Contemporary guideline-directed medical therapy in de novo, chronic, and worsening heart failure patients: First data from the TITRATE-HF study.

AIMS: Despite clear guideline recommendations for initiating four drug classes in all patients with heart failure (HF) with reduced ejection fraction (HFrEF) and the availability of rapid titration schemes, information on real-world implementation lags behind. Closely following the 2021 ESC HF guidelines and 2023 focused update, the TITRATE-HF study started to prospectively investigate the use, sequencing, and titration of guideline-directed medical therapy (GDMT) in HF patients, including the identification of implementation barriers. METHODS AND RESULTS: TITRATE-HF is an ongoing long-term HF registry conducted in the Netherlands. Overall, 4288 patients from 48 hospitals were included. Among these patients, 1732 presented with de novo, 2240 with chronic, and 316 with worsening HF. The median age was 71 years (interquartile range [IQR] 63-78), 29% were female, and median ejection fraction was 35% (IQR 25-40). In total, 44% of chronic and worsening HFrEF patients were prescribed quadruple therapy. However, only 1% of HFrEF patients achieved target dose for all drug classes. In addition, quadruple therapy was more often prescribed to patients treated in a dedicated HF outpatient clinic as compared to a general cardiology outpatient clinic. In each GDMT drug class, 19% to 36% of non-use in HFrEF patients was related to side-effects, intolerances, or contraindications. In the de novo HF cohort, 49% of patients already used one or more GDMT drug classes for other indications than HF. CONCLUSION: This first analysis of the TITRATE-HF study reports relatively high use of GDMT in a contemporary HF cohort, while still showing room for improvement regarding quadruple therapy. Importantly, the use and dose of GDMT were suboptimal, with the reasons often remaining unclear. This underscores the urgency for further optimization of GDMT and implementation strategies within HF management.

Regional management of worsening heart failure: rationale and design of the CHAIN-HF registry.

AIMS: Heart failure (HF) is a progressive disease in which periods of clinical stability are interrupted by episodes of clinical deterioration known as worsening heart failure (WHF). Patients who develop WHF are at high risk of subsequent death, rehospitalization, and excessive healthcare costs. As such, WHF could be seen as a separate disease stage and precursor of advanced HF. Whether WHF has a substantial health, societal, and economic impact evidence regarding its multifactorial nature and the specific barriers in treatment, including advanced HF therapies, remains scarce. The CHAIN-HF registry aims to describe the incidence, characteristics, current treatment, and outcomes of WHF. Additionally, it will promote structured regional collaboration and educate on increasing awareness for WHF and describe the implementation of guideline directed medical therapy and utilization of advanced HF therapies in a collaborative network. METHODS AND RESULTS: The CHAIN-HF registry is a prospective, observational, and multicentre study from the collaborating hospitals (Rijnmond HF Network) in the Rotterdam area. Unselected and consecutive patients (irrespective of ejection fraction) with a WHF event will be included. Comprehensive data including demographics, co-morbidities, treatment, and in-hospital and post-discharge outcomes will be collected. Notably, data on socio-economic status, treatment decisions, and referral for advanced HF therapies will be included. CONCLUSIONS: CHAIN-HF will be the first prospective, dedicated WHF registry in a collaborative network of hospitals that will provide robust real-world evidence on the incidence, characteristics, and outcomes of WHF. Moreover, it will provide information on of the value of regional collaboration to improve awareness and outcomes of WHF.

Effect of additional treatment with EXenatide in patients with an Acute Myocardial Infarction (EXAMI): study protocol for a randomized controlled trial.

BACKGROUND: Myocardial infarction causes irreversible loss of cardiomyocytes and may lead to loss of ventricular function, morbidity and mortality. Infarct size is a major prognostic factor and reduction of infarct size has therefore been an important objective of strategies to improve outcomes. In experimental studies, glucagon-like peptide 1 and exenatide, a long acting glucagon-like peptide 1 receptor agonist, a novel drug introduced for the treatment of type 2 diabetes, reduced infarct size after myocardial infarction by activating pro-survival pathways and by increasing metabolic efficiency. METHODS: The EXAMI trial is a multi-center, prospective, randomized, placebo controlled trial, designed to evaluate clinical outcome of exenatide infusion on top of standard treatment, in patients with an acute myocardial infarction, successfully treated with primary percutaneous coronary intervention. A total of 108 patients will be randomized to exenatide (5 µg bolus in 30 minutes followed by continuous infusion of 20 µg/24 h for 72 h) or placebo treatment. The primary end point of the study is myocardial infarct size (measured using magnetic resonance imaging with delayed enhancement at 4 months) as a percentage of the area at risk (measured using T2 weighted images at 3-7 days). DISCUSSION: If the current study demonstrates cardioprotective effects, exenatide may constitute a novel therapeutic option to reduce infarct size and preserve cardiac function in adjunction to reperfusion therapy in patients with acute myocardial infarction. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01254123.