Objective effects of a 6 months' endurance and strength training program in outpatients with congestive heart failure.

PURPOSE: The aim of this study was to assess the feasibility and the effects of a long-term training program with endurance and strength elements for patients with advanced congestive heart failure (CHF). METHODS: We studied 14 patients, mean age 57 yr, mean NYHA class 2.7, mean LVEF 29%, and mean VO2max 17.2 mL x kg(-1) x min(-1). They underwent a 6 months' outpatient "in-hospital" training program (80 sessions). After an introduction period the program was subdivided into four cycles in which endurance and strength were revalued and progressively increased. Endurance was measured by spiro-ergometric exercise testing with concomitant lactate determination, while strength was measured on an isokinetic dynamometer. RESULTS: The compliance ratio was 89% and there were no major problems during training. NYHA class improved from a mean of 2.7 to 1.5 (P = 0.0001), working capacity from 83 to 100 W (P = 0.001), VO2 from 16.7 to 18.4 mL x kg(-1) x min(-1) (P = 0.02), and maximal exercise lactate from 4.1 to 5.2 mmol x L(-1) (P = 0.01). At isokinetic testing we found a significant 18% increase in muscular endurance of knee flexors (P = 0.008) and 25% increase of knee extensors (P = 0.007). The increase of peak torque, total work, and average power reached statistical significance only for the knee extensors. CONCLUSION: This pilot study showed that progressively adapted global strength training in association with traditional endurance training is feasible for selected patients with CHF. Additional larger studies should be done to test the effects, the safety, and the composition of such supervised "in-hospital" training programs.

Hemodynamic and mechanical determinants of myocardial O2 consumption in normal human heart: effects of dobutamine.

The relationship of myocardial O2 consumption (MVO2) to its potential hemodynamic and mechanical determinants was investigated in eight healthy normal volunteers at rest and during infusion of dobutamine (5-10 micrograms.kg-1.min-1). MVO2 was calculated from the monoexponential myocardial clearance of [1-11C]acetate with positron emission tomography, and left ventricular mechanical function was assessed by two-dimensional echocardiography. Infusion of dobutamine increased heart rate by 53%, the tension-time index by 31%, and the rate-pressure product by 116%. Cardiac output (+70%), left ventricular ejection fraction (+24%), total mechanical energy [systolic pressure-volume area, (PVA) +84%], and left ventricular pressure-work index (+100%) also increased during infusion of dobutamine. During infusion of dobutamine, MVO2 increased from 96 +/- 17 to 233 +/- 19 J.min-1.100 g left ventricle-1, while myocardial efficiency (the ratio of PVA to MVO2) decreased from 46 +/- 8 to 35 +/- 4% (P < 0.001 each). MVO2 was best correlated (P < 0.001) with the PVA (r = 0.92) and the pressure-work index (r = 0.92). Infusion of dobutamine also resulted in a significant parallel upward shift of the PVA-MVO2 relationship, indicative of an increase in PVA-independent MVO2. Our data indicate that, in human subjects, MVO2 is mainly related to systolic PVA and that inotropic stimulation with dobutamine results in decreased efficiency of contraction, such as that previously described in isolated hearts.

Mechanisms of chronic regional postischemic dysfunction in humans. New insights from the study of noninfarcted collateral-dependent myocardium.

BACKGROUND: Even in the absence of a previous myocardial infarction, patients with coronary artery disease often present with chronic regional wall motion abnormalities that are reversible spontaneously or after coronary revascularization. In these patients, regional dysfunction has been proposed to result either from prolonged postischemic dysfunction (myocardial "stunning") or from adaptation to chronic hypoperfusion (myocardial "hibernation"). This study examines which of these two mechanisms is responsible for the chronic regional dysfunction often detected in patients with angina and noninfarcted collateral-dependent myocardium. METHODS AND RESULTS: Twenty-six anginal patients (19 men; mean age, 60 +/- 9 years old) with chronic occlusion of a major coronary artery but without previous infarction were studied. Positron emission tomography was performed to measure absolute regional myocardial blood flow with 13N-ammonia at rest (n = 26) and after intravenous dipyridamole (n = 11). The kinetics of 18F-deoxyglucose and 11C-acetate were measured to calculate the rate of exogenous glucose uptake and the regional oxidative metabolism (n = 15). Global and regional left ventricular function was evaluated by contrast ventriculography at baseline (n = 26) and after revascularization (n = 12). Transmural myocardial biopsies from the collateral-dependent area were obtained in seven patients during bypass surgery and analyzed by optical and electron microscopy. According to resting regional wall motion, patients were separated into groups with and without dysfunction of the collateral-dependent segments. In patients with normal wall motion (n = 9), regional myocardial blood flow, oxidative metabolism, and glucose uptake were similar among collateral-dependent and remote segments. By contrast, in patients with regional dysfunction (n = 17), collateral-dependent segments had lower myocardial blood flow (77 +/- 25 versus 95 +/- 27 mL.min-1.100 g-1, p < 0.001), smaller k values (slope of 11C clearance reflecting oxidative metabolism, 0.049 +/- 0.015 versus 0.068 +/- 0.020 min-1, p < 0.001) and higher glucose uptake (relative 18F-deoxyglucose-to-flow ratio of 1.9 +/- 1.6 versus 1.2 +/- 0.2, p < 0.05) compared with remote segments. However, myocardial blood flow and k values were similar among collateral-dependent segments of patients with and without segmental dysfunction. After intravenous dipyridamole, collateral-dependent myocardial blood flow increased from 78 +/- 5 to 238 +/- 54 mL.min-1.100 g-1 in three patients with normal wall motion and from 88 +/- 17 to only 112 +/- 44 mL.min-1.100 g-1 in eight patients with regional dysfunction. There was a significant (r = -0.85, p < 0.001) inverse correlation between wall motion abnormality and collateral flow reserve. Analysis of the tissue samples obtained at the time of bypass surgery showed profound structural changes in dysfunctioning collateral-dependent areas, including cellular swelling, loss of myofibrillar content, and accumulation of glycogen. Despite these alterations, the regional wall motion score improved significantly in the patients studied before and after revascularization (from 3.8 +/- 1.3 to 0.8 +/- 0.9, p < 0.005). CONCLUSIONS: In a subgroup of patients with noninfarcted collateral-dependent myocardium, immature or insufficiently developed collaterals do not provide adequate flow reserve. Despite nearly normal resting flow and oxygen consumption, these collateral-dependent segments exhibit chronically depressed wall motion and demonstrate marked ultrastructural alterations on morphological analysis. We propose that these alterations result from repeated episodes of ischemia as opposed to chronic hypoperfusion and represent the flow, metabolic, and morphological correlates of myocardial "hibernation."

Contribution of left ventricular diastolic function to exercise capacity in normal subjects.

Previous studies have established that most of the heterogeneity in exercise capacity seen with sedentariness, aging, or physical training can be accounted for by individual differences in the maximal rate of total body oxygen consumption (VO2 max) during dynamic exercise. However, the factors that limit VO2 max in normal subjects remain disputed. To test the hypothesis that differences in left ventricular diastolic performance contribute to the heterogeneity of VO2 max seen in healthy subjects, 57 normal sedentary volunteers (36 +/- 13 yr, range 20-76 yr) and 9 endurance athletes (37 +/- 8 yr, range 26-51 yr) were studied. Aerobic capacity was estimated as VO2 max during a multistage dynamic cycle exercise protocol, whereas resting left ventricular systolic and diastolic function was assessed by two-dimensional and Doppler echocardiography. The relationship of the left ventricular functional indexes with VO2 max was investigated by stepwise multiple regression analysis. VO2 max ranged from 25 to 58 ml.kg-1 x min-1 in sedentary subjects and from 44 to 60 ml.kg-1 x min-1 in athletes. With univariate analysis, significant correlations were observed between VO2 max and age (r = -0.60), maximal heart rate (r = 0.48), maximal work load (r = 0.80), left ventricular volumes at both end diastole (r = 0.51) and end systole (r = 0.62), peak early transmitral filling velocities (r = 0.80), and the ratio of early to late transmitral filling velocities (r = 0.87).(ABSTRACT TRUNCATED AT 250 WORDS)

Competition between palmitate and ketone bodies as fuels for the heart: study with positron emission tomography.

To test the ability of ketone bodies to inhibit myocardial fatty acid oxidation in vivo, the myocardial clearance kinetics of [1-11C]palmitate was assessed with positron emission tomography in six fasted volunteers and six instrumented dogs, studied repeatedly before and during infusion of 3-hydroxybutyrate (17 mumol.kg-1 x min-1). With the use of multiexponential fitting of tissue time-activity curves, the size, half time (T1/2), and index of the early rapid phase of 11C myocardial clearance, reflecting palmitate oxidation, were calculated. In humans, the relative size (-28%, P < 0.001) and index (-37%, P < 0.01) of the early rapid phase decreased significantly during infusion of 3-hydroxybutyrate, consistent with decreased fatty acid oxidation. Paradoxically, T1/2 decreased from 10.1 +/- 1.6 to 7.4 +/- 1.1 min (P < 0.01). To elucidate possible mechanisms, multiple coronary arteriovenous samples were obtained from the dogs to assess the efflux of oxidized and nonmetabolized tracer. Infusion of 3-hydroxybutyrate resulted in decreased myocardial [11C]CO2 production (-40%, P < 0.05) and reduced palmitate retention (-38%, P < 0.05). In three dogs, the arteriovenous difference in radiolabeled palmitate became negative 10 min after injection, indicating backdiffusion of nonmetabolized tracer from the myocardium. Thus a steady-state infusion of 3-hydroxybutyrate, resulting in physiological plasma levels, alters [1-11C]palmitate kinetics in vivo by decreasing myocardial long-chain fatty acid oxidation and by increasing backdiffusion of nonmetabolized tracer.

Hemodynamic and volume correlates of left ventricular diastolic relaxation and filling in patients with aortic stenosis.

OBJECTIVE: The aim of the present study was to evaluate the hemodynamic and volume correlates of early diastolic filling and isovolumetric relaxation in patients with aortic stenosis. BACKGROUND: Left ventricular diastolic relaxation and filling have been found to be heterogeneous in patients with aortic stenosis. Potential mechanisms underlying this heterogeneity include individual differences in the severity of muscle hypertrophy or systolic dysfunction, or both, in the presence and severity of mitral regurgitation and in the level of left atrial pressure. METHODS: Right (fluid-filled) and left (high fidelity micromanometer) ventricular pressures, left ventricular volumes (contrast angiography) and transmitral inflow dynamics (Doppler echocardiography) were measured in 17 patients with isolated severe aortic stenosis (valve area less than 0.75 cm2). Measurements included left ventricular end-diastolic and end-systolic volumes, left ventricular ejection fraction, peak positive and negative first derivative of left ventricular pressure (dP/dt), the time constant of isovolumetric relaxation (tau), left ventricular end-diastolic pressure, left ventricular mass, left ventricular end-systolic stress, mean capillary wedge pressure and peak early (E) and late (A) transmitral filling velocities. Patients were subclassified according to left ventricular ejection performance at rest and mean capillary wedge pressure. RESULTS: Patients with normal ejection performance and normal mean capillary wedge pressure had a normal rate of isovolumetric left ventricular pressure decay and an abnormal diastolic filling pattern, with diastolic filling occurring primarily during atrial systole. In contrast, in patients with systolic dysfunction and elevated mean capillary wedge pressure, isovolumetric pressure decay was prolonged and diastolic filling occurred essentially during the rapid filling period, with reduced atrial contribution to left ventricular filling and a short isovolumetric relaxation period. Stepwise multiple linear regression analysis identified two variables as independent predictors of transmitral velocity profile and three variables independently predictive of the rate of left ventricular pressure decay. The single most important predictor of transmitral filling pattern was the pulmonary capillary wedge pressure (p less than 0.0001), followed by the left ventricular peak negative dP/dt (p = 0.002). The single most powerful predictor of the rate of reduction in left ventricular pressure was left ventricular mass index (p less than 0.0001), followed by end-systolic volume index (p = 0.0002) and left ventricular peak negative dP/dt (p = 0.0029). CONCLUSIONS: In patients with aortic stenosis, left ventricular filling is essentially determined by left atrial pressure, whereas isovolumetric relaxation more closely depends on the severity of muscle hypertrophy and chamber dilation.