P1356 Effects of sacubitril/valsartan on vascular resistance in patients with heart failure with reduced ejection fraction and arterial hypertension

Abstract

Introduction: Vascular resistance as assessed by noninvasive measurement of the pulse-wave velocity (PWV) is a well-established separate risk factor for early cardiovascular morbidity and mortality. High vascular resistance leads to higher pulse wave velocities and augmented values of systolic blood pressure (SBP). That leads to elevation in myocardial oxygen consumption and elevated left ventricular (LV) wall stress, indirectly worsening the systolic function of an already failing LV. PWV can be taken as an integral index of the vascular structure and function. Sacubitril/valsartan is the first ARNI approved for the treatment of heart failure with reduced ejection fraction (HFrEF) - it simultaneously inhibits the renin-angiotensin-aldosterone system and employs the positive effects of the natriuretic peptides. The mechanisms of these remarkable effects - reduction of cardiovascular morbidity, of heart failure hospitalisations, of sudden cardiac death and of composite mortality, in patients with HFrEF are quite complex. The concomitant lowering of BP is an important element of the pathophysiologic process that improves the haemodynamic status of the patients. Purpose: To evaluate the effect of sacubitril/valsartan on vascular level parameters. Materials and methods: In 18 newly established patients with HFrEF and arterial hypertension we prescribed 6-month sacubitril/valsartan treatment protocol at a dose level 97/103 mg. We measured the baseline office pressure, LV ejection fraction, 2D LV strain and E/E1 values, and we performed analysis of the arterial rigidity by measuring the following parameters: Arterial elastance: Ea= systolic BP / LV stroke volume LV endsystolic elastance: EV = systolic BP / LV telesystolic volume End-systolic stress of the LV wall: ESS = (0.33 x TSDLV x SBP) / PW x (1 + PW) / TSDLV) Ventricular-arterial impedance: Zva = (SBP + mean transaortic gradient) / indexed LV stroke volume. At the end of the six months' treatment protocol we measured the same parameters again. Results: During the six months treating period the systolic arterial pressure fell significantly from 128 ± 9.8 mmHg to 113 ± 17 mmHg (p=0.002), and diastolic BP, also significantly, fell from 83.5 ± 9.5 mmHg to 70.1 ± 6.8 mmHg (p=0.001). There was a significant decrease in PWV, arterial elastance, end-systolic LV wall stress and in ventricular-arterial impedance, but not in the other measured parameters. Conclusion: Treatment with sacubitril/valsartan at a high dose level of 97/103 mg for six months improves the indices of arterial rigidity, but does not lead to significant change in ventricular-arterial coupling, despite of significant lowering of the arterial elastance and pulse wave velocity.