[Neurohormonal activation and maximal exercise capacity in diastolic dysfunction and diastolic heart failure]

Abstract

Background: Patients with diastolic dysfunction (DD) and diastolic heart failure (DHF) are known to suffer from reduced exercise capacity. However, there is only limited knowledge about the mechanisms involved in the development of exercise intolerance. This study was designed to investigate the direct association between neurohumoral activation and maximal exercise capacity in patients with diastolic dysfunction and diastolic heart failure and its dependency of parameters of diastolic function and clinical characteristics.

Methods: 54 patients (LVEF ≥ 50 %) with echocardiographically proven DD were prospectively included. Patients were divided into having DD or DHF according to NYHA functional class at presentation (NYHA I: DD; NYHA ≥ II: DHF). All patients underwent physical examination including medical history, comprehensive echocardiography with detailed measurement of diastolic function, spiroergometry and blood sampling under standardized conditions.

Results: Exercise capacity was significantly reduced in patients with DHF (peakVO₂ DD (30,5 ± 8,4 ml/kg/min) vs. DHF (15,7 ± 3,5 ml/kg/min) p < 0,001). N-terminal pro brain natriuretic peptide (NT-proBNP) was significantly higher in patients with DHF (DD 49,4 pg/ml [range 17,5 - 96,1] vs. DHF 285,3 pg/ml [190,4 - 426,0], p < 0,001). E/é ratio was not significantly different between groups (DD 11,3 ± 3,3 vs. DHF 12,9 ± 3,7, n. s.), in contrast to left atrial volume index (LAVI): DD 23,4 ± 5,9 ml/m² vs. DHF 29,6 ± 8,4 ml/m², p = 0,017). In bivariate correlation analyses age (r = -0,477, p < 0,001) gender (r = -0,418, p = 0,002) and NT-proBNP (r = -0,488, p < 0,001) were significantly related to peakVO₂, whereas LAVI (r = 0,106, p = 0,641) or E/é (r = 0,107, p = 0,441) were not. In multiple regression analyses, after adjustment for body mass index, E/é and LAVI, the association of NT-proBNP and peakVO₂ was independent of age and gender (p = 0,001).

Conclusion: NT-proBNP was siginificantly and independent of age and gender correlated to maximal exercise capacity, whereas resting diastolic function did not. Echocardiographically determined diastolic function is a prerequisite for the diagnosis of diastolic heart failure, but elevated NT-proBNP may rather play a key role in the development of signs and symptoms in these patients.