The similar two-year mortality in the hydralazine-isosorbide dinitrate arms in our previous Vasodilator-Heart Failure Trial (26 percent) and in the present trial (25 percent), as compared with that in the placebo arm in the previous trial, (34 percent) and the further survival benefit with enalapril in the present trial (18 percent) strengthen the conclusion that vasodilator therapy should be included in the standard treatment for heart failure. The different effects of the two regimens (enalapril and hydralazine-isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination.
Giant-cell myocarditis is a disease of relatively young, predominantly healthy adults. Patients usually die of heart failure and ventricular arrhythmia unless cardiac transplantation is performed. Despite the possibility of fatal disease recurrence, transplantation is the treatment of choice for most patients.
Low-intensity anticoagulation with warfarin prevented cerebral infarction in patients with nonrheumatic atrial fibrillation without producing an excess risk of major hemorrhage. This benefit extended to patients over 70 years of age.
Objectives
This study aimed to assess the factors limiting maximal exercise capacity in patients with chronic heart failure (CHF).
Background
Maximal exercise capacity, an important index of health in CHF, might be limited by central and/or peripheral factors; however, their contributions remain poorly understood.
Methods
We studied oxygen (O2) transport and metabolism at maximal cycle (centrally taxing) and knee-extensor (KE) (peripherally taxing) exercise in 12 patients with CHF and 8 healthy control subjects in normoxia and hyperoxia (100% O2).
Results
Peak oxygen uptake (VO2) while cycling was 33% lower in CHF patients than in control subjects. By experimental design, peak cardiac output was reduced during KE exercise when compared with cycling (approximately 35%); although muscle mass specific peak leg VO2 was increased equally in both groups (approximately 70%), VO2 in the CHF patients was still 28% lower. Hyperoxia increased O2 carriage in all cases but only facilitated a 7% increase in peak leg VO2 in the CHF patients during cycling, the most likely scenario to benefit from increased O2 delivery. Several relationships, peak leg VO2 (KE + cycle) to capillary-fiber-ratio and capillaries around a fiber to mitochondrial volume, were similar in both groups (r = 0.6-0.7).
Conclusions
Multiple independent observations, including a significant skeletal muscle metabolic reserve, suggest skeletal muscle per se contributes minimally to limiting maximal cycle exercise in CHF or healthy control subjects. However, the consistent attenuation of the convective and diffusive components of O2 transport (25% to 30%) in patients with CHF during both cycle and even KE exercise compared with control subjects reveals an underlying peripheral O2 transport limitation from blood to skeletal muscle in this pathology.
Objectives
This study sought to elucidate the mechanisms responsible for the benefits of small muscle mass exercise training in patients with chronic heart failure (CHF).
Background
How central cardiorespiratory and/or peripheral skeletal muscle factors are altered with small muscle mass training in CHF is unknown.
Methods
We studied muscle structure and oxygen (O2) transport and metabolism at maximal cycle (whole body) and knee-extensor exercise (KE) (small muscle mass) in 6 healthy controls and 6 patients with CHF who then performed 8 weeks of KE training (both legs, separately) and repeated these assessments.
Results
Pre-training cycling and KE peak leg O2 uptake (VO2peak) were ~17% and ~15% lower, respectively, in the patients compared to controls. Structurally, KE training increased quadriceps muscle capillarity and mitochondrial density by ~21 and ~25%, respectively. Functionally, despite not altering maximal cardiac output, KE training increased maximal O2 delivery (~54%), arterial-venous O2 (a–v O2) difference (~10%), and muscle O2 diffusive conductance (DMO2) (~39%) (assessed during KE), thereby increasing single leg VO2peak by ~53%, to a level exceeding that of the untrained controls. Post-training, during maximal cycling, O2 delivery (~40%), a–v O2 difference (~15%), and DMO2 (~52%) all increased, yielding an increase in VO2peak of ~40%, matching the controls.
Conclusions
In the face of continued central limitations, clear improvements in muscle structure, peripheral convective and diffusive O2 transport, and subsequently O2 utilization support the efficacy of local skeletal muscle training as a powerful approach to combat exercise intolerance in CHF.
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