The effect of kidney function on guideline-directed medical therapy implementation and prognosis in heart failure with reduced ejection fraction.

BACKGROUND: Kidney dysfunction (KD) is a main limiting factor of applying guideline-directed medical therapy (GDMT) and reaching the recommended target doses (TD) in heart failure (HF) with reduced ejection fraction (HFrEF). HYPOTHESIS: We aimed to assess the success of optimization, long-term applicability, and adherence of neurohormonal antagonist triple therapy (TT:RASi [ACEi/ARB/ARNI] + ßB + MRA) according to the KD after a HF hospitalization and to investigate its impact on prognosis. METHODS: The data of 247 real-world, consecutive patients were analyzed who were hospitalized in 2019-2021 for HFrEF and then were followed-up for 1 year. The application and the ratio of reached TD of TT at hospital discharge and at 1 year were assessed comparing KD categories (eGFR: ≥90, 60-89, 45-59, 30-44, <30 mL/min/1.73 m2 ). Moreover, 1-year all-cause mortality and rehospitalization rates in KD subgroups were investigated. RESULTS: Majority of the patients received TT at hospital discharge (77%) and at 1 year (73%). More severe KD led to a lower application ratio (p < .05) of TT (92%, 88%, 80%, 73%, 31%) at discharge and at 1 year (81%, 76%, 76%, 68%, 40%). Patients with more severe KD were less likely (p < .05) to receive TD of MRA (81%, 68%, 78%, 61%, 52%) at discharge and a RASi (53%, 49%, 45%, 21%, 27%) at 1 year. One-year all-cause mortality (14%, 15%, 16%, 33%, 48%, p < .001), the ratio of all-cause rehospitalizations (30%, 35%, 40%, 43%, 52%, p = .028), and rehospitalizations for HF (8%, 13%, 18%, 20%, 38%, p = .001) were significantly higher in more severe KD categories. CONCLUSIONS: KD unfavorably affects the application of TT in HFrEF, however poorer mortality and rehospitalization rates among them highlight the role of the conscious implementation and up-titration of GDMT.

The Impact of Specialised Heart Failure Outpatient Care on the Long-Term Application of Guideline-Directed Medical Therapy and on Prognosis in Heart Failure with Reduced Ejection Fraction.

(1) Background: Besides the use of guideline-directed medical therapy (GDMT), multidisciplinary heart failure (HF) outpatient care (HFOC) is of strategic importance in HFrEF. (2) Methods: Data from 257 hospitalised HFrEF patients between 2019 and 2021 were retrospectively analysed. Application and target doses of GDMT were compared between HFOC and non-HFOC patients at discharge and at 1 year. 1-year all-cause mortality (ACM) and rehospitalisation (ACH) rates were compared using the Cox proportional hazard model. The effect of HFOC on GDMT and on prognosis after propensity score matching (PSM) of 168 patients and the independent predictors of 1-year ACM and ACH were also evaluated. (3) Results: At 1 year, the application of RASi, MRA and triple therapy (TT: RASi + ßB + MRA) was higher (p < 0.05) in the HFOC group, as was the proportion of target doses of ARNI, ßB, MRA and TT. After PSM, the composite of 1-year ACM or ACH was more favourable with HFOC (propensity-adjusted HR = 0.625, 95% CI = 0.401-0.974, p = 0.038). Independent predictors of 1-year ACM were age, systolic blood pressure, application of TT and HFOC, while 1-year ACH was influenced by the application of TT. (4) Conclusions: HFOC may positively impact GDMT use and prognosis in HFrEF even within the first year of its initiation.

Incidence and predictors of heart failure with improved ejection fraction category in a HFrEF patient population.

AIMS: The aim of the study was to assess the incidence and predictive factors of the development of heart failure with improved ejection fraction (HFimpEF) category during a 1 year follow-up period in a heart failure with reduced ejection fraction (HFrEF) patient population managed in a heart failure outpatient clinic. METHODS AND RESULTS: The study evaluated data from patients enrolled in the Hungarian Heart Failure Registry (HHFR). The incidence and predictive factors of the development of the HFimpEF category after 1 year follow-up were assessed in the group of patients who had HFrEF at baseline. We evaluated the incidence and predictors of the development of HFimpEF after a 1 year follow-up in relation to time since diagnosis of HFrEF in patients diagnosed within 3 months, between 3 months and 1 year, and beyond 1 year. The predictive factors of the development of HFimpEF were analysed using univariate and multivariate logistic regression analysis. Of the 833 HFrEF patients enrolled in the HHFR, the development of HFimpEF was observed in 162 patients (19.5%) during 1 year follow-up. In the whole patient population, independent predictors of the development of HFimpEF were female gender [odds ratio (OR): 1.73; 95% confidence interval (CI): 1.01-2.96; P < 0.05], non-ischaemic aetiology (OR: 1.95; 95% CI: 1.15-3.30; P < 0.05), and left ventricular end-diastolic diameter (LVEDD) <60 mm (OR: 2.04; 95% CI: 1.18-3.51; P < 0.05). The 1 year incidence of HFimpEF decreased in relation to time since diagnosis of HFrEF. The incidence of HFimpEF was 27.1% in patients diagnosed within 3 months, 18.4% in patients diagnosed between 3 months and 1 year, and 12.2% in patients diagnosed beyond 1 year. Non-ischaemic aetiology (OR: 4.76; 95% CI: 1.83-12.4; P < 0.01) and QRS width (OR: 0.81; 95% CI: 0.71-0.94; P < 0.01) for patients diagnosed within 3 months, LVEDD (OR: 0.54; 95% CI: 0.32-0.90; P < 0.05) and left atrial diameter ≤45 mm (OR: 5.44; 95% CI: 1.45-20.4; P < 0.05) for patients diagnosed between 3 months and 1 year, and LVEDD < 67 mm (OR: 2.71; 95% CI: 1.07-6.88; P < 0.05) for patients diagnosed beyond 1 year were found to be independent predictive factors. CONCLUSIONS: In our study, in this HFrEF patient population managed in a heart failure outpatient clinic, the 1 year incidence of HFimpEF was found to be ~20%. The 1 year incidence of HFimpEF decreased in relation to time since diagnosis of HFrEF. The most important predictors of the development of HFimpEF were female sex, non-ischaemic aetiology, narrower QRS width, and smaller diameter of the left ventricle and left atrium.

[The effect of kidney function on the optimization of medical therapy and on mortality in heart failure with reduced ejection fraction]. / A vesefunkció hatása a gyógyszeres terápia optimalizálására és a mortalitásra csökkent ejekciós frakciójú szívelégtelenségben.

INTRODUCTION: Renal dysfunction is a main limiting factor of applying and up-titrating guideline-directed medical therapy (GDMT) among patients with heart failure with reduced ejection fraction (HFrEF). OBJECTIVE: Our retrospective monocentric observational study aimed to analyse the application ratio of combined neurohormonal antagonist therapy (RASi: ACEI/ARB/ARNI + ßB + MRA) and 12-month all-cause mortality differences in terms of renal dysfunction among HFrEF patients hospitalized for heart failure. METHOD: We retrospectively analysed the cohort of consecutive HFrEF patients, hospitalized at the Heart Failure Unit of our tertiary cardiological centre in 2019-2021. The application ratio of discharge triple therapy (TT) in five groups established on admission eGFR parameters, representing severity of renal dysfunction (eGFR≥90, eGFR = 60-89, eGFR = 45-59, eGFR = 30-44, eGFR<30 ml/min/1.73 m2) was investigated with chi-square test, while 12-month mortality differences were analysed with Kaplan-Meier method and log-rank test. RESULTS: 257 patients were included. Median eGFR was 57 (39-75) ml/min/1.73 m2, 54% of patients had eGFR<60 ml/min/1.73 m2. The proportion of patients in eGFR≥90, 60-89, 45-59, 30-44, <30 ml/min/1.73 m2 subgroups was 12%, 34%, 18%, 21%, 15%, respectively. 2% of patients were on dialysis. Even though the application rate of TT was notably high (77%) in the total cohort, more severe renal dysfunction led to a significantly lower implementation rate of TT (94%, 86%, 91%, 70%, 34%; p<0.0001): the application rate of RASi (100%, 98%, 96%, 89%, 50%, p<0.0001), ßB (94%, 88%, 96%, 79%, 68%; p = 0.003) and MRA therapy (97%, 99%, 98%, 94%, 82%; p = 0.001) differed significantly. 12-month all-cause mortality was 23% in the whole cohort. Mortality rates were higher in more severe renal dysfunction (3%, 15%, 22%, 31%, 46%; p<0.0001). CONCLUSION: Even though the proportion of patients on TT in the whole cohort was remarkably high, renal dysfunction led to a significantly lower application ratio of TT, associating with worse survival. Our results highlight that despite renal dysfunction the application of HFrEF cornerstone pharmacotherapy is essential. Orv Hetil. 2023; 164(35): 1387-1396.

The Optimization of Guideline-Directed Medical Therapy during Hospitalization among Patients with Heart Failure with Reduced Ejection Fraction in Daily Clinical Practice.

INTRODUCTION: Hospitalization due to heart failure (HF) progression is associated with poor prognosis. This highlights the role of the implementation of guideline-directed medical therapy (GDMT) in improving the morbidity and mortality of patients with heart failure with reduced ejection fraction (HFrEF). There are limited data about the intrahospital applicability of GDMT in real-world circumstances. We aimed to assess retrospectively the use of cornerstone GDMT including RASi (ACEI/ARB/ARNI), ßB, MRA, and SGLT2i treatment in a consecutive real-world HFrEF patient population admitted with signs and symptoms of HF to the HF Unit of a Hungarian tertiary cardiac center between 2019 and 2021. The independent predictors of therapy optimization and the applicability of new HFrEF medication (ARNI, SGLT2i, vericiguat) were also investigated. METHODS: Statistical comparison of admission and discharge medication was accomplished with Fisher's exact test. The independent predictors of the introduction of triple therapy (RASi + ßB + MRA) were analyzed using univariate and multivariate logistic regression. The proportion of patients eligible for vericiguat based on the inclusion and exclusion criteria of the VICTORIA trial was also investigated, as well as the number of patients suitable for ARNI and SGLT2i, taking into account the contraindications of application contained in the ESC 2021 HF Guidelines. RESULTS: 238 patients were included. During hospitalization, the use of RASi (69% vs. 89%) (ACEI/ARBs [58% vs. 70%], ARNI [10% vs. 19%]), ßBs (69% vs. 85%), and MRAs (61% vs. 95%) increased significantly (p < 0.05) compared to at admission, and the use of SGLT2i (3% vs. 11%) also rose (p = 0.0005). The application ratio of triple (RASi + ßB + MRA; 43% vs. 77%) and quadruple (RASi + ßB + MRA + SGLT2i; 2% vs. 11%) therapy increased as well (p < 0.0001). The independent predictors of discharge application of triple therapy revealed through multivariate logistic regression analysis were age, duration of hospitalization, eGFR, NTproBNP, and presence of diabetes mellitus. Sixty-eight percent of the cohort would have been suitable for vericiguat, 83% for ARNI, and 84% for SGLT2i. CONCLUSION: High rates of application of disease-modifying drugs are achievable among hospitalized HFrEF patients in severe clinical condition; thus, awareness of the need for their initiation must be raised.