Safety, Performance, and Efficacy of Cardiac Contractility Modulation Delivered by the 2-Lead Optimizer Smart System: The FIX-HF-5C2 Study.

Background: Prior studies of cardiac contractility modulation (CCM) employed a 3-lead Optimizer system. A new 2-lead system eliminated the need for an atrial lead. This study tested the safety and effectiveness of this 2-lead system compared with the 3-lead system.

Resistance Training Reduces Skeletal Muscle Work Efficiency in Weight-Reduced and Non-Weight-Reduced Subjects.

Objective: The objective of this study is to determine whether resistance training is similarly effective in reducing skeletal muscle efficiency and increasing strength in weight-reduced and maximal weight subjects.

Methods: This study examined the effects of supervised resistance exercise on skeletal muscle in 14 individuals with overweight and obesity sustaining a 10% or greater weight loss for over 6 months and a phenotypically similar group of 15 subjects who had not reduced weight and were weight stable at their maximal lifetime body weight. We assessed skeletal muscle work efficiency and fuel utilization (bicycle ergometry), strength (dynamometry), body composition (dual energy x-ray absorptiometry), and resting energy expenditure (indirect calorimetry) before and after 12 weeks of thrice-weekly resistance training.

Triiodothyronine and leptin repletion in humans similarly reverse weight-loss-induced changes in skeletal muscle.

Subjects maintaining a ≥10% dietary weight loss exhibit decreased circulating concentrations of bioactive thyroid hormones and increased skeletal muscle work efficiency largely due to increased expression of more-efficient myosin heavy chain (MHC) isoforms (MHC I) and significantly mediated by the adipocyte-derived hormone leptin. The primary purpose of this study was to examine the effects of triiodothyronine (T) repletion on energy homeostasis and skeletal muscle physiology in weight-reduced subjects and to compare these results with the effects of leptin repletion. Nine healthy in-patients with obesity were studied at usual weight (Wt) and following a 10% dietary weight loss while receiving 5 wk of a placebo (Wt) or T (Wt) in a single-blind crossover design.

A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation.

Objectives: This study sought to confirm a subgroup analysis of the prior FIX-HF-5 (Evaluate Safety and Efficacy of the OPTIMIZER System in Subjects With Moderate-to-Severe Heart Failure) study showing that cardiac contractility modulation (CCM) improved exercise tolerance (ET) and quality of life in patients with ejection fractions between 25% and 45%.

Background: CCM therapy for New York Heart Association (NYHA) functional class III and IV heart failure (HF) patients consists of nonexcitatory electrical signals delivered to the heart during the absolute refractory period.

Methods: A total of 160 patients with NYHA functional class III or IV symptoms, QRS duration <130 ms, and ejection fraction ≥25% and ≤45% were randomized to continued medical therapy (control, n = 86) or CCM (treatment, n = 74, unblinded) for 24 weeks.

Effects of weight loss and leptin on skeletal muscle in human subjects.

Maintenance of a 10% or greater reduced body weight results in decreases in the energy cost of low levels of physical activity beyond those attributable to the altered body weight. These changes in nonresting energy expenditure are due mainly to increased skeletal muscle work efficiency following weight loss and are reversed by the administration of the adipocyte-derived hormone leptin. We have also shown previously that the maintenance of a reduced weight is accompanied by a decrease in ratio of glycolytic (phosphofructokinase) to oxidative (cytochrome c oxidase) activity in vastus lateralis muscle that would suggest an increase in the relative expression of the myosin heavy chain I (MHC I) isoform.

The ventilatory anaerobic threshold in heart failure: a multicenter evaluation of reliability.

Background: The ventilatory threshold (VT) is usually determined by visual assessment of the point where the rate of elimination of carbon dioxide (VCO(2)) increases nonlinearly with respect to oxygen uptake (VO(2)) (the V-Slope method). We quantified the reliability of VT determination using data from a multicenter study in patients with heart failure.

Methods And Results: The Fix-Heart Failure-5 study of cardiac contractility modulation enrolled 428 patients from 50 centers in the United States.

Chronotropic incompetence, beta-blockers, and functional capacity in advanced congestive heart failure: time to pace?

Background: Chronotropic incompetence (CI) is often seen in subjects with chronic congestive heart failure (CHF). The prevalence of CI, its mechanisms and association with beta-blocker use as well as exercise capacity have not been clearly defined.

Methods And Results: Cardiopulmonary exercise tolerance testing data for 278 consecutive patients with systolic CHF was analyzed.

Association of heart rate recovery and maximum oxygen consumption in patients with chronic congestive heart failure.

Background: Peak oxygen consumption (peak VO2) is one of the strongest predictors of mortality in patients with congestive heart failure (CHF). In contrast to measurements of peak VO2, which requires analysis of expired gases, heart rate recovery, defined as maximum heart rate minus heart rate at 1 minute after exercise, is easily obtained. The current study was undertaken to determine the association between peak VO2 and heart rate recovery in patients with CHF.

New predictors of outcome in idiopathic pulmonary arterial hypertension.

Idiopathic pulmonary arterial hypertension (PAH) is a rare disease with a poor prognosis. New therapies have improved the outcome of this condition; accordingly, the factors that determine outcome may have changed. We aimed to identify determinants of survival in a cohort of consecutive patients with PAH: which was idiopathic, familial, or associated with anorexigen use.