Pulmonary function, cardiac function, and exercise capacity in a follow-up of patients with congestive heart failure treated with carvedilol

doi:10.1016/S0002-8703(99)70148-1

American Heart Journal

Volume 138, Issue 3, September 1999, Pages 460-467

https://doi.org/10.1016/S0002-8703(99)70148-1 Get rights and content

Abstract

Background Chronic heart failure causes disturbances in ventilation and pulmonary gas transfer that participate in limiting peak exercise oxygen uptake (VO_2p ). The β-adrenergic receptor blocker carvedilol improves left ventricular (LV) function and not VO_2p . This study was aimed at investigating the pulmonary response to changes in LV performance produced by carvedilol in patients with chronic heart failure. Methods Twenty-one patients with New York Heart Association class II to III heart failure were randomly assigned (2 to 1) to carvedilol (25 mg twice daily, n = 14) or placebo (n = 7) for 6 months. Rest forced expiratory volume (FEV₁ ), vital capacity, total lung capacity, carbon monoxide diffusing capacity, its alveolar-capillary membrane component, pulmonary venous and transmitral flows (for monitoring changes in LV end-diastolic pressure), LV diastolic and systolic dimensions, stroke volume, ejection fraction, and fiber shortening velocity were measured at baseline and at 3 and 6 months. VO_2p , peak ratio of dead space to tidal volume (VD/VT_p ), ventilatory equivalent for carbon dioxide production (VE/VCO₂ ), and VO₂ at anaerobic threshold (VO_2at ) were also determined. Results FEV₁ , vital capacity, total lung capacity, carbon monoxide diffusing capacity, and the alveolar-capillary membrane component were impaired in chronic heart failure compared with 14 volunteers and did not vary with treatment. Carvedilol reduced end-diastolic pressure, end-diastolic diameter, and end-systolic diameter and increased ejection fraction, stroke volume, and fiber shortening velocity without affecting VO_2p , VO_2at , VD/VT_p , or VE/VCO₂ at 3 and 6 months. Placebo did not produce significant changes. Conclusions In chronic heart failure carvedilol ameliorates LV function at rest and does not significantly affect ventilation and pulmonary gas transfer or functional capacity. These results suggest that improvement in cardiac hemodynamics with carvedilol does not reverse pulmonary dysfunction. Persistent lung impairment might have some role in the failure of carvedilol to improve exercise performance. (Am Heart J 1999;138:460-7.)

Section snippets

Patients and controls

Patients had either idiopathic dilated cardiomyopathy or ischemic heart disease (previous myocardial infarction and cardiac enlargement). Patients were enrolled if they (1) had chronic stable New York Heart Association functional class II to III heart failure from cardiac dysfunction, (2) had left ventricular ejection fraction ≤40%, (3) were in sinus rhythm, and (4) were able to complete a maximal cardiopulmonary bicycle ergometer exercise test. Patients were excluded if they (1) had history of

Pulmonary function

Patients with CHF exhibited a significant reduction of FEV₁ , maximal voluntary ventilation, VC, and TLC. Compared with normal individuals, DLCO and its 2 subcomponents (D_M and V_C ) were significantly altered. The reduction in DLCO was caused by reduction in D_M , and the alveolar-capillary diffusive resistance formed a greater proportion of the total pulmonary diffusive resistance (DLCO/D_M ) than in healthy patients. V_C was greater in patients than in controls (Table I).

. Anthropometric,

Discussion

Despite treatment with digitalis and diuretics, ejection fraction in these patients averaged 34%. Their mean VO_2p was 62.5% ± 12% of predicted normal value, and in any case was <20 mL/min/kg, which corresponds to class B, according to the classification proposed by Weber and Janicki.²³ This point makes us cautious concerning generalization of the study findings and suggests an application at present only to this category of patients with CHF.

As described in CHF,1, 2, 3 the lung function in

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Exercise training improved the rapidness and depth of breathing during exercise. Therefore, improvement of abnormal ventilatory patterns is correlated with exercise tolerance.
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Citation Excerpt :
Beta-blockers do not provide a similar reverse remodeling of the alveolar pneumocytes such as that occurring in the biological properties of cardiomyocytes. A 6 month follow-up with carvedilol did not promote any improvement in DLco or Dm.60 The concern that antiarrhythmic treatment with amiodarone may exert untoward effects on lung diffusion may very likely be excluded by the demonstration in a relatively large population of HF patients that no DLco changes occurred after 1 year of amiodarone treatment.61
Cardiac dysfunction of both systolic and diastolic origins leads to increased left atrial pressure, lung capillary injury and increased resistance to gas transfer. Acutely, pressure-induced trauma disrupts the endothelial and alveolar anatomical configuration and definitively causes an impairment of cellular pathways involved in fluid-flux regulation and gas exchange efficiency, a process well identified as stress failure of the alveolar–capillary membrane. In chronic heart failure (HF), additional stimuli other than pressure may trigger the true remodeling process of capillaries and small arteries characterized by endothelial dysfunction, proliferation of myofibroblasts, fibrosis and extracellular matrix deposition. In parallel there is a loss of alveolar gas diffusion properties due to the increased path from air to blood (thickening of extracellular matrix) and loss of fine molecular mechanism involved in fluid reabsorption and clearance. Deleterious changes in gas transfer not only reflect the underlying lung tissue damage but also portend independent prognostic information and may play a role in the pathogenesis of exercise limitation and ventilatory abnormalities observed in these patients. Few currently approved treatments for chronic HF have the potential to positively affect structural remodeling of the lung capillary network; angiotensin-converting enzyme inhibitors are one of the few currently established options. Recently, more attention has been paid to novel therapies specifically targeting the nitric oxide pathway as a suitable target to improve endothelial function and permeability as well as alveolar gas exchange properties.
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^☆: From the Istituto di Cardiologia dell’Università degli Studi, Centro di Studio per le Ricerche Cardiovascolari del Consiglio Nazionale delle Ricerche, Fondazione “Monzino”, I.R.C.C.S., Milano, Italy.

^☆☆: Supported in part by a grant from the National Research Council and the Monzino Foundation, Milan, Italy.

^★: Reprint requests: Marco Guazzi, MD, Istituto di Cardiologia, Via C. Parea, 4, 20138 Milano, Italy.

^★★: 0002-8703/99/$8.00 + 0 4/1/94802

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Pulmonary function, cardiac function, and exercise capacity in a follow-up of patients with congestive heart failure treated with carvedilol☆,☆☆,★,★★

Abstract

Section snippets

Patients and controls

Pulmonary function

Discussion

Am J Med

Am J Cardiol

Chest

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

Lancet

Pulmonary function abnormalities in chronic severe cardiomyopathy preceding cardiac transplantation

Am Rev Resp Dis

Reduced alveolar-capillary diffusing capacity in chronic heart failure. Its pathophysiological relevance and relationship to exercise performance

Circulation

Improvement in alveolar-capillary membrane diffusing capacity with enalapril in chronic heart failure and counteracting effect of aspirin

Circulation

Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure. The Precise trial

Circulation

Comparative hemodynamic, left ventricular functional and antiadrenergic effects of chronic treatment with metoprolol versus carvedilol in the failing heart

Circulation

Randomized placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease

Lancet