Prognostic implications of delayed heart rate recovery from maximal-incremental exercise in patients with pulmonary arterial hypertension

Abstract

Rationale: Early recovery from exercise is characterized by a marked reduction in heart rate (HR) due to sudden reintroduction of vagal tone and progressive withdrawal of sympathetic stimulation. HR recovery (HRR) is delayed in pulmonary arterial hypertension (PAH), a disabling condition associated with autonomic imbalance. Objective: To investigate the usefulness of HRR to estimate exercise impairment and prognosis in PAH patients. Methods: We evaluated 72 patients with PAH of varied aetiology (NYHA class I to IV) and 21 age- and gender-matched controls who underwent a maximal incremental cardiopulmonary exercise test (CPET) with HR being recorded up to the 5th minute of recovery. Results: HRR was consistently lower in patients compared to controls (p<0.05). The best cutoff for HRR in one minute (HRR_1min) to discriminate patients from controls was 18 beats (AUC 0.76 [0.66-0.86], p <0.05). “Normal” HRR_1min was associated with a range of maximal and sub-maximal variables indicative of better preserved exercise tolerance (p<0.05). On a multiple regression analysis which considered only CPET-independent variables (6-minute walking distance, NYHA class and PAH treatment), HRR_1min was the single predictor of mortality (hazard ratio (95% confidence interval)= 1.19 (1.03-1.37); p<0.05). Conclusions: Preserved HRR_1min (>18 beats) is associated with less impaired responses to exercise in patients with PAH. Conversely, an abnormal HRR_1min response has negative prognostic implications, a finding likely to be clinically useful when more sophisticated analyses provided by a full CPET are not readily available.