Nomograms to predict normal aortic root diameter for body surface area (BSA) in broad ranges of age have been widely used but are limited by lack of consideration of gender effects, jumps in upper ...limits of aortic diameter among age strata, and data from older teenagers. Sinus of Valsalva diameter was measured by American Society of Echocardiography convention in normal-weight, nonhypertensive, nondiabetic subjects ≥15 years old without aortic valve disease from clinical or population-based samples. Analyses of covariance and linear regression with assessment of residuals identified determinants and developed predictive models for normal aortic root diameter. In 1,207 apparently normal subjects ≥15 years old (54% women), aortic root diameter was 2.1 to 4.3 cm. Aortic root diameter was strongly related to BSA and height (r = 0.48 for the 2 comparisons), age (r = 0.36), and male gender (+2.7 mm adjusted for BSA and age, p <0.001 for all comparisons). Multivariable equations using age, gender, and BSA or height predicted aortic diameter strongly (R = 0.674 for the 2 comparisons, p <0.001) with minimal relation of residuals to age or body size: for BSA 2.423 + (age years × 0.009) + (BSA square meters × 0.461) − (gender 1 = man, 2 = woman × 0.267), SEE 0.261 cm; for height 1.519 + (age years × 0.010) + (height centimeters × 0.010) − (gender 1 = man, 2 = woman × 0.247), SEE 0.215 cm. In conclusion, aortic root diameter is larger in men and increases with body size and age. Regression models incorporating body size, age, and gender are applicable to adolescents and adults without limitations of previous nomograms.
Abstract Background Classification of chronic heart failure (HF) is on the basis of criteria that may not adequately capture disease heterogeneity. Improved phenotyping may help inform research and ...therapeutic strategies. Objectives This study used cluster analysis to explore clinical phenotypes in chronic HF patients. Methods A cluster analysis was performed on 45 baseline clinical variables from 1,619 participants in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) study, which evaluated exercise training versus usual care in chronic systolic HF. An association between identified clusters and clinical outcomes was assessed using Cox proportional hazards modeling. Differential associations between clinical outcomes and exercise testing were examined using interaction testing. Results Four clusters were identified (ranging from 248 to 773 patients in each), in which patients varied considerably among measures of age, sex, race, symptoms, comorbidities, HF etiology, socioeconomic status, quality of life, cardiopulmonary exercise testing parameters, and biomarker levels. Differential associations were observed for hospitalization and mortality risks between and within clusters. Compared with cluster 1, risk of all-cause mortality and/or all-cause hospitalization ranged from 0.65 (95% confidence interval 95% CI: 0.54 to 0.78) for cluster 4 to 1.02 (95% CI: 0.87 to 1.19) for cluster 3. However, for all-cause mortality, cluster 3 had a disproportionately lower risk of 0.61 (95% CI: 0.44 to 0.86). Evidence suggested differential effects of exercise treatment on changes in peak oxygen consumption and clinical outcomes between clusters (p for interaction <0.04). Conclusions Cluster analysis of clinical variables identified 4 distinct phenotypes of chronic HF. Our findings underscore the high degree of disease heterogeneity that exists within chronic HF patients and the need for improved phenotyping of the syndrome. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437 )
Exercise intolerance is the primary chronic symptom in heart failure with preserved ejection fraction (HFpEF), the most common form of heart failure in older patients; however its pathophysiology is ...not well understood. Recent data suggest that peripheral factors such as skeletal muscle (SM) dysfunction may be important contributors. Therefore, 38 participants, 23 patients with HFpEF (69 ± 7 years) and 15 age-matched healthy controls (HCs), underwent magnetic resonance imaging and cardiopulmonary exercise testing to assess for SM, intermuscular fat (IMF), subcutaneous fat, total thigh, and thigh compartment (TC) areas and peak exercise oxygen consumption (peak VO2 ). There were no significant intergroup differences in total thigh area, TC, subcutaneous fat, or SM. However, in the HFpEF versus HC group, IMF area (35.6 ± 11.5 vs 22.3 ± 7.6 cm2 , p = 0.01), percent IMF/TC (26 ± 5 vs 20 ± 5%, p = 0.005), and the ratio of IMF/SM (0.38 ± 0.10 vs 0.28 ± 0.09, p = 0.007) were significantly increased, whereas percent SM/TC was significantly reduced (70 ± 5 vs 75 ± 5, p = 0.009). In multivariate analyses, IMF area (partial r = −0.51, p = 0.002) and IMF/SM ratio (partial r = −0.45, p = 0.006) were independent predictors of peak VO2 whereas SM area was not (partial r = −0.14, p = 0.43). Thus, older patients with HFpEF have greater thigh IMF and IMF/SM ratio compared with HCs, and these are significantly related to their severely reduced peak VO2 . These data suggest that abnormalities in SM composition may contribute to the severely reduced exercise capacity in older patients with HFpEF. This implicates potential targets for novel therapeutic strategies in this common debilitating disorder of older persons.
Objectives The purpose of this study was to determine the mechanisms responsible for reduced aerobic capacity (peak V o2 ) in patients with heart failure with preserved ejection fraction (HFPEF). ...Background HFPEF is the predominant form of heart failure in older persons. Exercise intolerance is the primary symptom among patients with HFPEF and a major determinant of reduced quality of life. In contrast to patients with heart failure and reduced ejection fraction, the mechanism of exercise intolerance in HFPEF is less well understood. Methods Left ventricular volumes (2-dimensional echocardiography), cardiac output, V o2 , and calculated arterial-venous oxygen content difference (A-V o2 Diff) were measured at rest and during incremental, exhaustive upright cycle exercise in 48 HFPEF patients (age 69 ± 6 years) and 25 healthy age-matched controls. Results In HFPEF patients compared with healthy controls, V o2 was reduced at peak exercise (14.3 ± 0.5 ml·kg·min−1 vs. 20.4 ± 0.6 ml·kg·min−1 ; p < 0.0001) and was associated with a reduced peak cardiac output (6.3 ± 0.2 l·min−1 vs. 7.6 ± 0.2 l·min−1 ; p < 0.0001) and A-V o2 Diff (17 ± 0.4 ml·dl−1 vs. 19 ± 0.4 ml·dl−1 , p < 0.0007). The strongest independent predictor of peak V o2 was the change in A-V o2 Diff from rest to peak exercise (A-V o2 Diff reserve) for both HFPEF patients (partial correlate, 0.58; standardized β coefficient, 0.66; p = 0.0002) and healthy controls (partial correlate, 0.61; standardized β coefficient, 0.41; p = 0.005). Conclusions Both reduced cardiac output and A-V o2 Diff contribute significantly to the severe exercise intolerance in elderly HFPEF patients. The finding that A-V o2 Diff reserve is an independent predictor of peak V o2 suggests that peripheral, noncardiac factors are important contributors to exercise intolerance in these patients.
Objectives The purpose of this study was to evaluate the mechanisms for improved exercise capacity after endurance exercise training (ET) in elderly patients with heart failure and preserved ejection ...fraction (HFPEF). Background Exercise intolerance, measured objectively by reduced peak oxygen consumption (VO2 ), is the primary chronic symptom in HFPEF and is improved by ET. However, the mechanisms are unknown. Methods Forty stable, compensated HFPEF outpatients (mean age 69 ± 6 years) were examined at baseline and after 4 months of ET (n = 22) or attention control (n = 18). The VO2 and its determinants were assessed during rest and peak upright cycle exercise. Results After ET, peak VO2 in those patients was higher than in control patients (16.3 ± 2.6 ml/kg/min vs. 13.1 ± 3.4 ml/kg/min; p = 0.002). That was associated with higher peak heart rate (139 ± 16 beats/min vs. 131 ± 20 beats/min; p = 0.03), but no difference in peak end-diastolic volume (77 ± 18 ml vs. 77 ± 17 ml; p = 0.51), stroke volume (48 ± 9 ml vs. 46 ± 9 ml; p = 0.83), or cardiac output (6.6 ± 1.3 l/min vs. 5.9 ± 1.5 l/min; p = 0.32). However, estimated peak arterial-venous oxygen difference was significantly higher in ET patients (19.8 ± 4.0 ml/dl vs. 17.3 ± 3.7 ml/dl; p = 0.03). The effect of ET on cardiac output was responsible for only 16% of the improvement in peak VO2. Conclusions In elderly stable compensated HFPEF patients, peak arterial-venous oxygen difference was higher after ET and was the primary contributor to improved peak VO2 . This finding suggests that peripheral mechanisms (improved microvascular and/or skeletal muscle function) contribute to the improved exercise capacity after ET in HFPEF. (Prospective Aerobic Reconditioning Intervention Study PARIS; NCT01113840 )
Background Many African Americans carry an amyloidogenic transthyretin mutation (TTR V122I), with a high risk for cardiac TTR amyloid deposition after the age of 65 years. We wished to determine the ...allele frequency and its clinical penetrance in community-dwelling African Americans. Methods Five thousand consenting African Americans, aged 41 to 93 years, in 2 community studies of cardiovascular risk (CHS and ARIC) were included in the study. The following were performed: genotyping of banked DNA for TTR V122I allele status and review of cardiovascular and demographic parameters in CHS and ARIC databases, with statistical comparisons of the frequency of congestive heart failure, survival, and occurrence of features of cardiac amyloidosis in carriers of the amyloidogenic allele and controls. Results One hundred nineteen (3.23%) of 3,712 ARIC and 17 (2.12%) of 805 CHS African Americans carried TTR V122I. After the age of 65 years (CHS), the frequencies of congestive heart failure (38% vs 15%, relative risk 2.62, P = .04) and mortality (76% vs 53%, relative risk 1.46, P = .08) were higher in V122I allele carriers than in age-, gender- and ethnically matched controls. In ARIC (all subjects <65 years old), there were no differences between carriers and noncarriers in mortality, frequency of congestive heart failure, or findings consistent with cardiac amyloidosis. Conclusions Heterozygosity for the amyloidogenic TTR V122I mutation is relatively common in community-dwelling African Americans. Before the age of 65 years, the allele has no discernible impact on cardiac function or mortality. After the age of 70 years, carriers show a higher frequency of congestive failure and greater mortality with more echocardiographic evidence suggestive of cardiac amyloidosis, findings consistent with age-dependent clinical penetrance of this autosomal dominant gene.
Older patients with acute decompensated heart failure (ADHF) have persistently poor outcomes including frequent rehospitalization despite guidelines-based therapy. We hypothesized that such patients ...have multiple, severe impairments in physical function, cognition, and mood that are not addressed by current care pathways. We prospectively examined frailty, physical function, cognition, mood, and quality of life in 27 consecutive older patients with ADHF at 3 medical centers and compared these with 197 participants in 3 age-matched cohorts: stable heart failure (HF) with preserved ejection fraction (n = 80), stable HF with reduced ejection fraction (n = 56), and healthy older adults (n = 61). Based on Fried criteria, frailty was present in 56% of patients with ADHF versus 0 for the age-matched chronic HF and health cohorts. Patients with ADHF had markedly reduced Short Physical Performance Battery score (5.3 ± 2.8) and 6-minute walk distance (178 ± 102 m) (p <0.001 vs other cohorts), with severe deficits in all domains of physical function: balance, mobility, strength, and endurance. In the patients with ADHF, cognitive impairment (78%) and depression (30%) were common, and quality of life was poor. In conclusion, older patients with ADHF are frequently frail with severe and widespread impairments in physical function, cognition, mood, and quality of life that may contribute to their persistently poor outcomes, are frequently unrecognized, are not addressed in current ADHF care paradigms, and are potentially modifiable with targeted interventions.
Objectives The goal of this study was to compare the prognostic efficacy of the 6-min walk (6MW) and cardiopulmonary exercise (CPX) tests in stable outpatients with chronic heart failure (HF). ...Background CPX and 6MW tests are commonly applied as prognostic gauges for systolic HF patients, but few direct comparisons have been conducted. Methods Stable New York Heart Association (NYHA) functional class II and III systolic HF patients (ejection fraction ≤35%) from the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial were studied. 6MW distance (6MWD) and CPX indices (peak oxygen consumption VO2 and ventilatory equivalents for exhaled carbon dioxide VE/VCO2 slope) were compared as predictors of all-cause mortality/hospitalization and all-cause mortality over 2.5 years of mean follow-up. Results A total of 2,054 HF-ACTION participants underwent both CPX and 6MW tests at baseline (median age 59 years; 71% male; 64% NYHA functional class II and 36% NYHA functional class III/IV). In unadjusted models and in models that included key clinical and demographic covariates, C-indices of 6MWD were 0.58 and 0.65 (unadjusted) and 0.62 and 0.72 (adjusted) in predicting all-cause mortality/hospitalization and all-cause mortality, respectively. C-indices for peak VO2 were 0.61 and 0.68 (unadjusted) and 0.63 and 0.73 (adjusted). C-indices for VE/VCO2 slope were 0.56 and 0.65 (unadjusted) and 0.61 and 0.71 (adjusted); combining peak VO2 and VE/VCO2 slope did not improve the C-indices. Overlapping 95% confidence intervals and modest integrated discrimination improvement values confirmed similar prognostic discrimination by 6MWD and CPX indices within adjusted models. Conclusions In systolic HF outpatients, 6MWD and CPX indices demonstrated similar utility as univariate predictors for all-cause hospitalization/mortality and all-cause mortality. However, 6MWD or CPX indices added only modest prognostic discrimination to models that included important demographic and clinical covariates.
Abstract The primary chronic symptom in patients with clinically stable heart failure (HF) is reduced exercise tolerance, measured as decreased peak aerobic power (peak oxygen consumption V o2 ), and ...is associated with reduced quality of life and survival. Exercise-based cardiac rehabilitation (EBCR) is a safe and effective intervention to improve peak V o2 , muscle strength, physical functional performance, and quality of life and is associated with a reduction in overall and HF-specific hospitalization in clinically stable patients with HF. Despite these salient benefits, fewer than one-tenth of eligible patients with HF are referred for EBCR after hospitalization. In this review, selection for and timing of EBCR for patients with HF, as well as exercise prescription guidelines with special emphasis on the optimal exercise training intensity to improve peak Vo2 , are discussed.
Abstract The incidence and prevalence of most cardiovascular disorders increase with age, and cardiovascular disease is the leading cause of death and major disability in adults ≥75 years of age; ...however, despite the large impact of cardiovascular disease on quality of life, morbidity, and mortality in older adults, patients aged ≥75 years have been markedly underrepresented in most major cardiovascular trials, and virtually all trials have excluded older patients with complex comorbidities, significant physical or cognitive disabilities, frailty, or residence in a nursing home or assisted living facility. As a result, current guidelines are unable to provide evidence-based recommendations for diagnosis and treatment of older patients typical of those encountered in routine clinical practice. The objectives of this scientific statement are to summarize current guideline recommendations as they apply to older adults, identify critical gaps in knowledge that preclude informed evidence-based decision making, and recommend future research to close existing knowledge gaps. To achieve these objectives, we conducted a detailed review of current American College of Cardiology/American Heart Association and American Stroke Association guidelines to identify content and recommendations that explicitly targeted older patients. We found that there is a pervasive lack of evidence to guide clinical decision making in older patients with cardiovascular disease, as well as a paucity of data on the impact of diagnostic and therapeutic interventions on key outcomes that are particularly important to older patients, such as quality of life, physical function, and maintenance of independence. Accordingly, there is a critical need for a multitude of large population-based studies and clinical trials that include a broad spectrum of older patients representative of those seen in clinical practice and that incorporate relevant outcomes important to older patients in the study design. The results of these studies will provide the foundation for future evidence-based guidelines applicable to older patients, thereby enhancing patient-centered evidence-based care of older people with cardiovascular disease in the United States and around the world.
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