Chronotropic Incompetence and Abnormal Autonomic Modulation in Ambulatory Chagas Disease Patients

Abstract

Chagas disease (ChD) patients might present chronotropic incompetence during exercise, although its physiopathology remains uncertain. We evaluated the heart rate (HR) response to exercise testing in ChD patients in order to determine the role of autonomic modulation and left ventricular dysfunction in the physiopathology of chronotropic incompetence. ChD ambulatory patients (n = 170) and healthy controls (n = 24) underwent a standardized protocol including Doppler echocardiography, Holter monitoring, HR variability analysis, brain natriuretic peptide (BNP) measurement, and maximal exercise testing. The chronotropic response was calculated as the percentage of predicted HR achieved and the HR increment (DeltaHR) during exercise. ChD patients were divided according to the absence or presence of cardiopathy and chronotropic incompetence (<85% predicted HR). Chronotropic incompetence was present in 34 (20%) of all ChD patients. The group with cardiopathy displayed reduced DeltaHR (91 +/- 19 bpm) during exercise in comparison with ChD patients without cardiopathy (100 +/- 19 bpm). Both the values observed in ChD groups were significantly different from those of controls (112 +/- 13 bpm). Exercise duration, maximal oxygen consumption, and systolic blood pressure increment were significantly reduced in patients with abnormal chronotropic response. DeltaHR during the exercise was significantly correlated with markers of autonomic control of sinus node, such as rest HR (r =-0.498, P <or= 0.001), peak HR during exercise (r = 0.775, P <or= 0.001), minimal HR during Holter recording (r =-0.231, P = 0.003), and high- and low-frequency components of short-term HR variability (r = 0.188, P = 0.042 and r = 0.203, P = 0.027). Neither left ventricular function nor BNP levels were independently related to the presence of chronotropic incompetence. Chronotropic incompetence may be considered an early sign of autonomic dysfunction in ChD patients.