Jill Downing

The role of exercise training in heart failure.

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.

Changes in exercise capacity following cardiac rehabilitation in patients stratified according to age and gender. Results of the Massachusetts Association of Cardiovascular and Pulmonary Rehabilitation Multicenter Database.

BACKGROUND Using information collected prospectively from a multicenter cardiac rehabilitation database, this study was designed to evaluate baseline exercise tolerance and subsequent change in functional capacity among consecutive patients enrolled in supervised cardiac rehabilitation stratified according to age and gender. In addition, the study evaluated change in functional capacity among those with the lowest initial exercise tolerance (<5 METS) and assessed patient factors that correlate to the highest relative improvements in functional capacity after training. METHODS A total of 778 patients performed an initial exercise test upon entry into cardiac rehabilitation, during which peak heart rate, blood pressure, and estimated peak MET levels were derived, and ischemic responses were evaluated. After 10 +/- 2 weeks of supervised prescribed exercise, 500 patients who completed the program performed follow-up exercise testing. RESULTS The subjects included 558 men (72%) and 220 women (28%) of whom 492 (63%) were <65 years, 241 (31%) were 65 to 75 years, and 45 (6%) were >75 years. At baseline, the peak initial MET level for men was 8.6 +/- 3.4 METS and for women was 6.0 +/- 2.6 METs. The peak initial MET level declined with age: age <65 = 8.9 +/- 3.4 METS; age 65 to 75 = 6.6 +/- 2.6 METS; and age >75 = 5.7 +/- 2.9 METS. When stratified according to age and gender, the baseline exercise tolerance for men significantly (P <.0001) declined with age and was higher than that of women <65 and 65 to 75 years of age. After training, the relative improvement in exercise tolerance for each age and/or gender subgroup was: age <65: men 36%, women 41%; age 65 to 75: men 36%, women 50%; and age >75: men 36%, women 32%. Among 163 patients with an initial peak MET level <5, exercise tolerance rose from 4.1 +/- 0.7 to 8.3 +/- 3.5 METS (P <.0001). Multivariate analysis demonstrated that the greatest change in exercise tolerance with training was associated with those compliant patients with initial peak METS <5. No significant net change in the occurrence of exercise-induced ischemia was observed. CONCLUSIONS 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.

Relationship of Plasma Galectin-3 to Renal Function in Patients With Heart Failure: Effects of Clinical Status, Pathophysiology of Heart Failure, and Presence or Absence of Heart Failure

Background Galectin-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 Results Patients 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. Conclusions Plasma 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.

Preclinical Systolic and Diastolic Dysfunctions in Metabolically Healthy and Unhealthy Obese Individuals

Background—Despite the substantial overlap of obesity and metabolic disease, there is heterogeneity 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 (OB/MS−, n=37) MS were compared with nonobese 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 when compared with nonobese controls. Specifically, OB/MS− had 2.5% lower LS (SE, 0.7%; P=0.001 in multivariable-adjusted analyses) and 10.8 ms greater dyssynchrony (SE, 3.3 ms; P=0.002), and OB/MS+ had 1.0% lower LS (SE, 0.3%; P<0.001) and 7.8 ms greater dyssynchrony (SE, 1.5 ms; P<0.001) when 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 although diastolic dysfunction was more pronounced in OB/MS+ than in 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 seems to be associated with worse diastolic dysfunction. When compared with 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.

Impaired Right Ventricular Hemodynamics Indicate Preclinical Pulmonary Hypertension in Patients With Metabolic Syndrome

Background Metabolic 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 Results A 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. Conclusions MetS 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.

Assessing the safety of anthrax immunization in US Army aircrew members via physical examination.

Objective: Anthrax in weaponized form is the bioterrorism agent of most concern. Questions raised about the safety of the anthrax vaccine can be addressed by comparing immunized and unimmunized people in population-based studies. Methods: A retrospective evaluation of data from periodic physical examinations collected on anthrax-immunized and -unimmunized US Army aircrew members between 1998 and 2005 was performed to evaluate the safety of anthrax immunization. Mean changes in variables found on physical examination and laboratory analysis were compared by use of t tests. Multiple linear regression predicted change in outcome from baseline characteristics. Results: We compared 6820 immunized subjects and 4145 unimmunized controls based on US Army aircrew physical examination and screening laboratory tests. No association between anthrax immunization and a clinically relevant change in a tested physiologic parameter was detected. Conclusions: No attributable risk of anthrax immunization was observed in this group of Army aircrew members.

Preclinical Alterations in Myocardial Microstructure in People with Metabolic Syndrome

Metabolic syndrome (MetS) can lead to myocardial fibrosis, diastolic dysfunction, and eventual heart failure. This study evaluated alterations in myocardial microstructure in people with MetS by using a novel algorithm to characterize ultrasonic signal intensity variation.