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Prognostic Value of Heart Rate Recovery in Patients with Heart Failure
The 9th Annual Scientific Meeting
•
HFSA
S171
303
305
Prognostic Value of Heart Rate Recovery in Patients with Heart Failure Ross Arena1, Jonathan Myers2, Marco Guazzi3, Mary Ann Peberdy1, Joshua Abella2; 1Physical Therapy and Physiology, Virginia Commonwealth University, Richmond, VA; 2Cardiology, Palo Alto Veterans Affairs Health Care System, Palo Alto, CA; 3Cardiology, University of Milano, Milano, Italy
The Obesity Paradox in Acute Heart Failure: An Analysis of Body Mass Index and In-Hospital Mortality for 108,927 Hospitalizations in ADHERE Gregg C. Fonarow1, Maria R. Costanzo2, Guillermo B. Cintron3; 1Ahmanson-UCLA Cardiomyopathy Center, University of California, Los Angeles Medical Center, Los Angeles, CA; 2Midwest Heart Specialists, Naperville, IL; 3University of South Florida, Tampa, FL
Introduction: Cardiopulmonary exercise testing (CPET) yields valuable prognostic information in patients diagnosed with heart failure (HF). Peak oxygen consumption (VO2) and the minute ventilation (VE)/carbon dioxide production (VCO2) slope have consistently demonstrated prognostic significance and are therefore the most frequently assessed variables. In recent years, heart rate recovery (HRR) has demonstrated prognostic value in apparently healthy subjects as well as those diagnosed with cardiovascular disease but not with HF specifically. The purpose of the present study was to assess the prognostic value of HRR in a group of subjects with HF, independently and in combination with established CPET variables. Methods: Eightyfive subjects diagnosed with HF underwent CPET. Mean age and ejection fraction were 50.5 years (⫾13.7) and 28.0% (⫾13.6). Heart rate at one-minute post CPET was subtracted from maximal heart rate during the exercise test to produce a measure of HRR1 in beats per minute (BPM). Results: Mean peak respiratory exchange ratio, peak VO2, VE/VCO2 slope and HRR1 values were 1.1 (⫾0.1), 14.7 mlO2 · kg⫺1 · min⫺1 (⫾4.7), 36.5 (⫾8.7) and 11.0 BPM (⫾10.4) respectively. There were 10 cardiacrelated deaths and 26 cardiac related hospitalizations during the tracking period. While all three variables were significant univariate predictors of the composite endpoint (p ⬍ 0.001), multivariate Cox regression analysis only retained VE/VCO2 slope (Chisquare: 33.5, p ⬍ 0.001) and HRR1 (Residual chi-square: 12.2, p ⬍ 0.001) in the equation. Receiver operating characteristic (ROC) curve analysis assessed the VE/ VCO2 slope and HRR1 classification schemes. The optimal prognostic threshold values for the VE/VCO2 slope and HRR1 were ⱕ/⬎34.4 (ROC area; 0.82, p ⬍ 0.001, 78% sensitivity, 86% specificity) and ⬍ /ⱖ6.5 beats/min (ROC area; 0.73, p ⬍ 0.001, 82% sensitivity, 64% specificity) respectively. The hazard ratio for individuals possessing negative values for both VE/VCO2 slope (⬎34.4) and HRR1 (⬍6.5 BPM) was 7.9 (95% CI: 4.0–15.9, p ⬍ 0.001). Conclusion: The results of the present study indicate that HRR provides additional prognostic information in patients with HF undergoing CPET. Furthermore, given the independent prognostic value of HRR, this variable alone may provide valuable clinical information when ventilatory expired analysis is not available.
304 Higher Not Lower HbA1c Values Are Associated with Improved Survival in Patients with Diabetes and Advanced Heart Failure Shervin Eshaghian1, Tamara B. Horwich2, Gregg C. Fonarow2; 1Department of Medicine, Albert Einstein College of Medicine, Bronx, NY; 2Cardiology / Medicine, UCLA School of Medicine, Los Angeles, CA Objective: To evaluate the relationship between hemoglobin A1c (HbA1c) and survival in patients with diabetes and advanced heart failure (HF). Background: In diabetes, poor glycemic control, as indexed by HbA1c, is associated with increased risk of cardiovascular events and new onset HF. However, in patients with diabetes and chronic HF, the relationship between glucose control and survival has not been studied. Methods: We studied a cohort of 123 patients with diabetes and advanced systolic HF, referred to a single center for HF management and/or transplant evaluation who had HbA1c values measured at presentation. The patients were grouped based on HbA1c: HbA1c ⱕ 7.0 (n ⫽ 49) and HbA1c ⬎ 7.0 (n ⫽ 74). Results: The cohort was 70% male, with mean age of 56 ⫾ 11 years, mean EF of 25% ⫾ 7, 59% ischemic etiology, mean HbA1c serum level of 7.9 ⫾ 1.8, and average diabetes duration of 8.7 ⫾ 9.0 years. The HbA1c groups were similar in terms of age, gender, BMI, diabetes duration, insulin, metformin and glitazone use. HbA1c ⬎ 7.0 were associated with higher EF, increased beta-blocker and sulfonlyuria use, and lower NYHA class. Patients with HbA1c ⬎7.0 had significantly improved survival compared to those with HbA1c ⱕ 7.0 (75% vs. 50%, RR 0.39 95% CI 0.19–0.78) (P ⬍ 0.01) (Figure 1). Examination of HbA1c as a continuous variable reveled a 34% decrease relative risk for every 1% increase in HbA1c. In multivariate analysis adjusted for age, sex, EF, etiology, beta-blocker and ACE-I/ARB usage, diabetes duration, and insulin or oral medication usage, HbA1c ⬎ 7.0 was associated with a significant decrease in mortality (RR 0.67, 95% CI 0.55–0.88). Conclusion: Paradoxically, elevated serum HbA1c levels are associated with improved survival in this cohort of patients with diabetes and advanced HF. Further investigation is necessary to determine the nature of this relationship and optimal HbA1c in patients with diabetes and HF.
Background: Prior studies in chronic systolic heart failure (HF) have demonstrated that body mass index (BMI) is inversely associated with mortality, the so-called obesity paradox. Whether BMI influences the mortality risk in patients hospitalized with acute decompensated HF has not been previously studied. Methods: The ADHERE registry was analyzed for AHF hospitalizations from March 2001 to December 2004 with documented height and weight. Patients were divided into BMI (kg/m2) quartiles. Inhospital mortality by BMI quartiles for the overall cohort and those with reduced (n ⫽ 43,255) and preserved (n ⫽ 37,901) systolic function were assessed. Results: BMI quartiles in the 108,927 hospitalizations were Q1 (16–23.6 kg/m2), Q2 (23.7–27.7 kg/m2), Q3 (27.8–33.3 kg/m2), and Q4 (33.4–60 kg/m2). Patients in higher BMI quartiles were younger, with more diabetes, and higher LVEF. In-hospital mortality rates decreased in a near linear fashion across successively higher BMI quartiles (Table). After adjustment for age, gender, BUN, systolic BP, diastolic BP, creatinine, sodium, pulse, dyspnea at rest, BMI quartile still predicted mortality risk. For every 5-unit increase in BMI, the odds of risk-adjusted mortality were 10% lower (95% CI, 0.88–0.93) P ⬍ 0.0001. Conclusions: In a cohort of hospitalized HF patients, higher BMIs were associated with lower in-hospital mortality risk; overweight and obese HF patients had lower mortality. The reverse association between elevated BMI and outcomes in HF is strikingly different than the general population and deserves further study. Total Cohort BMI Quartiles
N
Mortality Rate (%)
I (16–23.6) II (23.7–27.7) III (27.8–33.3) IV (33.4–60)
27,224 27,304 27,088 27,311
5.0 3.9 2.8 2.2
LVEF ⱖ 40%
LVEF ⬍ 40%
N
Mortality Rate (%)
N
Mortality Rate (%)
8,063 8,691 9,627 11,520
4.5 3.0 2.2 1.9
12,083 11,951 10,800 8,421
4.9 4.0 3.1 2.6
306 In-Hospital Worsening Heart Failure in Patients with Acute Heart Failure: Relation to Renal Failure, Need for Intotropes, CAD, Hyponatremia and Increased Respiratory Rate. A Sub-Group Analysis from the VERITAS Trial Gad Cotter1, Isaac Kobrin2, Guillermo Torre-Amione1, John R. Teerlink1, John J. V. McMurry1, Robert C. Bourge1, Aline Frey2, Christopher M. O’Connor1; 1Cardiology, Veritas Steering Commiette; 2Clinical Development, Actelion Pharmaceuticals, Alschville, Switzerland A major limitation in AHF research is the absence of a short-term morbidity outcome measure. Analogous to the role of recurrent ischemia in ACS studies, the characterization of early worsening heart failure (WHF) as an early morbidity measure may help in advancing the research of AHF. Patients and Methods: VERITAS was a multicenter, placebo-controlled, randomized study that examined the effect of tezosentan, an endothelin antagonist, compared to placebo in patients with AHF. WHF was defined a s recurrent symptoms and signs of HF requiring IV or mechanical treatment within 7 days from randomization. Results: Of the 708 patients randomized to placebo, 184 patients (26.4%) experienced WHF during the first 7 days of the study. WHF events required IV furosemide only in 110 pts and other IV support in 74 Pts. Factors associated with more WHF events were [event rate (% increase/decrease over overall group) (95% confidence interval)]: Age ⬎ median (72 years) - 31.1% (⫹18%) (26.4– 36.1%), respiratory rate at baseline ⬎ 27 breaths/minute (higher quartile) – 33.0% (⫹25%) (27.4–39.0%), Baseline sodium ⬍ normal ( ⬍ 135 mmol/liter) – 41.6% (⫹62%) (31.9–51.8%), IV inotropes use before study enrolment 55.6% (⫹111%) (30.8– 78.5%) baseline BUN ⬎ median (9 mmol/loter) –36.7% (⫹39%) (30.9–42.7%) and calculated glomerular filtration rate at baseline ⬍ median (54 cc/min) – 35.0% (⫹33%) (29.2–41.1%). Factors associated with lower WHF rate were: Non-compliance as the main precipitating cause for the AHF event ⫺18.2% (⫺31%) (12.2–25.7%), absence of known coronary artery disease ⫺20.2% (⫺25%) (14.8–26.5%), non-ischemic etiology 21.2% (⫺23%) (16.2–26.9%), and indices of preserved renal function. Conclusions: Early WHF is a common event in patients admitted for AHF, predicted predominantly by baseline requirement of IV inotropes, measures of renal failure, age, non-adherence, absence of CAD, baseline sodium, and respiratory rate.
•
HFSA
S171
303
305
Prognostic Value of Heart Rate Recovery in Patients with Heart Failure Ross Arena1, Jonathan Myers2, Marco Guazzi3, Mary Ann Peberdy1, Joshua Abella2; 1Physical Therapy and Physiology, Virginia Commonwealth University, Richmond, VA; 2Cardiology, Palo Alto Veterans Affairs Health Care System, Palo Alto, CA; 3Cardiology, University of Milano, Milano, Italy
The Obesity Paradox in Acute Heart Failure: An Analysis of Body Mass Index and In-Hospital Mortality for 108,927 Hospitalizations in ADHERE Gregg C. Fonarow1, Maria R. Costanzo2, Guillermo B. Cintron3; 1Ahmanson-UCLA Cardiomyopathy Center, University of California, Los Angeles Medical Center, Los Angeles, CA; 2Midwest Heart Specialists, Naperville, IL; 3University of South Florida, Tampa, FL
Introduction: Cardiopulmonary exercise testing (CPET) yields valuable prognostic information in patients diagnosed with heart failure (HF). Peak oxygen consumption (VO2) and the minute ventilation (VE)/carbon dioxide production (VCO2) slope have consistently demonstrated prognostic significance and are therefore the most frequently assessed variables. In recent years, heart rate recovery (HRR) has demonstrated prognostic value in apparently healthy subjects as well as those diagnosed with cardiovascular disease but not with HF specifically. The purpose of the present study was to assess the prognostic value of HRR in a group of subjects with HF, independently and in combination with established CPET variables. Methods: Eightyfive subjects diagnosed with HF underwent CPET. Mean age and ejection fraction were 50.5 years (⫾13.7) and 28.0% (⫾13.6). Heart rate at one-minute post CPET was subtracted from maximal heart rate during the exercise test to produce a measure of HRR1 in beats per minute (BPM). Results: Mean peak respiratory exchange ratio, peak VO2, VE/VCO2 slope and HRR1 values were 1.1 (⫾0.1), 14.7 mlO2 · kg⫺1 · min⫺1 (⫾4.7), 36.5 (⫾8.7) and 11.0 BPM (⫾10.4) respectively. There were 10 cardiacrelated deaths and 26 cardiac related hospitalizations during the tracking period. While all three variables were significant univariate predictors of the composite endpoint (p ⬍ 0.001), multivariate Cox regression analysis only retained VE/VCO2 slope (Chisquare: 33.5, p ⬍ 0.001) and HRR1 (Residual chi-square: 12.2, p ⬍ 0.001) in the equation. Receiver operating characteristic (ROC) curve analysis assessed the VE/ VCO2 slope and HRR1 classification schemes. The optimal prognostic threshold values for the VE/VCO2 slope and HRR1 were ⱕ/⬎34.4 (ROC area; 0.82, p ⬍ 0.001, 78% sensitivity, 86% specificity) and ⬍ /ⱖ6.5 beats/min (ROC area; 0.73, p ⬍ 0.001, 82% sensitivity, 64% specificity) respectively. The hazard ratio for individuals possessing negative values for both VE/VCO2 slope (⬎34.4) and HRR1 (⬍6.5 BPM) was 7.9 (95% CI: 4.0–15.9, p ⬍ 0.001). Conclusion: The results of the present study indicate that HRR provides additional prognostic information in patients with HF undergoing CPET. Furthermore, given the independent prognostic value of HRR, this variable alone may provide valuable clinical information when ventilatory expired analysis is not available.
304 Higher Not Lower HbA1c Values Are Associated with Improved Survival in Patients with Diabetes and Advanced Heart Failure Shervin Eshaghian1, Tamara B. Horwich2, Gregg C. Fonarow2; 1Department of Medicine, Albert Einstein College of Medicine, Bronx, NY; 2Cardiology / Medicine, UCLA School of Medicine, Los Angeles, CA Objective: To evaluate the relationship between hemoglobin A1c (HbA1c) and survival in patients with diabetes and advanced heart failure (HF). Background: In diabetes, poor glycemic control, as indexed by HbA1c, is associated with increased risk of cardiovascular events and new onset HF. However, in patients with diabetes and chronic HF, the relationship between glucose control and survival has not been studied. Methods: We studied a cohort of 123 patients with diabetes and advanced systolic HF, referred to a single center for HF management and/or transplant evaluation who had HbA1c values measured at presentation. The patients were grouped based on HbA1c: HbA1c ⱕ 7.0 (n ⫽ 49) and HbA1c ⬎ 7.0 (n ⫽ 74). Results: The cohort was 70% male, with mean age of 56 ⫾ 11 years, mean EF of 25% ⫾ 7, 59% ischemic etiology, mean HbA1c serum level of 7.9 ⫾ 1.8, and average diabetes duration of 8.7 ⫾ 9.0 years. The HbA1c groups were similar in terms of age, gender, BMI, diabetes duration, insulin, metformin and glitazone use. HbA1c ⬎ 7.0 were associated with higher EF, increased beta-blocker and sulfonlyuria use, and lower NYHA class. Patients with HbA1c ⬎7.0 had significantly improved survival compared to those with HbA1c ⱕ 7.0 (75% vs. 50%, RR 0.39 95% CI 0.19–0.78) (P ⬍ 0.01) (Figure 1). Examination of HbA1c as a continuous variable reveled a 34% decrease relative risk for every 1% increase in HbA1c. In multivariate analysis adjusted for age, sex, EF, etiology, beta-blocker and ACE-I/ARB usage, diabetes duration, and insulin or oral medication usage, HbA1c ⬎ 7.0 was associated with a significant decrease in mortality (RR 0.67, 95% CI 0.55–0.88). Conclusion: Paradoxically, elevated serum HbA1c levels are associated with improved survival in this cohort of patients with diabetes and advanced HF. Further investigation is necessary to determine the nature of this relationship and optimal HbA1c in patients with diabetes and HF.
Background: Prior studies in chronic systolic heart failure (HF) have demonstrated that body mass index (BMI) is inversely associated with mortality, the so-called obesity paradox. Whether BMI influences the mortality risk in patients hospitalized with acute decompensated HF has not been previously studied. Methods: The ADHERE registry was analyzed for AHF hospitalizations from March 2001 to December 2004 with documented height and weight. Patients were divided into BMI (kg/m2) quartiles. Inhospital mortality by BMI quartiles for the overall cohort and those with reduced (n ⫽ 43,255) and preserved (n ⫽ 37,901) systolic function were assessed. Results: BMI quartiles in the 108,927 hospitalizations were Q1 (16–23.6 kg/m2), Q2 (23.7–27.7 kg/m2), Q3 (27.8–33.3 kg/m2), and Q4 (33.4–60 kg/m2). Patients in higher BMI quartiles were younger, with more diabetes, and higher LVEF. In-hospital mortality rates decreased in a near linear fashion across successively higher BMI quartiles (Table). After adjustment for age, gender, BUN, systolic BP, diastolic BP, creatinine, sodium, pulse, dyspnea at rest, BMI quartile still predicted mortality risk. For every 5-unit increase in BMI, the odds of risk-adjusted mortality were 10% lower (95% CI, 0.88–0.93) P ⬍ 0.0001. Conclusions: In a cohort of hospitalized HF patients, higher BMIs were associated with lower in-hospital mortality risk; overweight and obese HF patients had lower mortality. The reverse association between elevated BMI and outcomes in HF is strikingly different than the general population and deserves further study. Total Cohort BMI Quartiles
N
Mortality Rate (%)
I (16–23.6) II (23.7–27.7) III (27.8–33.3) IV (33.4–60)
27,224 27,304 27,088 27,311
5.0 3.9 2.8 2.2
LVEF ⱖ 40%
LVEF ⬍ 40%
N
Mortality Rate (%)
N
Mortality Rate (%)
8,063 8,691 9,627 11,520
4.5 3.0 2.2 1.9
12,083 11,951 10,800 8,421
4.9 4.0 3.1 2.6
306 In-Hospital Worsening Heart Failure in Patients with Acute Heart Failure: Relation to Renal Failure, Need for Intotropes, CAD, Hyponatremia and Increased Respiratory Rate. A Sub-Group Analysis from the VERITAS Trial Gad Cotter1, Isaac Kobrin2, Guillermo Torre-Amione1, John R. Teerlink1, John J. V. McMurry1, Robert C. Bourge1, Aline Frey2, Christopher M. O’Connor1; 1Cardiology, Veritas Steering Commiette; 2Clinical Development, Actelion Pharmaceuticals, Alschville, Switzerland A major limitation in AHF research is the absence of a short-term morbidity outcome measure. Analogous to the role of recurrent ischemia in ACS studies, the characterization of early worsening heart failure (WHF) as an early morbidity measure may help in advancing the research of AHF. Patients and Methods: VERITAS was a multicenter, placebo-controlled, randomized study that examined the effect of tezosentan, an endothelin antagonist, compared to placebo in patients with AHF. WHF was defined a s recurrent symptoms and signs of HF requiring IV or mechanical treatment within 7 days from randomization. Results: Of the 708 patients randomized to placebo, 184 patients (26.4%) experienced WHF during the first 7 days of the study. WHF events required IV furosemide only in 110 pts and other IV support in 74 Pts. Factors associated with more WHF events were [event rate (% increase/decrease over overall group) (95% confidence interval)]: Age ⬎ median (72 years) - 31.1% (⫹18%) (26.4– 36.1%), respiratory rate at baseline ⬎ 27 breaths/minute (higher quartile) – 33.0% (⫹25%) (27.4–39.0%), Baseline sodium ⬍ normal ( ⬍ 135 mmol/liter) – 41.6% (⫹62%) (31.9–51.8%), IV inotropes use before study enrolment 55.6% (⫹111%) (30.8– 78.5%) baseline BUN ⬎ median (9 mmol/loter) –36.7% (⫹39%) (30.9–42.7%) and calculated glomerular filtration rate at baseline ⬍ median (54 cc/min) – 35.0% (⫹33%) (29.2–41.1%). Factors associated with lower WHF rate were: Non-compliance as the main precipitating cause for the AHF event ⫺18.2% (⫺31%) (12.2–25.7%), absence of known coronary artery disease ⫺20.2% (⫺25%) (14.8–26.5%), non-ischemic etiology 21.2% (⫺23%) (16.2–26.9%), and indices of preserved renal function. Conclusions: Early WHF is a common event in patients admitted for AHF, predicted predominantly by baseline requirement of IV inotropes, measures of renal failure, age, non-adherence, absence of CAD, baseline sodium, and respiratory rate.