Cardiac Manifestations of Systemic Diseases
Toniya Singh
Ijeoma Isiadinso
Gina P. Lundberg
Nidhi Madan
INTRODUCTION
The cardiovascular (CV) system is a common target for systemic diseases. Effects can range from cellular changes in the myocardium to altering the risk for developing coronary artery disease (CAD). Understanding the cardiac manifestations of commonly encountered diseases is critical to appropriate patient assessment and management.
AUTOIMMUNE/INFLAMMATORY SYSTEMIC DISEASES
Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a chronic, multisystem inflammatory disease (Table 21.1). It is estimated that 50% of SLE patients have cardiac abnormalities.1 Although deaths because of SLE have decreased as a result of advances in medical therapies, cardiovascular disease (CVD) remains the leading cause of mortality accounting for more than one-third of deaths in these patients.
Premature atherosclerosis is a major contributing factor for the increased rate of ischemic heart disease in patients with SLE (Figure 21.1). The risk of myocardial infarction (MI) in SLE patients ranges from 2- to 10-fold higher than in the general population.2 Studies have shown a higher prevalence of traditional risk factors, such as hypertension, among SLE patients. However, even after adjusting for traditional CV risk factors, the risk of CVD is greater among SLE patients compared with the general population, suggesting that additional factors are also playing a role. SLE-specific risk factors, such as immune-complex factors, circulating inflammatory cytokines, antiphospholipid antibodies, and lupus nephritis, are also associated with an increased risk of CVD and mortality. Although corticosteroids are central to controlling systemic inflammation, they also contribute to the progression of atherosclerosis in SLE patients. Both higher doses and longer duration of steroid use are associated with accelerated atherosclerosis. Coronary artery calcification, which is a marker of subclinical atherosclerosis, is more common in patients with SLE3 than in unaffected individuals. Patients with SLE also have a proatherogenic lipid profile consisting of elevated total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), whereas high-density lipoprotein cholesterol (HDL-C) is reduced. Additionally, a dysfunctional, proinflammatory form of HDL (piHDL) is more prevalent in SLE patients. Unlike normal HDL, piHDL promotes oxidation of HDL and inhibits cholesterol efflux from foam cells. Studies have reported that up to 45% of SLE patients have piHDL.4
Nonbacterial endocarditis (Libman-Sacks endocarditis), valvular thickening, and mitral valve prolapse (MVP) occur with increased frequency in patients with SLE. Heart failure, with or without systolic dysfunction, can occur from ischemia, hypertension, valvular disease, or immune-mediated injury in SLE. Myocarditis is a rare but serious complication of SLE. Echocardiography and cardiac magnetic resonance imaging (CMR) may demonstrate systolic dysfunction and regional wall motion abnormalities. Areas of necrosis or scar can be detected on CMR as late gadolinium enhancement (LGE). Pericardial effusion and pericarditis are the most commonly recognized and presenting cardiac complications of SLE. Cardiac arrhythmias ranging from sinus tachycardia to atrial fibrillation may also be seen in SLE patients.
Rheumatoid Arthritis
Patients with rheumatoid arthritis (RA) have a higher morbidity and mortality from CVD compared to control populations. The risk of CVD is higher in patients with RA compared with the general population by nearly two-fold, similar to that of diabetes.5 Premature atherosclerosis in RA patients is one factor that leads to an increased risk of CAD. Additionally, studies have demonstrated underdiagnosis and undertreatment of traditional CVD risk factors in RA patients. There is a paradoxical relationship between body mass index (BMI) and CV risk in RA patients, such that low BMI is associated with increased CV risk. It is hypothesized that the low BMI is a reflection of a heightened inflammatory state. Conversely, RA patients who are rheumatoid factor negative or on steroid doses less than 7.5 do not appear to have an increased risk of CV events.6
Chronic inflammation may result in pericarditis, dyslipidemia, and heart failure in RA patients, with the latter primarily because of diastolic dysfunction rather than ischemic heart disease.7 Elevated interleukin-6 (IL-6) levels confer an increased risk of diastolic dysfunction and atherosclerosis in RA patients.8 Mitral regurgitation is the most common valvular disease in patients with RA.
Antirheumatic drugs can also negatively impact CV risk in RA patients. High-dose corticosteroids increase the risk of
dyslipidemia, insulin resistance, atherosclerosis, and hypertension. Nonsteroidal anti-inflammatory drugs can precipitate new-onset hypertension and worsen blood pressure in those with an established diagnosis of hypertension.
dyslipidemia, insulin resistance, atherosclerosis, and hypertension. Nonsteroidal anti-inflammatory drugs can precipitate new-onset hypertension and worsen blood pressure in those with an established diagnosis of hypertension.
TABLE 21.1 Cardiovascular Manifestations of Autoimmune/Inflammatory Systemic Diseases | ||||||||||||||||||||||||||||||||||||||||||||||||
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 FIGURE 21.1 Increased risk of myocardial infarction among patients with systemic lupus erythematosus. |
Psoriatic Arthritis
Psoriatic arthritis is a multisystem, autoinflammatory, seronegative arthritis affecting 20% of patients with psoriasis. Patients with psoriatic arthritis have an increased prevalence of
traditional CV risk factors.9 In addition, cyclosporine, which is used to treat psoriatic arthritis, can cause hypertension and dyslipidemia. However, the increased risk of CVD cannot be fully explained by the greater prevalence of CV risk factors. An important finding has been a common pathway of psoriatic plaque formation and atherosclerosis.10 T-helper cells are integral in the formation of plaque and inflammation in both disorders. Once activated, the T-helper cells secrete proinflammatory cytokines, including IL-2, tumor necrosis factor-alpha, and interferon-gamma, promoting the inflammatory cascade and atherosclerotic plaque formation.
traditional CV risk factors.9 In addition, cyclosporine, which is used to treat psoriatic arthritis, can cause hypertension and dyslipidemia. However, the increased risk of CVD cannot be fully explained by the greater prevalence of CV risk factors. An important finding has been a common pathway of psoriatic plaque formation and atherosclerosis.10 T-helper cells are integral in the formation of plaque and inflammation in both disorders. Once activated, the T-helper cells secrete proinflammatory cytokines, including IL-2, tumor necrosis factor-alpha, and interferon-gamma, promoting the inflammatory cascade and atherosclerotic plaque formation.
Systemic Sclerosis
Systemic sclerosis is a diffuse, multisystem connective tissue disorder of unknown etiology characterized by systemic inflammation, fibrosis of organs and skin, and vascular dysfunction. Fibrosis can be caused by profibrotic cytokines, including transforming growth factor-beta (TGF-β), IL-4, platelet-derived growth factor, and connective tissue growth factor, and lead to left ventricular (LV) systolic and diastolic dysfunction. Coronary microvascular disease is common in systemic sclerosis and is mediated by TGF-β, reactive oxygen species, and inflammatory mediators. Patients with systemic sclerosis have an increased risk of atherosclerosis because of endothelial dysfunction and inflammation resulting in the release of proinflammatory markers, including C-reactive protein and homocysteine, with hyperhomocysteinemia associated with increased risk of CVD. Systemic sclerosis is also responsible for a wide range of conduction abnormalities including supraventricular arrhythmias (including atrial fibrillation or flutter), premature ventricular contraction, and heart block.11
Ankylosing Spondylitis
Ankylosing spondylitis is a chronic, multisystem inflammatory disorder primarily affecting the sacroiliac joint and spine that occurs predominantly in males. Extra-articular involvement includes uveitis, inflammatory bowel disease (IBD), psoriasis, arthritis, and CV and pulmonary disease. Human leukocyte antigen (HLA)-B27 is present in the majority of ankylosing spondylitis patients and contributes to pathophysiologic mechanisms of the disease. The incidence of cardiac disease in ankylosing spondylitis is 2% to 10%. Thickening and scarring of the aortic wall result in aortic valve thickening, aortic root dilatation, and aortic valve regurgitation. Conduction abnormalities in ankylosing spondylitis are due to inflammation resulting in damage to the interventricular septum and myocardial scarring resulting in heart block.12
Inflammatory Bowel Disease
Crohn disease and ulcerative colitis are chronic, intestinal diseases that comprise IBD. There are several extraintestinal manifestations of IBD including CV involvement. Pericarditis is the most common CV complication of IBD,13 but immune-mediated myocarditis has also been reported. Aortic and mitral valve regurgitation are the most common valvulopathies seen in IBD patients. The valvular disease occurs due to systemic inflammation resulting in thickening and shortening of the valve leaflets. Atrioventricular conduction disorders may occur due to infliximab therapy, inflammation-related ischemia in the conduction system, vasculitis, or microvascular endothelial dysfunction.
Human Immunodeficiency Virus
Human immunodeficiency virus (HIV) is now considered a chronic disease as a result of effective antiviral therapy. HIV patients commonly have other comorbidities, including hypertension, dyslipidemia, atherosclerosis, diabetes, and obesity. One of the leading causes of non-HIV-related mortality is CVD. HIV infection can cause pericardial effusion, with most being asymptomatic. HIV may also result in cardiomyopathy because of the dysregulated immune response, atherosclerosis, and myocarditis. Antiretroviral therapy can also cause dyslipidemia and heart failure.
ROLE OF IMAGING IN EVALUATION OF CARDIAC MANIFESTATIONS OF INFLAMMATORY SYSTEMIC DISEASES
Echocardiography, cardiac computed tomography (CCT), and CMR are excellent noninvasive diagnostic imaging tools for the evaluation of CV complications of multisystem inflammatory diseases. Echocardiography can detect evidence of subclinical LV systolic and diastolic dysfunction in RA, pericardial effusion (in RA or SLE), valvular heart disease, and pericardial thickening.14,15,16 Valvular complications of systemic inflammatory diseases, including valvular thickening or regurgitation, can be easily seen on echocardiography.
In RA and SLE, CMR demonstrates LGE that reflects inflammation because of myocarditis.16 In addition to estimating ejection fraction and assessing wall motion abnormalities, CMR can also identify areas of inflammation, fibrosis, and edema. Coronary artery calcification, as measured by CCT, is more frequent and extensive among SLE patients when compared to patients without SLE.3 Among patients with RA, CAC correlated with the severity of inflammation.17
As noted in Table 21.1, CAD is a manifestation of CVD in several autoimmune inflammatory conditions. CCT can quantify the extent of epicardial CAD. Stress testing combined with echocardiography, CMR, single-photon emission computed tomography, or positron emission tomography can detect both epicardial CAD and coronary microvascular dysfunction based on the presence of myocardial wall motion abnormalities or perfusion defects.
ENDOCRINE/NEUROENDOCRINE DISORDERS
Thyroid Disorders
Thyroid disorders can affect cardiac function through changes in heart rate, rhythm, contractile strength, and the risk of CAD via their effects on blood pressure and inflammatory and lipid profiles (Table 21.2). Patients with either hypo- or
hyperthyroidism are at increased risk for CVD, even with subclinical disease.
hyperthyroidism are at increased risk for CVD, even with subclinical disease.
TABLE 21.2 Cardiac Manifestations of Endocrine Disorders | ||||||||||||||||||||||||||||||||||||||||||||||||
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