Abstract

Abstract Background According to the current guidelines in heart failure (HF) with reduced ejection fraction (HFrEF) the implementation and titration of guideline-directed medical therapy (GDMT) is recommended. Although just symptomatic hypotension is known as a factor limiting the initiation or uptitration of GDMT, in everyday practice asymptomatic hypotension often has a negative impact on the long-term application of GDMT in HFrEF, even though patients with lower systolic blood pressure (SBP) have worse prognosis. Aim To assess the application of combined neurohormonal antagonist therapy (triple therapy [TT]: RASi[ACEi/ARB/ARNI]+βB+MRA) based on SBP during an index HF hospitalization, and to evaluate the long-term application of TT on SBP and on mortality. Patients and methods: The data of 247 consecutive HFrEF patients (male:75%, age:66[56-74]years, ischemic:46%, diabetes:40%, hypertension:63%, atrial fibrillation:46%, LVEF:25[20-30]%, eGFR:58[39-73]ml/min/1.73m2,SBP:118[102-134]mmHg) were analysed retrospectively, who had been admitted to the HF Unit of our tertiary centre due to HF in 2019-2021 and then were followed up for one year. Patients were divided into three SBP categories based on SBP measured at admission: SBP1:<100mmHg (n = 46), SBP2:100-120mmHg (n = 98), SBP3:>120mmHg (n = 103) (respectively). The applicability of TT at hospital discharge and at 1 year were assessed comparing SBP categories with Chi-square test. The changes of SBP within each category were compared with Wilcoxon test. 1-year all-cause mortality (ACM) was investigated with Kaplan-Meier method and log-rank test. Results At discharge, 77% of the patients received TT in the total cohort. Lower SBP at admission led to lower application ratio of βB (72-89-87%, p = 0.019), while RASi and MRA use was consistent across SBP categories (87-89-89%; 91-98-93%, p>0.05). TT application at discharge did not differ significantly among the subgroups (65-81-79%, p = 0.107). 1-year ACM was 23% in the total cohort, with significantly higher mortality rates in lower SBP groups (33-27-15%, p = 0.022). At 1 year TT application remained high; 65% in SBP1, 78% in SBP2 and 72% in SBP3 group. No differences (p>0.05) were seen in terms of βB (87-88-91%), RASi (81-89-84%) and MRA use (77-86-82%) in SBP groups. In the effect of GDMT, in the SBP1 and SBP2 group, SBP significantly (p<0.0001) rose (SBP1: from 92[85-95] to 110[95-127]mmHg, SBP2: from 111[104-117] to 124[110-133]mmHg; discharge vs. 1 year), while in the highest SBP group significant decrease was verified (from 137[129-146] to 130[118-145]mmHg, p = 0.002). Conclusions Our study results confirmed that low SBP is associated with a poor prognosis in HFrEF. Low SBP is a relevant influencing factor of GDMT initiation and long-term application, even though among these patients increase in SBP can be expected due to the use of GDMT. Our results indicate that low SBP should not make physicians be hesitant to optimize therapy in severe HFrEF.

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