Relationship Between Impaired Chronotropic Response, Cardiac Output During Exercise, and Exercise Tolerance in Patients with Chronic Heart Failure

Abstract

SUMMARYThe present study was undertaken to investigate the relationship between the extent of impaired chronotropic response and cardiac output during exercise, and exercise tolerance in patients with chronic heart failure. The subjects consisted of 24 patients (mean 60.1 ± 14.0 years) who had mild chronotropic incompetence. Cardiopulmonary exercise testing was performed in all patients, and heart rate (HR), anaerobic threshold (AT), maximum oxygen uptake (peak VO 2 ), slope of the regression line relating the ventilatory equivalent to carbon dioxide output (VE/VCO 2 slope), and exercise time were measured. Cardiac output (CO) was measured by a thoracic bioimpedance method and cardiac index (CI) was calculated. Plasma norepinephrine (NE) was measured at rest and immediately after the exercise test. The changes in HR, NE, and CI from the resting state to immediately after exercise were calculated as ∆HR, ∆NE, and ∆CI, respectively. The ∆NE was converted to a logarithmic scale and ∆HR/log∆NE was used as a parameter of HR response to sympathetic nerve stimulation. The results were as follows: HR and NE in the resting state had no correlation with AT and with peak VO 2 . ∆HR/log∆NE correlated positively with both AT and peak VO 2 , and negatively with the VE/VCO 2 slope. ∆HR/ log∆NE correlated positively with peak CI, %∆CI, and ∆CI/exercise time. The data suggest that one of the mechanisms of low exercise tolerance in chronic heart failure patients was due to an inadequate increase in CO response against exercise caused by an impaired HR response to increased NE. (Jpn Heart J 2003; 44: 515-525)

Chronotropy

“…Interestingly, in healthy controls the HR reserve was highly correlated with the increase in plasma norepinephrine but this relationship was uncoupled in HF patients, suggesting diminished sinus node responsiveness in the latter group. This finding is consistent with other lines of evidence, including that from Samejima et al 18 who demonstrated that the ratio of change in HR to change in log of norepinephrine (delta HR/delta log NE), an index of sinoatrial node sympathetic responsiveness, decreased progressively with the severity of HF. Consequently, it appears that at least one mechanism responsible for this derangement has been determined, which will facilitate approaches to address this potential therapeutic ‘target’.…”

Impaired Heart Rate Recovery and Chronotropic Incompetence in Patients With Heart Failure With Preserved Ejection Fraction

“…24 The clinical sequalae of these autonomic changes include an impaired HR response to exercise (chronotropic incompetence), which may contribute to exercise limitation. 25,26 Indeed, studies have shown that as the severity of systolic heart failure worsens the more common chronotropic incompetence during exercise becomes in patients with CHF. 27 Nevertheless, even in asymptomatic patients with reduced LVEF and LV dilatation poor HR response has been reported.…”

Effect of β-Blocker Cessation on Chronotropic Incompetence and Exercise Tolerance in Patients With Advanced Heart Failure

“…4,9 It is believed that one of the survival benefits conferred by β-blockers in HF is mediated by an increase in both β-receptor density and sensitivity to adrenergic stimulation. 29,30 If β-blockers were indeed the dominant cause of CI in patients with advanced HF, then withdrawal of these agents should result in restoration of the normal chronotropic response to endogenous NE.…”

“…[1][2][3][4] Some studies have suggested that abnormal HR response underlies exercise intolerance in HF. 9,12,13 This finding has informed the development of new therapies, such as rate-responsive pacing, with the goal of improving exercise tolerance in this patient population. 14,15 However, in patients with HF who are taking β-blockers, controversy exists about whether CI and exercise intolerance are effects of disease progression alone or whether they also can be attributed to pharmacological β-blockade.…”