Exercise training in advanced heart failure patients: Discordance between improved exercise tolerance and unchanged NT-proBNP levels

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Abstract

Background

Exercise training can improve aerobic capacity and symptoms in congestive heart failure (CHF) patients.

Aims

To test the feasibility of exercise training in advanced CHF patients, and examine the potential benefit from peripheral vascular and muscular conditioning as well as improved central hemodynamic and neurohumoral status.

Methods and results

Thirty NYHA functional class III, CHF patients (mean age 61 ± 13 yr, ejection fraction 27 ± 4%, VO2max 11.3 ± 3.9 ml/kg/min) were enrolled. Exercise capacity, cardiovascular parameters and serum levels of brain natriuretic peptide (NT-proBNP) were determined at baseline and after 18 weeks of moderate intensity exercise training. Twenty eight (93%) patients, who completed the exercise program, experienced marked improvements in the 6 min walk (+ 39%) and exercise duration on the modified Bruce protocol (+ 66%). Smaller improvements were recorded in the cardiac index (a 15% increase), in the maximal oxygen consumption (a 13% increase in VO2max), in the left ventricular ejection fraction (an 11% increase) and in the systemic vascular resistance and pulmonary artery pressure (an 11% decrease). NT-proBNP levels were not significantly affected. They correlated with exercise capacity and VO2max on baseline measurement, but these correlations were not found after training.

Conclusion

Rehabilitation is feasible, even in advanced CHF, and leads to markedly improved exercise performance, but does not affect the level of the principal neurohumoral marker of prognosis — NT-proBNP. Resting cardiovascular performance and maximal oxygen consumption improve less than functional capacity, suggesting that an important benefit is derived from muscle conditioning and improved peripheral vascular response to exercise.

Introduction

Exercise intolerance is a cardinal manifestation of congestive heart failure (CHF). In advanced heart failure, functional capacity is, by definition, so poor that patients become symptomatic during minimal effort or even at rest. Limitations imposed by low cardiac output and decreased oxygen supply to skeletal muscle are followed by muscle deconditioning and eventually atrophy [1], [2], [3], [4], [5].

In the past, physical activity was considered contraindicated in heart failure patients. Recent studies indicate that exercise training programs can produce symptomatic benefit and improve functional class in individuals with left ventricular dysfunction [6], [7]. A meta-analysis summarizing 9 studies in a total of 801 patients found a trend for improved longevity [8], [9]. Limited data exist, however, on the feasibility, safety and the clinical benefits of exercise in patients with advanced heart failure.

We initiated an exercise rehabilitation program for patients with advanced heart failure. CHF patients who became stable at NYHA functional class III on maximal medical therapy were encouraged to undergo exercise rehabilitation.

Levels of brain natriuretic peptide (BNP) or its amino-terminal fragment (NT-proBNP) were established in prospective studies as a principal neurohumoral prognostic indicator in heart failure patients [10], [11]. The objective of the current study was to explore whether exercise training is also associated with improved cardiovascular performance and the principal indicators of prognosis: maximal aerobic capacity (VO2max) and blood levels of the brain natriuretic hormone (NT-proBNP).

Section snippets

Methods

Consecutive outpatients with advanced CHF (New York Heart Association functional class III, stage D) were referred from the Heart Failure Clinic of our Heart Institute to the Cardiac Rehabilitation Institute, to participate in a supervised exercise and rehabilitation program according to preexisting guidelines [12], [13]. Patients included were in a stable clinical condition and on optimal medical therapy. Patients who underwent percutaneous or surgical intervention, acute myocardial

Results

Thirty advanced heart failure patients with systolic left ventricular dysfunction, who stabilized on NYHA functional class III on optimal medical therapy, were enrolled (Table 1). Eighty percent were males, 77% had heart failure of ischemic etiology. Nearly all were treated with angiotensin converting enzyme or angiotensin receptor blocker and the majority were on digoxin and beta-adreno-receptor blockers. Seven (23%) had chronic renal failure defined as serum creatinine  1.5 mg/dl.

The exercise

Discussion

Our study demonstrates the great merit of rehabilitation therapy in otherwise maximally treated and severely symptomatic patients with advanced heart failure. A relatively short period of exercise training was associated with a major improvement in functional capacity. While the 66% increase in the duration of treadmill exercise may be, at least in part, attributed to habituation, the 39% increase in the 6 min walking distance apparently reflects the net benefit of training. The significant

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    These authors contributed equally to this work.

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