Uncovering difference: a glimpse at patients with heart failure in low-income and middle-income countries

Almost all the information we have on clinical epidemiology of patients with heart failure is collected in North America or in western European countries1Mozaffarian D Benjamin EJ Go AS et al.Turner on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics—2016 Update.Circulation. 2016; 133: e38-360Crossref PubMed Scopus (2332) Google Scholar, 2Roger VL Cardiovascular diseases in populations: secular trends and contemporary challenges-Geoffrey Rose lecture, European Society of Cardiology meeting 2014.Eur Heart J. 2015; 36: 2142-2146Crossref PubMed Scopus (20) Google Scholar, 3Guha K McDonagh T Heart failure epidemiology: European perspective.Curr Cardiol Rev. 2013; 9: 123-127Crossref PubMed Scopus (92) Google ScholarTherefore, the work of Hisham Dokainish and colleagues4Dokainish H Teo K Zhu J et al.INTER-CHF InvestigatorsGlobal mortality variations in patients with heart failure: results from the International Congestive Heart Failure (INTER-CHF) prospective cohort study.Lancet Glob Health. 2017; 5: 665-672Summary Full Text Full Text PDF PubMed Scopus (180) Google Scholar in this issue of The Lancet Global Health, is very welcome. Their study provides a clear picture of clinical characteristics and outcomes of patients with heart failure managed in regions of the world where these details are rarely reported, such as Africa, China, India, the Middle East, southeast Asia and South America. The International Congestive Heart Failure (INTER-CHF) study included 5823 patients, two thirds of whom were clinic outpatients and the rest were inpatients. Dokainish and colleagues present a systematic evaluation of prospectively enrolled heart failure patients in low-income and middle-income regions using standardised enrolment criteria and a uniform protocol. Patients were from a mix of rural and urban centres, specialist centres and primary-care clinics. Follow up was at 6 months and 12 months, with an impressive 98% follow-up rate. Overall 1-year all-cause mortality was 16·5%, but ranged from 9% to 34% and was highest in Africa and India (23%). 46% of deaths were from cardiac causes, 16% were noncardiac, and 38% were from unknown causes, although the rate of unknown causes was especially high in Africa (55%). At first glance, the most striking feature of the cohort is the young age of patients, especially in Africa and India (53 years and 56 years, respectively). Despite the young age, the proportion of women in this patient population is greater than that reported in European and North American studies. Another noteworthy feature in the African cohort is that only 20% of patients had heart failure that was ischaemic in origin. Patients with heart failure in the INTER-CHF regions of the world are so clinically different from those in Europe and North America. Therefore, it is difficult to imagine that pharmacological treatments––supported by results from clinical trials and recommended in international guidelines5Ponikowski P Voors AA Anker SD et al.2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.Eur Heart J. 2016; 37: 2129-2200Crossref PubMed Scopus (8811) Google Scholar, 6Yancy CW Jessup M Bozkurt B et al.2016 ACC/AHA/HFSA focused update on new pharmacological therapy for heart failure: an update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America.Circulation. 2016; 134: e282-e293Crossref PubMed Scopus (321) Google Scholar—can have exactly the same risk-benefit profile in the INTER-CHF cohort as in a comparatively older, male patient group with a predominance of coronary disease that is typical of populations usually included in randomised clinical trials. Despite the young age of patients in INTER-CHF 1-year all-cause mortality is extremely high in Africa and India, and this excess in the risk of death remains after multivariable analysis adjustment for not only clinical variables but also socioeconomic status and treatment type. Patients' clinical features, medications, demographic characteristics, or socioeconomic factors can explain 46% of variability in the mortality rate between regions, but the rest cannot be explained by the available variables. Access and quality of diagnostic and therapeutic procedures, different healthcare systems, genetic profile or environmental factors could have contributed to the large observed differences. The picture that emerges from this robust study, with a remarkable 98% completeness of follow-up, provides several points for consideration. First, while rates of cardiovascular death have fallen since the mid 1990s in North America and western Europe, the increasing rate noted in the other areas of the world is striking.7Roth GA Forouzanfar MH Moran AE et al.Demographic and epidemiologic drivers of global cardiovascular mortality.N Engl J Med. 2015; 372: 1333-1341Crossref PubMed Scopus (695) Google Scholar This trend suggests that clinical conditions, such as heart failure, not so relevant in the past for middle-income and low-income regions, could result in a future unsustainable burden on local health systems. The cost of drugs and access to appropriate care are considerable enough challenges in low-income and middle-income regions even before consideration of non-pharmacological treatments, such as the device implantation, which is an important part of heart failure care in high-income countries. Second, future research cannot overlook patients from regions included in the INTER-CHF study, who, with such different clinical characteristics from patients with heart failure in North American and Europe, need to be evaluated separately. Third, the information reported by Dokainish and colleagues should be considered as merely a starting point. More cohorts with large sample sizes and patients from a wide range of countries are needed to document, in even more reliable detail, the clinical characteristics of patients in low-income and middle-income countries. Studies in such groups would allow evaluation of the best management of patients with heart failure and concomitant comorbidities such as renal dysfunction, COPD, diabetes, anaemia and iron deficiency, which have a relevant effect on outcomes.8Mentz RJ Kelly JP von Lueder TG et al.Noncardiac comorbidities in heart failure with reduced versus preserved ejection fraction.J Am Coll Cardiol. 2014; 64: 2281-2293Crossref PubMed Scopus (361) Google Scholar Finally, the INTER-CHF study lends further support to the concept that observational research is necessary to explore clinical fields generally not covered by randomised controlled trials. A further extension of studies on the clinical epidemiology of heart failure in all the areas of the world is very much needed. APM has received personal fees to be part of study committees of clinical trials sponsored by Novartis, Cardiorentis, Bayer, and Fresenius. Global mortality variations in patients with heart failure: results from the International Congestive Heart Failure (INTER-CHF) prospective cohort studyMarked regional differences in mortality in patients with heart failure persisted after multivariable adjustment for cardiac and non-cardiac factors. Therefore, variations in mortality between regions could be the result of health-care infrastructure, quality and access, or environmental and genetic factors. Further studies in large, global cohorts are needed. Full-Text PDF Open Access