REPORT-HF reveals global inequalities in health care provision and prognosis of patients with acute heart failure

Heart failure (HF) is a common cause of hospitalization worldwide. In the last years, numerous therapeutic approaches aiming to improve outcome in patients with decompensated HF were unsuccessful. One reason for this disappointing development may lie in the major regional heterogeneity of patients studied in clinical trials and registries.1 Differences include patient-related factors as disease awareness, health literacy, clinical characteristics and presentation, HF aetiology, adherence to treatment, and structural factors as availability of diagnostic, therapeutic, monitoring resources, type of health care, and insurance system.1 So far, however, it was not possible to compare these differences on a common scale. The REPORT-HF (international REgistry to assess medical Practice and lOngitudinal obseRvation for Treatment of Heart Failure) addresses these shortcomings as a prospective global registry that was designed to characterize presentation, management, and outcome of patients hospitalized for new-onset HF or decompensation of chronic HF all over the world.2,3 More than 18 000 patients were enrolled in 358 centres from 44 countries across 6 continents and followed for 1 year after discharge.3 Participating countries were classified in seven geographic regions, i.e. Latin America, North America, Western Europe, Eastern Europe, Eastern Mediterranean and Africa, Southeast Asia, and Western Pacific. Compared with prior larger HF registries sampling patients from North America and Europe,4 or analysing one single geographic area,5 REPORT-HF for the first time provides a global perspective on the long-term longitudinal characterization on HF trajectories following hospitalization for acute HF. This first global snapshot provides new and extremely important information for the comprehension of geographical and socio-economic differences in aetiology, presentation, and management of decompensated HF, and confirms that there is marked variability in baseline characteristics and management of patients enrolled in different geographic regions.1 This heterogeneity underlines the need for strictly harmonized study protocols to allow cross-country comparisons. Such a structured effort is required to reliably recognize regional differences and biological commonalities of the HF syndrome. This aspect constitutes a major achievement of the REPORT-HF consortium, which successfully recruited representative groups of patients per region. The stark contrast between characteristics of patients enrolled in North America and Southeast Asia is paradigmatic of the wide regional variability of the HF syndrome. North American patients had a median body mass index (BMI) of 29 kg/m2 and were obese in 49% of cases, while the median BMI in Southeast Asia was 23 kg/m2 and only 4% of patients were obese. In North America, 80% of patients were admitted for decompensated chronic HF, while this was the case for only 21% of patients in Southeast Asia, who were mostly admitted for new-onset HF. Aetiology of HF and ejection fraction were also markedly different between regions. North American patients had ischaemic heart disease in 27%, and HF with preserved ejection fraction (HFpEF) in 40% of cases; in contrast, HF was ischaemic in origin in 48% of patients from the Eastern Mediterranean region and Africa, where HFpEF accounted only for 22% of cases. Finally, patients from Southeast Asia had more severe signs and symptoms at presentation, with 34% admitted with New York Heart Association class IV. Not surprisingly, these differences reflect the contrast between the HF populations of low- and high-income countries. When stratified according to income level, patients from lower-middle-income countries were almost 10 years younger, markedly leaner, and had more severe symptoms at admission. These patients also had a substantially lower comorbidity burden: all comorbidities assessed, except for diabetes mellitus, were more common in patients from high-income countries. Finally, the socio-economic status also impacted on HF management and prognosis. Patients from countries with lower income or greater income inequality were less likely to receive β-blockers or angiotensin-converting enzyme inhibitors at discharge and had higher 1-year mortality, the majority (60%) of deaths being due to cardiovascular causes. These findings from REPORT-HF confirm that (i) socio-economic disadvantages heavily impact on the way how HF is managed, and (ii) the quality of HF management impacts on prognosis. Therefore, stronger efforts need to be directed towards equalizing such regional and socio-economic differences to provide life-saving medical care to more patients around the world. Surprisingly, prognosis of patients from Eastern Europe was most favourable. This raises an important caveat to the interpretation of REPORT-HF data, as despite its comprehensive approach the picture that can be drawn remains incomplete. Prospective cohort studies select on willing participants, and an important fraction of patients evades characterization, namely patients unable or unwilling to consent. In North America and Europe, improvements in pharmacological and device therapy have contributed to HF-related mortality, consequently exposing the HF population to a higher prevalence of comorbidities. Therefore, the success of current HF therapy is ultimately reshaping the characteristics of the HF population and modifying the natural history of the syndrome, which becomes progressively governed by the co-occurrence of non-cardiovascular comorbidities. This is important as it will determine how we may approach future HF research and care. The transition of HF from a purely cardiovascular disorder to a complex clinical syndrome moulded by the profile of comorbid conditions has profound implications for the development of new therapeutic strategies that involves targeting metabolic and inflammatory processes beyond the mere antagonization of neuroendocrine activation. While preclinical research heavily relies on animal models, these often do not adequately reflect this emerging complexity. Since this imposes a relevant obstacle for mechanistic studies and their ensuing translation into the clinic, careful selection and/or development of animal models for preclinical research6 is essential to avoid failure of translation into clinical applications. The future of HF therapy lies in a personalized approach tailored to the comorbidity profile of each patient, and this might be especially relevant for HFpEF, where no therapeutic option with an impact on survival is currently available. Conflict of interest: none declared. C. M. is supported by the German Research Foundation (DFG; Ma 2528/7-1, SFB-894, TRR-219) and the Federal Ministry of Education and Research (BMBF; 01EO1504). Biography: Edoardo Bertero received his MD at the University of Genova (Italy) in 2016. In November 2016, he joined the group of Christoph Maack at the University of Saarland in Homburg, Germany. He is currently an MD/PhD student in the Department of Translational Science at the Comprehensive Heart Failure Center (CHFC) in Würzburg, Germany. His research focuses on the pathophysiology of chronic heart failure, with a special emphasis on mitochondrial and metabolic dysfunction in cardiac myocytes. Biography: Stefan Störk received his MD at the University of Homburg (Germany) in 1994. Besides training in internal medicine and cardiology, he earned an MSc and PhD at Universities of Rotterdam and Utrecht, Netherlands. In 2010, he became co-founder of the CHFC, where he leads the Department of Clinical Research and Epidemiology. His special interest is in implementation research. Biography: Christoph Maack received his MD at the University of Cologne (Germany) in 2000. From 2000 to 2017, he worked at the Department of Cardiology at the University of the Saarland in Homburg, Germany. Between 2002 and 2005, he was a post-doc in the lab of Brian O Rourke at the Department of Cardiology at Johns Hopkins University in Baltimore, MD, USA. In 2017, he became Chair of the Department of Translational Research at the Comprehensive Heart Failure Center (CHFC) and Spokesperson of the CHFC at the University Clinic in Würzburg, Germany. His work focuses on cellular defects in chronic heart failure, with a special emphasis on the mechanisms of contractile, mitochondrial and metabolic dysfunction in heart failure.