1405Sequential nephron blockade with diuretics improves diastolic dysfunction in patients with resistant hypertension, a substudy a the PHARES trial

Abstract

Abstract Introduction Hypertension is one of the major contributors to cardiac diastolic dysfunction as observed in patients with heart failure and preserved ejection fraction. Different therapeutics strategies have been proposed to control blood pressure (BP) but their independent impact on cardiac function remain undetermined. In patients referred to our center for uncontrolled hypertension, we compared changes in cardiac parameters between two strategies consisting of sequential nephron blockade with intensive diuretics (NBD) or sequential renin angiotensin blockade (RAB). Purpose To determine evolution of BNP levels and echocardiographic (TTE) parameters of diastolic dysfunction according to strategies to control BP. Methods After 4-weeks treatment with 300mg irbesartan + 12.5mg hydrochlorothiazide + 5mg amlodipine, 140 patients with uncontrolled hypertension were randomized to either complete nephron blockade with sequential introduction of 25mg spironolactone, 20 to 40mg furosemide and 5mg amiloride (NBD group, n=74) or complete RAAS blockade with 5 to 10mg ramipril and 5 to 10mg bisoprolol (RAB group, n=67). BNP levels and TTE parameters according to ESC guidelines were assessed at baseline and week 12. Results BNP levels were not significantly different in the two groups at baseline (mean±SD 30.1±37.0pg/mL in NBD versus 22.6±22.3pg/mL in RAB, p=0.147) but significantly decreased in NBD at week 12 (20.1±22.7pg/mL in NBD versus 55.2±60.4pg/mL in RAB, p<0.0001). At week 12, only 9 (12%) patients in NBD presented BNP levels >35pg/mL versus 37 (55%) in RAB (p<0.001). Concordantly, TTE parameters such as left ventricular end-diastolic diameter (mean±SD, 49±4mm in NBD and 52±5mm in RAB, p=0,004) and left atrial area (16.9±3.6cm2 in NBD and 19.1±3.7cm2 in RAB, p=0,003) improved significantly in NBD group. The proportions of patients presenting ≥2 criteria of diastolic dysfunction according to ESC guidelines in NBD and RAB group respectively were 31.2% and 19.3% at baseline vs. 3.1% and 32.2% after 12 weeks (p=0.001). In a multivariate analysis, NBD treatment was significantly associated with a decline in BNP levels (p<0.01) even after adjustment on daytime systolic BP lowering, heart rate, renal function, age and gender. Conclusion In patients with uncontrolled hypertension, intensive nephron blockade with sequential addition of diuretics improves markers of diastolic dysfunction independently of BP lowering.