Outline
Heart Failure: A Global Perspective, 385
Global Burden of Heart Failure in the Developing World, 385
Primary Cause and Type of Heart Failure in the Developing World, 387
Specific Aspects of Heart Failure in Key Regions in the Developing World, 388
Sub-Saharan Africa, 388
Heart Failure Overall, 388
Heart Failure Due to Hypertensive Heart Disease, 388
Heart Failure Due to Cardiomyopathies, 389
South America, 390
Asia and the Pacific Region, 391
Key Considerations for the Prevention and Management of Heart Failure in the Developing World, 392
What Is Needed for a Global Heart Failure Prevention Strategy?, 394
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.
| 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 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.
| 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 |
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.
Specific Aspects of Heart Failure in key Regions in the Developing World
Sub-Saharan Africa
Cardiomyopathy and rheumatic heart disease have historically been considered to be the major causes of heart failure in sub-Saharan Africa, accounting for almost half of all cases presenting to hospitals in the period between 1957 and 2005. They pose a great challenge even in the context of the increasing burden of other cardiovascular diseases (CVDs), such as hypertensive heart disease, because they are difficult to diagnose in resource-poor environments as a result of the lack of specialized facilities and access to echocardiography. There is also a limit in effective interventions, such as pharmacotherapy, device-based therapies, valve replacement, and heart transplantation. There has, at least, been important new research on the epidemiology, pathogenesis, and prognosis of heart failure and cardiomyopathy in Africa in the past decade, as well as a few outcome studies.
Heart Failure Overall
Acute decompensated heart failure is the most common primary diagnosis for patients admitted to a hospital with heart disease in Africa. Recent data from the Sub-Saharan Africa Survey of Heart Failure (THESUS-HF), the first and largest multicenter registry of acute heart failure in Africa to date, have characterized the causes and short-term outcomes in 1006 Africans with heart failure, from 12 tertiary cardiology centers in nine countries in sub-Saharan Africa. The diagnosis of heart failure in THESUS-HF was based on the presence of dyspnea associated with physical findings of congestive heart failure (CHF), necessitating admission to a hospital in a patient who was 12 years of age or older. Echocardiography was used in all patients included in the study. One of the most striking features is the relative youth of the African patients affected by acute heart failure (mean age 52 years). Acute heart failure therefore strikes the generation of breadwinners and caregivers in African patients, thereby having major economic implications. The younger African patients with acute heart failure have a lower frequency of ischemic heart disease, hypertension, diabetes mellitus, atrial fibrillation, and renal insufficiency compared with elderly heart failure sufferers in developed countries. Compared with a summary of the causes of heart failure in sub-Saharan Africa, based on the case series published between 1957 and 2005, THESUS-HF shows a changing trend in the epidemiology of acute heart failure in sub-Saharan Africa. There was a rise in the contribution of hypertension as a cause of heart failure (from 23% to 45%), a reduction in the role of rheumatic heart disease (from 22% to 14%), and an apparent increase in recognition of ischemic heart disease as a cause of heart failure (from 2% to almost 8%). The high incidence of hypertension and relatively low rate of coronary artery disease have also been observed in other single-center studies, such as the Heart of Soweto Study, where less than 10% of cases of heart failure were attributed to ischemic cardiomyopathy.
A recent publication by Ojji et al. reported on carefully characterized, consecutively captured patients residing in Abuja/Nigeria ( n = 1515), comparing them to 4626 patients from the Heart of Soweto project, South Africa, showing that hypertension contributed to even 60% of all cases presented with heart failure in Abuja versus 33% in Soweto. In the Soweto cohort, 66% had multiple risk factors versus only 12% in Abuja. On an age- and sex-adjusted basis, compared with the Soweto cohort, the Abuja cohort were more likely to present with a primary diagnosis of hypertension (adjusted odds ratio [OR] 2.10, 95% CI 1.85–2.42) or hypertensive heart disease/failure (OR 2.48, 95% CI 2.18–2.83); P < .001 for both. However, they were far less likely to present with coronary artery disease (OR 0.04, 95% CI 0.02–0.11) and right heart failure (2.5% vs. 27%).
Heart failure with systolic dysfunction appears to be the most common form in Africa. However, most of the larger hospital- and community-based studies on heart failure were performed before the emphasis on heart failure with preserved ejection fraction. Data on treatment pattern are limited. In a registry in South Africa, medication prescribed for patients presenting with systolic dysfunction ( n = 417) was appropriately prescribed as loop diuretics (85%), angiotensin-converting enzyme (ACE) inhibitors (70%), β-blocker (64%), aldosterone inhibitors (60%), and digitalis (19%). In the same cohort study, 373 patients had heart failure with preserved ejection fraction and received therapy with diuretics (43%), β-blocker (25%), aldosterone antagonists (22%), and a calcium antagonist (18%). The THESUS Study showed an inappropriately high prescription of aspirin and digitalis. Data on compliance are limited but, if available, were comparable with other regions.
A further report from the THESUS Study demonstrated that simple clinical parameters measured at baseline and prior to discharge (including baseline orthopnea, rales, edema, oxygen saturation and changes in physical status from admission to discharge) has the capacity to identify patients at high risk for 6-month mortality. A currently planned, multicenter trial of nurse-led, multidisciplinary heart failure management strategy adapted to the African context (the Pan-African Nurse-led And Community Enhanced cAre in Heart Failure—PANACEA-HF) will target such patients to reduce typically high levels of heart failure–related morbidity and mortality.
Heart Failure Due to Hypertensive Heart Disease
The global impact of elevated blood pressure (BP)/hypertension is profound, being responsible for more deaths worldwide than any other risk factor, including tobacco use, obesity, and lipid disorders ( see also Chapter 25 ). Taking Africa as a whole, a systematic review by Ibrahim and Damasceno estimate that the prevalence of hypertension (BP >160/95 mm Hg) in adults 55 years or older increased from 54% to 78% between 1998 and 2003. Based on the change in lifestyle (adopting Western lifestyles), the African Union estimates that 10 to 20 million people in sub-Saharan Africa may currently experience hypertension, providing a similar challenge to HIV/AIDS. Hypertension in the black African population is considered to be a distinct biologic entity. Not only do Africans develop more hypertension, but compared with other ethnic groups, hypertension in Africans is often more severe and more resistant to treatment, often leading to heart failure.
Studies on possible pathophysiologic mechanisms are not yet conclusive, particularly with respect to gender-based heterogeneity. However, observed gender-based differences in the underlying prevalence and characteristics of hypertension are often marked in black Africans. In the Heart of Soweto registry, detailed information was captured on more than 6000 de novo presentations (5328 with confirmed heart disease) presenting to the cardiology unit of the Baragwanath Hospital, which services a community in profound epidemiologic transition. African women were the single biggest contributors to case presentations (2863 or 54%), with 575 (20%) presenting with a primary diagnosis of hypertension and a further 1196 (42%) with a secondary diagnosis of hypertension. Among the latter, hypertensive heart failure (682/1196 or 57%, mean age 60 ± 14 years) was the most common manifestation of hypertensive heart disease. Interestingly, the level of education and noncommunicable risk factors, such as family history of CVD, smoking, obesity, and type 2 diabetes, correlated with advance disease.
A recent analysis of 320 cases of hypertensive heart failure (43% female and mean age 58–60 years) identified via the Abeokuta Heart Failure Registry in Nigeria provides further insights into this condition from an African perspective. Most cases presented as NYHA III/IV and one-third with preserved systolic function. The median length of hospital stay was 9 days, and the 6-month mortality was 12% (renal dysfunction being an independent modulator of survival). Compared to equivalent patients from neighboring Cameroon, Nigerian cases were older (+5 years). Alternatively, on average they were 2 years younger than South African cases and markedly younger than equivalent cases from North America.
Heart Failure Due to Cardiomyopathies
In adult Africans, cardiomyopathy accounts for 20% to 30% of cardiac cases and is a major cause of heart failure. Dilated cardiomyopathy (DCM) refers to a heterogeneous group of heart muscle diseases of diverse causes ( see also Chapter 20 ). Presentation is usually with progressive heart failure. Important causes in Africa include PPCM, EMF, HIV-related cardiomyopathies, genetic causes, and idiopathic cardiomyopathies.
Data from studies in Europe and North America have, for a long time, indicated that as many as 20% to 50% of patients with DCM may have familial disease, but little is known about the frequency and clinical genetics of this disease in Africa ( see also Chapter 24 ). Ntusi and coworkers found that familial DCM affected at least a quarter of African patients with DCM. Patients presented at a young age (29 years old) compared with patients with idiopathic DCM (39 years old). Furthermore, this was associated with PPCM (7%) and followed an autosomal dominant pattern of inheritance in most families. This was the first study to report on the frequency and the probable mode of inheritance of familial DCM in patients who presented at a tertiary center in Cape Town. The recommendation for family screening for familial DCM in all cases of unexplained DCM, including patients with PPCM, to African patients with the disease is supported by these findings.
Studies from South Africa have shown an association with HLA-DR1 and DRw10 antigens, as well as mitochondrial polymorphisms with idiopathic DCM. Isolated left ventricular noncompaction (ILVNC) is probably often unrecognized as a cause of heart failure and stroke.
The first population-based study of the epidemiologic features and early stages of EMF were reported by Mocumbi and coworkers. In a random sample (1063 subjects) of all age groups from rural Mozambique, the prevalence of EMF (19.8% overall) was determined by transthoracic echocardiography. Patients 10 to 19 years old presented with the highest prevalence of EMF (28.1%), and EMF was higher in male compared to female subjects. Biventricular EMF was found to be the most common form (prevalence 55.5%), followed by right-sided EMF (prevalence 29.0%), with most affected patients displaying mild to moderate structural and functional echocardiographic abnormalities, and only 48 being symptomatic with signs of heart failure (22.7%).
HIV/AIDS and its therapy can have effects on the cardiovascular system on several levels leading to heart failure ( Fig. 29.2 ) ( see also Chapter 30 ). Cardiomyopathy in HIV-seropositive patients is associated with a longer duration of HIV infection, low total lymphocyte count, low CD4 count, and high HIV-1 viral load. A prospective study of 157 patients from Kinshasa showed that almost 50% of the patients developed a cardiac abnormality over a 7-year period. A significant proportion of patients with HIV-associated cardiomyopathy are free of specific cardiac signs and symptoms. In the Heart of Soweto cohort, 24% of patients with HIV-associated cardiomyopathy had asymptomatic left ventricular (LV) dysfunction. Fortunately, the majority of HIV-positive patients in Africa now have access to antiretroviral therapy; although such therapy markedly improves the survival of those with HIV-associated cardiomyopathy it can by itself have negative cardiac effects leading to heart failure.
PPCM is a relatively rare idiopathic disease associated with severe heart failure and occurs toward the end of pregnancy or in the months following delivery ( see also Chapter 20 ). Recently published data from the PPCM EORP registry (ESC EURObservational Research Programme [ http://eorp.org ]) on 411 patients have shown that the condition occurs in women from different ethnic backgrounds globally. However, despite marked differences in socio-economic backgrounds, the mode of presentation was largely similar. Accurate data on the incidence of PPCM are unavailable as few population-based registries exist. Recent studies suggest a wide variation in the estimated incidences of PPCM ( Table 29.3 ).
| Author | Year | Country | Incidence | Cohort | Definition of peripartum cardiomyopathy | Echocardiographic assessment |
|---|---|---|---|---|---|---|
| Fett | 2002 | Haiti | 1 in 400 live births | Afro-Caribbean |
| EF <45% |
| Fett | 2005 | Haiti | 1 in 300 live births | Afro-Caribbean |
| EF <45% |
| Desai | 1995 | South Africa | 1 in 1000 live births | Black Africans |
| EF <45% |
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