Exercise training in patients with systolic heart failure (HF) is an accepted adjunct to an evidence-based management program. This review describes the pathophysiologic features that are thought to be responsible for the exercise intolerance experienced in the HF patient. Significant research has expanded our appreciation of the interplay of hemodynamic, ventilatory, and skeletal myopathic processes in this common, chronic condition. Randomized, controlled exercise trials designed to measure endothelial function, inflammatory markers, sympathetic neural activation, and skeletal muscle metabolism and structure have further defined the pathophysiology, documented the impact of exercise training on these processes, and confirmed the benefit of this therapy. Consistent with prior clinical research and patient experience are the recently published results of the HF-ACTION (Heart Failure-A Controlled Trial Investigating Outcomes of exercise TraiNing), which demonstrated a modest improvement in exercise capacity, reduction of symptoms, and improved self-reported measures of quality of life without adverse events. Consideration is given in this review to the benefits of variable intensity programs and the addition of resistance exercise to a standard aerobic prescription. Despite increasing validation of the role exercise training plays in the modification of exercise intolerance, challenges remain in its routine therapeutic application, including acceptance and use as an adjunctive intervention in the management of the patient with HF, limited insurance coverage for HF patients in cardiac rehabilitation, tailoring of exercise programs to best address the needs of subgroups of patients, and improved short- and long-term adherence to exercise training and a physically active lifestyle.

Background Despite the substantial overlap of obesity and metabolic disease, there is hetereogeneity with respect to cardiovascular risk. We sought to investigate preclinical differences in systolic and diastolic function in obesity, and specifically compare obese individuals with and without metabolic syndrome (MS). Methods and Results Obese individuals without cardiac disease with (OB/MS+, n=124) and without MS (OB/MS−, n=37) were compared to non-obese controls (n=29). Diastolic function was assessed by transmitral and tissue Doppler. Global longitudinal strain (LS) and time-based dyssynchrony were assessed by speckle tracking. Both Ob/MS− and OB/MS+ groups had similar ejection fraction but worse systolic mechanics as assessed by LS and dyssynchrony compared with non-obese controls. Specifically, OB/MS− had 2.5% lower LS (s.e. 0.7%, P=0.001 in multivariable-adjusted analyses) and 10.8 ms greater dyssynchrony (s.e. 3.3, P=0.002), and OB/MS+ had 1.0% lower LS (s.e. 0.3%, P<0.001) and 7.8 ms greater dyssynchrony (s.e. 1.5, P<0.001) compared with controls. Obesity was associated with impaired diastolic function regardless of MS status, as evidenced by greater left atrial diameter and left ventricular mass, though diastolic dysfunction was more pronounced in OB/MS+ compared with OB/MS− individuals. Conclusions Obesity is associated with subclinical differences in both systolic and diastolic function regardless of the presence or absence of MS, although MS appears to be associated with worse diastolic dysfunction. Compared to controls, ‘metabolically healthy’ obese had lower LS, greater dyssynchrony, and early diastolic dysfunction, supporting the notion that obesity per se may have adverse cardiovascular effects regardless of metabolic disease.

Health status measurement provides information that can supplement the usual measures of impairment in patients with cardiovascular disease. The findings of this study contribute to the understanding of health status of individuals who enroll in cardiac rehabilitation programs. The health status instrument used in this study has potential as a useful, practical measurement tool for use in the clinical setting.

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BackgroundGalectin-3 (GAL-3), a β-galactoside–binding protein, is a new clinical biomarker believed to reflect cardiac remodeling/fibrosis in patients with heart failure (HF). Plasma GAL-3 is inversely related to renal function. It is not known whether the relationship between renal function and GAL-3 is influenced by clinical decompensation, type of HF, or the presence or absence of clinical HF.Methods and ResultsPatients were prospectively categorized as having acute decompensated HF or stable HF on the basis of clinical status and as having HF with reduced left ventricular ejection fraction or HF with preserved left ventricular ejection fraction. Plasma GAL-3 was measured by enzyme-linked immunosorbent assay in patients with HF (n=75), control patients without HF (n=32), and control patients without HF with moderate renal insufficiency (n=12). Compared to controls without HF (14±4 ng/mL), GAL-3 was higher in patients with both acute decompensated HF (23±11 ng/mL) and stable HF (22±10 ng/mL) (P<0.001 versus controls for both) but did not differ between acute decompensated HF and stable HF (P=0.75). Likewise, GAL-3 was elevated in both HF with preserved left ventricular ejection fraction (23±9 ng/mL) and HF with reduced left ventricular ejection fraction (22±11 ng/mL) (P<0.001 versus controls for both) but did not differ between HF with preserved ejection fraction and HF with reduced ejection fraction (P=0.37). GAL-3 correlated strongly with estimated glomerular filtration rate, both in patients with HF (r=−0.75, P<0.001) and in patients without HF (r=−0.82, P<0.001), and this relationship was unaffected by the presence or absence of clinical HF.ConclusionsPlasma GAL-3 is inversely related to renal function in patients with and without clinical HF. Concentrations of plasma GAL-3 do not seem to depend on the level of compensation or type of HF. Furthermore, the relationship between GAL-3 and renal function seems to be affected little or not at all by the presence or absence of clinical HF.

Metabolic syndrome (MS) is commonly associated with left ventricular (LV) diastolic dysfunction and LV hypertrophy. We sought to examine whether preclinical LV diastolic dysfunction can occur independent of LV hypertrophy in MS. We recruited 90 consecutive participants with MS and without cardiovascular disease (mean age 46 years, 78% women), and 26 controls (no risk factors for MS; mean age 43 years, 65% women). Participants underwent echocardiography with tissue Doppler imaging. In age- and sex-adjusted analyses, MS was associated with higher left atrial (LA) diameter, higher LV mass, lower E/A ratio, and lower mean e' (P<0.001 for all). These associations remained significant after further adjusting for blood pressure, anti-hypertensive medication use, and body-mass index. After adjusting for LV mass, MS remained independently associated with higher LA diameter, lower E/A ratio and lower mean e' (P≤0.01 for all). Specifically, subjects with MS had a 1.8 cm/s lower mean e' compared with controls (P=0.01). Notably, differences in mean e' between those with and without MS were more pronounced at younger ages (P for interaction=0.003). In conclusion, MS was associated with preclinical LV diastolic dysfunction independent of LV mass, as reflected by higher LA diameter, lower E/A ratio, and lower mean e'. This suggests that MS can lead to the development of diastolic dysfunction via mechanisms independent of hypertrophy. Differences in diastolic function were more pronounced at younger ages, highlighting the potential importance of early risk factor modification and preventive strategies in MS.

BackgroundMetabolic disease can lead to intrinsic pulmonary hypertension in experimental models. The contributions of metabolic syndrome (MetS) and obesity to pulmonary hypertension and right ventricular dysfunction in humans remain unclear. We investigated the association of MetS and obesity with right ventricular structure and function in patients without cardiovascular disease.Methods and ResultsA total of 156 patients with MetS (mean age 44 years, 71% women, mean body mass index 40 kg/m2), 45 similarly obese persons without MetS, and 45 nonobese controls underwent echocardiography, including pulsed wave Doppler measurement of pulmonary artery acceleration time (PAAT) and ejection time. Pulmonary artery systolic pressure was estimated from PAAT using validated equations. MetS was associated with lower tricuspid valve e′ (right ventricular diastolic function parameter), shorter PAAT, shorter ejection time, and larger pulmonary artery diameter compared with controls (P<0.05 for all). Estimated pulmonary artery systolic pressure based on PAAT was 42±12 mm Hg in participants with MetS compared with 32±9 and 32±10 mm Hg in obese and nonobese controls (P for ANOVA <0.0001). After adjustment for age, sex, hypertension, diabetes, body mass index, and triglycerides, MetS remained associated with a 20‐ms–shorter PAAT (β=−20.4, SE=6.5, P=0.002 versus obese). This association persisted after accounting for left ventricular structure and function and after exclusion of participants with obstructive sleep apnea.ConclusionsMetS is associated with abnormal right ventricular and pulmonary artery hemodynamics, as shown by shorter PAAT and subclinical right ventricular diastolic dysfunction. Estimated pulmonary artery systolic pressures are higher in MetS and preclinical metabolic heart disease and raise the possibility that pulmonary hypertension contributes to the pathophysiology of metabolic heart disease.

Among consecutive patients enrolled in cardiac rehabilitation, baseline exercise tolerance differs relative to age and gender, with male gender and younger age demonstrating the highest functional capacity. Exercise training yielded significant improvements in exercise tolerance among men and women of every age group including those older than 75 years, and particularly among those with an initial peak MET level <5. Thus, referral to cardiac rehabilitation programs should be advocated for both men and women, and should not be limited by age.