Impaired chronotropic response to exercise in patients with congestive heart failure. Role of postsynaptic beta-adrenergic desensitization.

Abstract

The mechanism responsible for the attenuated heart rate (HR) response to exercise in patients with congestive heart failure (CHF) was investigated in 46 normal subjects and 59 patients with CHF stratified by peak exercise oxygen consumption (Vo2). The peak exercise HR and the increment in HR from rest to peak exercise were decreased in CHF patients, and both correlated strongly with peak Vo2 (r=0.810, p<0.0001; r=0.863, p <0.0001, respectively). Peak exercise norepinephrine level (NE) and the increment in NE from rest to peak exercise were not attenuated in CHF patients. Resting NE was elevated in CHF patients and correlated inversely with peak Vo2 (r=-0.595, p<0.001). However, no significant correlation occurred between peak Vo2 and either peak exercise NE or the exercise increment in NE. The ratio of the exercise increments in HR and NE, an indirect index of sinoatrial node sympathetic responsiveness, was markedly reduced in CHF patients and was inversely related to the severity of exercise impairment. Likewise, the HR response to a graded isoproterenol infusion was markedly reduced in CHF patients. Age-matching of normal subjects and CHF patients did not affect the foregoing observations. Infusion of CHF patients with the phosphodiesterase inhibitor milrinone caused a significant increase in the ratio of the exercise increments in HR and NE. These data strongly suggest that the attenuated HR response to exercise in CHF patients is due, at least in part, to postsynaptic desensitization of the 8-adrenergic receptor pathway. (Circulation 1989;80:314-323) P eak heart rate response to exercise is determined primarily by the magnitude of increase in sympathetic drive to the heart and the ability of f-adrenergic receptors in the sinoatrial node to respond to catecholamines. In patients with congestive heart failure (CHF), the chronotropic response to peak exercise is reduced and may contribute significantly to the impaired cardiac output response to exercise.1-4The mechanism responsible for a reduced chronotropic response to exercise in patients with CHF is not known. Although it is known that both the reflex stimulation of sympathetic nervous system

Exercise testing in pulmonary arterial hypertension and in chronic heart failure

“…Although this is classically described in CHF [22], it has only been reported in one other study on PPH patients [4]. Chronotropic incompetence in CHF is believed to be due to downregulation of badrenoreceptors [22]. The same explanation may hold true in PAH patients, in whom downregulation of right ventricular myocardial b-adrenoreceptors has also been reported [23].…”

“…Although this is classically described in CHF [22], it has only been reported in one other study on PPH patients [4]. Chronotropic incompetence in CHF is believed to be due to downregulation of badrenoreceptors [22].…”

Abnormal response of left ventricular systolic function to submaximal exercise in post-partial left ventriculotomy patients

“…Colucci et al (20) demonstrated that the chronotropic response to exercise is strongly associated with maximal exercise capacity evaluated by VO 2 peak in patients with heart failure. Our post-left ventriculotomy patients had more impairment in the chronotropic response to exercise when compared to the heart failure patients.…”

“…The reduction of maximal heart rate could be another mechanism contributing to the limited functional capacity of post-left ventriculotomy patients. Since chronotropic incompetence is associated with a desensitization of beta-adrenergic receptors in the sinus node (20), it is possible that partial left ventriculotomy does not improve this abnormality and patients would maintain a limited chronotropic response to exercise, further limiting functional capacity.…”

Em busca de novos paradigmas para o manejo da insuficiência cardíaca

“…A ativação crônica do sistema nervoso simpático contribui para aumento da pós-carga, alteração do metabolismo energético miocárdico, levando a dano focal no miocárdio, com liberação de radicais livres com conseqüente produção de citocinas, que desempenharão papel importante na patogênese do remodelamento adverso do VE 47,48 . Esta ativação simpática pode ser constatada por níveis elevados de catecolaminas circulantes, que se associam com a gravidade 49 e são preditores potentes de mortalidade na IC 50 .…”