomized trial conducted at 19 Dutch centers, was the first-ever randomized trial to evaluate the role of immediate coronary angiography in patients resuscitated from out-of-hospital cardiac arrest with no signs of ST elevation on ECG. The study hypothesis was that this practice would result in improved survival and other outcomes. But such was not the case in the previously reported 90-day analysis (N Engl J Med. 2019 Apr 11;380[15]:1397-407). Nonetheless, the new 1-year results were eagerly awaited because observational data had suggested that immediate angiography after cardiac arrest without STEMI might provide a survival advantage that manifests late.
It now appears the observational studies were misleading. The 1-year survival rate was 61.4% in the immediate angioplasty group and similar at 64% with delayed angioplasty.
By way of background, Dr. Lemkes noted that both European and American guidelines give a class 1 recommendation to immediate coronary angiography with percutaneous coronary intervention (PCI) in patients who present with STEMI and cardiac arrest. It’s an endorsement grounded in compelling clinical trials evidence demonstrating that this practice reduces mortality and recurrent ischemia, salvages myocardium, and restores left ventricular function. In contrast, current guidelines offer only a tepid recommendation for immediate PCI in patients with cardiac arrest without STEMI because the only supporting evidence has been observational, with its inherent susceptibility to bias.
Discussant Joaquin E. Cigarroa, MD, said that the 1-year outcomes shouldn’t be surprising, since the 90-day results failed to show any between-group differences in myocardial injury or ischemia.
“At present, the results of COACT with regards to primary and secondary outcomes should guide practitioners that angiography remains essential, but that early angiography does not improve outcomes, compared to delayed angiography,” declared Dr. Cigarroa, chief of cardiology and professor of medicine at Oregon Health & Science University, Portland.
His choice of the words “at present” was key, as COACT won’t be the last word on the subject. Dr. Cigarroa believes that it’s critically important to understand the relatively narrow profile of the patients included in the study, because the results may or may not prove to be generalizable to the broader population of out-of-hospital cardiac arrest patients encountered in clinical practice. Nearly 80% of COACT participants had a witnessed arrest, the median time to basic life support was just 2 minutes, and the median time to return of spontaneous circulation was 15 minutes.
He urged his colleagues to stay tuned for reports from ongoing randomized trials examining the potential role of immediate angiography in broader populations of patients with out-of-hospital cardiac arrest without STEMI, including the Swedish DISCO (Direct or Subacute Coronary Angiography in Out-of-Hospital Cardiac Arrest) trial and the smaller University of Minnesota–sponsored ACCESS trial.
Dr. Lemkes reported having no financial conflicts regarding the COACT trial, funded by the Netherlands Heart Institute and unrestricted research grants from Biotronik and AstraZeneca.
PHILADELPHIA – Immediate coronary angiography following restoration of spontaneous circulation after out-of-hospital cardiac arrest without ST-elevation MI (STEMI) offered no survival benefit at 1 year, compared with a strategy of delaying angiography until after neurologic recovery, in the landmark COACT trial, Jorrit Lemkes, MD, reported at the American Heart Association scientific sessions.
Nor was immediate coronary angiography advantageous in terms of any of the numerous secondary long-term endpoints, including rates of MI, revascularization, hospitalization for heart failure, implantable cardioverter defibrillator (ICD) shocks, or quality of life measures (see graphic), according to Dr. Lemkes, an interventional cardiologist at Amsterdam University Medical Center.
COACT, a 552-patient randomized trial conducted at 19 Dutch centers, was the first-ever randomized trial to evaluate the role of immediate coronary angiography in patients resuscitated from out-of-hospital cardiac arrest with no signs of ST elevation on ECG. The study hypothesis was that this practice would result in improved survival and other outcomes. But such was not the case in the previously reported 90-day analysis (N Engl J Med. 2019 Apr 11;380[15]:1397-407). Nonetheless, the new 1-year results were eagerly awaited because observational data had suggested that immediate angiography after cardiac arrest without STEMI might provide a survival advantage that manifests late.
It now appears the observational studies were misleading. The 1-year survival rate was 61.4% in the immediate angioplasty group and similar at 64% with delayed angioplasty.
By way of background, Dr. Lemkes noted that both European and American guidelines give a class 1 recommendation to immediate coronary angiography with percutaneous coronary intervention (PCI) in patients who present with STEMI and cardiac arrest. It’s an endorsement grounded in compelling clinical trials evidence demonstrating that this practice reduces mortality and recurrent ischemia, salvages myocardium, and restores left ventricular function. In contrast, current guidelines offer only a tepid recommendation for immediate PCI in patients with cardiac arrest without STEMI because the only supporting evidence has been observational, with its inherent susceptibility to bias.
Discussant Joaquin E. Cigarroa, MD, said that the 1-year outcomes shouldn’t be surprising, since the 90-day results failed to show any between-group differences in myocardial injury or ischemia.
“At present, the results of COACT with regards to primary and secondary outcomes should guide practitioners that angiography remains essential, but that early angiography does not improve outcomes, compared to delayed angiography,” declared Dr. Cigarroa, chief of cardiology and professor of medicine at Oregon Health & Science University, Portland.
His choice of the words “at present” was key, as COACT won’t be the last word on the subject. Dr. Cigarroa believes that it’s critically important to understand the relatively narrow profile of the patients included in the study, because the results may or may not prove to be generalizable to the broader population of out-of-hospital cardiac arrest patients encountered in clinical practice. Nearly 80% of COACT participants had a witnessed arrest, the median time to basic life support was just 2 minutes, and the median time to return of spontaneous circulation was 15 minutes.
He urged his colleagues to stay tuned for reports from ongoing randomized trials examining the potential role of immediate angiography in broader populations of patients with out-of-hospital cardiac arrest without STEMI, including the Swedish DISCO (Direct or Subacute Coronary Angiography in Out-of-Hospital Cardiac Arrest) trial and the smaller University of Minnesota–sponsored ACCESS trial.
Dr. Lemkes reported having no financial conflicts regarding the COACT trial, funded by the Netherlands Heart Institute and unrestricted research grants from Biotronik and AstraZeneca.
PHILADELPHIA – Immediate coronary angiography following restoration of spontaneous circulation after out-of-hospital cardiac arrest without ST-elevation MI (STEMI) offered no survival benefit at 1 year, compared with a strategy of delaying angiography until after neurologic recovery, in the landmark COACT trial, Jorrit Lemkes, MD, reported at the American Heart Association scientific sessions.
Nor was immediate coronary angiography advantageous in terms of any of the numerous secondary long-term endpoints, including rates of MI, revascularization, hospitalization for heart failure, implantable cardioverter defibrillator (ICD) shocks, or quality of life measures (see graphic), according to Dr. Lemkes, an interventional cardiologist at Amsterdam University Medical Center.
COACT, a 552-patient randomized trial conducted at 19 Dutch centers, was the first-ever randomized trial to evaluate the role of immediate coronary angiography in patients resuscitated from out-of-hospital cardiac arrest with no signs of ST elevation on ECG. The study hypothesis was that this practice would result in improved survival and other outcomes. But such was not the case in the previously reported 90-day analysis (N Engl J Med. 2019 Apr 11;380[15]:1397-407). Nonetheless, the new 1-year results were eagerly awaited because observational data had suggested that immediate angiography after cardiac arrest without STEMI might provide a survival advantage that manifests late.
It now appears the observational studies were misleading. The 1-year survival rate was 61.4% in the immediate angioplasty group and similar at 64% with delayed angioplasty.
By way of background, Dr. Lemkes noted that both European and American guidelines give a class 1 recommendation to immediate coronary angiography with percutaneous coronary intervention (PCI) in patients who present with STEMI and cardiac arrest. It’s an endorsement grounded in compelling clinical trials evidence demonstrating that this practice reduces mortality and recurrent ischemia, salvages myocardium, and restores left ventricular function. In contrast, current guidelines offer only a tepid recommendation for immediate PCI in patients with cardiac arrest without STEMI because the only supporting evidence has been observational, with its inherent susceptibility to bias.
Discussant Joaquin E. Cigarroa, MD, said that the 1-year outcomes shouldn’t be surprising, since the 90-day results failed to show any between-group differences in myocardial injury or ischemia.
“At present, the results of COACT with regards to primary and secondary outcomes should guide practitioners that angiography remains essential, but that early angiography does not improve outcomes, compared to delayed angiography,” declared Dr. Cigarroa, chief of cardiology and professor of medicine at Oregon Health & Science University, Portland.
His choice of the words “at present” was key, as COACT won’t be the last word on the subject. Dr. Cigarroa believes that it’s critically important to understand the relatively narrow profile of the patients included in the study, because the results may or may not prove to be generalizable to the broader population of out-of-hospital cardiac arrest patients encountered in clinical practice. Nearly 80% of COACT participants had a witnessed arrest, the median time to basic life support was just 2 minutes, and the median time to return of spontaneous circulation was 15 minutes.
He urged his colleagues to stay tuned for reports from ongoing randomized trials examining the potential role of immediate angiography in broader populations of patients with out-of-hospital cardiac arrest without STEMI, including the Swedish DISCO (Direct or Subacute Coronary Angiography in Out-of-Hospital Cardiac Arrest) trial and the smaller University of Minnesota–sponsored ACCESS trial.
Dr. Lemkes reported having no financial conflicts regarding the COACT trial, funded by the Netherlands Heart Institute and unrestricted research grants from Biotronik and AstraZeneca.
REPORTING FROM AHA 2019
Pharmacist BP telemonitoring cut cardiovascular events, turned profit
PHILADELPHIA – A home blood pressure telemonitoring program featuring pharmacist management of patients with uncontrolled hypertension reduced cardiovascular events by half and was cost saving over the course of 5 years, even though the intervention ended after year 1, Karen L. Margolis, MD, reported at the American Heart Association scientific sessions.
“The return on investment was 126%. That means that for every dollar spent on the intervention, that dollar was recouped by $1.00 plus another $1.26,” explained Dr. Margolis, a general internist who serves as executive director for research at the HealthPartners Institute in Bloomington, Minn., and professor of medicine at the University of Minnesota, Minneapolis.
She presented 5-year follow-up data from the Hyperlink (Home Blood Pressure Telemonitoring and Case Management to Control Hypertension) study, a cluster randomized controlled trial involving 16 primary care clinics. Half of the clinics were randomized to the intervention, which entailed home blood pressure telemonitoring and pharmacist-led case management in collaboration with the primary care team. The other eight clinics provided usual care. The intervention portion of the trial, which lasted for 12 months, included 450 adults with uncontrolled hypertension as defined by repeated on-treatment blood pressure readings of 140/90 mm Hg or more. Participants’ baseline mean blood pressure was 148/85 mm Hg while on an average of one and a half antihypertensive drug classes. On average, pharmacists ended up adding one additional drug from a different antihypertensive drug class to achieve improved blood pressure control.
The details of the intervention and the short-term blood pressure results have previously been reported (JAMA. 2013 Jul 3;310[1]:46-56). Briefly, 6 months into the study, patients in the intervention arm averaged 11/6 mm Hg lower blood pressure than did the usual care controls. At 12 months – when the intervention ended – the between-group difference was similar at 10/5 mm Hg. At 18 months, the difference, while attenuated, remained significant at 7/3 mm Hg in favor of the intervention group. However, at 54 months, the intervention group’s advantage – a 3–mm Hg lower SBP and a 1–mm Hg lower DBP than in controls – was no longer significant.
The exciting new findings Dr. Margolis presented at the AHA scientific sessions focused on 5-year outcomes. Since HealthPartners is an integrated health care system, follow-up was essentially complete.
“None of the other telemetry studies I’m aware of have published anything on cardiovascular events. And we were somewhat surprised when we looked at our data to see fairly substantial differences in our primary outcome,” she noted.
That outcome was a composite of MI, stroke, heart failure, or cardiovascular death occurring over 5 years. The rate was 4.4% in the intervention group and nearly double at 8.6% in controls. That translated to a 51% relative risk reduction. The biggest difference was in stroke: 4 cases in the intervention arm, 12 in usual care controls.
The 5-year coronary revascularization rate was 5.3% in the intervention arm and 10.4% in controls, for a 52% relative risk reduction.
A major caveat regarding the Hyperlink trial was that, even at 450 patients and 5 years of follow-up, the study was underpowered to show significant differences in event rates, with P =.09 for the primary endpoint.
That being said, the financial results were striking. The intervention cost $1,511 per patient in 2017 U.S. dollars. The cost of treatment for major adverse cardiovascular events totaled $758,000 in the intervention group and $1,538,000 in usual care controls. That works out to $3,420 less per patient in the intervention arm. Offset by the cost of the intervention, that spells a net savings of $1,908 per patient achieved by implementing the year-long intervention. It’s a rare instance in health care of an intervention that actually makes money.
These results were unusual enough that Dr. Margolis and her coinvestigators decided to feed their wealth of SBP readings into a microsimulation model, which they ran 1,000 times. The model predicted – in light of the fact that patients in the intervention group were on average 2 years older than the controls were – that the expected reduction in the primary endpoint was 12% rather than the observed 51% relative risk reduction.
How to explain the discrepancy? The Hyperlink results could have been due to chance. Or it could be, Dr. Margolis surmised, that the pharmacists helped accomplish improvements in other cardiovascular risk factors, such as hyperlipidemia, smoking, or sedentary behavior. That’s unknown, since the investigators focused on changes in blood pressure only. Future studies of home telemonitoring and pharmacist case management of uncontrolled hypertension should be powered to detect significant differences in cardiovascular events and should track additional risk factors, she concluded.
She reported having no financial conflicts regarding the study.
SOURCE: Margolis KL. AHA 2019. Abstract MDP232.
PHILADELPHIA – A home blood pressure telemonitoring program featuring pharmacist management of patients with uncontrolled hypertension reduced cardiovascular events by half and was cost saving over the course of 5 years, even though the intervention ended after year 1, Karen L. Margolis, MD, reported at the American Heart Association scientific sessions.
“The return on investment was 126%. That means that for every dollar spent on the intervention, that dollar was recouped by $1.00 plus another $1.26,” explained Dr. Margolis, a general internist who serves as executive director for research at the HealthPartners Institute in Bloomington, Minn., and professor of medicine at the University of Minnesota, Minneapolis.
She presented 5-year follow-up data from the Hyperlink (Home Blood Pressure Telemonitoring and Case Management to Control Hypertension) study, a cluster randomized controlled trial involving 16 primary care clinics. Half of the clinics were randomized to the intervention, which entailed home blood pressure telemonitoring and pharmacist-led case management in collaboration with the primary care team. The other eight clinics provided usual care. The intervention portion of the trial, which lasted for 12 months, included 450 adults with uncontrolled hypertension as defined by repeated on-treatment blood pressure readings of 140/90 mm Hg or more. Participants’ baseline mean blood pressure was 148/85 mm Hg while on an average of one and a half antihypertensive drug classes. On average, pharmacists ended up adding one additional drug from a different antihypertensive drug class to achieve improved blood pressure control.
The details of the intervention and the short-term blood pressure results have previously been reported (JAMA. 2013 Jul 3;310[1]:46-56). Briefly, 6 months into the study, patients in the intervention arm averaged 11/6 mm Hg lower blood pressure than did the usual care controls. At 12 months – when the intervention ended – the between-group difference was similar at 10/5 mm Hg. At 18 months, the difference, while attenuated, remained significant at 7/3 mm Hg in favor of the intervention group. However, at 54 months, the intervention group’s advantage – a 3–mm Hg lower SBP and a 1–mm Hg lower DBP than in controls – was no longer significant.
The exciting new findings Dr. Margolis presented at the AHA scientific sessions focused on 5-year outcomes. Since HealthPartners is an integrated health care system, follow-up was essentially complete.
“None of the other telemetry studies I’m aware of have published anything on cardiovascular events. And we were somewhat surprised when we looked at our data to see fairly substantial differences in our primary outcome,” she noted.
That outcome was a composite of MI, stroke, heart failure, or cardiovascular death occurring over 5 years. The rate was 4.4% in the intervention group and nearly double at 8.6% in controls. That translated to a 51% relative risk reduction. The biggest difference was in stroke: 4 cases in the intervention arm, 12 in usual care controls.
The 5-year coronary revascularization rate was 5.3% in the intervention arm and 10.4% in controls, for a 52% relative risk reduction.
A major caveat regarding the Hyperlink trial was that, even at 450 patients and 5 years of follow-up, the study was underpowered to show significant differences in event rates, with P =.09 for the primary endpoint.
That being said, the financial results were striking. The intervention cost $1,511 per patient in 2017 U.S. dollars. The cost of treatment for major adverse cardiovascular events totaled $758,000 in the intervention group and $1,538,000 in usual care controls. That works out to $3,420 less per patient in the intervention arm. Offset by the cost of the intervention, that spells a net savings of $1,908 per patient achieved by implementing the year-long intervention. It’s a rare instance in health care of an intervention that actually makes money.
These results were unusual enough that Dr. Margolis and her coinvestigators decided to feed their wealth of SBP readings into a microsimulation model, which they ran 1,000 times. The model predicted – in light of the fact that patients in the intervention group were on average 2 years older than the controls were – that the expected reduction in the primary endpoint was 12% rather than the observed 51% relative risk reduction.
How to explain the discrepancy? The Hyperlink results could have been due to chance. Or it could be, Dr. Margolis surmised, that the pharmacists helped accomplish improvements in other cardiovascular risk factors, such as hyperlipidemia, smoking, or sedentary behavior. That’s unknown, since the investigators focused on changes in blood pressure only. Future studies of home telemonitoring and pharmacist case management of uncontrolled hypertension should be powered to detect significant differences in cardiovascular events and should track additional risk factors, she concluded.
She reported having no financial conflicts regarding the study.
SOURCE: Margolis KL. AHA 2019. Abstract MDP232.
PHILADELPHIA – A home blood pressure telemonitoring program featuring pharmacist management of patients with uncontrolled hypertension reduced cardiovascular events by half and was cost saving over the course of 5 years, even though the intervention ended after year 1, Karen L. Margolis, MD, reported at the American Heart Association scientific sessions.
“The return on investment was 126%. That means that for every dollar spent on the intervention, that dollar was recouped by $1.00 plus another $1.26,” explained Dr. Margolis, a general internist who serves as executive director for research at the HealthPartners Institute in Bloomington, Minn., and professor of medicine at the University of Minnesota, Minneapolis.
She presented 5-year follow-up data from the Hyperlink (Home Blood Pressure Telemonitoring and Case Management to Control Hypertension) study, a cluster randomized controlled trial involving 16 primary care clinics. Half of the clinics were randomized to the intervention, which entailed home blood pressure telemonitoring and pharmacist-led case management in collaboration with the primary care team. The other eight clinics provided usual care. The intervention portion of the trial, which lasted for 12 months, included 450 adults with uncontrolled hypertension as defined by repeated on-treatment blood pressure readings of 140/90 mm Hg or more. Participants’ baseline mean blood pressure was 148/85 mm Hg while on an average of one and a half antihypertensive drug classes. On average, pharmacists ended up adding one additional drug from a different antihypertensive drug class to achieve improved blood pressure control.
The details of the intervention and the short-term blood pressure results have previously been reported (JAMA. 2013 Jul 3;310[1]:46-56). Briefly, 6 months into the study, patients in the intervention arm averaged 11/6 mm Hg lower blood pressure than did the usual care controls. At 12 months – when the intervention ended – the between-group difference was similar at 10/5 mm Hg. At 18 months, the difference, while attenuated, remained significant at 7/3 mm Hg in favor of the intervention group. However, at 54 months, the intervention group’s advantage – a 3–mm Hg lower SBP and a 1–mm Hg lower DBP than in controls – was no longer significant.
The exciting new findings Dr. Margolis presented at the AHA scientific sessions focused on 5-year outcomes. Since HealthPartners is an integrated health care system, follow-up was essentially complete.
“None of the other telemetry studies I’m aware of have published anything on cardiovascular events. And we were somewhat surprised when we looked at our data to see fairly substantial differences in our primary outcome,” she noted.
That outcome was a composite of MI, stroke, heart failure, or cardiovascular death occurring over 5 years. The rate was 4.4% in the intervention group and nearly double at 8.6% in controls. That translated to a 51% relative risk reduction. The biggest difference was in stroke: 4 cases in the intervention arm, 12 in usual care controls.
The 5-year coronary revascularization rate was 5.3% in the intervention arm and 10.4% in controls, for a 52% relative risk reduction.
A major caveat regarding the Hyperlink trial was that, even at 450 patients and 5 years of follow-up, the study was underpowered to show significant differences in event rates, with P =.09 for the primary endpoint.
That being said, the financial results were striking. The intervention cost $1,511 per patient in 2017 U.S. dollars. The cost of treatment for major adverse cardiovascular events totaled $758,000 in the intervention group and $1,538,000 in usual care controls. That works out to $3,420 less per patient in the intervention arm. Offset by the cost of the intervention, that spells a net savings of $1,908 per patient achieved by implementing the year-long intervention. It’s a rare instance in health care of an intervention that actually makes money.
These results were unusual enough that Dr. Margolis and her coinvestigators decided to feed their wealth of SBP readings into a microsimulation model, which they ran 1,000 times. The model predicted – in light of the fact that patients in the intervention group were on average 2 years older than the controls were – that the expected reduction in the primary endpoint was 12% rather than the observed 51% relative risk reduction.
How to explain the discrepancy? The Hyperlink results could have been due to chance. Or it could be, Dr. Margolis surmised, that the pharmacists helped accomplish improvements in other cardiovascular risk factors, such as hyperlipidemia, smoking, or sedentary behavior. That’s unknown, since the investigators focused on changes in blood pressure only. Future studies of home telemonitoring and pharmacist case management of uncontrolled hypertension should be powered to detect significant differences in cardiovascular events and should track additional risk factors, she concluded.
She reported having no financial conflicts regarding the study.
SOURCE: Margolis KL. AHA 2019. Abstract MDP232.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Treatment of heart failure with preserved ejection fraction is a work in progress
LOS ANGELES – When it comes to the optimal treatment of patients with heart failure with preserved ejection fraction and diabetes, cardiologists like Mark T. Kearney, MB ChB, MD, remain stumped.
“Over the years, the diagnosis of heart failure with preserved ejection fraction has been notoriously difficult [to treat], controversial, and ultimately involves aggressive catheterization of the heart to assess diastolic dysfunction, complex echocardiography, and invasive tests,” Dr. Kearney said at the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease. “These patients have an ejection fraction of over 50% and classic signs and symptoms of heart failure. Studies of beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers have been unsuccessful in this group of patients. We’re at the beginning of a journey in understanding this disorder, and it’s important, because more and more patients present to us with signs and symptoms of heart failure with an ejection fraction greater than 50%.”
In a recent analysis of 1,797 patients with chronic heart failure, Dr. Kearney, British Heart Foundation Professor of Cardiovascular and Diabetes Research at the Leeds (England) Institute of Cardiovascular and Metabolic Medicine, and colleagues examined whether beta-blockers and ACE inhibitors were associated with differential effects on mortality in patients with and without diabetes (Diabetes Care. 2018;41:136-42). Mean follow-up was 4 years.
For the ACE inhibitor component of the trial, the researchers correlated the dose of ramipril to outcomes and found that each milligram increase of ramipril reduced the risk of death by about 3%. “In the nondiabetic patients who did not receive an ACE inhibitor, mortality was about 60% – worse than most cancers,” Dr. Kearney said. “In patients with diabetes, there was a similar pattern. If you didn’t get an ACE inhibitor, mortality was 70%. So, if you get patients on an optimal dose of an ACE inhibitor, you improve their mortality substantially, whether they have diabetes or not.”
The beta-blocker component of the trial yielded similar results. “Among patients who did not receive a beta-blocker, the mortality was about 70% at 5 years – really terrible,” he said. “Every milligram of bisoprolol was associated with a reduction in mortality of about 9%. So, if a patient gets on an optimal dose of a beta-blocker and they have diabetes, it’s associated with prolongation of life over a year.”
Dr. Kearney said that patients often do not want to take an increased dose of a beta-blocker because of concerns about side effects, such as tiredness. “They ask me what the side effects of an increased dose would be. My answer is: ‘It will make you live longer.’ Usually, they’ll respond by agreeing to have a little bit more of the beta-blocker. The message here is, if you have a patient with ejection fraction heart failure and diabetes, get them on the optimal dose of a beta-blocker, even at the expense of an ACE inhibitor.”
In 2016, the European Society of Cardiology introduced guidelines for physicians to make a diagnosis of heart failure with preserved ejection fraction. The guidelines mandate that a diagnosis requires signs and symptoms of heart failure, elevated levels of natriuretic peptide, and echocardiographic abnormalities of cardiac structure and/or function in the presence of a left ventricular ejection fraction of 50% or more (Eur J Heart Fail. 2016;18[8]:891-975).
“Signs and symptoms of heart failure, elevated BNP [brain natriuretic peptide], and echocardiography allow us to make a diagnosis of heart failure with preserved ejection fraction,” Dr. Kearney, who is also dean of the Leeds University School of Medicine. “But we don’t know the outcome of these patients, we don’t know how to treat them, and we don’t know the impact on hospitalizations.”
In a large, unpublished cohort study conducted at Leeds, Dr. Kearney and colleagues evaluated how many patients met criteria for heart failure with reduced ejection fraction or heart failure with preserved ejection fraction after undergoing a BNP measurement. Ultimately, 959 patients met criteria. After assessment, 23% had no heart failure, 44% had heart failure with preserved ejection fraction, and 33% had heart failure with reduced ejection fraction. They found that patients with preserved ejection fraction were older (mean age, 84 years); were more likely to be female; and had less ischemia, less diabetes, and more hypertension. In addition, patients with preserved ejection fraction had significantly better survival than patients with reduced ejection fraction over 5 years follow-up.
“What was really interesting were the findings related to hospitalization,” he said. “All 959 patients accounted for 20,517 days in the hospital over 5 years, which is the equivalent of 1 patient occupying a hospital bed for 56 years. This disorder [heart failure with preserved ejection fraction], despite having a lower mortality than heart failure with reduced ejection fraction, leads to a significant burden on health care systems.”
Among patients with preserved ejection fraction, 82% were hospitalized for a noncardiovascular cause, 6.9% because of heart failure, and 11% were caused by other cardiovascular causes. Most of the hospital admissions were because of chest infections, falls, and other frailty-linked causes. “This link between systemic frailty and heart failure with preserved ejection fraction warrants further investigation,” Dr. Kearney said. “This is a major burden on patient hospital care.”
When the researchers examined outcomes in patients with and without diabetes, those with diabetes were younger, more likely to be male, and have a higher body mass index. They found that, in the presence of diabetes, mortality was increased in heart failure with preserved and reduced ejection fraction. “So, even at the age of 81 or 82, diabetes changes the pathophysiology of mortality in what was previously believed to be a benign disease,” he said.
In a subset analysis of patients with and without diabetes who were not taking a beta-blocker, there did not seem to be increased sympathetic activation in the patients with diabetes and heart failure with preserved ejection fraction, nor a difference in heart rate between the nondiabetic patients and patients with diabetes. However, among patients with heart failure with reduced ejection fraction, those with diabetes had an increased heart rate.
“Is heart failure with preserved ejection fraction in diabetes benign? I think the answer is no,” Dr. Kearney said. “It increases hospitalization and is a major burden on health care systems. What should we do? We deal with comorbidity and fall risk. It’s good old-fashioned doctoring, really. We address frailty and respiratory tract infections, but the key thing here is that we need more research.”
Dr. Kearney reported having no relevant financial disclosures.
LOS ANGELES – When it comes to the optimal treatment of patients with heart failure with preserved ejection fraction and diabetes, cardiologists like Mark T. Kearney, MB ChB, MD, remain stumped.
“Over the years, the diagnosis of heart failure with preserved ejection fraction has been notoriously difficult [to treat], controversial, and ultimately involves aggressive catheterization of the heart to assess diastolic dysfunction, complex echocardiography, and invasive tests,” Dr. Kearney said at the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease. “These patients have an ejection fraction of over 50% and classic signs and symptoms of heart failure. Studies of beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers have been unsuccessful in this group of patients. We’re at the beginning of a journey in understanding this disorder, and it’s important, because more and more patients present to us with signs and symptoms of heart failure with an ejection fraction greater than 50%.”
In a recent analysis of 1,797 patients with chronic heart failure, Dr. Kearney, British Heart Foundation Professor of Cardiovascular and Diabetes Research at the Leeds (England) Institute of Cardiovascular and Metabolic Medicine, and colleagues examined whether beta-blockers and ACE inhibitors were associated with differential effects on mortality in patients with and without diabetes (Diabetes Care. 2018;41:136-42). Mean follow-up was 4 years.
For the ACE inhibitor component of the trial, the researchers correlated the dose of ramipril to outcomes and found that each milligram increase of ramipril reduced the risk of death by about 3%. “In the nondiabetic patients who did not receive an ACE inhibitor, mortality was about 60% – worse than most cancers,” Dr. Kearney said. “In patients with diabetes, there was a similar pattern. If you didn’t get an ACE inhibitor, mortality was 70%. So, if you get patients on an optimal dose of an ACE inhibitor, you improve their mortality substantially, whether they have diabetes or not.”
The beta-blocker component of the trial yielded similar results. “Among patients who did not receive a beta-blocker, the mortality was about 70% at 5 years – really terrible,” he said. “Every milligram of bisoprolol was associated with a reduction in mortality of about 9%. So, if a patient gets on an optimal dose of a beta-blocker and they have diabetes, it’s associated with prolongation of life over a year.”
Dr. Kearney said that patients often do not want to take an increased dose of a beta-blocker because of concerns about side effects, such as tiredness. “They ask me what the side effects of an increased dose would be. My answer is: ‘It will make you live longer.’ Usually, they’ll respond by agreeing to have a little bit more of the beta-blocker. The message here is, if you have a patient with ejection fraction heart failure and diabetes, get them on the optimal dose of a beta-blocker, even at the expense of an ACE inhibitor.”
In 2016, the European Society of Cardiology introduced guidelines for physicians to make a diagnosis of heart failure with preserved ejection fraction. The guidelines mandate that a diagnosis requires signs and symptoms of heart failure, elevated levels of natriuretic peptide, and echocardiographic abnormalities of cardiac structure and/or function in the presence of a left ventricular ejection fraction of 50% or more (Eur J Heart Fail. 2016;18[8]:891-975).
“Signs and symptoms of heart failure, elevated BNP [brain natriuretic peptide], and echocardiography allow us to make a diagnosis of heart failure with preserved ejection fraction,” Dr. Kearney, who is also dean of the Leeds University School of Medicine. “But we don’t know the outcome of these patients, we don’t know how to treat them, and we don’t know the impact on hospitalizations.”
In a large, unpublished cohort study conducted at Leeds, Dr. Kearney and colleagues evaluated how many patients met criteria for heart failure with reduced ejection fraction or heart failure with preserved ejection fraction after undergoing a BNP measurement. Ultimately, 959 patients met criteria. After assessment, 23% had no heart failure, 44% had heart failure with preserved ejection fraction, and 33% had heart failure with reduced ejection fraction. They found that patients with preserved ejection fraction were older (mean age, 84 years); were more likely to be female; and had less ischemia, less diabetes, and more hypertension. In addition, patients with preserved ejection fraction had significantly better survival than patients with reduced ejection fraction over 5 years follow-up.
“What was really interesting were the findings related to hospitalization,” he said. “All 959 patients accounted for 20,517 days in the hospital over 5 years, which is the equivalent of 1 patient occupying a hospital bed for 56 years. This disorder [heart failure with preserved ejection fraction], despite having a lower mortality than heart failure with reduced ejection fraction, leads to a significant burden on health care systems.”
Among patients with preserved ejection fraction, 82% were hospitalized for a noncardiovascular cause, 6.9% because of heart failure, and 11% were caused by other cardiovascular causes. Most of the hospital admissions were because of chest infections, falls, and other frailty-linked causes. “This link between systemic frailty and heart failure with preserved ejection fraction warrants further investigation,” Dr. Kearney said. “This is a major burden on patient hospital care.”
When the researchers examined outcomes in patients with and without diabetes, those with diabetes were younger, more likely to be male, and have a higher body mass index. They found that, in the presence of diabetes, mortality was increased in heart failure with preserved and reduced ejection fraction. “So, even at the age of 81 or 82, diabetes changes the pathophysiology of mortality in what was previously believed to be a benign disease,” he said.
In a subset analysis of patients with and without diabetes who were not taking a beta-blocker, there did not seem to be increased sympathetic activation in the patients with diabetes and heart failure with preserved ejection fraction, nor a difference in heart rate between the nondiabetic patients and patients with diabetes. However, among patients with heart failure with reduced ejection fraction, those with diabetes had an increased heart rate.
“Is heart failure with preserved ejection fraction in diabetes benign? I think the answer is no,” Dr. Kearney said. “It increases hospitalization and is a major burden on health care systems. What should we do? We deal with comorbidity and fall risk. It’s good old-fashioned doctoring, really. We address frailty and respiratory tract infections, but the key thing here is that we need more research.”
Dr. Kearney reported having no relevant financial disclosures.
LOS ANGELES – When it comes to the optimal treatment of patients with heart failure with preserved ejection fraction and diabetes, cardiologists like Mark T. Kearney, MB ChB, MD, remain stumped.
“Over the years, the diagnosis of heart failure with preserved ejection fraction has been notoriously difficult [to treat], controversial, and ultimately involves aggressive catheterization of the heart to assess diastolic dysfunction, complex echocardiography, and invasive tests,” Dr. Kearney said at the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease. “These patients have an ejection fraction of over 50% and classic signs and symptoms of heart failure. Studies of beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers have been unsuccessful in this group of patients. We’re at the beginning of a journey in understanding this disorder, and it’s important, because more and more patients present to us with signs and symptoms of heart failure with an ejection fraction greater than 50%.”
In a recent analysis of 1,797 patients with chronic heart failure, Dr. Kearney, British Heart Foundation Professor of Cardiovascular and Diabetes Research at the Leeds (England) Institute of Cardiovascular and Metabolic Medicine, and colleagues examined whether beta-blockers and ACE inhibitors were associated with differential effects on mortality in patients with and without diabetes (Diabetes Care. 2018;41:136-42). Mean follow-up was 4 years.
For the ACE inhibitor component of the trial, the researchers correlated the dose of ramipril to outcomes and found that each milligram increase of ramipril reduced the risk of death by about 3%. “In the nondiabetic patients who did not receive an ACE inhibitor, mortality was about 60% – worse than most cancers,” Dr. Kearney said. “In patients with diabetes, there was a similar pattern. If you didn’t get an ACE inhibitor, mortality was 70%. So, if you get patients on an optimal dose of an ACE inhibitor, you improve their mortality substantially, whether they have diabetes or not.”
The beta-blocker component of the trial yielded similar results. “Among patients who did not receive a beta-blocker, the mortality was about 70% at 5 years – really terrible,” he said. “Every milligram of bisoprolol was associated with a reduction in mortality of about 9%. So, if a patient gets on an optimal dose of a beta-blocker and they have diabetes, it’s associated with prolongation of life over a year.”
Dr. Kearney said that patients often do not want to take an increased dose of a beta-blocker because of concerns about side effects, such as tiredness. “They ask me what the side effects of an increased dose would be. My answer is: ‘It will make you live longer.’ Usually, they’ll respond by agreeing to have a little bit more of the beta-blocker. The message here is, if you have a patient with ejection fraction heart failure and diabetes, get them on the optimal dose of a beta-blocker, even at the expense of an ACE inhibitor.”
In 2016, the European Society of Cardiology introduced guidelines for physicians to make a diagnosis of heart failure with preserved ejection fraction. The guidelines mandate that a diagnosis requires signs and symptoms of heart failure, elevated levels of natriuretic peptide, and echocardiographic abnormalities of cardiac structure and/or function in the presence of a left ventricular ejection fraction of 50% or more (Eur J Heart Fail. 2016;18[8]:891-975).
“Signs and symptoms of heart failure, elevated BNP [brain natriuretic peptide], and echocardiography allow us to make a diagnosis of heart failure with preserved ejection fraction,” Dr. Kearney, who is also dean of the Leeds University School of Medicine. “But we don’t know the outcome of these patients, we don’t know how to treat them, and we don’t know the impact on hospitalizations.”
In a large, unpublished cohort study conducted at Leeds, Dr. Kearney and colleagues evaluated how many patients met criteria for heart failure with reduced ejection fraction or heart failure with preserved ejection fraction after undergoing a BNP measurement. Ultimately, 959 patients met criteria. After assessment, 23% had no heart failure, 44% had heart failure with preserved ejection fraction, and 33% had heart failure with reduced ejection fraction. They found that patients with preserved ejection fraction were older (mean age, 84 years); were more likely to be female; and had less ischemia, less diabetes, and more hypertension. In addition, patients with preserved ejection fraction had significantly better survival than patients with reduced ejection fraction over 5 years follow-up.
“What was really interesting were the findings related to hospitalization,” he said. “All 959 patients accounted for 20,517 days in the hospital over 5 years, which is the equivalent of 1 patient occupying a hospital bed for 56 years. This disorder [heart failure with preserved ejection fraction], despite having a lower mortality than heart failure with reduced ejection fraction, leads to a significant burden on health care systems.”
Among patients with preserved ejection fraction, 82% were hospitalized for a noncardiovascular cause, 6.9% because of heart failure, and 11% were caused by other cardiovascular causes. Most of the hospital admissions were because of chest infections, falls, and other frailty-linked causes. “This link between systemic frailty and heart failure with preserved ejection fraction warrants further investigation,” Dr. Kearney said. “This is a major burden on patient hospital care.”
When the researchers examined outcomes in patients with and without diabetes, those with diabetes were younger, more likely to be male, and have a higher body mass index. They found that, in the presence of diabetes, mortality was increased in heart failure with preserved and reduced ejection fraction. “So, even at the age of 81 or 82, diabetes changes the pathophysiology of mortality in what was previously believed to be a benign disease,” he said.
In a subset analysis of patients with and without diabetes who were not taking a beta-blocker, there did not seem to be increased sympathetic activation in the patients with diabetes and heart failure with preserved ejection fraction, nor a difference in heart rate between the nondiabetic patients and patients with diabetes. However, among patients with heart failure with reduced ejection fraction, those with diabetes had an increased heart rate.
“Is heart failure with preserved ejection fraction in diabetes benign? I think the answer is no,” Dr. Kearney said. “It increases hospitalization and is a major burden on health care systems. What should we do? We deal with comorbidity and fall risk. It’s good old-fashioned doctoring, really. We address frailty and respiratory tract infections, but the key thing here is that we need more research.”
Dr. Kearney reported having no relevant financial disclosures.
EXPERT ANALYSIS FROM WCIRDC 2019
FUEL trial: Post-Fontan udenafil shows mixed results
PHILADELPHIA – In adolescents who have had a Fontan procedure for congenital heart disease, a randomized trial of the phosphodiesterase type 5 inhibitor udenafil showed that it achieved improved exercise performance but did not lead to significant improvement in oxygen levels or myocardial performance.
That’s according to results of the Pediatric Heart Network’s Fontan Udenafil Exercise Longitudinal Trial (FUEL) presented at the American Heart Association scientific sessions. “Treatment with udenafil was not associated with a statistically significant improvement in oxygen consumption at peak exercise, but it was associated with statistically significant improvements in exercise performance at the ventilatory anaerobic threshold,” said David J. Goldberg, MD, of Children’s Hospital of Philadelphia in reporting the FUEL results. The results were published simultaneously in Circulation (2019 Nov 17. doi: 10.1161/CIRCULATIONAHA.119.044352).
“This is the first large clinical trial to show improvement in measures of clinically relevant exercise performance in those with single-ventricle heart disease after Fontan palliation,” he said.
FUEL enrolled 400 male and female adolescents with a single functional ventricle after Fontan surgical palliation. In these patients, pulmonary vascular resistance (PVR) is critical for the efficient flow of blood through the lungs without the benefit of a ventricular pump. “While this circulation is typically stable through childhood, cardiovascular efficiency deteriorates over time, associated with a decline in exercise performance and the accrual of Fontan-associated morbidities,” Dr. Goldberg said. “Given the importance of pulmonary vascular resistance, modulators of PVR make sense as potential therapies.”
FUEL evaluated the effect of udenafil 87.5 mg twice daily versus placebo in post-Fontan patients who’d been on anticoagulation or antiplatelet therapy. The treatment group had a higher percentage of female patients (44% vs. 36% on placebo), but all other baseline characteristics were similar between the two groups.
While the trial found the drug was well tolerated and safe, with side effects typical of PDE5 inhibitors, it did not lead to changes in myocardial performance index, reactive hyperemia index, or log brain natriuretic peptide, Dr. Goldberg said.
At 6 months, both groups showed a decline in exercise data, “as expected,” Dr. Goldberg said. “But that decline was attenuated in the group receiving udenafil,” he said, with peak oxygen consumption declining an average of 0.23 and 0.89 mL/kg per minute in the treatment and placebo groups, respectively (P = 0.092).
Total oxygen consumption, however, actually improved in the udenafil group and declined in the placebo group, 44 mL/min on average versus –3.7 mL/min (P = 0.071).
“There was no significant difference in the change in peak heart rate or the change in peak oxygen saturation between the groups,” Dr. Goldberg said. But three measures at the ventilatory aerobic threshold (VAT) – oxygen consumption, work rate, and ventilation/carbon dioxide output – all showed statistically significant improvement in exercise performance.
“This has important clinical implications,” Dr. Goldberg said of the study findings. “Our study extends recent findings in highlighting the importance of submaximal exercise in the understanding of Fontan physiology. And unlike peak oxygen consumption, submaximal exercise is not constrained by the physiologic ceiling of central venous pressure inherent in exercise physiology after Fontan palliation.”
Maximum oxygen consumption at VAT is likely a more relevant measure after Fontan palliation than is central venous pressure, discussant Craig A. Sable, MD, a pediatric cardiologist in Potomac, Md., noted in his comments. “This is because VAT occurs at about 70% of maximum VO2 [oxygen consumption] in Fontan as opposed to 55% in two-ventricle physiology,” Dr. Sable said.
In adults with congenital heart disease, maximal VO2 of 45%-50% of predicted levels portends increased risk of heart failure and death. “Therefore, a medication that addresses the central deficiencies of Fontan physiology and results in improved exercise performance may allow for a longer period of symptom-free survival,” he said.
In an invited commentary in Circulation (2019 Nov 17. doi: 10.1161/CIRCULATIONAHA.119.044512), Marc Gewillig, MD, and Alexander van de Bruaene, MD, of University Hospitals Leuven (Belgium) said that the findings of FUEL and other trials of pulmonary vasodilators after Fontan leave “open for debate” whether the treatment effects of a 3%-5% improvement in oxygen consumption is clinically meaningful for adolescents. “For failing Fontan patients (not studied in FUEL), these improvements are minimal but maybe relevant,” the commentators wrote. But the studies do not resolve whether that’s enough to prevent further decline.
Dr. Goldberg disclosed receiving research grants from trial sponsor Mezzion Pharmaceuticals and the National Heart Lung and Blood Institute. Dr. Sable, Dr. Gewillig, and Dr. van de Bruaene have no financial relationships to disclose.
SOURCE: Goldberg D. AHA 2019, Late Breaking Science Session 5.
PHILADELPHIA – In adolescents who have had a Fontan procedure for congenital heart disease, a randomized trial of the phosphodiesterase type 5 inhibitor udenafil showed that it achieved improved exercise performance but did not lead to significant improvement in oxygen levels or myocardial performance.
That’s according to results of the Pediatric Heart Network’s Fontan Udenafil Exercise Longitudinal Trial (FUEL) presented at the American Heart Association scientific sessions. “Treatment with udenafil was not associated with a statistically significant improvement in oxygen consumption at peak exercise, but it was associated with statistically significant improvements in exercise performance at the ventilatory anaerobic threshold,” said David J. Goldberg, MD, of Children’s Hospital of Philadelphia in reporting the FUEL results. The results were published simultaneously in Circulation (2019 Nov 17. doi: 10.1161/CIRCULATIONAHA.119.044352).
“This is the first large clinical trial to show improvement in measures of clinically relevant exercise performance in those with single-ventricle heart disease after Fontan palliation,” he said.
FUEL enrolled 400 male and female adolescents with a single functional ventricle after Fontan surgical palliation. In these patients, pulmonary vascular resistance (PVR) is critical for the efficient flow of blood through the lungs without the benefit of a ventricular pump. “While this circulation is typically stable through childhood, cardiovascular efficiency deteriorates over time, associated with a decline in exercise performance and the accrual of Fontan-associated morbidities,” Dr. Goldberg said. “Given the importance of pulmonary vascular resistance, modulators of PVR make sense as potential therapies.”
FUEL evaluated the effect of udenafil 87.5 mg twice daily versus placebo in post-Fontan patients who’d been on anticoagulation or antiplatelet therapy. The treatment group had a higher percentage of female patients (44% vs. 36% on placebo), but all other baseline characteristics were similar between the two groups.
While the trial found the drug was well tolerated and safe, with side effects typical of PDE5 inhibitors, it did not lead to changes in myocardial performance index, reactive hyperemia index, or log brain natriuretic peptide, Dr. Goldberg said.
At 6 months, both groups showed a decline in exercise data, “as expected,” Dr. Goldberg said. “But that decline was attenuated in the group receiving udenafil,” he said, with peak oxygen consumption declining an average of 0.23 and 0.89 mL/kg per minute in the treatment and placebo groups, respectively (P = 0.092).
Total oxygen consumption, however, actually improved in the udenafil group and declined in the placebo group, 44 mL/min on average versus –3.7 mL/min (P = 0.071).
“There was no significant difference in the change in peak heart rate or the change in peak oxygen saturation between the groups,” Dr. Goldberg said. But three measures at the ventilatory aerobic threshold (VAT) – oxygen consumption, work rate, and ventilation/carbon dioxide output – all showed statistically significant improvement in exercise performance.
“This has important clinical implications,” Dr. Goldberg said of the study findings. “Our study extends recent findings in highlighting the importance of submaximal exercise in the understanding of Fontan physiology. And unlike peak oxygen consumption, submaximal exercise is not constrained by the physiologic ceiling of central venous pressure inherent in exercise physiology after Fontan palliation.”
Maximum oxygen consumption at VAT is likely a more relevant measure after Fontan palliation than is central venous pressure, discussant Craig A. Sable, MD, a pediatric cardiologist in Potomac, Md., noted in his comments. “This is because VAT occurs at about 70% of maximum VO2 [oxygen consumption] in Fontan as opposed to 55% in two-ventricle physiology,” Dr. Sable said.
In adults with congenital heart disease, maximal VO2 of 45%-50% of predicted levels portends increased risk of heart failure and death. “Therefore, a medication that addresses the central deficiencies of Fontan physiology and results in improved exercise performance may allow for a longer period of symptom-free survival,” he said.
In an invited commentary in Circulation (2019 Nov 17. doi: 10.1161/CIRCULATIONAHA.119.044512), Marc Gewillig, MD, and Alexander van de Bruaene, MD, of University Hospitals Leuven (Belgium) said that the findings of FUEL and other trials of pulmonary vasodilators after Fontan leave “open for debate” whether the treatment effects of a 3%-5% improvement in oxygen consumption is clinically meaningful for adolescents. “For failing Fontan patients (not studied in FUEL), these improvements are minimal but maybe relevant,” the commentators wrote. But the studies do not resolve whether that’s enough to prevent further decline.
Dr. Goldberg disclosed receiving research grants from trial sponsor Mezzion Pharmaceuticals and the National Heart Lung and Blood Institute. Dr. Sable, Dr. Gewillig, and Dr. van de Bruaene have no financial relationships to disclose.
SOURCE: Goldberg D. AHA 2019, Late Breaking Science Session 5.
PHILADELPHIA – In adolescents who have had a Fontan procedure for congenital heart disease, a randomized trial of the phosphodiesterase type 5 inhibitor udenafil showed that it achieved improved exercise performance but did not lead to significant improvement in oxygen levels or myocardial performance.
That’s according to results of the Pediatric Heart Network’s Fontan Udenafil Exercise Longitudinal Trial (FUEL) presented at the American Heart Association scientific sessions. “Treatment with udenafil was not associated with a statistically significant improvement in oxygen consumption at peak exercise, but it was associated with statistically significant improvements in exercise performance at the ventilatory anaerobic threshold,” said David J. Goldberg, MD, of Children’s Hospital of Philadelphia in reporting the FUEL results. The results were published simultaneously in Circulation (2019 Nov 17. doi: 10.1161/CIRCULATIONAHA.119.044352).
“This is the first large clinical trial to show improvement in measures of clinically relevant exercise performance in those with single-ventricle heart disease after Fontan palliation,” he said.
FUEL enrolled 400 male and female adolescents with a single functional ventricle after Fontan surgical palliation. In these patients, pulmonary vascular resistance (PVR) is critical for the efficient flow of blood through the lungs without the benefit of a ventricular pump. “While this circulation is typically stable through childhood, cardiovascular efficiency deteriorates over time, associated with a decline in exercise performance and the accrual of Fontan-associated morbidities,” Dr. Goldberg said. “Given the importance of pulmonary vascular resistance, modulators of PVR make sense as potential therapies.”
FUEL evaluated the effect of udenafil 87.5 mg twice daily versus placebo in post-Fontan patients who’d been on anticoagulation or antiplatelet therapy. The treatment group had a higher percentage of female patients (44% vs. 36% on placebo), but all other baseline characteristics were similar between the two groups.
While the trial found the drug was well tolerated and safe, with side effects typical of PDE5 inhibitors, it did not lead to changes in myocardial performance index, reactive hyperemia index, or log brain natriuretic peptide, Dr. Goldberg said.
At 6 months, both groups showed a decline in exercise data, “as expected,” Dr. Goldberg said. “But that decline was attenuated in the group receiving udenafil,” he said, with peak oxygen consumption declining an average of 0.23 and 0.89 mL/kg per minute in the treatment and placebo groups, respectively (P = 0.092).
Total oxygen consumption, however, actually improved in the udenafil group and declined in the placebo group, 44 mL/min on average versus –3.7 mL/min (P = 0.071).
“There was no significant difference in the change in peak heart rate or the change in peak oxygen saturation between the groups,” Dr. Goldberg said. But three measures at the ventilatory aerobic threshold (VAT) – oxygen consumption, work rate, and ventilation/carbon dioxide output – all showed statistically significant improvement in exercise performance.
“This has important clinical implications,” Dr. Goldberg said of the study findings. “Our study extends recent findings in highlighting the importance of submaximal exercise in the understanding of Fontan physiology. And unlike peak oxygen consumption, submaximal exercise is not constrained by the physiologic ceiling of central venous pressure inherent in exercise physiology after Fontan palliation.”
Maximum oxygen consumption at VAT is likely a more relevant measure after Fontan palliation than is central venous pressure, discussant Craig A. Sable, MD, a pediatric cardiologist in Potomac, Md., noted in his comments. “This is because VAT occurs at about 70% of maximum VO2 [oxygen consumption] in Fontan as opposed to 55% in two-ventricle physiology,” Dr. Sable said.
In adults with congenital heart disease, maximal VO2 of 45%-50% of predicted levels portends increased risk of heart failure and death. “Therefore, a medication that addresses the central deficiencies of Fontan physiology and results in improved exercise performance may allow for a longer period of symptom-free survival,” he said.
In an invited commentary in Circulation (2019 Nov 17. doi: 10.1161/CIRCULATIONAHA.119.044512), Marc Gewillig, MD, and Alexander van de Bruaene, MD, of University Hospitals Leuven (Belgium) said that the findings of FUEL and other trials of pulmonary vasodilators after Fontan leave “open for debate” whether the treatment effects of a 3%-5% improvement in oxygen consumption is clinically meaningful for adolescents. “For failing Fontan patients (not studied in FUEL), these improvements are minimal but maybe relevant,” the commentators wrote. But the studies do not resolve whether that’s enough to prevent further decline.
Dr. Goldberg disclosed receiving research grants from trial sponsor Mezzion Pharmaceuticals and the National Heart Lung and Blood Institute. Dr. Sable, Dr. Gewillig, and Dr. van de Bruaene have no financial relationships to disclose.
SOURCE: Goldberg D. AHA 2019, Late Breaking Science Session 5.
REPORTING FROM AHA 2019
PACT-HF: Transitional care derives no overall benefit
Women respond more to intervention
PHILADELPHIA – A clinical trial of a program that transitions heart failure patients after they’re discharged from the hospital didn’t result in any appreciable improvement in all-cause death, readmissions or emergency department visits after 6 months overall, but it did show that women responded more favorably than men.
Harriette G.C. Van Spall, MD, MPH, reported 6-month results of the Patient-Centered Transitional Care Services in Heart Failure (PACT-HF) trial of 2,494 HF patients at 10 hospitals in Ontario during February 2015 to March 2016. They were randomized to the care-transition program or usual care. The findings, she said at the American Heart Association scientific sessions, “highlight the gap between efficacy that’s often demonstrated in mechanistic clinical trials and effectiveness when we aim to implement these results in real-world settings.” Three-month PACT-HF results were reported previously (JAMA. 2019 Feb 26;321:753-61).
The transitional-care model consisted of a comprehensive needs assessment by a nurse who also provided self-care education, a patient-centered discharge summary, and follow-up with a family physician within 7 days of discharge, which Dr. Van Spall noted “is not current practice in our health care system.”
Patients deemed high risk for readmission or death also received nurse home visits and scheduled visits to a multidisciplinary heart function clinic within 2-4 weeks of discharge and continuing as long as clinically suitable, said Dr. Van Spall, a principal investigator at the Population Health Research Institute, Hamilton, Ont., and assistant professor in cardiology at McMaster University in Hamilton.
The trial found no difference between the intervention and usual-care groups in the two composite endpoints at 6 months, Dr. Van Spall said: all-cause death, readmissions, or ED visits (63.1% and 64.5%, respectively; P = .50); or all-cause readmissions or ED visits (60.8% and 62.4%; P = .36).
“Despite the mutual overall clinical outcomes, we noted specific differences in response to treatment,” she said. With regard to the composite endpoint that included all-cause death, “Men had an attenuated response to the treatment with a hazard ratio of 1.05 (95% confidence interval, 0.87-1.26), whereas women had a hazard ratio of 0.85 (95% CI, 0.71-1.03), demonstrating that women have more of a treatment response to this health care service,” she said.
In men, rates for the first primary composite outcome were 66.3% and 64.1% in the intervention and usual-care groups, whereas in women those rates were 59.9% and 64.8% (P = .04 for sex interaction).
In the second composite endpoint, all-cause readmission or ED visit, “again, men had an attenuated response” with a HR of 1.03, whereas women had a HR of 0.83. Results were similar to those for the first primary composite outcome: 63.4% and 61.7% for intervention and usual care in men and 57.7% and 63% in women (P = .03 for sex interaction).
In putting the findings into context, Dr. Van Spall said tailoring services to risk in HF patients may be fraught with pitfalls. “We delivered intensive services to those patients at high risk of readmission or death, but it is quite possible they are the least likely to derive benefit by virtue of their advanced heart failure,” she said. “It may be that more benefit would have been derived had we chosen low- or moderate-risk patients to receive the intervention.”
She also said the sex-specific outcomes must be interpreted with caution. “But they do give us pause to consider that services could be titrated more effectively if delivered to patients who are more likely to derive benefit,” Dr. Van Spall said. The finding that women derived more of a benefit is in line with other prospective and observational studies that have found that women have a higher sense of self-care, self-efficacy, and confidence in managing their own health care needs than men.
Dr. Van Spall has no financial relationships to disclose.
Women respond more to intervention
Women respond more to intervention
PHILADELPHIA – A clinical trial of a program that transitions heart failure patients after they’re discharged from the hospital didn’t result in any appreciable improvement in all-cause death, readmissions or emergency department visits after 6 months overall, but it did show that women responded more favorably than men.
Harriette G.C. Van Spall, MD, MPH, reported 6-month results of the Patient-Centered Transitional Care Services in Heart Failure (PACT-HF) trial of 2,494 HF patients at 10 hospitals in Ontario during February 2015 to March 2016. They were randomized to the care-transition program or usual care. The findings, she said at the American Heart Association scientific sessions, “highlight the gap between efficacy that’s often demonstrated in mechanistic clinical trials and effectiveness when we aim to implement these results in real-world settings.” Three-month PACT-HF results were reported previously (JAMA. 2019 Feb 26;321:753-61).
The transitional-care model consisted of a comprehensive needs assessment by a nurse who also provided self-care education, a patient-centered discharge summary, and follow-up with a family physician within 7 days of discharge, which Dr. Van Spall noted “is not current practice in our health care system.”
Patients deemed high risk for readmission or death also received nurse home visits and scheduled visits to a multidisciplinary heart function clinic within 2-4 weeks of discharge and continuing as long as clinically suitable, said Dr. Van Spall, a principal investigator at the Population Health Research Institute, Hamilton, Ont., and assistant professor in cardiology at McMaster University in Hamilton.
The trial found no difference between the intervention and usual-care groups in the two composite endpoints at 6 months, Dr. Van Spall said: all-cause death, readmissions, or ED visits (63.1% and 64.5%, respectively; P = .50); or all-cause readmissions or ED visits (60.8% and 62.4%; P = .36).
“Despite the mutual overall clinical outcomes, we noted specific differences in response to treatment,” she said. With regard to the composite endpoint that included all-cause death, “Men had an attenuated response to the treatment with a hazard ratio of 1.05 (95% confidence interval, 0.87-1.26), whereas women had a hazard ratio of 0.85 (95% CI, 0.71-1.03), demonstrating that women have more of a treatment response to this health care service,” she said.
In men, rates for the first primary composite outcome were 66.3% and 64.1% in the intervention and usual-care groups, whereas in women those rates were 59.9% and 64.8% (P = .04 for sex interaction).
In the second composite endpoint, all-cause readmission or ED visit, “again, men had an attenuated response” with a HR of 1.03, whereas women had a HR of 0.83. Results were similar to those for the first primary composite outcome: 63.4% and 61.7% for intervention and usual care in men and 57.7% and 63% in women (P = .03 for sex interaction).
In putting the findings into context, Dr. Van Spall said tailoring services to risk in HF patients may be fraught with pitfalls. “We delivered intensive services to those patients at high risk of readmission or death, but it is quite possible they are the least likely to derive benefit by virtue of their advanced heart failure,” she said. “It may be that more benefit would have been derived had we chosen low- or moderate-risk patients to receive the intervention.”
She also said the sex-specific outcomes must be interpreted with caution. “But they do give us pause to consider that services could be titrated more effectively if delivered to patients who are more likely to derive benefit,” Dr. Van Spall said. The finding that women derived more of a benefit is in line with other prospective and observational studies that have found that women have a higher sense of self-care, self-efficacy, and confidence in managing their own health care needs than men.
Dr. Van Spall has no financial relationships to disclose.
PHILADELPHIA – A clinical trial of a program that transitions heart failure patients after they’re discharged from the hospital didn’t result in any appreciable improvement in all-cause death, readmissions or emergency department visits after 6 months overall, but it did show that women responded more favorably than men.
Harriette G.C. Van Spall, MD, MPH, reported 6-month results of the Patient-Centered Transitional Care Services in Heart Failure (PACT-HF) trial of 2,494 HF patients at 10 hospitals in Ontario during February 2015 to March 2016. They were randomized to the care-transition program or usual care. The findings, she said at the American Heart Association scientific sessions, “highlight the gap between efficacy that’s often demonstrated in mechanistic clinical trials and effectiveness when we aim to implement these results in real-world settings.” Three-month PACT-HF results were reported previously (JAMA. 2019 Feb 26;321:753-61).
The transitional-care model consisted of a comprehensive needs assessment by a nurse who also provided self-care education, a patient-centered discharge summary, and follow-up with a family physician within 7 days of discharge, which Dr. Van Spall noted “is not current practice in our health care system.”
Patients deemed high risk for readmission or death also received nurse home visits and scheduled visits to a multidisciplinary heart function clinic within 2-4 weeks of discharge and continuing as long as clinically suitable, said Dr. Van Spall, a principal investigator at the Population Health Research Institute, Hamilton, Ont., and assistant professor in cardiology at McMaster University in Hamilton.
The trial found no difference between the intervention and usual-care groups in the two composite endpoints at 6 months, Dr. Van Spall said: all-cause death, readmissions, or ED visits (63.1% and 64.5%, respectively; P = .50); or all-cause readmissions or ED visits (60.8% and 62.4%; P = .36).
“Despite the mutual overall clinical outcomes, we noted specific differences in response to treatment,” she said. With regard to the composite endpoint that included all-cause death, “Men had an attenuated response to the treatment with a hazard ratio of 1.05 (95% confidence interval, 0.87-1.26), whereas women had a hazard ratio of 0.85 (95% CI, 0.71-1.03), demonstrating that women have more of a treatment response to this health care service,” she said.
In men, rates for the first primary composite outcome were 66.3% and 64.1% in the intervention and usual-care groups, whereas in women those rates were 59.9% and 64.8% (P = .04 for sex interaction).
In the second composite endpoint, all-cause readmission or ED visit, “again, men had an attenuated response” with a HR of 1.03, whereas women had a HR of 0.83. Results were similar to those for the first primary composite outcome: 63.4% and 61.7% for intervention and usual care in men and 57.7% and 63% in women (P = .03 for sex interaction).
In putting the findings into context, Dr. Van Spall said tailoring services to risk in HF patients may be fraught with pitfalls. “We delivered intensive services to those patients at high risk of readmission or death, but it is quite possible they are the least likely to derive benefit by virtue of their advanced heart failure,” she said. “It may be that more benefit would have been derived had we chosen low- or moderate-risk patients to receive the intervention.”
She also said the sex-specific outcomes must be interpreted with caution. “But they do give us pause to consider that services could be titrated more effectively if delivered to patients who are more likely to derive benefit,” Dr. Van Spall said. The finding that women derived more of a benefit is in line with other prospective and observational studies that have found that women have a higher sense of self-care, self-efficacy, and confidence in managing their own health care needs than men.
Dr. Van Spall has no financial relationships to disclose.
REPORTING FROM AHA 2019
HRS urges consumers to direct questions about wearables’ data to clinicians
With much of the public now wearing devices on their wrists or elsewhere capable of recording a range of vital signs, including heart rate abnormalities, the Heart Rhythm Society launched a guide for American consumers about wearables and the data they collect during a session on Jan. 9 at CES 2020 in Las Vegas.
While providing a succinct but comprehensive overview of the types of wearables and the health metrics they can record, the main and recurring message of the 10-page e-pamphlet is that, when a layperson has a question or concern about their data, the best course is to consult a clinician.
The “Guidance for Wearable Health Solutions,” produced by the Heart Rhythm Society (HRS) along with the Consumer Technology Association (CTA, which presents the annual CES exhibition), cautions that “most wearables are primarily suited for fitness and wellness,” and stresses that wearables “are not a substitute for medical devices prescribed by a clinician.” And in all cases, the document advises, when questions arise about the data – including an apparently high heart rate; a reading the device identifies as abnormal; and when symptoms appear such as a rapid heart rate, dizziness, or fluttering or flopping of the heart – the response that the guidance advocates is consistent: Talk with your clinician.
“Heart Rhythm Society members are seeing more and more patients with their own data collected by wearables,” said Nassir F. Marrouche, MD, professor of medicine and director of electrophysiology at Tulane University, New Orleans, and a member of the panel that wrote the guidance document for the HRS and CTA. “Every provider is dealing with consumer wearable data. The need is important for consumers to be supported. Consumers and patients are buying over-the-counter devices and using them for diagnosis and management, with little to no guidance, and we want to help them feel supported in managing their data and understand what to do with it,” Dr. Marrouche said in an interview.
“This is a new reality in medicine; the direction of information is changing. Consumers are collecting data themselves and coming to physicians already informed. There is a new shift in how information is collected, shared, and used.” Dr. Marrouche was 1 of 5 cardiac electrophysiologists who served on the 11-member writing group.
The new document for consumers “addresses an unmet need,” and the HRS collaboration with the CTA was “a unique opportunity to develop useful guidance that supports education and empowers consumers,” said Christina Wurster, chief strategy officer for the HRS in Washington and a member of the writing panel. “The questions outlined in the document are questions our members receive daily. The document is a resource they can direct people to.”
The HRS and CTA will “partner with consumer advocacy groups and professional societies to further disseminate the document,” added Ms. Wurster. “We’ll also have a strong push on social media to reach consumer audiences and drive awareness of this new resource,” she said in an interview. In addition, HRS “has strategic partnerships with other societies and will aim to work with them for dissemination, including societies related to internal medicine, emergency medicine, cardiology, and nursing, as well as also working with patient and consumer advocacy groups to reach the public.” The CTA will also actively publicize and disseminate the guidance document through their members.
Clinical guidelines play catch-up
Ironically, the HRS has issued this guidance to the public and has told people to take their wearable-collected heart data to clinicians before the HRS or any other medical group has advised clinicians on how they should handle, interpret, and use heart rhythm data collected this way.
Presumably, many if not most of the people with questions about their heart data from wearables are asymptomatic, because symptoms are what usually drive patients with a cardiac arrhythmia to consult a physician – they don’t wait to see what their device tells them. But the best way to manage asymptomatic arrhythmias like atrial fibrillation (AFib) remains a big clinical uncertainty today, with no evidence base as a guide, although several studies exploring this question are in progress.
“There are no clear and definitive data showing that treating subclinical atrial fibrillation improves outcomes. That’s what we need, and until we get these data you won’t see strong recommendations in guidelines” to screen patients for asymptomatic AFib or other arrhythmias, said Sana M. Al-Khatib, MD, a cardiac electrophysiologist and professor of medicine at Duke University, Durham, N.C., during the 2019 American Heart Association scientific sessions in Philadelphia in a talk about wearables and guidelines.
“If you intervene with silent AFib, do you improve outcomes? That evidence is lacking,” she said. Another shortcoming of current evidence is a clear understanding of what AFib burden warrants intervention, added Dr. Al-Khatib. “We see high-rate AFib episodes recorded in patients with implanted cardiac devices [and no symptoms], and we don’t know what to do with that either.”
The closest any existing guideline from a medical society comes to currently endorsing screening for AFib by a wearable is the 2016 European Society of Cardiology’s AFib management guidelines, which give “opportunistic screening” among people aged older than 65 years a IB recommendation, but specifically for screening by taking a patient’s pulse or with a ECG recording, with no mention of the screening role for wearables (Eur Heart J. 2016 Oct 7;37[38]:2893-967), Dr. Al-Khatib noted.
The most extensive data on screening for asymptomatic AFib in an unselected population came in the recently reported results from the Apple Heart Study, which enrolled more than 419,000 people monitored by a smart watch for a median of 117 days. During this screening, 2,161 people (0.52%) received a notification of having an irregular pulse (including 3.1% of those who were aged at least 65 years), which triggered more intensive assessment with an ECG patch for a median of 13 days in 450 of the 2,161 screening positives (21%) who agreed to participate in this follow-up. Among those 450 people, the patch test identified 34% as having actual AFib (N Engl J Med. 2019 Nov 14;381[20]:1909-17). But while this study provided evidence that screening for an irregular heartbeat with a wearable can identify AFib with some level of success, the results did not address whether this approach improved short- or long-term patient outcomes.
In addition, what the Apple Heart Study results showed was that this sort of screening results in a relatively large volume of follow-up testing. Of the 2,161 participants who received an irregular pulse notification, 1,376 (64%) returned a 90-day survey. Of these, 787 (57%) reported contact with a health care provider outside the study, 28% were prescribed a new medication, 33% were recommended to see a specialist (such as a cardiologist), and 36% were recommended to have additional testing.
“The results raise the question that a lot of resources were used,” to assess patients with a positive screening result, noted Paul A. Heidenreich, MD, a cardiologist and professor of medicine at Stanford (Calif.) University who studies quality of care for patients with heart disease. He estimated that, in the Apple Heart Study, each of the more than 2,000 patients who screening positive for an irregular heartbeat and underwent subsequent assessment ran up about $700 worth of follow-up testing. But he added that, in the case of AFib, the primary intervention that many previously undiagnosed AFib patients receive is some sort of anticoagulation for stroke prevention. Moreover, because this intervention is so effective there is a lot of money to play with to make AFib screening cost effective, as judged by typical, contemporary metrics of cost efficacy that value a quality-adjusted life-year (QALY) gain as reasonable for society to pay if the cost of an incremental QALY is $50,000-$150,000.
If the benchmark is a cost that’s within $50,000/QALY, then an average follow-up cost of $116/person to assess screened positives can fall within this cost ceiling. If the benchmark is $150,000/QALY, then follow-up costs can run as high as $491/person screened, said Dr. Heidenreich during the same AHA session where Dr. Al-Khatib spoke last November.
Despite this good news for screening for AFib with a wearable from a cost-effectiveness perspective, “there is so much uncertainty regarding the benefit and the consequences of incidental findings that we need an outcomes study before widespread implementation” of this type of screening, Dr. Heidenreich concluded. “We need an outcomes study to feel comfortable” with screening. “There is a huge potential for extra care that we don’t understand.”
Dr. Marrouche agreed that collecting adequate evidence to drive changes in clinical guidelines on how to use data from wearables has lagged behind the rapid spread of wearables and the information they can produce among the American public. “Outcomes and evidence will support guidelines development, but in the meantime, we’re offering education to clinicians, patients, and consumers. Consumers own their data, and they can share them with whomever they choose.”
The document notes that people who use wearables are, in general, “enthusiastic about tracking their data, not only for their own use, but also to share” with others, often on social media websites.
“We cannot control that, but our goal in the document is focused on the clinical relevance [of the data] and to help people better understand their data and use it in a meaningful and safe way,” Dr. Marrouche said.
Dr. Marrouche has been a consultant to, advisor to, or received research support from Abbott, Biosense Webster, Biotronik, GE Healthcare, Medtronic, Preventice, Sanofi-Aventis, Siemens, and Vytronus. Ms. Wurster is an employee of the Heart Rhythm Society. Dr. Al-Khatib has been a consultant to Milestone Pharmaceuticals and Medtronic, and she has also received other financial benefits from Medtronic. Dr. Heidenreich had no disclosures,
With much of the public now wearing devices on their wrists or elsewhere capable of recording a range of vital signs, including heart rate abnormalities, the Heart Rhythm Society launched a guide for American consumers about wearables and the data they collect during a session on Jan. 9 at CES 2020 in Las Vegas.
While providing a succinct but comprehensive overview of the types of wearables and the health metrics they can record, the main and recurring message of the 10-page e-pamphlet is that, when a layperson has a question or concern about their data, the best course is to consult a clinician.
The “Guidance for Wearable Health Solutions,” produced by the Heart Rhythm Society (HRS) along with the Consumer Technology Association (CTA, which presents the annual CES exhibition), cautions that “most wearables are primarily suited for fitness and wellness,” and stresses that wearables “are not a substitute for medical devices prescribed by a clinician.” And in all cases, the document advises, when questions arise about the data – including an apparently high heart rate; a reading the device identifies as abnormal; and when symptoms appear such as a rapid heart rate, dizziness, or fluttering or flopping of the heart – the response that the guidance advocates is consistent: Talk with your clinician.
“Heart Rhythm Society members are seeing more and more patients with their own data collected by wearables,” said Nassir F. Marrouche, MD, professor of medicine and director of electrophysiology at Tulane University, New Orleans, and a member of the panel that wrote the guidance document for the HRS and CTA. “Every provider is dealing with consumer wearable data. The need is important for consumers to be supported. Consumers and patients are buying over-the-counter devices and using them for diagnosis and management, with little to no guidance, and we want to help them feel supported in managing their data and understand what to do with it,” Dr. Marrouche said in an interview.
“This is a new reality in medicine; the direction of information is changing. Consumers are collecting data themselves and coming to physicians already informed. There is a new shift in how information is collected, shared, and used.” Dr. Marrouche was 1 of 5 cardiac electrophysiologists who served on the 11-member writing group.
The new document for consumers “addresses an unmet need,” and the HRS collaboration with the CTA was “a unique opportunity to develop useful guidance that supports education and empowers consumers,” said Christina Wurster, chief strategy officer for the HRS in Washington and a member of the writing panel. “The questions outlined in the document are questions our members receive daily. The document is a resource they can direct people to.”
The HRS and CTA will “partner with consumer advocacy groups and professional societies to further disseminate the document,” added Ms. Wurster. “We’ll also have a strong push on social media to reach consumer audiences and drive awareness of this new resource,” she said in an interview. In addition, HRS “has strategic partnerships with other societies and will aim to work with them for dissemination, including societies related to internal medicine, emergency medicine, cardiology, and nursing, as well as also working with patient and consumer advocacy groups to reach the public.” The CTA will also actively publicize and disseminate the guidance document through their members.
Clinical guidelines play catch-up
Ironically, the HRS has issued this guidance to the public and has told people to take their wearable-collected heart data to clinicians before the HRS or any other medical group has advised clinicians on how they should handle, interpret, and use heart rhythm data collected this way.
Presumably, many if not most of the people with questions about their heart data from wearables are asymptomatic, because symptoms are what usually drive patients with a cardiac arrhythmia to consult a physician – they don’t wait to see what their device tells them. But the best way to manage asymptomatic arrhythmias like atrial fibrillation (AFib) remains a big clinical uncertainty today, with no evidence base as a guide, although several studies exploring this question are in progress.
“There are no clear and definitive data showing that treating subclinical atrial fibrillation improves outcomes. That’s what we need, and until we get these data you won’t see strong recommendations in guidelines” to screen patients for asymptomatic AFib or other arrhythmias, said Sana M. Al-Khatib, MD, a cardiac electrophysiologist and professor of medicine at Duke University, Durham, N.C., during the 2019 American Heart Association scientific sessions in Philadelphia in a talk about wearables and guidelines.
“If you intervene with silent AFib, do you improve outcomes? That evidence is lacking,” she said. Another shortcoming of current evidence is a clear understanding of what AFib burden warrants intervention, added Dr. Al-Khatib. “We see high-rate AFib episodes recorded in patients with implanted cardiac devices [and no symptoms], and we don’t know what to do with that either.”
The closest any existing guideline from a medical society comes to currently endorsing screening for AFib by a wearable is the 2016 European Society of Cardiology’s AFib management guidelines, which give “opportunistic screening” among people aged older than 65 years a IB recommendation, but specifically for screening by taking a patient’s pulse or with a ECG recording, with no mention of the screening role for wearables (Eur Heart J. 2016 Oct 7;37[38]:2893-967), Dr. Al-Khatib noted.
The most extensive data on screening for asymptomatic AFib in an unselected population came in the recently reported results from the Apple Heart Study, which enrolled more than 419,000 people monitored by a smart watch for a median of 117 days. During this screening, 2,161 people (0.52%) received a notification of having an irregular pulse (including 3.1% of those who were aged at least 65 years), which triggered more intensive assessment with an ECG patch for a median of 13 days in 450 of the 2,161 screening positives (21%) who agreed to participate in this follow-up. Among those 450 people, the patch test identified 34% as having actual AFib (N Engl J Med. 2019 Nov 14;381[20]:1909-17). But while this study provided evidence that screening for an irregular heartbeat with a wearable can identify AFib with some level of success, the results did not address whether this approach improved short- or long-term patient outcomes.
In addition, what the Apple Heart Study results showed was that this sort of screening results in a relatively large volume of follow-up testing. Of the 2,161 participants who received an irregular pulse notification, 1,376 (64%) returned a 90-day survey. Of these, 787 (57%) reported contact with a health care provider outside the study, 28% were prescribed a new medication, 33% were recommended to see a specialist (such as a cardiologist), and 36% were recommended to have additional testing.
“The results raise the question that a lot of resources were used,” to assess patients with a positive screening result, noted Paul A. Heidenreich, MD, a cardiologist and professor of medicine at Stanford (Calif.) University who studies quality of care for patients with heart disease. He estimated that, in the Apple Heart Study, each of the more than 2,000 patients who screening positive for an irregular heartbeat and underwent subsequent assessment ran up about $700 worth of follow-up testing. But he added that, in the case of AFib, the primary intervention that many previously undiagnosed AFib patients receive is some sort of anticoagulation for stroke prevention. Moreover, because this intervention is so effective there is a lot of money to play with to make AFib screening cost effective, as judged by typical, contemporary metrics of cost efficacy that value a quality-adjusted life-year (QALY) gain as reasonable for society to pay if the cost of an incremental QALY is $50,000-$150,000.
If the benchmark is a cost that’s within $50,000/QALY, then an average follow-up cost of $116/person to assess screened positives can fall within this cost ceiling. If the benchmark is $150,000/QALY, then follow-up costs can run as high as $491/person screened, said Dr. Heidenreich during the same AHA session where Dr. Al-Khatib spoke last November.
Despite this good news for screening for AFib with a wearable from a cost-effectiveness perspective, “there is so much uncertainty regarding the benefit and the consequences of incidental findings that we need an outcomes study before widespread implementation” of this type of screening, Dr. Heidenreich concluded. “We need an outcomes study to feel comfortable” with screening. “There is a huge potential for extra care that we don’t understand.”
Dr. Marrouche agreed that collecting adequate evidence to drive changes in clinical guidelines on how to use data from wearables has lagged behind the rapid spread of wearables and the information they can produce among the American public. “Outcomes and evidence will support guidelines development, but in the meantime, we’re offering education to clinicians, patients, and consumers. Consumers own their data, and they can share them with whomever they choose.”
The document notes that people who use wearables are, in general, “enthusiastic about tracking their data, not only for their own use, but also to share” with others, often on social media websites.
“We cannot control that, but our goal in the document is focused on the clinical relevance [of the data] and to help people better understand their data and use it in a meaningful and safe way,” Dr. Marrouche said.
Dr. Marrouche has been a consultant to, advisor to, or received research support from Abbott, Biosense Webster, Biotronik, GE Healthcare, Medtronic, Preventice, Sanofi-Aventis, Siemens, and Vytronus. Ms. Wurster is an employee of the Heart Rhythm Society. Dr. Al-Khatib has been a consultant to Milestone Pharmaceuticals and Medtronic, and she has also received other financial benefits from Medtronic. Dr. Heidenreich had no disclosures,
With much of the public now wearing devices on their wrists or elsewhere capable of recording a range of vital signs, including heart rate abnormalities, the Heart Rhythm Society launched a guide for American consumers about wearables and the data they collect during a session on Jan. 9 at CES 2020 in Las Vegas.
While providing a succinct but comprehensive overview of the types of wearables and the health metrics they can record, the main and recurring message of the 10-page e-pamphlet is that, when a layperson has a question or concern about their data, the best course is to consult a clinician.
The “Guidance for Wearable Health Solutions,” produced by the Heart Rhythm Society (HRS) along with the Consumer Technology Association (CTA, which presents the annual CES exhibition), cautions that “most wearables are primarily suited for fitness and wellness,” and stresses that wearables “are not a substitute for medical devices prescribed by a clinician.” And in all cases, the document advises, when questions arise about the data – including an apparently high heart rate; a reading the device identifies as abnormal; and when symptoms appear such as a rapid heart rate, dizziness, or fluttering or flopping of the heart – the response that the guidance advocates is consistent: Talk with your clinician.
“Heart Rhythm Society members are seeing more and more patients with their own data collected by wearables,” said Nassir F. Marrouche, MD, professor of medicine and director of electrophysiology at Tulane University, New Orleans, and a member of the panel that wrote the guidance document for the HRS and CTA. “Every provider is dealing with consumer wearable data. The need is important for consumers to be supported. Consumers and patients are buying over-the-counter devices and using them for diagnosis and management, with little to no guidance, and we want to help them feel supported in managing their data and understand what to do with it,” Dr. Marrouche said in an interview.
“This is a new reality in medicine; the direction of information is changing. Consumers are collecting data themselves and coming to physicians already informed. There is a new shift in how information is collected, shared, and used.” Dr. Marrouche was 1 of 5 cardiac electrophysiologists who served on the 11-member writing group.
The new document for consumers “addresses an unmet need,” and the HRS collaboration with the CTA was “a unique opportunity to develop useful guidance that supports education and empowers consumers,” said Christina Wurster, chief strategy officer for the HRS in Washington and a member of the writing panel. “The questions outlined in the document are questions our members receive daily. The document is a resource they can direct people to.”
The HRS and CTA will “partner with consumer advocacy groups and professional societies to further disseminate the document,” added Ms. Wurster. “We’ll also have a strong push on social media to reach consumer audiences and drive awareness of this new resource,” she said in an interview. In addition, HRS “has strategic partnerships with other societies and will aim to work with them for dissemination, including societies related to internal medicine, emergency medicine, cardiology, and nursing, as well as also working with patient and consumer advocacy groups to reach the public.” The CTA will also actively publicize and disseminate the guidance document through their members.
Clinical guidelines play catch-up
Ironically, the HRS has issued this guidance to the public and has told people to take their wearable-collected heart data to clinicians before the HRS or any other medical group has advised clinicians on how they should handle, interpret, and use heart rhythm data collected this way.
Presumably, many if not most of the people with questions about their heart data from wearables are asymptomatic, because symptoms are what usually drive patients with a cardiac arrhythmia to consult a physician – they don’t wait to see what their device tells them. But the best way to manage asymptomatic arrhythmias like atrial fibrillation (AFib) remains a big clinical uncertainty today, with no evidence base as a guide, although several studies exploring this question are in progress.
“There are no clear and definitive data showing that treating subclinical atrial fibrillation improves outcomes. That’s what we need, and until we get these data you won’t see strong recommendations in guidelines” to screen patients for asymptomatic AFib or other arrhythmias, said Sana M. Al-Khatib, MD, a cardiac electrophysiologist and professor of medicine at Duke University, Durham, N.C., during the 2019 American Heart Association scientific sessions in Philadelphia in a talk about wearables and guidelines.
“If you intervene with silent AFib, do you improve outcomes? That evidence is lacking,” she said. Another shortcoming of current evidence is a clear understanding of what AFib burden warrants intervention, added Dr. Al-Khatib. “We see high-rate AFib episodes recorded in patients with implanted cardiac devices [and no symptoms], and we don’t know what to do with that either.”
The closest any existing guideline from a medical society comes to currently endorsing screening for AFib by a wearable is the 2016 European Society of Cardiology’s AFib management guidelines, which give “opportunistic screening” among people aged older than 65 years a IB recommendation, but specifically for screening by taking a patient’s pulse or with a ECG recording, with no mention of the screening role for wearables (Eur Heart J. 2016 Oct 7;37[38]:2893-967), Dr. Al-Khatib noted.
The most extensive data on screening for asymptomatic AFib in an unselected population came in the recently reported results from the Apple Heart Study, which enrolled more than 419,000 people monitored by a smart watch for a median of 117 days. During this screening, 2,161 people (0.52%) received a notification of having an irregular pulse (including 3.1% of those who were aged at least 65 years), which triggered more intensive assessment with an ECG patch for a median of 13 days in 450 of the 2,161 screening positives (21%) who agreed to participate in this follow-up. Among those 450 people, the patch test identified 34% as having actual AFib (N Engl J Med. 2019 Nov 14;381[20]:1909-17). But while this study provided evidence that screening for an irregular heartbeat with a wearable can identify AFib with some level of success, the results did not address whether this approach improved short- or long-term patient outcomes.
In addition, what the Apple Heart Study results showed was that this sort of screening results in a relatively large volume of follow-up testing. Of the 2,161 participants who received an irregular pulse notification, 1,376 (64%) returned a 90-day survey. Of these, 787 (57%) reported contact with a health care provider outside the study, 28% were prescribed a new medication, 33% were recommended to see a specialist (such as a cardiologist), and 36% were recommended to have additional testing.
“The results raise the question that a lot of resources were used,” to assess patients with a positive screening result, noted Paul A. Heidenreich, MD, a cardiologist and professor of medicine at Stanford (Calif.) University who studies quality of care for patients with heart disease. He estimated that, in the Apple Heart Study, each of the more than 2,000 patients who screening positive for an irregular heartbeat and underwent subsequent assessment ran up about $700 worth of follow-up testing. But he added that, in the case of AFib, the primary intervention that many previously undiagnosed AFib patients receive is some sort of anticoagulation for stroke prevention. Moreover, because this intervention is so effective there is a lot of money to play with to make AFib screening cost effective, as judged by typical, contemporary metrics of cost efficacy that value a quality-adjusted life-year (QALY) gain as reasonable for society to pay if the cost of an incremental QALY is $50,000-$150,000.
If the benchmark is a cost that’s within $50,000/QALY, then an average follow-up cost of $116/person to assess screened positives can fall within this cost ceiling. If the benchmark is $150,000/QALY, then follow-up costs can run as high as $491/person screened, said Dr. Heidenreich during the same AHA session where Dr. Al-Khatib spoke last November.
Despite this good news for screening for AFib with a wearable from a cost-effectiveness perspective, “there is so much uncertainty regarding the benefit and the consequences of incidental findings that we need an outcomes study before widespread implementation” of this type of screening, Dr. Heidenreich concluded. “We need an outcomes study to feel comfortable” with screening. “There is a huge potential for extra care that we don’t understand.”
Dr. Marrouche agreed that collecting adequate evidence to drive changes in clinical guidelines on how to use data from wearables has lagged behind the rapid spread of wearables and the information they can produce among the American public. “Outcomes and evidence will support guidelines development, but in the meantime, we’re offering education to clinicians, patients, and consumers. Consumers own their data, and they can share them with whomever they choose.”
The document notes that people who use wearables are, in general, “enthusiastic about tracking their data, not only for their own use, but also to share” with others, often on social media websites.
“We cannot control that, but our goal in the document is focused on the clinical relevance [of the data] and to help people better understand their data and use it in a meaningful and safe way,” Dr. Marrouche said.
Dr. Marrouche has been a consultant to, advisor to, or received research support from Abbott, Biosense Webster, Biotronik, GE Healthcare, Medtronic, Preventice, Sanofi-Aventis, Siemens, and Vytronus. Ms. Wurster is an employee of the Heart Rhythm Society. Dr. Al-Khatib has been a consultant to Milestone Pharmaceuticals and Medtronic, and she has also received other financial benefits from Medtronic. Dr. Heidenreich had no disclosures,