Overview of cardiac and vascular diseases in patients with HIV

INTRODUCTION — 

With increasing global access to antiretroviral therapy and an aging population with human immunodeficiency virus (HIV), the burden of cardiovascular disease among people with HIV has tripled over the last two decades and continues to increase worldwide [1]. Even when treated, HIV is associated with increased risk for cardiac and vascular diseases compared to people without HIV, including increased risk of atherosclerotic cardiovascular disease, heart failure, and arrythmias [2].

This article will provide an overview of the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of atherosclerotic coronary artery disease, cardiomyopathy, arrhythmias, and other less common cardiac and vascular diseases among people with HIV.

The epidemiology and management of cardiovascular risk factors is discussed separately. (See "Epidemiology of cardiovascular disease and risk factors in patients with HIV" and "Management of cardiovascular risk (including dyslipidemia) in patients with HIV".)

Pathogenesis and biomarkers of cardiovascular disease in patients with HIV is also discussed separately. (See "Pathogenesis and biomarkers of cardiovascular disease in patients with HIV".)

GENERAL PRINCIPLES — 

There are a few guiding principles when thinking about cardiac and vascular disease in patients with HIV.

Impact of HIV — Among people with HIV, there is heterogeneity with regards to cardiovascular risk. Both HIV-specific mechanisms and traditional risk factors contribute to the increased burden of cardiovascular disease as well as the earlier onset of cardiovascular disease, including among people with HIV who are virally suppressed. Because of the complexity and multiple underlying mechanisms, we consider HIV to be a risk-enhancing factor when considering an individual's predicted cardiovascular risk [2]. (See "Epidemiology of cardiovascular disease and risk factors in patients with HIV".)

Drug-drug interactions with ART — A common pitfall when taking care of non-HIV-related conditions in patients with HIV is not checking for drug interactions between common cardiac drugs and the patient's antiretroviral regimen.

Many commonly used antiretroviral therapy (ART) drugs, including integrase strand transfer inhibitors (such as bictegravir and dolutegravir, for example), have minimal drug-drug interactions. Most drug-drug interactions occur with older ART regimens that include protease inhibitor boosters such as ritonavir or cobicistat (eg, darunavir/ritonavir). These drugs are potent CYP450 inhibitors and raise serum levels of drugs that are metabolized by the CYP450 system. Examples of common drugs that interact with CYP450 inhibitors include:

●Most statins

●Antiplatelet medications (eg, ticagrelor)

●Anticoagulants (eg, rivaroxaban)

●Amiodarone

●Antiarrhythmics (eg, dofetilide)

●Calcium-channel blockers (eg, verapamil, diltiazem)

●Eplerenone

●Ranolazine

This list provides examples of common drug-drug interactions and is not exhaustive. Drug-drug interactions can be assessed with many available online tools, including the UpToDate drug interactions program and the Liverpool HIV Drug Interactions Database.

Prognosis and outcomes — People with HIV who develop heart disease have worse long-term prognoses compared to people without HIV. As an example, in a meta-analysis of over 2 million individuals with prior acute coronary syndromes or percutaneous coronary intervention, people with HIV had 64 percent higher risk of mortality, 11 percent higher risk of major adverse cardiovascular events, 83 percent higher risk of recurrent acute coronary syndromes, and 39 percent higher risk of new heart failure [3]. Similarly, in another study, people with HIV and heart failure had 55 percent higher risk of all-cause mortality compared to people with heart failure without HIV [4]. While outcomes may be even worse among people with uncontrolled HIV, these estimates largely represent people with treated HIV on ART.  

CORONARY ARTERY DISEASE

Epidemiology — People with HIV are at increased risk of developing coronary artery disease (CAD) compared with the general population [1,5,6]. People with HIV develop cardiovascular disease approximately ten years younger, on average, compared to people without HIV. Cardiovascular disease accounts for 2.6 million disability-adjusted life years per year among people with HIV worldwide, with variation across regions of the world [1].

The relative risk of myocardial infarction is greater among women with HIV compared to men with HIV and men and women without HIV [7,8]. Modeling studies predict that the prevalence of cardiovascular disease in people with HIV will continue to grow as the population with HIV ages [9,10]. In low- and middle-income countries where the majority of people with HIV worldwide reside, the predominant forms of cardiovascular disease include heart failure (see 'Heart failure' below), pericardial disease especially in places where tuberculosis is endemic (See 'Pericardial disease' below.), and stroke (See 'Stroke' below.) [11,12].

Epidemiology of cardiovascular disease is discussed in more detail separately. (See "Epidemiology of cardiovascular disease and risk factors in patients with HIV".)

Pathogenesis — The pathogenesis of coronary artery disease among people with HIV arises from increased prevalence of "traditional" cardiovascular risk factors and HIV-specific factors, which includes effects of antiretroviral therapy, HIV viremia, and chronic immune activation and inflammation (figure 1). Even among people with HIV who are virally suppressed with antiretroviral therapy, there is significant chronic inflammation which may be a driver of atherosclerosis and myocardial infarction [13-15]. Atherosclerosis may also be impacted by social determinants of health and may be accelerated among communities facing discrimination and social and community inequities, which includes communities who bear a disproportionate burden of HIV.

The pathogenesis of cardiovascular disease in people with HIV is discussed in detail separately. (See "Pathogenesis and biomarkers of cardiovascular disease in patients with HIV".)

Clinical manifestations — Coronary artery disease usually presents similarly among people with HIV as in the general population without HIV. People with HIV tend to have a higher proportion of type II myocardial infarctions (or supply-demand mismatch) rather than acute plaque rupture events, especially among younger people with HIV [16,17]. The type II myocardial infarctions are commonly caused by sepsis, bacteremia, and illicit drug use. For those with type I myocardial infarction (acute plaque rupture), people with HIV are more likely to have single-vessel obstructive disease (rather than multivessel disease) on invasive angiography [18].

Diagnosis — Diagnostic approach to CAD in people with HIV is similar to the general population.

●Assessing risk – Since people with HIV are at increased risk for CAD, clinicians should have a low threshold to suspect cardiovascular disease (CVD) in people with HIV who present with symptoms of chest pain or dyspnea, including in younger aged patients in whom CVD would not typically be suspected. Risk calculators, such as the Pooled Cohort Equations, which are endorsed by the American Heart Association (AHA) and American College of Cardiology (ACC), tend to underestimate risk of cardiovascular disease among people with HIV [19], especially among women [20] and Black/African American people. HIV-specific calculators do not appear to perform better [21]. An American Heart Association Scientific Statement on cardiovascular disease in HIV suggested adjusting calculated risk upward by 1.5 to 2-fold in the setting of HIV-related CVD risk-enhancing factors [2].

Current evidence does not support the use of imaging to determine the presence or absence of atherosclerosis among people with HIV [2]. The use of coronary artery calcium scoring to further risk-stratify individuals at low-intermediate risk has not been validated among people with HIV, among whom non-calcified plaque is common and more likely to cause events [22,23]. (See "Screening for coronary heart disease".)

Detailed discussion of the role of risk prediction calculators in patients with HIV is found elsewhere. (See "Management of cardiovascular risk (including dyslipidemia) in patients with HIV", section on 'Assessing cardiovascular risk'.)

●Evaluation for CVD in symptomatic patients – In patients with HIV and symptoms concerning for CAD, workup is the same as in people without HIV. Among patients with angina without known obstructive coronary artery disease, use of stress testing modalities that allow for quantification of microvascular function (ie, myocardial blood flow reserve using positron emission tomography) may be useful among people with HIV, in whom coronary microvascular dysfunction is more common compared to people without HIV [24]. (See "Approach to the patient with suspected angina pectoris".)

Management — Management of CAD in people with HIV is the same as the general population. People with HIV have similar short-term outcomes after revascularization but continue to have elevated risk of recurrent events and mortality, even those with treated HIV [3,25]. Long-term outcomes after coronary artery bypass graft surgery have not been reported by HIV status, but short-term outcomes are similar [26]. (See "Chronic coronary syndrome: Overview of care".)

In the acute setting, if the patient is on a ritonavir or cobicistat-boosted antiretroviral therapy (ART) regimen, we consider discussing with the patient's HIV provider regarding modifying the ART regimen prior to hospital discharge due to the decreased efficacy of clopidogrel and increased bleeding risk with ticagrelor when used in combination with these regimens [27]. However, the much more commonly used integrase inhibitors dolutegravir and bictegravir do not interact with clopidogrel or ticagrelor. (See 'General principles' above.)

Prevention

●Primary prevention – Primary prevention of CAD in people with HIV consists of three main principles. First, early treatment of HIV with ART probably prevents cardiovascular events. Second, promotion of cardiovascular health (eating a healthy diet, engaging in physical activity, quitting tobacco and other drugs, and getting enough sleep, and optimizing weight, cholesterol, blood pressure, and glycemic control) are critical to mitigate the excess cardiovascular risk from "traditional" risk factors among people with HIV. Third, there is now evidence to support broader use of statins for primary prevention of cardiovascular disease among people with HIV [28]. Detailed discussion of primary prevention among people with HIV is found elsewhere. (See "Management of cardiovascular risk (including dyslipidemia) in patients with HIV".)

●Secondary prevention – Secondary prevention (prevention of a recurrent cardiovascular event) for people with HIV is the same as for the general population. Although one study suggested that clopidogrel monotherapy may be better than aspirin among people with HIV who do not have an indication for dual antiplatelet therapy, [29] we continue to manage people with HIV similarly to those without HIV. When initiating new medications, it is important to consider the possibility of drug-drug interactions with some less commonly used (older) ART regimens. (See 'Drug-drug interactions with ART' above.)  

HEART FAILURE — 

Heart failure has many different etiologies and the cause is often uncertain even after ruling out common causes (ischemic cardiomyopathy, hypertensive heart disease, valvular heart disease, etc). Both heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) are increased among people with HIV, even among those who are treated with antiretroviral therapy [30]. Nonischemic dilated cardiomyopathy resulting in HFrEF is more common among those who are not virally suppressed, while HFpEF is more common among those who are virally suppressed [12].

People with HIV have approximately 1.2-1.8-fold higher risk of heart failure compared to people without HIV [30,31]. In Sub-Saharan Africa, heart failure is the most common cardiovascular complication of HIV, accounting for approximately two-thirds of hospitalizations for new diagnoses of heart disease among people with HIV [32].

Heart failure attributed to HIV — In some cases, HIV is the primary risk factor identified in a patient who presents with heart failure, usually after other common causes are excluded. In other cases, HIV may act as a risk accelerator or contributing factor (such as an individual with HIV, hypertension, and stimulant use, for example).

●Epidemiology – A dilated, nonischemic cardiomyopathy attributed to solely to HIV without other identified risk factors, sometimes called "HIV cardiomyopathy," was much more common prior to widespread use of ART. Incidence has significantly decreased in resource-rich settings where ART is widely available, but remains a common cause of heart failure in Sub-Saharan Africa.

●Pathogenesis – The underlying mechanisms by which HIV causes heart failure are still incompletely understood, and there is no standard definition of HIV-associated cardiomyopathy [12]. Mechanisms may differ among people with uncontrolled viremia compared to people who are virally suppressed, as those who are not virally suppressed with low CD4 counts are more likely to present with HFrEF. Chronic inflammation and immune dysfunction including proinflammatory monocytes and tissue macrophages likely lead to cardiac inflammation, steatosis, and interstitial fibrosis, and possibly endothelial injury and microvascular dysfunction. People with HIV, especially those with advanced immune dysfunction, have a greater degree of left ventricular hypertrophy and diastolic dysfunction [33,34]. On cardiac magnetic resonance imaging, people with HIV have evidence of increased myocardial fibrosis and steatosis compared to comparators without HIV which is likely related to immune activation and inflammation and possibly microvascular dysfunction [12]. On autopsy, people with HIV have evidence of increased interstitial myocardial fibrosis compared to people without HIV [35].  

●Clinical manifestations – People with heart failure in the setting of HIV typically present similarly to people with heart failure in the general population, with symptoms such as bilateral lower extremity swelling and dyspnea and/or orthopnea. Some individuals may be identified as having left ventricular systolic dysfunction prior to the onset of symptoms on echocardiograms obtained for other clinical indications. (See "Heart failure: Clinical manifestations and diagnosis in adults", section on 'Clinical presentation'.)

●Diagnosis – Other causes of heart failure besides HIV should be considered (eg, cardiac catheterization to evaluate for ischemic heart disease) and ruled out prior to attributing cardiomyopathy to HIV. (See "Determining the etiology and severity of heart failure or cardiomyopathy".)

●Treatment – Treatment of cardiomyopathy attributed to HIV includes both controlling the HIV viral load and improving immune function through ART and administering evidence-based heart failure medications to manage symptoms, prevent hospitalization, and increase survival. (See "Overview of the management of heart failure with reduced ejection fraction in adults".)

Other causes of heart failure — Patients with HIV, even those with suppressed viral load, are still at increased risk for developing heart failure including from other causes than HIV. (See "Determining the etiology and severity of heart failure or cardiomyopathy".)

●Epidemiology and pathogenesis – As patients with HIV live longer and develop more cardiometabolic comorbidities, they are at increased risk for developing heart failure, similar to the general population.

There are important differences in the pathogenesis of heart failure by world region. For example, ischemic cardiomyopathy and substance-related heart (eg, alcohol and stimulant-related) failure are more common among people with HIV in the United States and Europe while hypertensive heart disease or heart failure due to other infections like tuberculosis or rheumatic heart disease is more predominant in Sub-Saharan Africa. (See "Pathophysiology of heart failure with reduced ejection fraction: Hemodynamic alterations and remodeling" and "Pathophysiology of heart failure with preserved ejection fraction" and "Pathophysiology of heart failure: Neurohumoral adaptations".)

●Clinical manifestations, diagnosis, and management – The clinical manifestations, diagnosis, and management of non-HIV cardiomyopathy heart failure in patients with HIV is the same as that for the general population. (See "Heart failure: Clinical manifestations and diagnosis in adults" and "Overview of the management of heart failure with reduced ejection fraction in adults" and "Treatment and prognosis of heart failure with preserved ejection fraction".)

OTHER CARDIAC AND VASCULAR DISEASE

Pericardial disease — Incidence of pericardial disease has fallen drastically after the introduction of combination antiretroviral therapy (ART), and pericardial disease attributed to HIV is now rarely seen outside of Sub-Saharan Africa.

●Epidemiology – Pericardial effusions were a common manifestation of end-stage acquired immunodeficiency syndrome (AIDS) in the pre-antiretroviral therapy era [36] and are a poor prognostic sign of end-stage AIDS associated with a much shorter survival, typically on the order of months [36]. In places with less access to antiretroviral therapy, they remain common; in the Heart of Soweto Study in South Africa, 25 percent of people with HIV admitted to the cardiology service from 2006 to 2008 were admitted for pericardial disease. In places where tuberculosis is endemic, HIV-associated tuberculous pericarditis is the leading cause of pericardial disease.

●Pathogenesis – Pericardial effusions are a marker of severe immune dysfunction, but also occur as a result of opportunistic infections including tuberculosis and as a result of HIV-related malignancies including Kaposi's Sarcoma and HIV-associated lymphomas, for example (table 1). (See "Etiology of pericardial disease" and "Overview of pericardial disease".)

●Clinical manifestations – Most of these effusions are small and asymptomatic. There are no clinical manifestations specific to HIV. Pericardial effusions are often asymptomatic and incidentally identified. Symptoms among patients with acute pericarditis typically include pleuritic chest pain. Patients with tamponade may present with syncope, fatigue, or dyspnea. (See "Overview of pericardial disease".)

●Diagnosis – Diagnosis of pericardial effusion is often made with ultrasound or limited transthoracic echocardiography. (See "Overview of pericardial disease".)

Certain echocardiographic findings can suggest pericardial constriction, such as abnormal septal bounce or intraventricular independence, exaggerated respiratory variation in mitral and tricuspid inflow and decreased lateral tissue velocity relative to the medial tissue velocity. If pericardial constriction is noted, cardiac catheterization may be required to identify elevation and equalization of pressures at end-diastole as well as other supportive findings [37].

Diagnostic pericardiocentesis is usually not necessary, since often the cause can be determined by history, physical exam, and basic laboratory testing and imaging. We perform diagnostic pericardiocentesis in patients with pericardial tamponade or in whom the effusion is not improving despite treatment and/or resolution of other causes (eg, viral infections, tuberculosis, HIV), especially in patients with viremia and CD4 count <200 cells/microL. When sending fluid for analysis, we typically include parameters that evaluate for tuberculosis, such as adenosine deaminase (estimated sensitivity of 88 percent and specificity of 83 percent [38]) and tuberculosis NAAT (sensitivity 67 percent, specificity 98.5 percent [39]) since tuberculosis is a common cause of pericardial effusions in patients with HIV.

●Treatment – There are no specific treatment recommendations for pericardial disease among people with HIV. We typically treat pericarditis similarly to people without HIV. For pericardial disease caused by HIV itself, initiation of ART and improving immune function is the mainstay of treatment. (See "Overview of pericardial disease".)

Pulmonary hypertension — The prevalence of pulmonary hypertension among people with HIV in the pre-antiretroviral therapy era was initially estimated to be up to 5 per 1000 [40] which is much higher than estimates in the general population (5 to 25 cases per million) [41]. The Veterans Aging Cohort Study estimated an 18 percent increased risk of pulmonary hypertension attributable to HIV [42]. Asymptomatic mildly elevated pulmonary artery pressures are even more common [43].

Pulmonary hypertension can be due to a variety of causes, including HIV itself, long-standing lung disease, and left-sided heart failure (table 2). HIV predisposes to chronic systemic inflammation and increased circulation of vascular endothelial growth factor and platelet-derived growth factor (figure 2). Detailed discussion of the pathogenesis of pulmonary hypertension caused by HIV is found separately (see "Pulmonary arterial hypertension associated with human immunodeficiency virus", section on 'Pathogenesis'). Pathogenesis of pulmonary hypertension due to other causes are discussed separately as well. (See "Pulmonary hypertension due to left heart disease (group 2 pulmonary hypertension) in adults", section on 'Pathogenesis' and "Pulmonary hypertension due to lung disease and/or hypoxemia (group 3 pulmonary hypertension): Epidemiology, pathogenesis, and diagnostic evaluation in adults", section on 'Pathogenesis' and "Epidemiology, pathogenesis, clinical manifestations and diagnosis of chronic thromboembolic pulmonary hypertension", section on 'Pathogenesis'.)

Clinical presentation of pulmonary hypertension is similar to people without HIV, often presenting with shortness of breath, dyspnea on exertion, and lower extremity swelling. Diagnosis and treatment of pulmonary hypertension related to HIV is discussed separately. (See "Pulmonary arterial hypertension associated with human immunodeficiency virus".)

Venous thromboembolism — Venous thromboembolism risk is significantly increased among people with HIV compared to people without HIV [44,45]. HIV itself leads to hypercoagulability via chronic immune activation and inflammation, with people with HIV viremia at greatest risk. Traditional risk factors for unprovoked venous thromboembolism such as smoking and injection drug use (which are more prevalent in patients with HIV) also contribute to the increased risk. The clinical presentation, diagnosis, and management of venous thromboembolism is similar among PWH as among those without HIV. (See "Overview of the causes of venous thrombosis in adults" and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity" and "Overview of the treatment of lower extremity deep vein thrombosis (DVT)".)

Peripheral artery disease — HIV is associated with increased risk of peripheral arterial disease due to the increased risk for systemic atherosclerosis [46,47]. HIV is also associated with aortic aneurysms [48,49]; risk is higher among those with lower CD4 counts and viremia [49]. The clinical presentation, diagnosis, and management of peripheral arterial disease is similar among people with HIV as among those without HIV. (See "Overview of lower extremity peripheral artery disease".)

Stroke — The incidence of ischemic stroke among people with HIV is approximately 40 percent higher than the general population [50-52]. Like acute myocardial infarction, people with HIV present with stroke at younger ages and are more likely to be male, but the relative risk is even greater among females [53]. Risk is increased due to a combination of traditional risk factors (eg, hypertension, dyslipidemia) and HIV-specific factors, which may include HIV infiltration of the central nervous system, small vessel thinning, remodeling, systemic and local (neuro)inflammation, or predisposition to opportunistic infections. ART and higher CD4 counts are protective against stroke [54]. The clinical presentation, diagnosis, and management of stroke for people with HIV is the same as for people without HIV [55]. (See "Stroke: Etiology, classification, and epidemiology" and "Overview of the evaluation of stroke" and "Initial assessment and management of acute stroke".)

Valvular disease — Overall, the risk of valvular heart disease among people with HIV is similar to people without HIV. Among those with advanced AIDS, nonbacterial thrombotic endocarditis has been reported on autopsy, but this finding is extremely rare in the setting of treated HIV. (See "Valvular heart disease in older adults".)

Endocarditis is more prevalent among people with HIV due to shared common risk factors with the general population, especially injection drug use. Mortality among patients diagnosed with endocarditis is similar among people with HIV compared to people without HIV [56]. Among people with HIV, those with CD4 count <200 cells/mL have higher risk of mortality compared to those with CD4 counts >200 cells/mL [56]. Treatment for infective endocarditis, including evaluation for and indications for urgent or emergent valve surgery, should be the same for people with and without HIV, with consideration for prompt initiation of antiretroviral therapy for those with untreated HIV at the time of diagnosis with endocarditis. (See "Overview of management of infective endocarditis in adults".)

Cardiac rhythm disturbances

Long QT syndrome — Acquired long QT syndrome is common among people with HIV, especially among those with advanced HIV disease and low CD4 counts [57]. There is some evidence that the HIV transactivator protein (tat) inhibits potassium currents via KCNH2. Acquired long QT syndrome can also be caused by medications including older protease inhibitors and opioid agonist therapy (eg, methadone). In addition, protease inhibitors (eg, darunavir/ritonavir) which inhibit the CYP P450 system may slow down metabolism of other drugs that prolong the QTc interval. Among patients with HIV on medications that may prolong the corrected QT interval, we check the QTc prior to adding a new medication that prolongs the QTc interval (eg, antibiotics, antifungals). (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes" and "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management".)

Atrial fibrillation — Atrial fibrillation is the most common rhythm abnormality among people with HIV, especially in the aging population in North America and Europe. It's unclear whether people with HIV are at increased risk for atrial fibrillation. In a database cohort study of over 17 million patients (including over 18,000 patients with HIV), those with HIV had a 1.5-fold higher risk of incident atrial fibrillation (18 versus 9 per 1000 person years) compared with the general population, with even greater risk among younger patients, Black and Hispanic patients, and those without diabetes, hypertension, or alcohol use disorder [58]. However, in another cohort study of over 1500 males (half of whom had HIV), there was no increased risk of atrial fibrillation between those with and without HIV [59].

There is no HIV-specific evidence to guide the choice of rate versus rhythm control in atrial fibrillation. One study of patients with and without HIV undergoing catheter ablation identified that recurrence was more common among people with HIV and was attributed to non-pulmonary vein triggers including in the coronary sinus and left atrial appendage [60]. In contrast, another study suggested that there was no difference in freedom from atrial fibrillation between people with and without HIV and found that non-pulmonary vein substrates were uncommon [61].

CHA₂DS₂-VASc scores may underestimate and poorly predict risk of stroke and systemic thromboembolism in patients with HIV [62,63].

When initiating rate or rhythm control agents and anticoagulation therapy, drug interactions with the patient's ART regimen should be considered. Beta-blockers are generally considered safe and dabigatran has the fewest drug-drug interactions out of the anticoagulants. Meanwhile, diltiazem, verapamil, and rivaroxaban may interact with older less commonly used ART regimens (eg, darunavir/ritonavir, elvitegravir/cobicistat) [64,65]. (See 'Drug-drug interactions with ART' above.)

Detailed information on atrial fibrillation in the general population is found elsewhere. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".)

Autonomic dysfunction — HIV-associated autonomic dysfunction is common. The chronic immune activation and inflammation that results with HIV infection, even among those who are treated and virally suppressed, is thought to lead to a hyperadrenergic state (sympathetic dominance) and vagal dysfunction (parasympathetic withdrawal) [66-68]. This imbalance in the autonomic nervous system leads to reduced heart rate variability and chronotropic incompetence, which is the inability of the body to augment the heart rate to meet metabolic demands during exercise and physical exertion. This phenomenon is associated with increased risk of mortality and cardiac events in the general population and in one study, has been linked to increased risk of cardiovascular events in people with HIV [69]. The prevalence of chronotropic incompetence in people with HIV living in the United States is thought to be around 30 to 40 percent [70,71]. Whether autonomic dysfunction contributes to the increased risk of sudden cardiac death among people with HIV is uncertain. (See "HIV-associated distal symmetric polyneuropathy (HIV-DSPN)" and "Mechanisms, causes, and evaluation of orthostatic hypotension".)

Sudden cardiac death — Patients with HIV are at a 2-fold higher risk of out-of-hospital cardiac arrest compared with the general population. Majority of the excess risk is seen in patients with uncontrolled HIV who have viremia and CD4 counts <200 cells/microL [72]. Another risk factor is opioid abuse; in a study of 47 individuals with HIV and sudden cardiac death who underwent autopsy, the most common underlying cause was occult drug overdose (one-third of cases) [35]. Patients with HIV also tend to be younger at the time of the event [35,73,74]. In one study, the median age at the time of cardiac arrest was 52 years of age, about 17 years younger than in the general population [74]. (See "Overview of sudden cardiac arrest and sudden cardiac death", section on 'Epidemiology'.)

The two most effective interventions to reduce risk of sudden cardiac death in patients with HIV include prevention of HIV cardiomyopathy by controlling the HIV infection and preventing myocardial infarction by optimizing cardiovascular risk factors and initiating statin therapy (see "Management of cardiovascular risk (including dyslipidemia) in patients with HIV", section on 'Statin use'). Treatment of substance use disorders and overdose prevention may also have a role among people with HIV who use stimulants or opioids. (See "Overview of sudden cardiac arrest and sudden cardiac death", section on 'Primary prevention'.)

Cardiac tumors — Cardiac tumors are rare among people with HIV, especially those treated with antiretroviral therapy. Among those with advanced HIV disease and AIDS, Kaposi sarcoma and primary cardiac lymphoma may occur. Both can cause pericardial effusions and rarely pericardial tamponade. Cardiac lymphomas can present either as a diffuse infiltrative process or with intracavitary lesions. Cardiac tumors are discussed in detail elsewhere. (See "Cardiac tumors".)

SUMMARY AND RECOMMENDATIONS

●General principles

•The global burden of human immunodeficiency virus (HIV)-associated cardiac and vascular diseases is increasing dramatically as access to antiretroviral therapy (ART) increases and the global population with HIV ages. Causes of these diseases are multifactorial. Both HIV-specific mechanisms and traditional risk factors contribute to the increased burden of cardiovascular disease. Because of the complexity and multiple underlying mechanisms, we consider HIV to be a risk-enhancing factor when considering an individual's predicted cardiovascular risk.

•Drug-drug interactions between ART regimens and cardiac medications is the most important consideration when managing cardiac and vascular diseases in people with HIV. Many commonly used ART drugs, including integrase strand transfer inhibitors such as bictegravir and dolutegravir, have minimal drug-drug interactions. However, boosted protease inhibitors (eg, darunavir with ritonavir) are associated with many drug-drug interactions. (See 'Drug-drug interactions with ART' above.)

●Coronary artery disease – People with HIV are at increased risk of developing coronary artery disease (CAD) compared with the general population. The pathogenesis of coronary artery disease among people with HIV arises from increased prevalence of "traditional" cardiovascular risk factors as well as HIV-specific factors, including effects of antiretroviral therapy, HIV viremia, and chronic immune activation and inflammation. Since people with HIV are at increased risk for CAD, clinicians should have a low threshold to suspect CAD in people with HIV who present with symptoms of chest pain or dyspnea, including in younger aged patients in whom CAD would not typically be suspected. (See 'Coronary artery disease' above.)

●Heart failure – Heart failure has many different causes. Both heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) are increased among people with HIV, even among those who are treated with antiretroviral therapy. Nonischemic dilated cardiomyopathy resulting in HFrEF is more common among those who are not virally suppressed, while HFpEF is more common among those who are virally suppressed. (See 'Heart failure' above.)

●Other cardiac and vascular diseases – People with HIV are also at increased risk for pericardial disease, pulmonary hypertension, venous thromboembolism, peripheral artery disease, stroke, arrhythmias, autonomic dysfunction, and sudden cardiac death. Clinical presentation, diagnosis, and management of these entities are similar to that in the general population. (See 'Other cardiac and vascular disease' above.)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Melvin D Cheitlin, MD, who contributed to earlier versions of this topic review.