Viral cardiovascular surgical diseases: global burdens, challenges and opportunities

Abstract

Globally, more than one billion people are vulnerable to neglected tropical diseases, many of which have viral origins and cardiovascular implications. Access to cardiovascular care is limited in countries where these conditions are endemic. Six billion people lack access to safe, timely and affordable cardiac surgical care, whereby over 100 countries and territories lack a single cardiac surgeon. Moreover, while clinically unique, the surgical consequences of neglected cardiovascular diseases with viral origins have been poorly described in the current literature. This review provides an overview of the global burden of viral cardiovascular disease, describes access to cardiac surgical care in regions where these conditions are endemic, and further highlights surgical consequences and considerations to manage patients requiring cardiac surgical care.

Plain language summary

Article Highlights.

• Cardiovascular disease is the leading cause of morbidity and mortality in low-and middle-income countries (LMICs). Despite the considerable burden of neglected viral cardiovascular diseases, these conditions have largely gone unnoticed on the global health agenda.

• Myocarditis is the most common cardiovascular consequence of viral infection, with an estimated 1.8 million cases worldwide. In high-income countries, myocarditis is predominantly caused by viral infections, while in LMICs, it is more often attributed to bacterial and parasitic infections such as tuberculosis, Chagas disease, and malaria, alongside viral origins.

• Over six billion people lack access to safe, timely and affordable cardiac surgical care, as a result of geographical distance, no or limited infrastructural capacity, low-quality care and financial barriers.

• Myocarditis and acute and chronic inflammatory cardiomyopathy are two of the major etiologies of viral infections impacting the heart muscle. Progressive disease may require mechanical circulatory support and cardiac surgical care, which are poorly accessible in endemic areas.

• Community-driven and patient-centered efforts are necessary to meet the needs of communities most burdened by untreated cardiovascular viral diseases and avoid further divergence in terms of health status and outcomes, socioeconomic development and access to essential cardiovascular care.

• Multidisciplinary and international efforts, such as the NET-Heart Project, are growing to systematically study the link between neglected tropical diseases and cardiovascular diseases.

1. Background

Historically, cardiovascular diseases have been considered burdens predominantly affecting high-income countries (HICs); however, today, they are the primary cause of morbidity and mortality in low- and middle-income countries (LMICs) and create a major barrier to sustainable human development [1,2]. Cardiovascular diseases result in over three-times as many deaths each year as HIV/AIDS, malaria and tuberculosis combined [3]. The number of premature cardiovascular deaths is rising, particularly in LMICs, where the burden of communicable disease is declining and an epidemiological transition toward non-communicable disease burdens is becoming apparent [4]. For instance, the premature death rate from ischemic heart disease is highest in Central Asia, while the number of stroke deaths is highest in Sub-Saharan Africa and Asia [5]. Indeed, more than 80% of deaths from cardiovascular diseases occur in LMICs, thus representing a much larger absolute burden of cardiovascular disease than in HICs [6].

Socioeconomic status is the position of a person or a household within a society that may be explained by a combination of occupation, education, income, wealth, and place of residence, and has been found to be a predictor of cardiovascular disease and death [7]. The incidence and prevalence of cardiovascular disease, secondary trends in cardiovascular mortality, survival with cardiovascular disease, the prevalence of cardiovascular risk factors and access to high-quality care and diagnostic services for cardiovascular disease are consistently correlated with socioeconomic status [8]. The world's poorest billion have a particularly unique and neglected cardiovascular disease profile [9]. The Lancet Commission on Reframing Non-communicable Diseases and Injuries (NCDIs) for the Poorest Billion (Lancet NCDI Poverty Commission) found that the severity of extreme poverty will likely have an impact on the total burden of NCDIs and their makeup [10,11]. Cardiovascular behavioral, metabolic, environmental and occupational risk factors are disproportionately concentrated in impoverished communities and those who reside in LMICs [12]. However, given the urban bias of data on cardiovascular mortality and morbidity, estimating the prevalence and impact of cardiovascular disease in lower-income, predominantly rural populations is difficult [9].

Neglected tropical diseases are a range of conditions that are primarily endemic in remote and tropical regions and disproportionately affect lower-income, marginalized and remote populations. Although many individual conditions are rare, more than one billion people suffer from the consequences of neglected tropical diseases [13]. These conditions have considerable morbidity and mortality rates, in part because of their common involvement in the cardiovascular system [14]. Despite the significant disparity between the burden of disease for neglected tropical diseases and cardiovascular diseases and the research focused on affected populations, these conditions have largely gone unnoticed on the global health agenda. Moreover, the surgical consequences of neglected cardiovascular conditions with viral origins have been poorly described.

In this review, we provide an overview of the global burden of viral cardiovascular disease, describe access to cardiac surgical care in regions where these conditions are endemic, and highlight surgical consequences and considerations to manage patients when requiring cardiac surgical care. We conclude by highlighting gaps and opportunities to address this neglected area of global health in the near future.

2. Global burden & presentation of viral cardiovascular disease

Viral cardiovascular diseases generally present as either myocarditis or a form of cardiomyopathy, whereby the latter may be a chronic consequence of the former. Myocarditis is the most common cardiovascular consequence of viral infection and portends a host of pathological sequelae, such as heart failure, arrhythmia and sudden cardiac death. It remains challenging to accurately gauge the incidence of myocarditis (best diagnosed through endomyocardial biopsy), but recent estimates report up to 1.8 million cases per year, with a prevalence ranging from 10 to 106 per 100,000 people worldwide [15]. Geographical location plays a complex role in both the prevalence of myocarditis and its key precipitants. The incidence of myocarditis peaks in high-income Asian-Pacific countries, with 45.6 (95% confidence interval, 95% CI: 41.4–50.1) cases per 100,000 people in 2017 [16]. Myocarditis is predominantly caused by viral infections in HICs; in LMICs, it is more often attributed to bacterial and parasitic infections, such as tuberculosis, Chagas disease and malaria, although the large population sizes result in non-negligible viral myocarditis burdens [17]. HICs have also experienced the steepest decline in age-standardized prevalence of myocarditis over the past 30 years, with ongoing cases in the Asia-Pacific driven chiefly by high rates of hepatitis C and HIV infection [16].

Epidemiological studies have found the most common viral causes of myocarditis to be Coxsackie B, Parvovirus B19, adenovirus, influenza and human herpes virus 6 [18]. In endemic regions, other cardiotropic viruses include the Epstein-Barr virus and human Bocavirus [19]. Enteroviruses, such as Coxsackie B, have been found in as many as 34% of patients with myocarditis and dilated cardiomyopathy [20]. The presence of Coxsackie B viral DNA was correlated with a mortality rate of 25% compared with 4% in the general population with myocarditis, highlighting its direct adverse impacts on cardiovascular function. By contrast, Parvovirus B19, another common source of viral myocarditis, has been found in 35% of patients with dilated cardiomyopathy, but its pathogenicity remains unclear [21,22]. One nucleic acid amplification study found Parvovirus B19 DNA in 73% of individuals with myocarditis and cardiomyopathy, compared with 26% of healthy individuals [22]. Moreover, the source of DNA appeared to originate from inflammatory monocytes as opposed to cardiac myocytes. For these reasons, some have labeled Parvovirus as a ‘bystander’ pathogen that is not clinically relevant when it comes to acute myocarditis [23]. Finally, a great deal of emerging evidence has drawn connections between COVID-19 and other upper respiratory tract infections such as adenovirus and influenza as major risk factors for developing viral myocarditis and acute coronary syndrome. One study found cardiovascular involvement in 15–42% of people infected with COVID-19. In a cohort of 39 patients who died of COVID-19, SARS-CoV-2 RNA was found in over 61.5% of post-mortem hearts, contributing to one pathogenic theory that COVID-19 causes myocarditis and left ventricular dysfunction through aggressive infiltration of myocardial tissue [24]. Its effect is also likely to be multifactorial; SARS-CoV-2 has been directly linked to myocardial infarction through histological evidence of RNA in intramural vessels, and indirectly linked through initiating cytokine storms resulting in plaque rupture, coronary spasm, or microthrombi [25]. Similarly, the influenza virus has been associated with cardiovascular pathology [26]. This is particularly concerning given the vast burden of influenza worldwide: every year, approximately 400,000 deaths are attributed to influenza, whereas at least five million people are hospitalized with influenza each year [27,28]. As such, the influenza vaccine has not only been proposed to prevent the infection itself but also influenza-associated cardiovascular complications, such as myocardial infarction. Indeed, current estimates place the efficacy of the influenza vaccine in preventing acute myocardial infarction within the ranges of smoking cessation, statins and antihypertensive therapy [29].

Chronic viral infections such as HIV, hepatitis C and Epstein-Barr can also lead to serious cardiovascular consequences. Over 38.4 million people around the world were estimated to have HIV in 2021, of which over 51% of new infections occur in Sub-Saharan Africa [30]. HIV infection has been associated with coronary artery disease: the Multicenter AIDS Cohort Study found that HIV-positive individuals had a 50% higher odds of 50% or more coronary stenosis, in conjunction with a higher prevalence of non-calcified arterial plaques [31]. A higher risk of acute ischemic events for HIV-positive individuals also portends an increased prevalence of heart failure: the Veterans Aging Cohort Study found that individuals with HIV have a hazard ratio of 1.21 (95%CI: 1.03–1.41) for heart failure with preserved ejection fraction and 1.61 (95%CI: 1.40–1.86) for heart failure with reduced ejection fraction [32]. Moreover, HIV-associated cardiomyopathy may increase the likelihood of acute myocarditis: in South Africa, 21% of patients with HIV-associated cardiomyopathy experienced acute myocarditis compared with none with idiopathic cardiomyopathy [33]. Hepatitis C affects 58 million people worldwide and almost 40% develop either isolated cardiovascular complications or those in conjunction with renal or liver failure [34]. Epstein-Barr virus is a common herpesvirus estimated to affect more than 90% of the global population [35]. Most people remain asymptomatic or minimally symptomatic; however, serious complications may develop in rare instances. While rare, the vast global number of lifetime infections ultimately results in a non-negligible burden of Epstein-Barr with cardiovascular consequences. When chronically active, up to 17.9% of patients with Epstein-Barr may develop cardiovascular complications, especially in the form of coronary artery aneurysms or myocarditis [36,37].

Neglected tropical diseases are rarer but particularly endemic in regions with poorer diagnostic, preventive and curative health services. Dengue is endemic to over 100 countries in Africa, South America, the Middle East, Asia and the Pacific Islands and represents an ongoing public health issue. Severe Dengue fever has been associated with cardiovascular sequelae including myocarditis, left ventricular dysfunction, arrhythmias, pulmonary edema and tricuspid regurgitation [38,39]. Although a majority of patients with Dengue fever have no cardiac symptoms, up to 62.5% demonstrate underlying ECG changes such as bradycardia, heart block, atrial fibrillation or ventricular asystole [40]. Those who do not recover require surgical intervention in the form of permanent pacemaker implantation. Similarly, rabies is endemic to Asia and Africa, with 80% of cases occurring in resource-limited regions where insufficient canine immunization rates intersect with poor access to post-exposure prophylaxis [41]. The primary cause of death has historically been attributed to encephalitis. However, post-mortem studies have also found viral dissemination in the cardiac ganglia, thus raising the question of whether myocardial infarction and arrhythmias resulting in cardiac arrest are other causes of mortality [41]. Lastly, the Zika virus has been identified in over 80 countries but is mostly endemic in tropical climates, largely in the Americas [42]. Although cardiovascular sequelae are rare, the virus may result in myocarditis, pericarditis, heart failure and arrhythmias, among other cardiovascular complications [42]. When transmitted from mother to child during pregnancy, congenital Zika syndrome can occur, which is associated with congenital heart defects. In a Brazilian cross-sectional study of children with in-utero exposure to Zika, 40% of infants had cardiac defects on echocardiography, whereas 11% had major cardiac defects [43]. The risks of cardiac surgery in patients with active or recent Zika virus are poorly understood, as are the risks of contracting the virus in the immediate post-cardiac surgery setting. Nevertheless, there are notable risks related to transmission to treating teams as viral infections often present without symptoms or symptoms misdiagnosed as other febrile illnesses [44]. In addition, blood transfusions are commonly necessary during cardiac surgery; reports from Brazil suggest that receiving blood products from individuals with the Zika virus may result in the transmission of the virus, thereby placing patients at higher postoperative risks [45].

3. Overview of the global cardiac surgery landscape

While cardiovascular disease is the leading cause of death worldwide [6], access to primary, secondary and tertiary prevention and care is limited for most of the world's population. Approximately half of the world's population cannot access essential health services, disproportionately affecting people in LMICs and endemic areas [46]. There are a variety of factors that impact viral disease prevention, which differ considerably between HICs and LMICs as outlined in Table 1 [47–49]. In addition, over 800 million people spend at least 10% of their household income on essential health services, whereas 100 million people are pushed into poverty merely for requiring these services each year [46]. Although access to cardiology services is poorly defined, over six billion people lack access to safe, timely and affordable cardiac surgical care, as a result of geographical distance, no or limited infrastructural capacity, low-quality care and financial barriers [50,51]. This issue has been further exacerbated due to the COVID-19 pandemic, which created additional strain on healthcare resources and led to the cancellation of scheduled cardiac and non-cardiac surgical cases and thus a delay in treatment for many years to come [52]. More than 70% of the world's population lives in LMICs, yet the majority of cardiac surgeons live and practice in HICs [50,51]. There is an estimated 100-fold difference per million population between the number of cardiac surgeons practicing in HICs compared with low-income countries [50,51]. More specifically, approximately 7.15 cardiac surgeons per million population practice in HICs, compared with a mere 0.04 per million in low-income countries [50,51]. There is also substantial variation in adult and pediatric surgeons across and within regions. In North America, there are approximately 11.12 adult cardiac surgeons and 2.08 pediatric cardiac surgeons per million population, compared with 0.12 adult cardiac surgeons and 0.08 cardiac surgeons per million population in Sub-Saharan Africa. The lack of trained local surgeons and other healthcare personnel is a considerable driving force behind the lack of access to cardiac surgical care across the globe.

Table 1.

Differences in viral disease prevention between low- and middle-income countries and high-income countries.

Areas impacting viral disease prevention	LMIC	HIC
Healthcare infrastructure	Often face challenges due to inadequate medical facilities, shortage of healthcare workers (especially those trained in areas that require additional education)	Infrastructure supports efficient disease surveillance, early detection and containment. HICs have resources to develop advanced facilities, sufficient numbers of well-trained healthcare professionals and better access to medical technologies
Access to vaccines and medications	Challenges with accessing vaccines and medications due to financial constraints, leading to challenges in disease prevention	Greater access to vaccines and medications due to funding and purchasing power
Public health education and awareness	Dissemination of health information is limited, particularly due to lower literacy rates, and limited resources for comprehensive public health campaigns	Range of programs that raise awareness about viral disease, preventative measures and the importance of vaccination
Sanitation and hygiene	Poorer sanitation infrastructure, lack of clean water, inadequate hygiene practices in combination with areas of greater population density leading to rapid spread of viral diseases	Greater sanitation infrastructure and subsequently better hygiene practices reducing the spread of viral diseases, namely through access to clean water, proper sanitation facilities and education on hygiene
Surveillance and healthcare response	Delayed healthcare responses in combination with limited surveillance capabilities leading to challenges with viral disease detection and containment	Robust surveillance systems and quicker healthcare responses due to stronger health infrastructure, enabling quicker detection and containment of outbreaks
Economic and social factors	Economic challenges make it difficult to allocate resources for healthcare when there are competing interests alongside viral disease prevention	Increased economic stability and social support systems, which can aid in implementing preventative measures

HIC: High-income country; LMIC: Low- and middle-income country.

Globally there are 5111 cardiac centers across 230 countries and territories [53]; however, in LMICs there is less than one center per 10 million people, on average [14]. Despite holding 14.1% of the world population, Sub-Saharan Africa has access to only 1.1% of the cardiac surgical workforce, whereas North America, which makes up 4.8% of the world's population, contains 32.8% of the total cardiac surgical workforce [54]. To further illustrate these disparities, a retrospective study on cardiac surgery capacity in Africa was conducted between 2011 and 2012, finding a total of 78 cardiac centers performing regular open-heart operations in Africa during this time period [55]. Of these, 56 centers were in North Africa and 22 centers were in Sub-Saharan Africa. Among the 22 centers in Sub-Saharan Africa equipped to perform open-heart operations, in 2012, only approximately two operations per million population were performed. These widespread disparities in the cardiac surgical workforce continue to contribute to a lack of access to care for both adult and pediatric patient populations.

Individuals' social determinants of health are important factors that influence the development and progression of cardiovascular disease, as well as access to the appropriate preventive and care services. In cardiovascular care, rheumatic heart disease (RHD), while not viral, illustrates this best. RHD is a known complication of acute rheumatic fever that remains a neglected disease strongly linked with poverty, among other social determinants of health [56,57]. Over 30 million people live with RHD, of which most live in LMICs [58]. Socioeconomic factors known to be associated with RHD include poor housing conditions, overcrowding and low health literacy [56,57]. Successes in lowering RHD incidence have been attributable to higher socioeconomic status, investments made to improve healthcare infrastructure and widespread distribution and use of penicillin G benzathine to treat streptococcal pharyngitis [56]. There is a stark contrast in the diagnosis and management of cardiac conditions between LMICs and HICs. In regions with a high sociodemographic index, RHD has been virtually eliminated due to a significant reduction in the occurrence of acute rheumatic fever with timely detection and antibiotic management of streptococcal pharyngitis [56]. In Africa, more than 60% of surgical RHD cases receive a mechanical prosthetic valve and require long-term medical management and follow-up [57]. The prognosis of RHD, however, is equally strongly linked to social determinants of health, and, despite improvements in HICs, LMICs have been less successful in lowering the burden of this disease due to systemic barriers including a lack of preventive resources, fragmented primary care infrastructure and scarce availability of specialist care, including cardiologists and cardiac surgeons, to manage downstream complications [57]. Surgical considerations that pose obstacles to performing cardiac surgery in LMICs include scarce heart valve availability, limited perfusion techniques and inadequate diagnosis and management of pre-existing cardiac conditions which can lead to suboptimal surgical results [59]. Similar observations are likely for neglected cardiovascular viral diseases. Thus, there is an urgent need to increase resource allocation toward sustainable efforts to improve access to cardiovascular care for those in need.

4. Surgical consequences of viral infections

Myocarditis and acute and chronic inflammatory cardiomyopathy are two of the major etiologies of viral infections impacting the heart muscle [24]. Acute viral myocarditis may complicate into fulminant myocarditis in 5–10% of cases, with rapid deterioration of patients' clinical and hemodynamic status [60]. In such cases, temporary cardiac mechanical support may be required to facilitate the heart's recovery. The European Society of Cardiology and American Heart Association/American College of Cardiology Foundation societies have outlined guidelines for the management of fulminant myocarditis [61,62]. Mechanical circulatory support should be considered whenever optimal medical therapy, including multiple inotropes and pressors, fails to maintain adequate hemodynamics, although there are no specific recommendations for the intraoperative technique for mechanical support implantation in patients with acute fulminant viral myocarditis. Examples of temporary support include extracorporeal membrane oxygenation (ECMO) and axial flow pump support. The advantages of ECMO over other temporary cardiac mechanical support are its wide availability and ease of implantation (considering fulminant myocarditis can evolve rapidly). Additionally, patients requiring ECMO for myocarditis have a good prognosis of ECMO weaning. In 2012, the Extracorporeal Life Support Organization (ELSO) reported that, outside the neonatal group, extracorporeal life support for myocarditis had the best survival of the cardiac indications [63]. Among 444 adult patients with cardiomyopathy and 200 adult patients with myocarditis, survival on extracorporeal life support for cardiac failure was 61 and 67%, respectively. Among 6,225 pediatric patients needing VA-ECMO for myocarditis, 65% were weaned successfully. Furthermore, ECMO can also be used in cases of biventricular failure. In rare instances, myocardial damage is irreversible and heart transplantation or durable VAD support may be considered. A contemporary study of 57 male patients aged 37.6 ± 11.8 years who underwent VA-ECMO for fulminant myocarditis for an average period of 9.9 ± 19 days showed that 75% were successfully weaned from ECMO, and 72% were discharged from the hospital alive [64]. Five-year survival was 65.2 ± 7.9%, with two patients presenting recurrent fulminant myocarditis within the first year of follow-up and one heart transplantation. A meta-analysis of 54 studies with 2,388 patients supported with VA-ECMO for fulminant myocarditis described a pooled short-term mortality of 35% (95%CI: 29–40%) [65]. However, the availability of ECMO and VADs varies widely among HICs and is particularly lacking in variable-resource contexts [66].

With regards to SARS-CoV-2 infection, a study investigating cardiac magnetic resonance imaging in 100 patients who had recently recovered from severe COVID-19, identified 78% with cardiac involvement and 60% with ongoing myocardial inflammation [67]. In two patients, nasopharyngeal swabs tested negative for SARS-CoV-2, hence it is likely that cardiac inflammation development is delayed following previous infection. Additionally, case reports have documented left ventricular dysfunction and myocardial inflammation related to SARS-CoV-2 infection with a latency period of 4 weeks after the onset of pulmonary symptoms. These factors should be taken into consideration when planning for cardiac surgery [68].

Other viral infections, such as HIV and Hepatitis C, have dramatically changed their course over the past decades. Optimal medical management of HIV with combined antiretroviral therapy has led to undetectable viral load in most patients. Likewise, Hepatitis C is now a curable disease. Hence, for patients with access to these treatments, there are no additional intraoperative precautions required [69]. Nonetheless, access to optimal medical care is not a reality for most people in the world. In such cases, patients with HIV have a substantial risk of sudden cardiac death due to accelerated coronary artery disease. In addition, patients with HIV may also develop non-ischemic cardiomyopathy and even myocarditis by opportunistic pathogens. In Hepatitis C, despite having a cure, the degree of liver failure will dictate a patient's surgical eligibility for cardiac surgery, as patients with cirrhosis have an increased risk of intraoperative uncontrollable bleeding.

Similar to any other surgical procedure, a sterile technique is required during surgery, minimizing the risk of contamination or transmission to healthcare workers. Postoperatively, isolation protocols should be at the discretion of the infectious diseases division of each institution, based on the viral etiology.

5. Remaining gaps, challenges & opportunities

Several gaps remain that need to be elucidated. The burden of cardiovascular viral diseases is poorly defined due to less-established surveillance systems in endemic areas and the limited number of published case-finding studies [70]. One cannot manage what one does not measure; tackling the global burden of cardiovascular viral diseases will require robust epidemiological data and impact metrics to implement, evaluate and refine interventions to best manage individuals living with these conditions. Volumetric data are limited for cardiac surgery in general, especially in low-and middle-income countries, and even more limited at a subspecialty level. Estimates suggest that low-, lower-middle-income and upper-middle-income countries would benefit from 40.2, 55.1 and 86.1 cardiac surgical procedures per 100,000 population, respectively [71]. Estimates for procedures for viral cardiovascular conditions are lacking, but they are expected to be only a small (but non-negligible) part of this. The world's poorest billion are simultaneously most likely to be affected by cardiovascular viral diseases and least likely to be able to access the cardiovascular care they need [72]. There is a scarcity of efforts to tackle the cardiovascular consequences of viral diseases globally. Community-driven and patient-centered efforts are necessary to meet the needs of communities most burdened by cardiovascular viral diseases and avoid further divergence in terms of health status and outcomes, socioeconomic development and access to essential cardiovascular care. Multidisciplinary and international efforts, such as the NET-Heart Project [14], are growing to systematically study the link between neglected tropical disease and cardiovascular diseases; however, these efforts require further professional societal support to ensure the expansion and implementation of the gaps identified and knowledge generated. The World Heart Federation (WHF) has focused efforts on other neglected cardiovascular diseases, such as RHD and Chagas cardiomyopathy. As of 2016, the WHF has developed roadmaps targeted at global healthcare professionals and policymakers, specifically for these neglected cardiovascular diseases, to establish a foundation for plans of action to improve these conditions in specific contexts [73,74]. While these conditions are not viral in consequence, challenges related to primordial prevention, social determinants of health and cardiovascular care capacity in endemic regions are shared, enabling opportunities for individuals living with viral conditions to benefit from improvements in these non-viral conditions.

Simultaneously, certain challenges need to be navigated as they may impede timely progress within the field. Endemic areas are riddled with competing health agendas and priorities that need to be considered [75]. The prioritization of different issues is a complex issue, although earmarked funding often disproportionally sways health agendas toward a given priority area of prominent aid agencies [76]. Additionally, non-health sectors, such as education, sanitation and transportation, are often pressing. Nevertheless, each of these areas is required for robust health systems, ranging from preventive measures (community education and clean sanitation) to timely care (efficient referrals and transportation networks). Moreover, social determinants of health are difficult to address within a single generation [72], especially when they pertain to systemic barriers. Crowded living, poor sanitation and high unemployment rates are drivers of neglected cardiovascular diseases and must be considered [57,72,77]; however, progress in international development to date is slow and set back by the COVID-19 pandemic. Lastly, research and programs addressing these conditions are severely underfunded, similar to those tackling RHD [78]. A select few areas of global health make up the majority of global health financing (e.g., tuberculosis, malaria and HIV/AIDS make up 50% of all global health funding [76,79]), whereas the near-absence of neglected cardiovascular diseases in HICs has further reduced academic and global health funding dedicated to cardiovascular viral diseases.

Despite this grim outlook, there are multiple opportunities that can already be leveraged. First, there is a need to stop siloing communicable versus non-communicable diseases and work toward multidisciplinary collaboration [80]. Many communicable diseases have non-communicable disease sequelae (e.g., acute rheumatic fever and RHD), whereas optimal prevention and care for communicable and non-communicable diseases require effective primary, secondary and tertiary care levels. Second, the integration of cardiovascular viral diseases into existing cardiovascular, non-communicable and communicable diseases and global surgical health policy may improve awareness about the burden and disparities facing vulnerable populations worldwide [75,81–83]. Historically, global health has focused on vertical (i.e., siloed disease) interventions, as opposed to horizontal (health systems) or diagonal (combination) interventions [84]. Infection control practices globally are dependent on access to a combination of resources including humans, technology and finances. Many under-resourced areas lack the infrastructure to optimize infection prevention practices. Consistent infection surveillance is also often not performed. Figure 1 summarizes vertical and horizontal interventions for infection control globally. This has resulted in the fragmentation of efforts to address disease umbrellas, such as non-communicable diseases and systems, whether health systems or surgical systems [85]. Coalescing global health efforts and meeting the needs of the world's poorest will require concerted action to integrate neglected cardiovascular diseases. Table 2 summarizes the gaps, challenges and opportunities.

Figure 1.

Vertical versus horizontal approaches to infection control and cardiovascular diseases.

Table 2.

Gaps, challenges and opportunities surrounding the global burden of viral disease requiring and influencing cardiovascular surgical care.

	Gaps	Challenges	Opportunities
Epidemiology	Poorly available epidemiological data in endemic areas	Absent or less-established surveillance systems in endemic areas	Strengthening surveillance systems Promoting regional, between- and within-country partnerships
	Link between social determinants of health and pathology		Increasing case-finding and community-based research
Diagnosis	Late or no diagnosis of cardiovascular disease or complications	Lack of familiarity with pathology	Education and awareness of public and health workers
		Limited human and diagnostic resources	Task-sharing to promote diagnosis within communities
Management	Late or no access to cardiovascular care, including surgery	Limited human resources and surgical infrastructure Fragmented supply chains	Earlier disease detection and referral to mitigate disease progression and complications
	Inability to afford tertiary cardiovascular care	Limited inclusion of tertiary cardiovascular care in public health insurance	Inclusion of cardiovascular care within national and international health policy
Financing	Limited out-of-pocket means and financial risk protection among the world's poorest billion	Minimal global health funding for non-communicable and surgical diseases Slow progress toward UHC	Allocating global health funding consistent with disease burdens and population needs Prioritizing health systems strengthening over vertical disease silos
Other	Limited inclusion of cardiovascular and surgical care in national and international health policy	Competing health agendas, resulting in lower political priority	Data-driven and grassroots advocacy

UHC: Universal health coverage.

6. Conclusion

The global burden of viral cardiovascular disease remains poorly described and neglected, despite their pressing and unmet surgical and non-surgical needs. Access to cardiovascular care in endemic regions is limited with most people suffering from surgical cardiovascular disease unable to access cardiac surgical care. Academic and policy efforts are needed to better understand the true disease burdens and gaps in care, strengthen prevention, and support capacity-building and financial risk protection to timely detect and manage viral cardiovascular surgical diseases globally.

7. Future perspective

The gradual expansion of the cardiovascular care capacity globally will eventually introduce novel challenges regarding forgotten and neglected pathologies within global health, as their diagnosis and access to care improve. Due to their systemic roots, which often result from poor social determinants of health, neglected cardiovascular diseases require interventions beyond the operating room. As such, existing and budding communicable, non-communicable, surgical and health systems efforts must recognize the hidden burden of viral cardiovascular diseases and their cardiovascular and cardiac surgical implications. Collaborative research efforts must be encouraged and supported to increase evidence generation surrounding cardiac surgical needs and best practices in patients living with viral cardiac surgical conditions. This will require partnerships between centers and countries, including from a diagnostic, preventive and research perspective, to stop neglecting the neglected.

Author contributions

This statement certifies that all authors contributed to the following substantial contributions to the conception or design of the work; or the acquisition, analysis or interpretation of data for the work; and drafting the work or revising it critically for important intellectual content; and final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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