Supervised Exercise Training for Chronic Heart Failure With Preserved Ejection Fraction: A Scientific Statement From the American Heart Association and American College of Cardiology.

Heart failure with preserved ejection fraction (HFpEF) is one of the most common forms of heart failure; its prevalence is increasing, and outcomes are worsening. Affected patients often experience severe exertional dyspnea and debilitating fatigue, as well as poor quality of life, frequent hospitalizations, and a high mortality rate. Until recently, most pharmacological intervention trials for HFpEF yielded neutral primary outcomes. In contrast, trials of exercise-based interventions have consistently demonstrated large, significant, clinically meaningful improvements in symptoms, objectively determined exercise capacity, and usually quality of life. This success may be attributed, at least in part, to the pleiotropic effects of exercise, which may favorably affect the full range of abnormalities-peripheral vascular, skeletal muscle, and cardiovascular-that contribute to exercise intolerance in HFpEF. Accordingly, this scientific statement critically examines the currently available literature on the effects of exercise-based therapies for chronic stable HFpEF, potential mechanisms for improvement of exercise capacity and symptoms, and how these data compare with exercise therapy for other cardiovascular conditions. Specifically, data reviewed herein demonstrate a comparable or larger magnitude of improvement in exercise capacity from supervised exercise training in patients with chronic HFpEF compared with those with heart failure with reduced ejection fraction, although Medicare reimbursement is available only for the latter group. Finally, critical gaps in implementation of exercise-based therapies for patients with HFpEF, including exercise setting, training modalities, combinations with other strategies such as diet and medications, long-term adherence, incorporation of innovative and more accessible delivery methods, and management of recently hospitalized patients are highlighted to provide guidance for future research.

Supervised Exercise Training for Chronic Heart Failure With Preserved Ejection Fraction: A Scientific Statement From the American Heart Association and American College of Cardiology.

Heart failure with preserved ejection fraction (HFpEF) is one of the most common forms of heart failure; its prevalence is increasing, and outcomes are worsening. Affected patients often experience severe exertional dyspnea and debilitating fatigue, as well as poor quality of life, frequent hospitalizations, and a high mortality rate. Until recently, most pharmacological intervention trials for HFpEF yielded neutral primary outcomes. In contrast, trials of exercise-based interventions have consistently demonstrated large, significant, clinically meaningful improvements in symptoms, objectively determined exercise capacity, and usually quality of life. This success may be attributed, at least in part, to the pleiotropic effects of exercise, which may favorably affect the full range of abnormalities-peripheral vascular, skeletal muscle, and cardiovascular-that contribute to exercise intolerance in HFpEF. Accordingly, this scientific statement critically examines the currently available literature on the effects of exercise-based therapies for chronic stable HFpEF, potential mechanisms for improvement of exercise capacity and symptoms, and how these data compare with exercise therapy for other cardiovascular conditions. Specifically, data reviewed herein demonstrate a comparable or larger magnitude of improvement in exercise capacity from supervised exercise training in patients with chronic HFpEF compared with those with heart failure with reduced ejection fraction, although Medicare reimbursement is available only for the latter group. Finally, critical gaps in implementation of exercise-based therapies for patients with HFpEF, including exercise setting, training modalities, combinations with other strategies such as diet and medications, long-term adherence, incorporation of innovative and more accessible delivery methods, and management of recently hospitalized patients are highlighted to provide guidance for future research.

Gradient and Acceleration of Decline in Physical and Cognitive Functions in Older Adults: A Disparity Analysis.

BACKGROUND: Substantive previous work has shown that both gait speed and global cognition decline as people age. Rates of their decline, as opposed to cross-sectional measurements, could be more informative of future functional status and other clinical outcomes because they more accurately represent deteriorating systems. Additionally, understanding the sex and racial disparity in the speed of deterioration, if any, is also important as ethnic minorities are at an increased risk of mobility disability and dementia. METHOD: Data from 2 large longitudinal intervention studies were integrated. Rates of decline were derived from individual-level measures of gait speed of 400-m walk and scores on the Modified Mini Mental State Examination (3MSE). We also assessed age-associated declines and accelerations in changes across the ages represented in the studies (age range 53-90). RESULTS: The mean rate of decline in 400-m gait speed across individuals was 0.03 m/s per year, and multivariable analysis showed a significant acceleration in decline of -0.0013 m/s/y2 (p < .001). Both race and sex moderated the rate of decline. For global cognition, the mean rate of decline was 0.05 of a point per year on the 3MSE scale, and acceleration in the rate of decline was significant (-0.017 point/y2, p < .001), but neither sex nor race moderated the decline. CONCLUSION: Rate of decline in physical but not cognitive function appears moderated by sex and race. This finding, as well as rates and accelerations of decline estimated herein, could inform future intervention studies. CLINICAL TRIALS REGISTRATION NUMBER: NCT00017953 (Look AHEAD); NCT01410097 (Look AHEAD ancillary); NCT00116194 (LIFE).

Survive and thrive: Personal stories of persistence and resilience in aging research.

An academic career in aging research is filled with the incredible highs of important discoveries that improve the lives of older adults and repeated lows when papers and grants are rejected or studies are negative. To normalize the experience of setbacks and failures in aging research, we invited three senior investigators to share their journeys of persistence and resilience as they have navigated their research careers. This career development symposium was presented at the 2021 Annual Scientific Meeting of the American Geriatrics Society, which was held virtually. We aimed to connect researchers in aging, especially trainees and junior investigators, through personal stories of persistence and shared strategies to build resilience and respond to setbacks with a growth mindset.

Economic Outcomes of Rehabilitation Therapy in Older Patients With Acute Heart Failure in the REHAB-HF Trial: A Secondary Analysis of a Randomized Clinical Trial.

Importance: In the Rehabilitation Therapy in Older Acute Heart Failure Patients (REHAB-HF) trial, a novel 12-week rehabilitation intervention demonstrated significant improvements in validated measures of physical function, quality of life, and depression, but no significant reductions in rehospitalizations or mortality compared with a control condition during the 6-month follow up. The economic implications of these results are important given the increasing pressures for cost containment in health care. Objective: To report the economic outcomes of the REHAB-HF trial and estimate the potential cost-effectiveness of the intervention. Design, Setting, Participants: The multicenter REHAB-HF trial randomized 349 patients 60 years or older who were hospitalized for acute decompensated heart failure to rehabilitation intervention or a control group; patients were enrolled from September 17, 2014, through September 19, 2019. For this preplanned secondary analysis of the economic outcomes, data on medical resource use and quality of life (via the 5-level EuroQol 5-Dimension scores converted to health utilities) were collected. Medical resource use and medication costs were estimated using 2019 US Medicare payments and the Federal Supply Schedule, respectively. Cost-effectiveness was estimated using the validated Tools for Economic Analysis of Patient Management Interventions in Heart Failure Cost-Effectiveness Model, which uses an individual-patient simulation model informed by the prospectively collected trial data. Data were analyzed from March 24, 2019, to December 1, 2020. Interventions: Rehabilitation intervention or control. Main Outcomes and Measures: Costs, quality-adjusted life-years (QALYs), and the lifetime estimated cost per QALY gained (incremental cost-effectiveness ratio). Results: Among the 349 patients included in the analysis (183 women [52.4%]; mean [SD] age, 72.7 [8.1] years; 176 non-White [50.4%] and 173 White [49.6%]), mean (SD) cumulative costs per patient were $26 421 ($38 955) in the intervention group (excluding intervention costs) and $27 650 ($30 712) in the control group (difference, -$1229; 95% CI, -$8159 to $6394; P = .80). The mean (SD) cost of the intervention was $4204 ($2059). Quality of life gains were significantly greater in the intervention vs control group during 6 months (mean utility difference, 0.074; P = .001) and sustained beyond the 12-week intervention. Incremental cost-effectiveness ratios were estimated at $58 409 and $35 600 per QALY gained for the full cohort and in patients with preserved ejection fraction, respectively. Conclusions and Relevance: These analyses suggest that longer-term benefits of this novel rehabilitation intervention, particularly in the subgroup of patients with preserved ejection fraction, may yield good value to the health care system. However, long-term cost-effectiveness is currently uncertain and dependent on the assumption that benefits are sustained beyond study follow-up, which needs to be corroborated in future trials in this patient population.

Temporal Trends and Factors Associated With Cardiac Rehabilitation Participation Among Medicare Beneficiaries With Heart Failure.

OBJECTIVES: The purpose of this study was to assess temporal trends and factors associated with cardiac rehabilitation (CR) enrollment and participation among Medicare beneficiaries after the 2014 Medicare coverage expansion. BACKGROUND: CR improves exercise capacity, quality of life, and clinical outcomes in heart failure (HF) with reduced ejection fraction (HFrEF). In 2014, Medicare coverage for CR was expanded to include chronic HFrEF. METHODS: Among Medicare beneficiaries from quarter (Q) 1 2014 to Q2 2016, 11,696 patients from 14,258 hospitalizations with primary discharge diagnosis of HF were identified. Patients with HF with preserved ejection fraction were excluded. Quarterly CR participation rates among hospitalized HF patients within 6 months of discharge were identified through outpatient administrative claims. The predictors of CR participation were assessed with the use of a multivariable logistic regression model that included patient- and hospital-level characteristics. A secondary analysis to assess participation rates of CR after outpatient encounters for HF was performed. RESULTS: Overall, only 611 (4.3%) and 349 (2.2%) eligible patients participated CR after primary hospitalization or outpatient visit for HF, respectively. There was a modest, statistically significant increase in CR participation after HF admissions (2.8% in Q1 2014; 5.0% in Q2 2016; p < 0.001) without significant increase after outpatient visits for HF (2.6% to 3.8%; p = 0.21). Younger age, male sex, nonblack race, previous cardiovascular procedures, and hospitalization at hospitals with available CR facilities were all independently associated with CR participation. CONCLUSIONS: CR participation among eligible Medicare beneficiaries with HFrEF was low with minimal increase since 2014 Medicare coverage decision. Sex, race, and institution-dependent variables were independent predictors of CR participation.

Frailty Is Intertwined With Heart Failure: Mechanisms, Prevalence, Prognosis, Assessment, and Management.

Frailty, a syndrome characterized by an exaggerated decline in function and reserve of multiple physiological systems, is common in older patients with heart failure (HF) and is associated with worse clinical and patient-reported outcomes. Although several detailed assessment tools have been developed and validated in the geriatric population, they are cumbersome, not validated in patients with HF, and not commonly used in routine management of patients with HF. More recently, there has been an increasing interest in developing simple frailty screening tools that could efficiently and quickly identify frail patients with HF in routine clinical settings. As the burden and recognition of frailty in older patients with HF increase, a more comprehensive approach to management is needed that targets deficits across multiple domains, including physical function and medical, cognitive, and social domains. Such a multidomain approach is critical to address the unique, multidimensional challenges to the care of these high-risk patients and to improve their functional status, quality of life, and long-term clinical outcomes. This review discusses the burden of frailty, the conceptual underpinnings of frailty in older patients with HF, and potential strategies for the assessment, screening, and management of frailty in this vulnerable patient population.

Contemporary Assessment of Left Ventricular Diastolic Function in Older Adults: The Atherosclerosis Risk in Communities Study.

BACKGROUND: Although age-associated changes in left ventricular diastolic function are well recognized, limited data exist characterizing measures of diastolic function in older adults, including both reference ranges reflecting the older adult population and prognostically relevant values for incident heart failure (HF), as well as their associations with circulating biomarkers of HF risk. METHODS: Among 5801 elderly participants in the ARIC study (Atherosclerosis Risk in Communities; age range, 67-90 years; mean age, 76±5 years; 42% male; 21% black), we determined the continuous association of diastolic measures (tissue Doppler imaging [TDI] e', E/e', and left atrial size) with concomitant N-terminal pro-brain natriuretic peptide and subsequent HF hospitalization or death. We also determined sex-specific 10th and 90th percentile limits for these measures using quantile regression in 401 participants free of prevalent cardiovascular disease and risk factors. RESULTS: Each measure of diastolic function was robustly associated with N-terminal pro-brain natriuretic peptide and incident HF or death. ARIC-based reference limits for TDI e' (4.6 and 5.2 cm/s for septal and lateral TDI e', respectively) were substantially lower than guideline cut points (7 and 10 cm/s, respectively), whereas E/e' and left atrial size demonstrated good agreement with guideline cut points. TDI e' was nonlinearly associated with incident HF or death, with inflection points for risk supportive of ARIC-based limits. ARIC-based limits for diastolic function improved risk discrimination over guideline-based cut points based on the integrated discrimination improvement (P<0.001) and continuous net reclassification improvement (P<0.001), reclassifying 42% of the study population as having normal diastolic function. We replicate these findings in the Copenhagen City Heart Study. With these limits, 46% had normal diastolic function and were at low risk of HF hospitalization or death (1%/y over a mean 1.7-year follow-up), 49% had 1 or 2 abnormal measures and were at intermediate risk (2.4%/y), and all 3 diastolic measures were abnormal in 5% who were at high risk (7.5%/y). CONCLUSIONS: Our findings suggest that left ventricular longitudinal relaxation velocity declines as a part of healthy aging and is largely prognostically benign. The use of age-based normative values when considering an elderly population improves the risk discrimination of diastolic measures for incident HF or death.

Longitudinal assessment of concurrent changes in left ventricular ejection fraction and left ventricular myocardial tissue characteristics after administration of cardiotoxic chemotherapies using T1-weighted and T2-weighted cardiovascular magnetic resonance.

BACKGROUND: In a murine anthracycline-related cardiotoxicity model, increases in cardiovascular magnetic resonance myocardial contrast-enhanced T1-weighted signal intensity are associated with myocellular injury and decreases with left ventricular ejection fraction. We sought to determine whether T1- and T2-weighted measures of signal intensity associate with decreases in left ventricular ejection fraction in human subjects receiving potentially cardiotoxic chemotherapy. METHODS AND RESULTS: In 65 individuals with breast cancer (n=51) or a hematologic malignancy (n=14), we measured left ventricular volumes, ejection fraction, and contrast-enhanced T1-weighted and T2-weighted signal intensity before and 3 months after initiating potentially cardiotoxic chemotherapy using blinded, unpaired analysis of cardiovascular magnetic resonance images. Participants were aged 51 ± 12 years, of whom 55% received an anthracycline, 38% received a monoclonal antibody, and 6% received an antimicrotubule agent. Overall, left ventricular ejection fraction decreased from 57 ± 6% to 54 ± 7% (P<0.001) because of an increase in end-systolic volume (P<0.05). T1-weighted signal intensities also increased from 14.1 ± 5.1 to 15.9 ± 6.8 (P<0.05), with baseline values trending higher among individuals who received chemotherapy before study enrollment (P=0.06). Changes in T1-weighted signal intensity did not differ within the 17 LV myocardial segments (P=0.97). Myocardial edema quantified from T2-weighted images did not change significantly after 3 months (P=0.70). CONCLUSIONS: Concordant with previous animal studies, cardiovascular magnetic resonance measures of contrast-enhanced T1-weighted signal intensity occur commensurate with small but significant left ventricular ejection fraction declines 3 months after the receipt of potentially cardiotoxic chemotherapy. These data indicate that changes in T1-weighted signal intensity may serve as an early marker of subclinical injury related to the administration of potentially cardiotoxic chemotherapy in human subjects.

Sex differences in clinical characteristics and outcomes in elderly patients with heart failure and preserved ejection fraction: the Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) trial.

BACKGROUND: There are few sex-specific outcome data in heart failure with preserved ejection fraction. METHODS AND RESULTS: We assessed sex differences in baseline characteristics and outcomes among 4128 patients with heart failure with preserved ejection fraction in the Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) trial. Women (n=2491) with heart failure with preserved ejection fraction were ≈1 year older (72±7 years versus 71±7 years) and more likely to be obese (46% versus 35%) and have chronic kidney disease (34% versus 26%) and hypertension (91% versus 85%) than men but less likely to have an ischemic cause (19% versus 34%), atrial fibrillation (27% versus 33%), or chronic obstructive pulmonary disease (8% versus 13%) (all P<0.001). During a mean of 49.5 months, there were 881 deaths (447 in women, 434 in men; risk ratio, 0.64; 95% CI, 0.56-0.74) and 5776 hospitalizations (3239 in women, 2537 in men; risk ratio, 0.80; 95% CI, 0.76-0.84). Women had lower risk of all-cause events (deaths and hospitalizations), even after adjusting for baseline characteristics (adjusted hazards ratio, 0.81; 95% CI, 0.73-0.89). However, the sex-related difference in risk of all-cause events was modified in the presence or absence of atrial fibrillation, renal dysfunction, stable angina pectoris, or advanced New York Heart Association class symptoms. CONCLUSIONS: In patients with typical heart failure with preserved ejection fraction, there were prominent sex differences in baseline characteristics and outcomes. Women had better overall prognosis, although the presence of 4 common baseline characteristics seemed to moderate this finding.

Angiotensin receptor blockers and outcomes in real-world older patients with heart failure and preserved ejection fraction: a propensity-matched inception cohort clinical effectiveness study.

AIMS: To examine the clinical effectiveness of angiotensin receptor blockers (ARBs) in older patients with heart failure and preserved ejection fraction (HF-PEF). METHODS AND RESULTS: Of the 10 570 hospitalized HF-PEF patients, aged ≥ 65 years, EF ≥ 40%, in OPTIMIZE-HF (2003-2004), linked to Medicare data (up to 31 December 2008), 3806 were not receiving angiotensin-converting enzyme inhibitors or prior ARB therapy. Of these, 303 (8%) patients received new discharge prescriptions for ARBs. Propensity scores for the receipt of ARBs, estimated for each of the 3806 patients, were used to assemble a cohort of 296 pairs of patients receiving and not receiving ARBs, who were balanced on 114 baseline characteristics. Patients had a mean age of 80 years, mean EF of 55%, 69% were women, and 12% were African American. During 6 years of follow-up, the primary composite endpoint of all-cause mortality or HF hospitalization occurred in 79% (235/296) and 81% (241/296) of patients receiving and not receiving ARBs, respectively [hazard ratio (HR) associated with ARB use 0.88, 95% confidence interval (CI) 0.74-1.06; P = 0.179]. ARB use had no association with individual endpoints of all-cause mortality (HR 0.93, 95% CI 0.76-1.14; P = 0.509), HF hospitalization (HR 0.90, 95% CI, 0.72-1.14; P = 0.389), or all-cause hospitalization (HR 0.91, 95% CI 0.77-1.08; P = 0.265). These associations remained unchanged when we compared any (prevalent and new prescriptions) ARB use vs. non-use in a separately assembled propensity-matched cohort of 1137 pairs of HF-PEF patients. CONCLUSIONS: In real-world older HF-PEF patients, ARB use was not associated with improved clinical outcomes.

The effect of intentional weight loss on all-cause mortality in older adults: results of a randomized controlled weight-loss trial.

BACKGROUND: Despite the reported benefits, weight loss is not always advised for older adults because some observational studies have associated weight loss with increased mortality. However, the distinction between intentional and unintentional weight loss is difficult to make in an observational context, so the effect of intentional weight loss on mortality may be clarified in the setting of a randomized controlled trial. OBJECTIVE: The objective was to determine the effect of intentional weight loss on all-cause mortality by using follow-up data from a randomized trial completed in 1995 that included a weight-loss arm. DESIGN: The Trial of Nonpharmacologic Intervention in the Elderly (TONE) used a 2 × 2 factorial design to determine the effect of dietary weight loss, sodium restriction, or both on blood pressure control in 585 overweight or obese older adults being treated for hypertension (mean ± SD age: 66 ± 4 y; 53% female). All-cause mortality was ascertained by using the Social Security Index and National Death Index through 2006. RESULTS: The mortality rate of those who were randomly assigned to the weight-loss intervention (n = 291; mean weight loss: 4.4 kg) did not differ significantly from that of those who were not randomly assigned to this group (n = 294; mean weight loss: 0.8 kg). The adjusted HR was 0.82 (95% CI: 0.55, 1.22). CONCLUSIONS: Intentional dietary weight loss was not significantly associated with increased all-cause mortality over 12 y of follow-up in older overweight or obese adults. Additional studies are needed to confirm and extend our findings to older age groups. This trial is registered at clinicaltrials.gov as NCT00000535.

The effect of randomization to weight loss on total mortality in older overweight and obese adults: the ADAPT Study.

BACKGROUND: Although weight loss reduces risk for comorbid diseases, many observational studies suggest that weight loss is associated with increased mortality risk, leading to reluctance by clinicians to consider weight reduction as a strategy to maintain health and independence in older adults. However, whether the observed weight loss is intentional is difficult to determine and may not accurately represent the mortality risk associated with intentional weight reduction. Data from the Arthritis, Diet, and Activity Promotion Trial (ADAPT) were used to determine whether randomization to a weight reduction program was associated with total mortality in overweight/obese older adults. METHODS: ADAPT (n = 318; mean age 69 +/- 6 years, body mass index 34 +/- 5 kg/m2, 72% female) assessed the influence of weight loss (achieved through dietary counseling and lifestyle modification) and/or exercise on function in overweight/obese older adults with knee osteoarthritis. ADAPT ended in December 1999. Participant vital was ascertained status through December 2006 using the National Death and Social Security Indexes. RESULTS: The mortality rate for those randomized to the 18-month weight loss intervention (n = 159, mean weight loss = -4.8 kg, 15 deaths) was lower than that for those not randomized to the weight loss intervention (n = 159, mean weight loss = -1.4 kg, 30 deaths; hazard rate ratio = 0.5, 95% confidence interval 0.3-1.0). Results were not appreciably changed when analyses were stratified by age, gender, baseline weight status, or magnitude of weight loss. CONCLUSIONS: In older adults, intentional weight loss was not associated with increased total mortality and may reduce mortality risk. Observational studies of weight loss, especially when intentionality cannot be rigorously established, may be misleading with respect to the effect of weight loss on mortality.

Application of assessing care of vulnerable elders-3 quality indicators to patients with advanced dementia and poor prognosis.

OBJECTIVES: To use a formal decision-making strategy to reach clinically appropriate, internally consistent decisions on the application of quality indicators (QIs) to vulnerable elders (VEs) with advanced dementia (AD) or poor prognosis (PP). DESIGN: Using a conceptual model that classifies QIs principally by aim and burden of the care process, 12 clinical experts rated whether each Assessing Care of Vulnerable Elders-3 (ACOVE-3) QI should be applied in evaluating quality of care for older persons with AD or PP. QI exclusions were assessed for each of the 26 conditions and by whether these conditions were mainly medical (e.g., diabetes mellitus), geriatric (e.g., falls), or crosscutting processes of care (e.g., pain management). QI exclusions were also identified for older persons who decided against hospitalization or surgery. RESULTS: Of 392 ACOVE-3 QIs, 140 (36%) were excluded for patients with AD and 135 (34%) for patients with PP; 57% of QIs focusing on medical conditions were excluded from patients with AD and 53% from patients with PP, whereas only 20% of QIs for geriatric conditions were excluded from AD and 15% from PP. All QIs with care processes judged to carry a heavy burden were excluded; 86% of moderate-burden QIs were excluded from AD and 92% from PP. All QIs aimed at long-term goals were excluded; 83% of intermediate-term goal QIs were excluded from AD and 98% from PP. Individuals holding a preference to forgo hospitalization or surgery would be excluded from 7% of potentially applicable QIs. CONCLUSION: Measurement of quality of care for VEs with AD, PP, and less-aggressive care preferences should include only a subset of the ACOVE-3 QIs, largely those whose burden is light and whose goal is continuity or short-term improvement or prevention.

Assessment of the interaction of heritability of volume load and left ventricular mass: the HyperGEN offspring study.

BACKGROUND: Left ventricular mass (LVM) is more closely associated with volume load than pressure load. We assessed whether part of the genetic heritability of LVM can be explained by stroke volume (SV) inheritance. METHODS: Echocardiographic LVM, SV and peripheral resistance were measured in 527 families with at least two relatives from the HyperGEN study (51% African-American, 43% men, 44% obese, 53% hypertensive). Included were 1792 subjects without prevalent cardiovascular disease, diabetes and renal failure. Ethnic-specific genetic correlations were estimated using a variance components procedure (SOLAR). RESULTS: Significant genetic correlations existed between LVM and SV after adjusting for age, sex, race, field center, systolic blood pressure, number of antihypertensive medications, and body mass index (rhog = 0.93 in African-Americans and 0.70 in Caucasians; both P < 0.0001). Urinary Na excretion or serum creatinine did not influence these correlations. After adjusting for covariates, heritability of LVM was greater (h = 0.46 in African-Americans and 0.47 in Caucasians; both P < 0.0001) than that for SV (h = 0.18 in African-Americans and 0.29 in Caucasians; both P < 0.02). Heritability of LVM slightly decreased in African-Americans (h = 0.34), but not in Caucasians (h = 0.45; both P < 0.0001) when SV was added to covariates. Heritability of SV almost disappeared by addition of LVM into the model in African-Americans (h = 0.04, P = not significant), whereas it was slightly reduced in Caucasians (h = 0.20, P < 0.005). CONCLUSION: LVM and SV share a common genetic profile, but with only a modest reciprocal influence. Variability of LVM has some effect on calculated heritability of SV, especially in African-Americans, whereas the role of heritable volume load in determining the variability of LVM was modest only in African-Americans.