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Heart Failure in the Developing World
Heart Failure: a Global Perspective
At any one time it has been estimated there are approximately 26 million cases of heart failure globally. Although many of these cases reside in the developing world, our understanding of heart failure is largely framed by studies undertaken in high-income countries. The characteristics and consequences of heart failure have also been framed by its clinical diagnosis (with normal values for cardiac indices largely derived from Caucasian populations) and the pivotal clinical trials (e.g., the recent PARADIGM Trial) that have led to the introduction of new treatment modalities. Table 29.1 summarizes some of the key definitions that have shaped our collective perceptions of heart failure, from a predominantly “systolic dysfunction” phenomenon mainly affecting men, to one that acknowledged neurohormonal activation and wider systemic responses to a “failing heart” and, more latterly, the concept of both impaired and preserved systolic dysfunction affecting both sexes.
TABLE 29.1
A Historical Perspective on Heart Failure Definitions
Data adapted from Krum H, Jelinek MV, Stewart S, et al. 2011 update to National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand Guidelines for the prevention, detection and management of chronic heart failure in Australia, 2006. Med J Aust. 2011;194:405–409.
| Wood, 1968 | “A state in which the heart fails to maintain an adequate circulation for the needs of the body despite a satisfactory venous filling pressure.” |
| Braunwald & Grossman, 1992 | “A state in which an abnormality of cardiac function is responsible for the failure of the heart to pump blood at a rate commensurate with the requirements of the metabolizing tissues or, to do so only from an elevated filling pressure.” |
| Packer, 1988 | “A complex clinical syndrome characterized by abnormalities of left ventricular function and neurohormonal regulation which are accompanied by effort intolerance, fluid retention, and reduced longevity.” |
| Poole-Wilson, 1987 | “A clinical syndrome caused by an abnormality of the heart and recognized by a characteristic pattern of hemodynamic, renal, neural, and hormonal responses.” |
| AHA/ACC Heart Failure Guidelines, 2005 | “Heart failure is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood.” |
| ESC Heart Failure Guidelines, 2005 | “A syndrome in which the patients should have the following features: symptoms of heart failure, typically breathlessness or fatigue, either at rest or during exertion, or ankle swelling and objective evidence of cardiac dysfunction at rest.” |
| AHA/ACC Heart Failure Guidelines, 2009 (Update) | Definition essentially unchanged, with reinforcement of these stages of heart failure (see legend below; note that the first two stages are not heart failure) and the central importance of the following statement: “The single most useful diagnostic test in the evaluation of patients with heart failure is the comprehensive two-dimensional echocardiogram coupled with Doppler flow studies to determine whether abnormalities of myocardium, heart valves, or pericardium are present and which chambers are involved. Three fundamental questions must be addressed: (1) Is the LV ejection fraction preserved or reduced? (2) Is the structure of the LV normal or abnormal? (3) Are there other structural abnormalities such as valvular, pericardial, or right ventricular abnormalities that could account for the clinical presentation?” |
| ESC Heart Failure Guidelines, 2012 (Update) | “A syndrome in which patients have typical symptoms (e.g., breathlessness, ankle swelling, and fatigue) and signs (e.g., elevated jugular venous pressure, pulmonary crackles, and displaced apex beat) resulting from an abnormality of cardiac structure or function.” |
The AHA/ACC guidelines provide a map of the natural history of heart failure (from a developed world perspective) in respect to four distinct stages: Stage A: Those at risk for heart failure, but who have not yet developed structural heart changes (i.e., those with diabetes or coronary disease without prior infarct). Stage B: Individuals with structural heart disease (i.e., reduced ejection fraction, left ventricular hypertrophy, chamber enlargement); however, no symptoms of heart failure have ever developed. Stage C: Patients who have developed clinical heart failure. Stage D: Patients with refractory heart failure requiring advanced intervention (biventricular pacemakers, left ventricular assist device, or transplantation).
AHA/ACC, American Heart Association/American College of Cardiology.
The concept of heart failure as more than just a product of coronary artery disease and predominantly affecting men is critical when considering heart failure in the developing world. Accordingly, preliminary data from the developed world suggest there are many different pathways to the syndrome. Based on a number of important factors, including different risk factors (including high levels of communicable disease and exposure to indoor pollutants), high levels of poverty and malnutrition, and suboptimal access to health care systems, it is not surprising that the pattern of heart failure in vulnerable communities in the developing world is different—with potentially more women than men being affected, and with much younger cases typically presenting with more advanced heart disease.
This chapter outlines the pattern of heart failure from a developing world perspective while clearly acknowledging the challenge of comparing data from heterogeneous sources and the variety of methods/definitions used to detect and report on heart failure in low-resource settings. Even if a coherent picture of heart failure is not entirely possible, it is important to note the enormous burden the syndrome imposes on the developing world. This burden is likely to rise as the influence of the traditional killers (malnutrition and infectious diseases) decline and many individuals adopt the lifestyle behaviors (e.g., smoking, high fat diets, and sedentary behaviors) that have fueled an epidemic of heart failure in the developed world.
Global Burden of Heart Failure in the Developing World
Based on different risk factor prevalence among the wide spectrum of ethnic groups influenced by socioeconomic factors, it is inevitable that the epidemiological and clinical profile of heart failure will vary across the globe. Moreover, differential coding of the syndrome, coupled with nuanced differences in defining cases, defies simple regional comparisons, particularly from a developed world perspective. For example, the current International Classification of Diseases system classifies heart failure as an intermediate and not an underlying cause of death. The recently published Global Burden of Disease (GBD) studies, undertaken in 1990 and 2000, reported global death for 235 causes, including cardiovascular and circulatory diseases such as rheumatic heart disease, ischemic heart disease, cardiomyopathy, and others, and list heart failure as a nonfatal health outcome only. Left-sided and right-sided symptomatic heart failure was one of the 289 impairments included in the GBD cause–sequelae list in many locations. Contrasting with more conservative estimates, worldwide an estimate of 37.7 million cases of prevalent heart failure was recorded in 2010, leading to 4.2 years lived with disability (YLDs). Heart failure was distributed across a number of causes ( Table 29.2 ). In stark contrast to clinical trial cohorts, more than two-thirds (68.7%) of heart failure globally was attributable to four underlying causes: ischemic heart disease, chronic obstructive pulmonary disease, and hypertensive and rheumatic heart disease. As expected, there were marked regional differences, with hypertensive heart disease, rheumatic heart disease, cardiomyopathy, and myocarditis making a larger contribution in developing countries.
TABLE 29.2
Global Years Lived With Disability for Heart Failure From a Comprehensive List of 289 Causes and Select Sequelae in 1990 and 2010 for All Ages, Both Sexes Combined, and per 100,000
Data from Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2163–2196.
| All Ages YLDs (thousands) | YLDs (per 100,000) | |||||
|---|---|---|---|---|---|---|
| Cause of HF | 1990 | 2010 | % Δ | 1990 | 2010 | % Δ |
| Cardiovascular and circulatory diseases | 14,373 (11,094–18,134) | 21,985 (16,947–27,516) | 53.0% | 271 (209–342) | 319 (246–399) | 17.7 |
| Rheumatic HD | 290 (191–412) | 420 (278–592) | 45.1% | 5 (4–8) | 6 (4–9) | 11.6 |
| Ischemic HD | 894 (609–1236) | 1518 (1038–2128) | 69.9% | 17 (11–23) | 22 (15–31) | 30.8 |
| Hypertensive HD | 292 (202–412) | 460 (315–639) | 57.4% | 6 (4–8) | 7 (5–9) | 21.1 |
| HF due to cardiomyopathy and myocarditis | 272 (183–378) | 394 (269–551) | 44.8% | 5 (3–7) | 6 (4–8) | 11.4 |
| HF due to endocarditis | 42 (28–59) | 61 (42–87) | 45.8% | 1 (1–1) | 1 (1–1) | 12.2 |
| HF due to other circulatory diseases | 183 (123–259) | 268 (180–372) | 46.3% | 3 (2–5) | 4 (3–5) | 12.6 |
HD , Heart disease; HF , heart failure; YLDs , years lived with disability.
What Do We Know About the Variation of Risk Factor Prevalence?
A systematic review of worldwide risk factors for heart failure by Khatibzadeh and colleagues found 53 full-text surveys of heart failure patients eligible for inclusion and, after excluding 15 full-text papers, sorted 38 studies by region, using them for a qualitative synthesis. From these surveys it was found that ischemic heart disease was the major risk factor for heart failure in more than 50% of patients in Western high-income regions, as well as Eastern and Central European regions. In contrast, it contributed to 30% to 40% of heart failure cases in East Asia, Asia Pacific high-income regions, Latin America, and the Caribbean. At the lowest end of the scale, in sub-Saharan Africa, ischemic heart disease contributed to less than 10% of cases.
Hypertension proved to be a more consistent contributor to heart failure globally (17% or more crude prevalence among all cases). However, after age and gender adjustment, hypertension was distinctly more common in Eastern and Central Europe (35%, range 32.7%–37.3%) and sub-Saharan Africa (32.6%, range 29.6%–35.7%). Of the other two commonly reported antecedents, rheumatic heart disease was particularly prevalent in East Asia (34%) and sub-Saharan Africa (14%) cases. The heterogeneous group of cardiomyopathy, which can include numerous causes such as familial, peripartum, infectious, infiltrative, autoimmune, postmyocarditis, idiopathic, and many others, were particularly prevalent in sub-Saharan Africa (age- and gender-adjusted prevalence 25.7%, range 22.8%–28.5%). Latin America and the Caribbean, as well as Asia Pacific high-income countries, had a prevalence of 19.8% (16.5%–23.4%) and 16.5% (12.8%–20.6%). Notably, this review relied on data from many studies that exclude younger patients and those with preclinical heart failure, while rarely documenting duration of heart failure symptoms.
What Do We Not Know?
As data from many regions of the world are scarce, there is a particular lack of data estimating urban/rural differences as well as change in contributing factors to heart failure over time. There is an overall underreporting on the specific factors contributing to the spectrum of cardiomyopathy because these investigations are costly and there is a shortage of diagnostic facilities in those areas where, in particular, infectious causes of cardiomyopathy occur. In general, right heart failure per se, or as a contributing factor to left-sided heart failure, is poorly documented and there is a paucity of detailed description of the subtypes of valvular heart disease, such as different types of rheumatic valve disease or function valve disease. Congenital heart disease, either operated or not operated, usually gets lumped in the category “other causes contributing to heart failure” and warrants further investigation. This is particularly important as the proportion of cases with operated congenital heart disease is increasing and congenital heart disease altogether is more commonly diagnosed. The early stages of heart failure need to be diagnosed in a timely manner as they can be managed in multidisciplinary teams using pharmacologic or nonpharmacologic interventions.
Primary Cause and Type of Heart Failure in the Developing World
Heart failure in the developing world is mainly due to non-ischemic causes, such as hypertensive heart disease, valvular heart disease as a result of rheumatic fever and its sequelae, and heart muscle disease caused by infectious or unknown agents. This includes region-specific cardiomyopathies, such as endomyocardial fibrosis (EMF) in Africa, Chagas disease in South America (profiled in Fig. 29.1 ), and peripartum cardiomyopathy (PPCM), which has a particularly high prevalence in the black African population. Cardiac manifestations of HIV include forms of HIV cardiomyopathy. Reporting on the etiology and primary cause of heart failure was, in the past, only clinically based and only in the past 10 to 20 years it has been supported by echocardiography. In addition, the focus is mainly on the causes of heart failure due to systolic dysfunction. Reporting on heart failure with preserved systolic function, as commonly seen due to hypertensive heart disease or in addition to systolic heart failure, is rare from the developing world. This needs to be addressed in future studies, because it is likely that the profile of heart failure will also change in those regions as a result of the shifts in population demographics, the prevalence of specific risk factors, and the influence of the evolution of and access to therapeutic options.
The contribution of communicable disease, including HIV/AIDS (see below) to the overall burden of heart failure in the developing world cannot be underestimated. For example, in the Global Rheumatic Heart Disease Registry Cohort of 3343 predominantly younger individuals (two-thirds female and median age 28 years) patients recruited from 25 centers in 14 low- and middle-income countries in Africa and Asia, heart failure was a major contributor to observed mortality. Overall, 2-year mortality was 17%, and concurrent heart failure conveyed a twofold increased risk of death (adjusted hazard ratio of 2.16, 95% confidence interval [CI] 1.70–2.72). Those cases from the lowest socioeconomic backgrounds had the worse outcomes at a younger age.
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