The Upcoming Epidemic of Heart Failure in South Asia

October 29, 2020 Editor

In 2020, the population of South Asian countries—India, Pakistan, Bangladesh, Sri Lanka, Nepal, Bhutan, and Maldives—is 1.8 billion, comprising 23% of the world’s population (Figure 1).¹ Also, in countries such as the United States, Canada, the United Kingdom, and other European and Asian nations, persons of South Asian ancestry represent one of the largest and fastest-growing minority groups.^2–5

**Figure 1.** **Population of South Asian countries in 2020.** Numbers presented in millions of persons.

With rapid industrialization, increased survival from acute conditions and population aging, chronic noncommunicable diseases (NCDs) and particularly cardiovascular disease (CVD) are becoming a major concern in low- and middle-income countries (LMICs), including the densely populated South Asian nations.^6–11 A wealth of research has shown that South Asians are at increased risk of type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD),^6,12–18 resulting in calls to enhance the prevention of these conditions in South Asian countries and migrant groups.^16–18 However awareness about the current and anticipated importance of heart failure (HF) in South Asians remains limited.

HF is a devastating, resource-intensive syndrome that results in premature mortality, disability, impaired functional capacity, reduced quality of life, and need for multiple pharmacotherapies.^7,8 HF is also a main cause of hospitalization and healthcare expenditure in many countries.^7,8,19–22 For these reasons, HF represents a major threat to patients, health systems and societies; particularly in nations with resource-constrained systems and economies. In this context, recent studies suggest that South Asians may also be at increased risk of HF, and that it may manifest in average 10 to 15 years earlier in life in South Asians than in other geographic and racial/ethnic groups.^15,23–30 These phenomena combined with a very large,¹ progressively aging population in South Asia may result in a massive number of cases of HF in the coming decades, with the potential to have large health and economic consequences.

In this narrative review, we discuss recent studies portraying these trends, describe the mechanisms that may explain an increased risk of premature HF in South Asians compared with other groups and evaluate the implications of an anticipated HF epidemic in South Asian countries. We then discuss proposed interventions aimed at curbing these adverse trends, as well as management approaches that can improve the prognosis of prevalent HF in South Asian countries.

HF in South Asians Living in Diaspora Countries and Multinational Studies

Studies of migrant and local groups living in Asian, European, and North American countries allow to compare the characteristics of various racial/ethnic groups in settings in which the quality of the health information tends to be high and reasonably homogeneous across strata. This research has yielded valuable insights, consistently pointing towards an increased risk of HF and particularly of premature HF in South Asians compared with several other racial/ethnic groups. A summary of key studies from the Middle East, Europe, and North America is presented in Table 1, Figures 2 and 3.

Table 1. Summary of Studies of HF Epidemiology in South Asians Living in Diaspora Countries and Multinational Studies of Patients With HF

Region/Author Country(ies) Year Study Population Key Findings

Middle East

Panduranga²³ Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, United Arab Emirates, Yemen 2012 4539 hospitalized patients with acute decompensated chronic HF or new-onset acute HF from the Gulf Acute Heart Failure Registry, a clinical registry comprising 47 hospitals Patients with HF of Indian ancestry were 6 y younger than the native Middle Easterners and 16 y younger than patients in similar European and United States HF registries, such as EHFS II and ADHERE.^31,32 Indian patients presented with concurrent acute coronary syndromes more often (46% vs 26%), were more likely to be smokers (36% vs 21%), to have diabetes mellitus (56% vs 49%), and had a higher frequency of HFrEF (76% vs 65%). In-hospital mortality similar in both groups.

Europe

Blackledge²⁴ England (Leicestershire) 1998–2001 5,789 consecutive patients newly admitted with HF South Asians had higher age-adjusted HF admission rates than the White population (rate ratios of 3.8 for men, 5.2 for women), higher hospital incidence rates (rate ratios of 2.2 and 2.9, respectively), and were on average 8 y younger (70 vs 78 y). South Asians more frequently had either a history of or concurrent MI, and 46% had diabetes mellitus compared with 16% among Whites.

Bhopal²⁵ Scotland 2001 (Census data) onward Cohort study of 4.65 million people living in Scotland (SHELS) South Asians particularly Pakistanis, Bangladeshis, and Indian men had the highest rates of HF admission compared with the local white population and all other immigrant groups, including persons of African and Chinese origin. SHELS also confirmed that United Kingdom South Asians were the youngest group at the time of a first HF admission. Differences between South Asians and Whites in terms of HF rates were less striking than in the study by Blackledge et al.²⁴

van Oeffelen²⁶ The Netherlands 1998–2010 Nationwide prospective cohort study of 189 069 first HF admissions Local South Asians were much younger than the Dutch population (median ages 58 and 79 y, respectively).

Cainzos-Achirica¹⁵ Spain (Catalonia) 2017 Regionwide study including ≈60 000 mostly Pakistani South Asian immigrants South Asian women ≥65 y of age had a much higher prevalence of HF than the local Spanish population or any other LMIC immigrant group. Also, South Asian men had the highest prevalence of HF at ages 55–65 y and also led the prevalence of HF among men ≥80 y among all groups evaluated.

North America

Singh²⁷ Canada 1997–1999 Retrospective cohort of patients hospitalized with a primary diagnosis of HF South Asians were younger than local white patients and had diabetes mellitus more frequently. In-hospital survival was similar between the 2 groups, although South Asians had a higher prevalence of high-risk features at discharge.

Choi²⁸ Canada (Ontario) 2000–2011 1671 patients with HF followed in 2 specialized HF clinics Average mean age was ≈8 y lower in South Asians compared with Chinese patients and ≈5 y lower than in non-Asian individuals. South Asians more frequently had a history of diabetes mellitus, MI and 3-vessel disease, and needed coronary revascularization procedures more often than the other groups.

Jose²⁹ United States 2003–2010 Study of more than 10.4 million death records evaluated cardiovascular mortality trends among the 6 largest local Asian-American subgroups Women of South Asian ancestry had the highest age-adjusted yearly mortality rates from HF among all Asian subgroups evaluated (11.3 per 100 000 persons), and South Asian men had the second-highest rate (8.7 per 100 000) only surpassed by Filipinos (11.5 per 100 000). Nevertheless, mortality rates from HF were higher among non-Hispanic Whites. United States South Asians comprise a highly educated, high-income, healthier South Asian diaspora subgroup.¹⁶

Multinational

Lam³⁰ Various 2012–2015 ASIAN-HF international registry of 5276 chronic HFrEF patients from China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore, Taiwan, and Thailand South Asians were the youngest patients in the registry (mean age 57.8 y, compared with 62.1 in Northeast Asians and 58.9 in Southeast Asians) yet had a higher burden of underlying CHD and diabetes mellitus (51% and 37%, respectively) than Northeast Asians (38% and 31%, respectively). Rheumatic valvular disease was an exclusion criterion, which may explain the slightly higher mean age of South Asian participants compared with other studies.

Figure 2. Relative risk of first hospitalization and mortality for heart failure in the SHELS (Scottish Health and Ethnicity Linkage Study). Age range was 30 to 74 y. RR indicates rate ratios. Adapted from Bhopal et al²⁵ with permission. Copyright ©2012, BMJ Publishing Group Ltd.

Figure 3. Prevalence and incidence of heart failure in Catalonia (Spain) by geographic group, age, and sex. The number of South Asian men ages ≥65 y included in the database was low. Adapted from Cainzos-Achirica et al¹⁵ with permission. Copyright ©2019, BMJ Publishing Group Ltd.

Although the findings of those studies might be influenced, at least in part, by the adverse socioeconomic circumstances faced by first generation South Asian immigrants in many countries, the burden of HF in South Asians has been shown to be higher than that observed among immigrants from other LMICs.^{15,23–25,28,29} Also, several of those trends, particularly an earlier age of presentation, are consistent with those portrayed in multinational studies comparing the characteristics of patients with HF across various nations, including the ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure)³⁰ and the INTER-CHF (International Congestive Heart Failure; Table 1).³³

Epidemiology of HF in South Asian Countries

Granular epidemiological data on the incidence and prevalence of HF from South Asian countries is currently limited. This is the consequence of scarce surveillance systems and patient registries particularly at the national level, together with the challenges associated with the complex diagnosis of HF, which may represent a big barrier in resource-constrained settings. Recently, the Indian Council of Medical Research has funded a HF registry that aims to collect information from 10 000 patients from 53 hospitals in India.³⁴ Although results are not available yet, this pivotal effort will provide crucial data to inform evidence-based interventions.

Epidemiological Transition, Population Aging, and Implications for HF

Despite limited available data, the consequences of fast epidemiological transition, which are particularly relevant to HF, are evident in South Asia. On the one hand, life expectancy has increased markedly in the last two decades in the region. South Asian populations are aging, with an estimated ≈500 million individuals above the age of 60 living in South Asia by 2050.³⁵ It is estimated that the population will surpass 1.94 billion during 2020, a 13% increase since the year 2010.³⁶ On the other hand, industrialization, westernization of lifestyles and aging come with a rising incidence and prevalence of cardiovascular risk factors, while CVD prevention efforts are still in their early stages in South Asian nations.^{10,11,16,18,37} The strong association between these processes and NCDs, particularly CVD, is evident in South Asia: for example, from 1990 to 2016 all states in India experienced a shift from the majority of disease burden from communicable conditions to NCDs, with CVD representing the number one cause of death.¹⁰

These phenomena together with the very large size of the population herald the potential for a large absolute number of cases of HF in South Asian countries in the coming years. Currently, South Asia accounts for a quarter of the world population, yet it already claims ≈60% of the global burden of heart disease.³⁸ Also, despite rapid industrialization in certain areas, South Asian countries are highly heterogeneous in terms of urbanization and development, and still face a large burden of conditions typical of earlier stages of the epidemiological transition, including infectious, nutritional, and congenital diseases. Many of these have the potential to lead to HF, such as rheumatic fever, tuberculosis, peripartum cardiomyopathy, congenital heart diseases, and various nutritional deficits.

Preliminary Estimates and Local Registries

The limited available estimates of the prevalence of HF in South Asians suggest that as of 2014 the number of cases of HF in India ranged between 1.3 and 4.6 million.¹¹ Pakistan had an estimated 2.8 million patients with HF in 2006.³⁹ For Bangladesh, there are no prevalence estimates available, although it was reported that among all adult hospitalizations occurring in the country in 2016, 14% to 25% were due to HF.⁴⁰ The incidence of HF in India is estimated to be at least between 0.5 and 1.7 cases per 1000 person per year, for a total of 492 000 to 1.8 million new cases per year. This would be similar to that of South American countries, the United States, or Portugal, and lower than Spain or the United Kingdom.⁴¹ Nevertheless, the age-specific incidence for India is unknown, and because HF is strongly associated with age and the population of India is on average younger than that of those countries, incidence comparisons without adjusting for age are misleading—although they suggest an increased risk of HF in India at earlier ages than in countries such as the United States. HF incidence estimates for Pakistan and Bangladesh are currently not available.

Local HF Registries

Consistent with the findings from diaspora and multinational studies, local HF registries confirm a lower average age at admission in HF patients from South Asian countries compared with that of patients from reference HF populations in Western countries.⁴² For instance, in the Trivandrum Heart Failure Registry in India which included 1205 HF hospital admissions during 2013, mean age was 61 years. The most common cause of HF was CHD (72%), and hospital length of stay was longer than that in Western registries, and so was the in-hospital mortality. Patients with HF in other South Asian countries may be even younger on average: in a small HF registry from Lahore, Pakistan, mean age was 54 years, ≈7 years lower than that of Trivandrum and ≈18 years lower than that of a reference US HF population.⁴³

Key Mechanisms Potentially Contributing to an Increased Risk of HF in South Asians Compared With Other Groups

The very large size of the South Asian population together with its within-group heterogeneity call for caution when making generalizations in terms of risk factors and mechanisms of disease. Also, HF is a complex syndrome resulting from multiple, heterogenous causes.^44,45 Nonetheless, some characteristics highly prevalent in South Asian countries and migrant subgroups are of particular relevance to understanding a potentially increased risk of HF and especially of premature HF in South Asians compared with other groups, such as whites (Figure 4).

Figure 4. Potential mechanisms leading to an increased risk heart failure (HF) in South Asians. CHD indicates coronary heart disease; CKD, chronic kidney disease; LV, left ventricle; PM, particulate matter; and RV, right ventricle.

Coronary Heart Disease

The higher burden of CHD among South Asians compared with most other racial/ethnic groups has been well documented in the literature, the potential underlying factors being multiple.^6,12–16 CHD is one of the strongest risk factors for the development of HF, particularly of HF with reduced ejection fraction (HFrEF) but also with preserved ejection fraction.^45,46 In several diaspora HF studies a large proportion of South Asians either presented with a concurrent myocardial infarction or had a history of CHD. Increasing rates of CHD in South Asian countries combined with suboptimal management (eg, limited use of acute revascularization therapies, door-to-balloon delays, low use of class I medications)^11,18 will likely contribute to a prolonged surge in the incidence of HF in coming years. Of note, the INTERHEART study (Effect of Potentially Modifiable Risk Factors Associated With Myocardial Infarction) demonstrated that myocardial infarctions occur an average of 10 years earlier in South Asian countries than in other geographic regions,¹² and reports of premature CHD are ubiquitous in South Asian migrants living elsewhere.^13–16,47 Precocious CHD is likely to play a relevant part in the early presentation of HF in South Asians.

Type 2 Diabetes Mellitus

Besides its role as a key risk factor for CHD, T2DM is also a strong, independent risk factor for the development of HF even among individuals without clinically overt CHD. Diabetic cardiomyopathy leads to myocardial dysfunction and eventually to clinical HF through various mechanisms, including not only atherogenesis but also myocardial fibrosis, dysfunctional remodeling and associated diastolic dysfunction, and eventual systolic dysfunction.^48,49 Importantly, the prevalence of T2DM in the densely populated South Asian nations is among the world’s highest, resulting in a very large absolute number of individuals with diabetes mellitus, which often presents at early age.^6,15,16,50 In addition, poor metabolic control of T2DM further accentuates HF risk.^48,49 In South Asian countries, this is often suboptimal—for instance, average levels of glycosylated hemoglobin are 9% in patients with diabetes mellitus in India,⁵¹ with only one-third of patients achieving the <7% treatment goal.¹⁸ The same has been reported in some South Asian migrant studies.^52,53 Importantly, the prevalence of prediabetes and metabolic syndrome are also disproportionately high in South Asians.¹⁶

Body Composition and Abdominal Obesity

South Asians have a higher proportion of total, abdominal, subcutaneous abdominal, and visceral fat for a given body mass index compared with whites. Abdominal obesity is highly prevalent among South Asians, particularly South Asian men, even in those with a normal body mass index.¹⁶ In India, according to the Indian Council of Medical Research–India Diabetes, the prevalence of abdominal obesity ranged between 17% and 36% in 2015,⁵⁴ resulting once again in a very large absolute number of cases. The prevalence increases with age and is even more striking among South Asians living in some Western countries. For example, in the United States, among 40- to 80-year-old CVD-free participants included in the MASALA study (Mediators of Atherosclerosis in South Asians Living in America), the majority of whom were of Indian ancestry, abdominal obesity is highly prevalent.⁵⁵ Compelling research has demonstrated an independent association between obesity and incident HF,⁵⁶ and studies have also reported associations between abdominal obesity, the risk of HF and adverse HF outcomes independent of body mass index.^57,58

Air Pollution and Pesticides

Levels of various air pollutants are extremely high in many South Asian urban areas, particularly in large Indian cities. According to international air quality data for 2019, 21 of the 30 most polluted cities in the world were in India, 5 in Pakistan, and one in Bangladesh.⁵⁹ Robust evidence suggests that levels of carbon monoxide, sulfur dioxide and nitrogen dioxide, and increases in particulate matter concentration are independently associated with HF hospitalization and mortality.⁶⁰ Potential mechanisms include cardiac dysrhythmias, systemic vasoconstriction leading to increased systemic blood pressure, pulmonary vasoconstriction, increased diastolic filling pressures in both ventricles, reduced myocardial contractility, myocardial injury, adverse ventricular remodeling, and myocardial fibrosis, the combination of which leads to acute decompensated HF and death.⁶⁰ Exposure to other persistent organic pollutants such as pesticides is also very high in countries such as India, and these have also been associated with incident HF.⁶¹ These potential causal factors would not be so relevant among South Asian immigrants living in less polluted world areas, particularly among second and subsequent generation immigrants.

Pretransition Diseases: Rheumatic Heart Disease and Other Conditions

While some South Asian diaspora groups face adverse socioeconomic circumstances and these likely contribute to their burden of HF, in South Asian countries poverty is a powerful contributor to the local burden of the disease. For example, in spite of rapid industrialization, LMICs including South Asian nations still face a large burden of pretransition diseases. Specifically, rheumatic heart disease remains an important cause of HF in South Asia,¹¹ although prevalence estimates are limited by insufficient surveillance systems and marked heterogeneity across published epidemiological studies. In INTER-CHF, among 2661 Asian participants, 32% of which were Indian, 10% of HF cases were considered secondary to rheumatic valvular disease.³³ Because exposure to group A streptococci usually occurs early in life, rheumatic heart disease is likely to be a relevant contributor to the early presentation of HF in South Asians. Another example of a pretransition condition with implications for HF is tuberculosis, which remains highly prevalent in South Asian countries and can cause HF through constrictive pericarditis.⁶²

Underdeveloped Healthcare Systems

The risk factors described above are further compounded by the underdevelopment of public healthcare systems in many South Asian regions, which are overloaded particularly in densely populated rural areas and lowest-income states.^11,18 Infrastructures are often insufficient to serve a very large population, and there is a scarcity of quality assurance measures. These features have direct implications for access and quality of care, and commonly result in the suboptimal acute and chronic management of key risk factors relevant to the development of HF, such as T2DM and CHD.^11,18 Of note, epidemic cardiovascular diseases in South Asian countries likely contribute to perpetuating this situation and the economic underlying factors through loss of productivity, years of disability-free life lost, and direct and indirect costs (Figure 4). Limited health insurance coverage and affordability of therapies are also relevant issues in South Asia.

Other Key Lifestyle Contributors to HF Risk in South Asians

Besides the features described above, which are particularly relevant in South Asian populations, expansion of other lifestyle risk factors in South Asian countries resulting from rapid industrialization and westernization of lifestyles further contributes to an increased population-level risk of HF. Although the prevalence of these risk factors is currently not as high as in other world areas, in the densely populated South Asian nations these translate into in a very large absolute number of individuals at risk of developing HF. Moreover, these combined with the features described above can create a perfect storm for the eventual onset of HF.

Tobacco Products

Use of tobacco products (not only cigarettes, but also bidis and chewable tobacco) is very common in South Asia.¹⁶ In 2003, 47% of Indian men and 14% of women either smoked or chewed tobacco.⁶³ With regards to smoked tobacco, while taxation initiatives have been recently implemented in India resulting in promising declining trends, tobacco control efforts have so far been insufficient in other South Asian countries^18,64: in 2010, 29% of the South Asian male population and 4% of South Asian women smoked tobacco for a total of 171 million tobacco smokers, the prevalence being highest among Bangladeshi and Pakistani men.⁶⁴ According to most recent estimates from the World Health Organization, the age-standardized prevalence of tobacco smoking in India, Pakistan, and Bangladesh is now 20%, 42%, and 40%, respectively.⁶⁵ For reference, the age-adjusted prevalence is 19.5% in the United States, 30% in France, 48% in China, and 59% in Russia. Besides its effects as a risk factor for CHD, studies have demonstrated that smoking tobacco is independently associated with higher N-terminal pro-B-type natriuretic peptide levels, incident left ventricle hypertrophy, systolic dysfunction, and HF admission after accounting for CHD.^66,67 Bidis and smokeless tobacco, which account for 80% of tobacco product use in India,¹¹ also have deleterious cardiovascular effects, including a marked increase in the risk of myocardial infarction.⁶⁸

Hypertension

High blood pressure is a major contributor to CVD in South Asia.^6,11,16,18 The prevalence of hypertension continues to grow in South Asian countries: in India, recent nationally representative studies reported an age-standardized prevalence in 2014 of 24.5% in men and 20% in women.^69,70 Although this is lower than that of Western countries such as the United States,⁷¹ there is an increasing trend since 1950,^69,70 with a projected surge from 118 million cases in year 2000 to 214 million in 2025.¹¹ This is believed to be the consequence of population aging, industrialization, adoption of Western lifestyles, high salt intake, and accumulation of precipitating factors such as obesity and tobacco use, particularly in most developed states and urban areas.⁷⁰ Of concern, awareness of hypertension status is low and blood pressure control is often suboptimal in South Asia.^70,72 High blood pressure is not only a strong risk factor for CHD but also a major cause of HF.⁷³ Longstanding hypertension causes diastolic dysfunction in the left ventricle, hypertrophy and concentric remodeling, which eventually lead to clinically overt hypertensive heart disease. In some patients, pressure and volume overload eventually lead to dilated cardiomyopathy and impaired left ventricular ejection fraction.⁷³

General Obesity

General obesity is independently associated with incident HF.⁵⁶ Besides the epidemiological importance of highly prevalent abdominal obesity as a risk factor for HF particularly among South Asian men, recent data suggest that generalized obesity is also growing in South Asia. For example, according to the Indian Council of Medical Research–India Diabetes the prevalence in India ranged between 12% and 31% in 2015,⁵⁴ with a greater prevalence in urban areas and among older South Asian women.⁷⁴ This has also been reported in various migrant studies—for example, in a 2017 study in Catalonia (Spain), local South Asian women had a much higher prevalence of obesity than local whites.¹⁵ The prevalence of obesity was also high among Newcastle (United Kingdom) South Asians,⁴⁴ as well as among other South Asian subgroups living in Western countries.¹⁶ The association between obesity and HF occurs through a number of mechanisms including inflammation, adipokine release, insulin resistance, endothelial dysfunction, and atherogenesis, all of which may lead to deleterious changes in cardiac hemodynamics, structure, function, and conduction. Also, obesity is associated with an increased risk of conditions strongly associated with incident HF, such as most traditional CVD risk factors, atrial fibrillation, and chronic kidney disease.^74,75

The Role of Genetics

To date, the role of genetic and epigenetic factors as underlying causes of the increased burden of CVD among South Asians remains a matter of debate. Formal genetic studies have failed to identify South Asian-specific genetic variants linked with T2DM or CHD,⁷⁶ and INTERHEART demonstrated that the excess burden of CHD in South Asian countries could be mostly explained by a higher burden of traditional risk factors.¹² Moreover, in the United Kingdom, where individuals of South Asian ancestry now have access to high-quality healthcare similar to that of other racial/ethnic groups, their cardiovascular outcomes in the presence of diabetes mellitus are now similar or even better than those of white patients with diabetes mellitus, arguing against a strong genetic cause leading to CVD in this group.⁷⁷

Nevertheless, metabolic risk factors indeed have a genetic component, and there is consensus regarding the importance of features such as body composition in the increased odds of T2DM and subsequent CHD observed in South Asians.^16,54,55 Specifically for HF, some genetic variants associated with the development of cardiomyopathies, such as a variant of cardiac MYBPC3 (myosin binding protein C), have been noted to be highly frequent in South Asians.⁷⁸ However, whether these significantly contribute to the higher population-level burden of HF observed among South Asians living in diaspora studies, and to the premature presentation of HF is uncertain. Further research is, therefore, needed to better understand the contribution of these and other potential genetic mechanisms to the burden of HF in South Asians. Should a role of genetics be confirmed, opportunities for genetic screening and novel therapeutic targets would have to be explored.

HF Prognosis

In the recent Global Non-Interventional Heart Failure Disease Registry, a patient registry including HF with preserved ejection fraction and patients with HFrEF evaluating postdischarge outcomes in 18 102 patients hospitalized for HF across 44 countries on 6 continents, patients from lower-income regions and those from areas with greater income inequality had 58% and 25% higher 1-year mortality compared with patients with HF from regions with the highest income and lowest-income inequality, respectively.⁷⁹ Of note, patients with HF from lower-income regions were more frequently Asian (83%) than those from high-income regions (14%). Sub-analyses among Asian countries revealed that patients with HF from South Asia and Southeast Asia had higher 1-year mortality rates (17% and 23%, respectively) than those from Northeast Asia and Western Pacific (both 15%) despite a younger mean age.⁷⁹

One-year mortality in INTER-CHF participants from India was also high, particularly among hospitalized HF patients, only surpassed by that observed in African patients.³³ The fact that in most diaspora studies the prognosis of cardiovascular conditions, including HF, was similar in South Asians and in native local populations suggests that the worse HF outcomes observed in South Asia may likely be the consequence of limited resources and suboptimal management, rather than of any underlying biological mechanisms. Indeed, 1-year mortality rates in South Asian participants in ASIAN-HF were significantly lower than in INTER-CHF and the Global Non-interventional Heart Failure Disease Registry, likely the consequence of the inclusion criteria of each study together with greater use of guideline-endorsed HF therapies specifically in ASIAN-HF.⁸⁰

Time to Curb the HF Epidemic in South Asia—An Urgent Call for Action

If the observed trends described above are confirmed and eventually result in a surge of HF cases in South Asian nations in the coming decades, this would have catastrophic consequences for the public’s health, for the sustainability of the local healthcare systems, and for the societies of those countries. Moreover, the economic impact of a very large absolute number of HF cases would perpetuate the disadvantage with higher-income world regions. Frequent presentation of HF at a premature age would accentuate these issues further, resulting in premature mortality, additional years of life lost and lower productivity. These potential consequences stress the need for timely, effective interventions.

Prevention

The recent COVID-19 pandemic has confirmed once again the central importance of implementing preventive interventions in a timely manner to avoid overwhelming healthcare systems and the resulting dramatic increases in morbidity and mortality. In the coming years, health officials in South Asian countries will need to prioritize reducing the incidence of CVD, with special attention to HF. The latter will have to be accomplished through the primordial and primary prevention of its risk factors and of CHD, together with their early detection and aggressive management. Preventive interventions already recommended for curtailing T2DM and CHD^16–18 in South Asian countries and migrant groups become even more relevant in light of their potential to curb this additional cardiovascular epidemic.

Table 2 summarizes proposed approaches that may be particularly relevant to the prevention of HF in South Asian populations. Importantly, in a context of resource-constrained economies, the widespread use of costly, individual-level preventive interventions, of tests for the early diagnosis of the disease, and of costly therapies once present, without reducing the number of at-risk individuals may not be affordable. Policies aimed at reducing population exposure to preventable risk factors through sensible regulations (eg, ban tobacco products, reduce the content of refined sugar, salt, and trans fatty acids in foods) represent the most cost-effective, fast, impactful preventive actions.^{11,18,64,81,82} Also, physical activity will have to be aggressively promoted as means to simultaneously curb various cardiovascular epidemics.^16,17 Similar preventive actions should also target South Asian migrant groups.¹⁷ Reduction of air pollution levels and pesticides should also become a top policy priority.

Table 2. Proposed Interventions for the Prevention of HF in South Asians

Primordial

National prioritization of policies and strategies aimed at reducing exposure to cardiovascular risk factors and increasing exposure to health factors

Increase taxation, enforce public smoking bans, warnings on packets, and advertisement restrictions, affecting smoked tobacco but also other tobacco products (including branded bidis and smokeless tobacco)

Decrease content of salt, refined sugars and trans fatty acids in foods through national policies; use of mandatory food labels

Taxations for sugar-sweetened beverages, saturated and trans fats, coconut oil, palm oil, Vanaspati, ghee

Aggressively promote a culture of increased levels of physical activity both at the workplace and during leisure time

Promote a cultural shift towards healthy diets and foods

Provision of health education to the general population, including since early ages (interventions at schools, healthy living included in the curriculum)

Target entire households and communities

Enhance cultural competency of interventions

Policies to reduce air pollution: cooking fuel, industry and transportation regulations

Policies to minimize the use of pesticides with deleterious health effects

Enhance the detection, acute-phase management, and follow-up of rheumatic fever

Primary

Aggressive detection of cardiovascular risk factors at early adult ages with special attention to diabetes mellitus, obesity, hypertension, and atherogenic dyslipidemia

Develop local, regional and nationwide cardiovascular risk factor screening programs

Optimized lifestyle and pharmacological management since early stages

Secondary

Optimized acute-phase management of CHD once present: increase awareness, develop primary angioplasty networks, minimize door to balloon delays

Enhanced chronic management of CHD: optimize lifestyle and pharmacological management during follow-up, long-term use of class I therapies such as statins and ACE inhibitors

Culturally appropriate CHD rehabilitation, such as yoga and Bollywood dance

Early detection and aggressive management of subclinical left ventricular systolic dysfunction (stage B HF) following relevant clinical practice guidelines

In parallel, development and strengthening of public healthcare systems should be considered a national priority in South Asian countries (Table 3).¹⁸ In rural Pakistan, the COBRA-BPS (Control of Blood Pressure and Risk Attenuation—Bangladesh, Pakistan, and Sri Lanka) investigators demonstrated that availability of public high-quality care not only improved the management of risk factors such as blood pressure, but also reduced mortality in a dramatic manner (>30% after only 2 years of follow-up).⁸³

Table 3. Proposed Health Systems Strengthening Approaches Aimed at Improving the Prevention and Management of HF in South Asian Countries

General approaches

Political prioritization of CVD prevention and of quality of care

Increase the % of gross domestic product devoted to healthcare

Provide public universal healthcare coverage

Improve health education and CVD health awareness in the general population

Expansion of healthcare workforce to meet WHO recommendations

Strengthen primary care systems with special attention to the management of complex, resource-intensive chronic conditions such as HF

Enhance involvement of cardiovascular scientific societies in the design, implementation, and evaluation of relevant health policies

Development and implementation of clinical practice guidelines

Implement and monitor quality and practice improvement programs, periodic audits

Approaches specific to key HF risk factors

Develop protocols and units for the optimal management of rheumatic fever

Train cardiovascular prevention and cardiometabolic medicine specialists

Improve availability of weight-loss and tobacco cessation services and clinics

Develop and monitor primary angioplasty networks

Facilitate access to class I pharmacological and invasive therapies for T2DM, hypertension and CHD, reduce costs

Expand availability of cardiac rehabilitation units

Develop, expand, and improve T2DM and CHD surveillance systems and registries

Approaches aimed at enhancing HF care

Expand access to tools (echocardiography, NT-proBNP) and implement protocols for the early detection of left ventricle systolic dysfunction in patients with key risk factors particularly CHD

Develop HF clinics and chronic HF management programs

Enhance postdischarge transitional care and coordination

Further involvement of nonphysician health workers (eg, nurses, chronic care case managers) in the care of patients with HF, and enhance coordination between relevant specialists: primary care, internal medicine, cardiology, case managers, nurses

Facilitate access to class I lifestyle, pharmacological and invasive therapies for HF, reduce costs

Empower patients with HF to improve their self-care, monitor vital signs and early detect HF exacerbations

Day hospitals for the management of mild HF exacerbations

Leverage novel technologies: telemedicine, remote monitoring, self-monitoring wearable devices

Develop, expand and improve HF surveillance systems and patient registries

Management of HF

Even if much warranted prevention efforts were further developed, in a context of population aging, the number of cases of HF will most likely grow in South Asia in the coming years in a dramatic manner. This will require optimized acute and chronic management approaches aimed at reducing mortality, morbidity, disability, need for re-hospitalizations, and costs. The substantially higher HF case fatality rate in LMICs illustrates the importance of health system strengthening and quality improvement, which should occur at all levels. Of particular importance will be the development of sustainable chronic care models including cardiac rehabilitation and structured follow-up, which have proven effective in South Asian communities and will need to be widely implemented.^84,85

Special attention will also have to be paid to the early detection of HF, as well as to its aggressive, optimal management since the very early stages of the disease process. Although South Asians have been underrepresented in most landmark HF trials and research specifically in South Asian patients is warranted,⁸⁶ there is no a priori reason to expect that currently recommended class I HF therapies would be less effective in South Asians.^45,87 Indeed, subgroup analyses by geographic region of landmark randomized controlled HFrEF trials have not identified significant effect modification by region, and observational studies of Asian patients with HF suggest a consistent beneficial effect of guideline-endorsed pharmacotherapies and devices in these populations.^88,89 Access to such therapies will, therefore, need to be enhanced through generic drugs, polypill combination therapies for patients with established disease, and other initiatives.⁹⁰

Of concern, available data across Asia demonstrate large gaps in the use of evidence-based HF therapies in the region. In the ASIAN-HF HFrEF registry, ACE (angiotensin-converting enzyme) inhibitors or ARBs (angiotensin II receptor blockers) were prescribed to 77%, β-blockers to 79%, and mineralocorticoid receptor antagonists to 58% of Asian patients. Nevertheless, there was substantial variation across South, Southeast, and Northeast Asian regions, with India having the second lowest use of β-blockers.⁸⁹ Moreover, guideline-recommended drug doses were achieved in only 17% for ACE inhibitors/ARBs, 13% for β-blockers, and 29% for mineralocorticoid receptor antagonists overall. There was also marked heterogeneity in the utilization of implantable cardioverter defibrillators among eligible patients, ranging from 1.5% in Indonesia, 1.8% in the Philippines and 4.9% in India, to 21.1% in Hong Kong and 52.5% in Japan.⁸⁸ Use of key HF therapies was also low in the Trivandrum Heart Failure Registry patient registry (only 25% received optimal medical therapy), and patients in which management was suboptimal had increased mortality.⁴² These treatment gaps may contribute to the higher mortality rates among patients with HF from specific Asian countries, including South Asian nations, and warrant urgent attention.

Of note, some novel therapies for T2DM have demonstrated cardiovascular benefits, such as GLP-1 (glucagon-like peptide-1) receptor agonists⁹¹; and medications originally intended for the management of T2DM have now expanded their breadth as therapeutic options for patients with HFrEF (eg, dapagliflozin, a SGLT-2 [sodium-glucose co-transporter 2] inhibitor).⁹² GLP-1 receptor agonists will represent relevant therapeutic options in South Asian patients with diabetes mellitus to reduce their risk of CVD, so will SGLT-2 inhibitors in South Asian patients with HF with and without diabetes mellitus. Again, cost may represent a barrier for the uptake of GLP-1s, SGLT-2s, and other medications in South Asian countries, and cost-reduction strategies will need to be explored.

Importantly, in 2018 the Cardiological Society of India released a position statement describing standards for the prevention and management of HF in India.⁹³ This is a crucial step forward and should be followed by similar initiatives in other South Asian countries. Implementation of the recommendations included in this document in the coming years will be key to reduce the incidence and improve the outcomes of Indian patients with HF. Of note, an improved management of HF in South Asian countries in the coming years will most likely have overall beneficial effects for the local health systems, as well as for other patient subpopulations. For example, optimal chronic HF management may result in a better design and enhanced implementation of chronic care models for other diseases such as diabetes mellitus, CHD, and chronic obstructive pulmonary disease; greater experience in the use of novel therapies such as SGLT-2s; or potential developments driven by this public health threat, such as lower-cost defibrillators or additional generic drug options.

A Global Priority

The same way that no nation would ignore the health needs of 25% of their citizens, we pose that in our current globalized world a coordinated response is needed to address epidemic NCDs, particularly CVDs such as HF, in South Asian nations, as these may not be able to tackle these challenges alone.^18,93 The same is true for other LMICs: indeed, while the central thrust of this review focuses on HF in South Asia, other low- and middle-income regions of the world may face HF epidemics only a few years later than in South Asia. For example, in sub-Saharan Africa, acute HF is already the leading cause for patient admission into cardiac units.⁹⁴ Southeast Asia is also becoming a hotspot of T2DM, CHD, and premature HF.^30,95–98 Therefore, the recommendations provided here should stimulate discussion about timely HF prevention and optimized management in other LMICs as well.

The World Health Organization, the World Bank, the International Monetary Fund, and other international development agencies and nonprofit institutes can play a key role through expert evidence-based guidance, provision of support in the implementation of key prevention policies, and financial assistance in the strengthening of public health, health promotion and healthcare systems in South Asia. This is consistent with the World Health Organization Millennium Development Goals’ actions to support countries.⁹⁸ Also, international efforts aimed at enhancing the economies of South Asian and other LMICs may be the most powerful root intervention towards improved health and sustainability. A global coordinated response is likely to have enormous benefits, as the global annual financial burden of HF is estimated to be $108 billion.⁹⁹

A Call for Further Research

More research is needed to better establish the true incidence and prevalence of HF in South Asian countries, the characteristics and prognosis of HF in South Asian populations, as well as further characterize the absolute and relative contributions of different risk factors, including genetics and epigenetics. In addition, evidence-based prevention and management of HF specifically in South Asian populations both need to be further improved. Table 4 presents a summary of key prevailing research gaps in this field. These research initiatives should be pursued both in South Asian countries as well as in nations hosting large South Asian immigrant populations. Increased attention towards HF in the coming years driven by an eventual epidemic in the very large South Asian population may further our understanding of its pathophysiology, mechanisms, prevention, optimal management approaches, and novel therapeutic targets, overall as well as among key patient subgroups such as those with HF with preserved ejection fraction.

Table 4. Key Evidence Gaps and Research Needs in South Asian Populations

HF surveillance and epidemiology

National and regional estimates of HF prevalence and incidence

Descriptive epidemiological studies: HF demographics, subtypes, risk factors, temporal trends, comorbidities, mortality

Characterization of national, subnational, and cultural heterogeneity in HF epidemiology

HF direct and indirect costs, healthcare expenditure

Mechanistic research

Further identification of unique underlying determinants of excess HF risk in South Asians, overall and by HF subtypes (HFrEF, HFpEF)

Further characterization of genetic variants and mechanisms associated with HF in South Asians

Identification of novel pharmacological therapeutic targets relevant to South Asian populations

Identification of opportunities to improve care of CHD patients and CVD risk factors

HF management

HF trials with enhanced representation of South Asian participants

Epidemiology of HF drug prescription, use and adherence

Characterization of HF therapy costs to patients and affordability in South Asian countries

Effectiveness of HF guideline-recommended pharmacotherapies in South Asians compared with other groups

Translational science

Evaluation of NT-proBNP and other biomarkers for the diagnosis of HF in South Asians

Definition of South Asian-specific biomarker cutpoints, overall and by sex and age groups

Evaluation of screening approaches aimed at the early detection of HF in the general population and in specific subgroups at higher risk (eg, CHD and diabetes mellitus)

Policy

Comparative effectiveness of different primary prevention policies

Cost-effectiveness evaluations

Outcomes research

Identification of optimal acute HF management algorithms

Identification and characterization of chronic HF management strategies aimed at improving transitional and chronic care and preventing early rehospitalization after discharge for a hospital admission for HF

Cost-effectiveness studies

Similar research should also be pursued in other LMICs. Ongoing international HF studies such as the Global Congestive Heart Failure registry, which aims to include 25 000 patients with HF from 335 sites in 42 countries will provide valuable updated insights on the global and regional epidemiology of the disease.¹⁰⁰ The study was started in 2016 and is planned to extend until 2024.

Conclusions

Although frequently underrecognized compared with CHD and T2DM, international studies suggest that South Asians may also be at an increased risk of HF compared with other racial/ethnic groups, and that HF presents at earlier ages in South Asians. These phenomena are likely the consequence of a high, double burden of key pre- and post-epidemiological transition HF risk factors in South Asian populations since young ages. Combined with the very large size of progressively aging populations in South Asian countries, this would most likely result in a surge of HF cases in the coming decades. An eventual HF epidemic could have dramatic consequences, and urgent interventions are needed to flatten the curve of HF in South Asia. We call for urgent action to curb these trends, with a focus on interventions aimed at reducing the incidence of HF, particularly through policy action and strengthening of healthcare systems, and optimizing the management of prevalent HF. This will require aggressive health protection policies, local prioritization of resources in South Asian countries towards the prevention and management of NCDs, and a global collaborative effort.

Nonstandard Abbreviation and Acronyms

ACE
angiotensin-converting enzyme

ARB
angiotensin II receptor blockers

ASIAN-HF
Asian Sudden Cardiac Death in Heart Failure

CHD
coronary heart disease

COBRA-BPS
Control of Blood Pressure and Risk Attenuation—Bangladesh, Pakistan, and Sri Lanka

CVD
cardiovascular disease

GLP-1
glucagon-like peptide-1

HF
heart failure

HFrEF
heart failure with reduced ejection fraction

INTER-CHF
International Congestive Heart Failure

INTERHEART
Effect of Potentially Modifiable Risk Factors Associated with Myocardial Infarction

LMIC
low- and middle-income countries

MASALA
Mediators of Atherosclerosis in South Asians Living in America

MYBPC3
myosin binding protein C

NCDs
noncommunicable diseases

SGLT-2
sodium-glucose co-transporter 2

T2DM
type 2 diabetes mellitus

Sources of Funding

Naveed Sattar acknowledges funding support from the British Heart Foundation Research Excellence Award (RE/18/6/34217).

Disclosures

Dr Shah has received research grants from Actelion, AstraZeneca, Corvia, Novartis, and Pfizer; and has received consulting fees from Actelion, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Cardiora, Eisai, Ionis, Ironwood, Merck, Novartis, Pfizer, Sanofi, and United Therapeutics. The other authors report no conflicts.

Footnotes

*Dr Martinez-Amezcua and Waqas Haque contributed equally to this work.

For Sources of Funding and Disclosures, see page 544.

Correspondence to: Miguel Cainzos-Achirica, MD, MPH, PhD, Division of Cardiovascular Prevention and Wellness, Department of Cardiology, Houston Methodist DeBakey Heart & Vascular Center, 6550 Fannin Bldg 5-019, Houston, TX 77030. Email [email protected]org

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**Table 1.** Summary of Studies of HF Epidemiology in South Asians Living in Diaspora Countries and Multinational Studies of Patients With HF
Region/Author	Country(ies)	Year	Study Population	Key Findings
Middle East
Panduranga²³	Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, United Arab Emirates, Yemen	2012	4539 hospitalized patients with acute decompensated chronic HF or new-onset acute HF from the Gulf Acute Heart Failure Registry, a clinical registry comprising 47 hospitals	Patients with HF of Indian ancestry were 6 y younger than the native Middle Easterners and 16 y younger than patients in similar European and United States HF registries, such as EHFS II and ADHERE.^31,32 Indian patients presented with concurrent acute coronary syndromes more often (46% vs 26%), were more likely to be smokers (36% vs 21%), to have diabetes mellitus (56% vs 49%), and had a higher frequency of HFrEF (76% vs 65%). In-hospital mortality similar in both groups.
Europe
Blackledge²⁴	England (Leicestershire)	1998–2001	5,789 consecutive patients newly admitted with HF	South Asians had higher age-adjusted HF admission rates than the White population (rate ratios of 3.8 for men, 5.2 for women), higher hospital incidence rates (rate ratios of 2.2 and 2.9, respectively), and were on average 8 y younger (70 vs 78 y). South Asians more frequently had either a history of or concurrent MI, and 46% had diabetes mellitus compared with 16% among Whites.
Bhopal²⁵	Scotland	2001 (Census data) onward	Cohort study of 4.65 million people living in Scotland (SHELS)	South Asians particularly Pakistanis, Bangladeshis, and Indian men had the highest rates of HF admission compared with the local white population and all other immigrant groups, including persons of African and Chinese origin. SHELS also confirmed that United Kingdom South Asians were the youngest group at the time of a first HF admission. Differences between South Asians and Whites in terms of HF rates were less striking than in the study by Blackledge et al.²⁴
van Oeffelen²⁶	The Netherlands	1998–2010	Nationwide prospective cohort study of 189 069 first HF admissions	Local South Asians were much younger than the Dutch population (median ages 58 and 79 y, respectively).
Cainzos-Achirica¹⁵	Spain (Catalonia)	2017	Regionwide study including ≈60 000 mostly Pakistani South Asian immigrants	South Asian women ≥65 y of age had a much higher prevalence of HF than the local Spanish population or any other LMIC immigrant group. Also, South Asian men had the highest prevalence of HF at ages 55–65 y and also led the prevalence of HF among men ≥80 y among all groups evaluated.
North America
Singh²⁷	Canada	1997–1999	Retrospective cohort of patients hospitalized with a primary diagnosis of HF	South Asians were younger than local white patients and had diabetes mellitus more frequently. In-hospital survival was similar between the 2 groups, although South Asians had a higher prevalence of high-risk features at discharge.
Choi²⁸	Canada (Ontario)	2000–2011	1671 patients with HF followed in 2 specialized HF clinics	Average mean age was ≈8 y lower in South Asians compared with Chinese patients and ≈5 y lower than in non-Asian individuals. South Asians more frequently had a history of diabetes mellitus, MI and 3-vessel disease, and needed coronary revascularization procedures more often than the other groups.
Jose²⁹	United States	2003–2010	Study of more than 10.4 million death records evaluated cardiovascular mortality trends among the 6 largest local Asian-American subgroups	Women of South Asian ancestry had the highest age-adjusted yearly mortality rates from HF among all Asian subgroups evaluated (11.3 per 100 000 persons), and South Asian men had the second-highest rate (8.7 per 100 000) only surpassed by Filipinos (11.5 per 100 000). Nevertheless, mortality rates from HF were higher among non-Hispanic Whites. United States South Asians comprise a highly educated, high-income, healthier South Asian diaspora subgroup.¹⁶
Multinational
Lam³⁰	Various	2012–2015	ASIAN-HF international registry of 5276 chronic HFrEF patients from China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore, Taiwan, and Thailand	South Asians were the youngest patients in the registry (mean age 57.8 y, compared with 62.1 in Northeast Asians and 58.9 in Southeast Asians) yet had a higher burden of underlying CHD and diabetes mellitus (51% and 37%, respectively) than Northeast Asians (38% and 31%, respectively). Rheumatic valvular disease was an exclusion criterion, which may explain the slightly higher mean age of South Asian participants compared with other studies.

**Table 2.** Proposed Interventions for the Prevention of HF in South Asians
Primordial
National prioritization of policies and strategies aimed at reducing exposure to cardiovascular risk factors and increasing exposure to health factors
Increase taxation, enforce public smoking bans, warnings on packets, and advertisement restrictions, affecting smoked tobacco but also other tobacco products (including branded bidis and smokeless tobacco)
Decrease content of salt, refined sugars and trans fatty acids in foods through national policies; use of mandatory food labels
Taxations for sugar-sweetened beverages, saturated and trans fats, coconut oil, palm oil, Vanaspati, ghee
Aggressively promote a culture of increased levels of physical activity both at the workplace and during leisure time
Promote a cultural shift towards healthy diets and foods
Provision of health education to the general population, including since early ages (interventions at schools, healthy living included in the curriculum)
Target entire households and communities
Enhance cultural competency of interventions
Policies to reduce air pollution: cooking fuel, industry and transportation regulations
Policies to minimize the use of pesticides with deleterious health effects
Enhance the detection, acute-phase management, and follow-up of rheumatic fever
Primary
Aggressive detection of cardiovascular risk factors at early adult ages with special attention to diabetes mellitus, obesity, hypertension, and atherogenic dyslipidemia
Develop local, regional and nationwide cardiovascular risk factor screening programs
Optimized lifestyle and pharmacological management since early stages
Secondary
Optimized acute-phase management of CHD once present: increase awareness, develop primary angioplasty networks, minimize door to balloon delays
Enhanced chronic management of CHD: optimize lifestyle and pharmacological management during follow-up, long-term use of class I therapies such as statins and ACE inhibitors
Culturally appropriate CHD rehabilitation, such as yoga and Bollywood dance
Early detection and aggressive management of subclinical left ventricular systolic dysfunction (stage B HF) following relevant clinical practice guidelines

**Table 3.** Proposed Health Systems Strengthening Approaches Aimed at Improving the Prevention and Management of HF in South Asian Countries
General approaches
Political prioritization of CVD prevention and of quality of care
Increase the % of gross domestic product devoted to healthcare
Provide public universal healthcare coverage
Improve health education and CVD health awareness in the general population
Expansion of healthcare workforce to meet WHO recommendations
Strengthen primary care systems with special attention to the management of complex, resource-intensive chronic conditions such as HF
Enhance involvement of cardiovascular scientific societies in the design, implementation, and evaluation of relevant health policies
Development and implementation of clinical practice guidelines
Implement and monitor quality and practice improvement programs, periodic audits
Approaches specific to key HF risk factors
Develop protocols and units for the optimal management of rheumatic fever
Train cardiovascular prevention and cardiometabolic medicine specialists
Improve availability of weight-loss and tobacco cessation services and clinics
Develop and monitor primary angioplasty networks
Facilitate access to class I pharmacological and invasive therapies for T2DM, hypertension and CHD, reduce costs
Expand availability of cardiac rehabilitation units
Develop, expand, and improve T2DM and CHD surveillance systems and registries
Approaches aimed at enhancing HF care
Expand access to tools (echocardiography, NT-proBNP) and implement protocols for the early detection of left ventricle systolic dysfunction in patients with key risk factors particularly CHD
Develop HF clinics and chronic HF management programs
Enhance postdischarge transitional care and coordination
Further involvement of nonphysician health workers (eg, nurses, chronic care case managers) in the care of patients with HF, and enhance coordination between relevant specialists: primary care, internal medicine, cardiology, case managers, nurses
Facilitate access to class I lifestyle, pharmacological and invasive therapies for HF, reduce costs
Empower patients with HF to improve their self-care, monitor vital signs and early detect HF exacerbations
Day hospitals for the management of mild HF exacerbations
Leverage novel technologies: telemedicine, remote monitoring, self-monitoring wearable devices
Develop, expand and improve HF surveillance systems and patient registries

**Table 4.** Key Evidence Gaps and Research Needs in South Asian Populations
HF surveillance and epidemiology
National and regional estimates of HF prevalence and incidence
Descriptive epidemiological studies: HF demographics, subtypes, risk factors, temporal trends, comorbidities, mortality
Characterization of national, subnational, and cultural heterogeneity in HF epidemiology
HF direct and indirect costs, healthcare expenditure
Mechanistic research
Further identification of unique underlying determinants of excess HF risk in South Asians, overall and by HF subtypes (HFrEF, HFpEF)
Further characterization of genetic variants and mechanisms associated with HF in South Asians
Identification of novel pharmacological therapeutic targets relevant to South Asian populations
Identification of opportunities to improve care of CHD patients and CVD risk factors
HF management
HF trials with enhanced representation of South Asian participants
Epidemiology of HF drug prescription, use and adherence
Characterization of HF therapy costs to patients and affordability in South Asian countries
Effectiveness of HF guideline-recommended pharmacotherapies in South Asians compared with other groups
Translational science
Evaluation of NT-proBNP and other biomarkers for the diagnosis of HF in South Asians
Definition of South Asian-specific biomarker cutpoints, overall and by sex and age groups
Evaluation of screening approaches aimed at the early detection of HF in the general population and in specific subgroups at higher risk (eg, CHD and diabetes mellitus)
Policy
Comparative effectiveness of different primary prevention policies
Cost-effectiveness evaluations
Outcomes research
Identification of optimal acute HF management algorithms
Identification and characterization of chronic HF management strategies aimed at improving transitional and chronic care and preventing early rehospitalization after discharge for a hospital admission for HF
Cost-effectiveness studies

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