807-2 Effect of Age on Left Ventricular Diastolic Filling Patterns During Orthostatic Stress

Although numerous studies have demonstrated reduced early diastolic left ventricular (LV) peak filling velocity IE) and accentuated late filling velocity (A) with advancing age in the supine position, the effect of orthostatic stress on age-associated diastolic filling patterns is unknown. Accordingly, 30 healthy normotensive volunteers ages 19 to 90 years from the Baltimore Longitudinal Study of Aging underwent sequential Doppler echocardiography after 3 minutes each in the supine, seated, and standing positions. In the overall sample, standing was accompanied by an increase in heart rate (HR) of 8.8±1.7 beats/min, and decreases in E(20.6±2.7cm/sl. A 150±2.7cm/s)and LV diastolic dimension (LVDD) (7.8±0.8mm), x±SEM, each p<0.001 versus supine values. Systolic blood pressure (SBP) and atrial filling fraction (AFF) were unaffected by posture. Correlation coefficients versus age for relevant Doppler and hemodynamic variables are shown.EAE/AAFFHRSBPLVDDSupine-0.58†0.80†-0.78†0.84†0.010.56†-0.14Sit-0.360.77†-0.83†0.78†-0.040.37*-0.07Stand-0.240.60†-0.69†0.71†-0.320.47†0.09ΔSupine → Stand0.53†-0.46†0.56†-0.17-0.61†0.220.40**p<005†p<001Thus, orthostatic stress abolishes the reduction of E and attenuates the exaggerated A observed with advancing age in the supine position. probably because of the blunted standing-induced HR increase in older subjects. However, the supine age-associated increase in AFF is unaffected by orthostasis

Relationship of Beta-Blocker Dose With Outcomes in Ambulatory Heart Failure Patients With Systolic Dysfunction Results From the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) Trial

ObjectivesThis study sought to examine the association between baseline beta-blocker (BB) dose and outcomes in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial.BackgroundBeta-blockers reduce morbidity and mortality in chronic heart failure (HF) patients with reduced ejection fraction, but it is unclear whether titrating to higher BB doses improves outcomes in this setting.MethodsThe HF-ACTION trial was a randomized, multicenter trial enrolling 2,331 ambulatory HF patients with systolic dysfunction (New York Heart Association functional class II to IV, left ventricular ejection fraction <0.35) randomized to exercise training versus usual care, with median follow-up of 2.5 years. The BB dose at baseline was standardized with carvedilol equivalents and analyzed as a continuous variable and by discrete dose groups. The relationship between BB dose and the primary endpoint of all-cause mortality or all-cause hospitalization and other cardiovascular secondary endpoints was determined before and after adjustment for variables significantly associated with outcomes in the HF-ACTION cohort.ResultsNinety-five percent of patients were receiving a BB. There was a significant inverse relationship between BB dose and all-cause death or hospitalization but not other cardiovascular endpoints after adjustment for other predictors of outcome, with a linear benefit up to the 50-mg daily dose. There was a significant association between BB dose and change in peak VO2 at 3 months. There was no increase in bradycardia with higher doses of BB.ConclusionsThere was a significant inverse relationship between BB dose and the endpoint of all-cause death or all-cause hospitalization in this well-treated HF cohort with systolic dysfunction, supporting recommendations that titrating doses up to 50 mg/day might confer a benefit in such patients. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437

Statins and Exercise Training Response in Heart Failure Patients: Insights From HF-ACTION.

OBJECTIVES: The aim of this study was to assess for a treatment interaction between statin use and exercise training (ET) response. BACKGROUND: Recent data suggest that statins may attenuate ET response, but limited data exist in patients with heart failure (HF). METHODS: HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) was a randomized trial of 2,331 patients with chronic HF with ejection fraction ≤35% who were randomized to usual care with or without ET. We evaluated whether there was a treatment interaction between statins and ET response for the change in quality of life and aerobic capacity (peak oxygen consumption and 6-min walk distance) from baseline to 3 months. We also assessed for a treatment interaction among atorvastatin, simvastatin, and pravastatin and change in these endpoints with ET. Multiple linear regression analyses were performed for each endpoint, adjusting for baseline covariates. RESULTS: Of 2,331 patients in the HF-ACTION trial, 1,353 (58%) were prescribed statins at baseline. Patients treated with statins were more likely to be older men with ischemic HF etiology but had similar use of renin angiotensin system blockers and beta-blockers. There was no evidence of a treatment interaction between statin use and ET on changes in quality of life or exercise capacity, nor was there evidence of differential association between statin type and ET response for these endpoints (all p values \u3e0.05). CONCLUSIONS: In a large chronic HF cohort, there was no evidence of a treatment interaction between statin use and short-term change in aerobic capacity and quality of life with ET. These findings contrast with recent reports of an attenuation in ET response with statins in a different population, highlighting the need for future prospective studies. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437)

Effects of Aerobic Exercise Training in Community-Based Subjects Aged 80 and Older: A Pilot Study

To assess the ability of sedentary, frail subjects aged 80 and older to train in a community-based exercise program and to evaluate clinical factors that predict improvements in peak oxygen consumption (VO 2 peak). DESIGN: Pretest, posttest. SETTING: Charlestown Retirement Community, Catonsville, Maryland PARTICIPANTS: Twenty-two (11 male, 11 female; mean age ± standard deviation = 84 ± 4.0, range 80–92) self-referred. INTERVENTION: Six months of moderate-intensity aerobic exercise training, two to three sessions/week, 20 to 30 minutes per session. Training modes included treadmill walking and/or stationary cycling. MEASUREMENTS: Baseline and follow-up maximal exercise treadmill tests (ETTs) with electrocardiogram monitoring and respiratory gas analysis. RESULTS: Six months of aerobic exercise training resulted in significant increases (mean ± standard deviation) in ETT duration (11.9 ± 3.3 vs 15.9 ± 4.3 minutes; P = .01), VO 2 peak (1.23 ± 0.37 vs 1.31 ± 0.36 L/min; P = .04), and oxygen pulse (9.3 ± 2.8 vs 10.1 ± 3.2; P = .03). Mean heart rate was significantly lower during submaximal ETT stages 1 through 4 ( P < .05), and resting systolic blood pressure decreased (146 ± 18 vs 133 ± 14 mmHg; P = .01) after training. Multiple regression analysis indicated that baseline VO 2 peak ( r = 0.75, P = .002) and the total amount of time spent in exercise training ( r = 0.55, P = .008) were independent predictors of the training-related improvements in VO 2 peak. CONCLUSION: Subjects aged 80 and older can increase aerobic capacity and reduce systolic blood pressure in a community-based exercise program of moderate intensity. The most important predictors of change in VO 2 peak were baseline VO 2 peak and the time spent in exercise training. Subjects with a lower baseline VO 2 peak had the greatest improvements in VO 2 peak after training.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65501/1/j.1532-5415.2002.50613.x.pd

Influence of ejection fraction on cause‐specific mortality in heart failure with preserved ejection fraction

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143697/1/ejhf1040.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143697/2/ejhf1040_am.pd

Spironolactone in Patients With Heart Failure, Preserved Ejection Fraction, and Worsening Renal Function

BACKGROUND Treatment of heart failure with preserved ejection fraction (HFpEF) with spironolactone is associated with lower risk of heart failure hospitalization (HFH) but increased risk of worsening renal function (WRF). The prognostic implications of spironolactone-associated WRF in HFpEF patients are not well understood. OBJECTIVES The purpose of this study was to investigate the association between WRF, spironolactone treatment, and clinical outcomes in patients with HFpEF. METHODS In 1,767 patients randomized to spironolactone or placebo in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial)-Americas study, we examined the incidence of WRF (doubling of serum creatinine) by treatment assignment. Associations between incident WRF and subsequent risk for the primary study endpoint of cardiovascular (CV) death, HFH, or aborted cardiac arrest and key secondary outcomes, including CV death, HFH, and all-cause mortality according to treatment assignment, were examined in time-updated Cox proportional hazards models with an interaction term. RESULTS WRF developed in 260 (14.7%) patients with higher rates in those assigned to spironolactone compared to placebo (17.8% vs. 11.6%; odds ratio: 1.66; 95% confidence interval: 1.27 to 2.17; p < 0.001). Regardless of treatment, incident WRF was associated with increased risk for the primary endpoint (hazard ratio: 2.04; 95% confidence interval: 1.52 to 2.72; p < 0.001) after multivariable adjustment. Although there was no statistical interaction between treatment assignment and WRF regarding the primary endpoint (interaction p = 0.11), spironolactone-associated WRF was associated with lower risk of CV death (interaction p = 0.003) and all-cause mortality (interaction p = 0.001) compared with placebo-associated WRF. CONCLUSIONS Among HFpEF patients enrolled in TOPCAT-Americas, spironolactone increased risk of WRF compared with placebo. Rates of CV death were lower with spironolactone in both patients with and without WRF. (c) 2021 the American College of Cardiology Foundation. Published by Elsevier. All rights reserved

Effects of Digoxin on Morbidity and Mortality in Diastolic Heart Failure: The Ancillary Digitalis Investigation Group Trial

About half of the 5 million heart failure patients in the United States have diastolic heart failure (clinical heart failure with normal or near normal ejection fraction). Except for candesartan, no drugs have been tested in randomized clinical trials in these patients. Although digoxin was tested in an appreciable number of diastolic heart failure patients in the Digitalis Investigation Group ancillary trial, detailed findings from this important study has not been previously published

Hospitalizations Due to Unstable Angina Pectoris in Diastolic and Systolic Heart Failure

Patients with diastolic heart failure (HF) i.e. clinical HF with normal or near normal left ventricular ejection fraction (LVEF) may experience unstable angina pectoris (UAP) due to epicardial atherosclerotic coronary artery disease (CAD) and/or to subendocardial ischemia, even in the absence of CAD. However, the risk of UAP among ambulatory diastolic HF patients has not been well studied. We examined incident hospitalizations due to UAP among 916 diastolic HF (LVEF >45%) patients without significant valvular heart disease and 6800 systolic HF (LVEF ≤45%) patients in the Digitalis Investigation Group trial. During a 38-month median follow-up, 12% (797/6,800) of systolic HF patients (incidence rate, 435/10,000 person-years) and 15% (138/916) of diastolic HF patients (incidence rate, 536/10,000 person-years) were hospitalized for UAP (adjusted hazard ratio for diastolic HF, 1.22; 95% confidence interval, 1.02–1.47; p=0.032). There was a graded increase in incident hospital admissions for UAP with increasing LVEF. Hospitalizations for UAP occurred in 11% (520/4,808; incidence rate, 407/10,000 person-years), 14% (355/2556; incidence rate, 496/10,000 person-years) and 17% (60/352; incidence rate, 613/10,000 person-years) of HF patients, respectively, with LVEF 55%. Compared with HF patients with LVEF 55% were respectively 1.17 (1.02–1.34; p=0.028) and 1.57 (1.20–2.07; p=0.026). In conclusion, in ambulatory chronic HF patients, higher LVEF was associated with increased risk of hospitalizations due to UAP. As in patients with systolic HF, those with diastolic HF should be routinely evaluated for myocardial ischemia and managed accordingly

Spironolactone for heart failure with preserved ejection fraction

BACKGROUND: Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction. METHODS: In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. RESULTS: With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P = 0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P = 0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 μmol per liter) or higher, or dialysis. CONCLUSIONS: In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure