Systemic Lupus Erythematosus
Rheumatology is the branch of medicine that is concerned with connective tissue diseases of various etiology and pathogenesis. A common feature of these diseases is joint involvement. The most common connective tissue diseases include systemic lupus erythematosus, antiphospholipid syndrome, ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis, and systemic sclerosis, all of which will be discussed in this chapter. All these conditions are characterised by involvement of the cardiovascular system in most patients, although the heart is, of course, not the principal affected organ. Also, there are no pathognomonic symptoms of cardiovascular system involvement. Symptoms usually include palpitation, chest pain (more often atypical or pricking) and, with disease progression, development of heart failure. Echocardiography usually shows involvement of the pericardium, cardiac valves (particularly mitral and aortic), and left and right ventricular myocardium. In some patients, intracardiac thrombi or pulmonary hypertension may occur.
Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a systemic connective tissue disease. Its prevalence is currently estimated at 40-200 per 100,000 of the general population. SLE is ninefold more common in women than in men. The onset of the disease is usually at 16-55 years of age (in 65% of patients). It is characterised by production of autoantibodies directed against several components of the nucleus, cytoplasm and cell surface. This justifies a wide range of clinical manifestations that may reflect involvement of nearly every organ or tissue. Earlymortality is related to the disease activity and infectious complications, while late mortality primarily results from cardiovascular complications.
Cardiac symptoms are present inmost SLE patients (> 50%) although they may occur in various stages of the disease. Alterations are noted in:
- Valvular apparatus;
- Conduction system; and
- Coronary arteries.
The most common form of cardiovascular involvement is lupus pericarditis. In autopsies, it is found in 43-83% of SLE patients but its clinical manifestations are present in only about 25% of patients. Constrictive or purulent pericarditis is rare. Cardiac tamponade due to pericardial effusion has been occasionally reported. Pericarditis usually develops at the onset of the disease or during recurrences. Pericardial fluid is rich in leukocytes, mostly neutrophils, and its pH is below 7.0. In a few reports, the presence of hematoxylin bodies and LE cells has been described. The most commonly noted finding is pericardial thickening. In addition to pericardial thickening secondary to fibroblast proliferation, microscopic examination may showedema and infiltrates ofmononuclear cells,mostly plasmocytes and lymphocytes. This pattern is not specific and may resemble tuberculous pericarditis or lymphocytic pericarditis occurring in other conditions such as rheumatoid arthritis. Direct immunofluorescence has shown granular immunoglobulin deposits and complement components C1q and C3 in pericardial vessel walls.
Myocardial dysfunction in SLE patients may result from:
- Myocarditis (found in 80% of autopsies);
- Drug toxicity; and
- Ischemia secondary to coronary artery involvement.
Myocarditis is usually clinically silent. Currently, with more effective SLE therapies, a decrease in the incidence of myocarditis (to about 6%) has been observed. Symptoms are various and unspecific. They may suggest chest infection, ischemic heart disease, or heart failure.Untreated myocarditis may lead to arrhyth-mias, dilated cardiomyopathy, heart failure, and cardiac death. Lupus myocarditis may be accompanied by skeletal muscle inflammation. In patients with SLE and myocarditis, low levels of albumin, and complement components C3 and C4 have been noted, as well as high ESR and elevated levels of C-reactive protein, CK-MB, and cardiac troponins T and I. In addition, anti-double strandedDNA antibodies (anti-dsDNA) have been identified. Another mechanism of myocardial damage in SLE patients may be drug toxicity, e.g., toxic effects of hydrochloroquine/ chloroquine, although published reports have not been consistent. Myocardial damage may also result from myocardial infarction due to coronary artery disease. In SLE patients, the risk of coronary artery disease and myocardial infarction is significantly higher compared to the general population. In addition to conventional risk factors for coronary artery disease and myocardial infarction, other risk factors may also be present in SLE patients, including immunological risk factors (endothelial damage due to the presence of immune complexes, antiphospholipid antibodies, proinflammatory cytokines), and risk factors directly related to SLE and its treatment, such as renal disease, hormonal abnormalities, high serum homocysteine level, and chronic glucocorticoid use. Histological findings in patients with lupus myocarditis are unspecific and similar to those in other forms of myocarditis, including viral-induced myocarditis. Perivascular interstitial infiltrates of plasmocytes, lymphocytes, and macrophages have been reported, along with cardiomyocyte damage withmyocardial tissue degeneration, fibrosis and, in advanced disease, scarring. All these changes may lead to dilated cardiomyopathy. In some SLE patients, histological findings include small-vessel vasculitis with microthrombi, endothelial damage, and perivascular infiltrates. Immunofluorescence studies showed the presence of small granular deposits of immune complexes and complement component C1q in vessel walls and perivascular spaces. Cardiac valvular involvement is a common cardiac manifestation of SLE. Echocardiography shows pathological changes in the valvular apparatus in up to 60% of patients (Fig. 1, 2), and they have been reported in 13-74% of cases in autopsy studies. These changes include valve leaflet thickening, vegetations, and valvular regurgitation or stenosis. Most commonly, mitral valve leaflet thickening withmild tomoderate regurgitation is seen. Cardiac valvular lesions usually remain asymptomatic for a long time but ultimately lead to valve dysfunction, primarily regurgitation and more rarely stenosis. Valve replacement becomes necessary in 3-4% of patients. Libman-Sacks endocarditis is the most characteristic form of cardiac involvement in SLE but it has become less frequently reported since the introduction of glucocorticoid therapy. It was described for the first time in 1924 and is characterised by the presence of atypical papillary lesions within the pericardial and valvular endocardium, most commonly on the mitral valve.
FIGURE 2. A female patient with antiphospholipid syndrome secondary to systemic lupus erythematosus. Moderate tricuspid regurgitation may be noted in color Doppler (arrow) in the parasternal short-axis view (A). Based on the velocity of the tricuspid regurgitant jet measured with continuous wave Doppler (B), right ventricular systolic pressure was estimated at about 45 mm Hg.
Libman-Sacks endocarditis usually develops in patients with long duration of SLE, high disease activity, and anticardiolipinantibodies. Patients with Libman-Sacks endocarditis are at high risk of embolic events which may lead tomyocardial infarction, stroke or transient ischemic attacks. Pathologically, Libman-Sacks vegetations are granular, brown-red structures of varying shape, from flat to cauliflower-like lesions. They may be stemless or papillary, ranging in size from a pinhead to 4 mm. They are usually firmly attached to valve edges, leaflet commissures, tendinous chords, or papillarymuscles, andmostly located on the surface ofmitral leaflets.
Histologically, they consist of platelets, fibrin, degenerated blood morphotic elements, active fibroblasts, and newly forming vessels. Infiltrates of inflammatory mononuclear cells and in some cases calcium deposits have been reported within valve leaflets and the annulus. Long-term multicenter observational clinical studies have shown that the risk of coronary artery disease and myocardial infarction in patients with SLE is increased more than fivefold compared to the age-matched general population. In female SLE patients aged 35-44 years, incidence of myocardial infarction was increased 50 times compared to women of similar age without SLE. Overall, the incidence of cardiovascular events in patients with SLE has been estimated at 6-10%, or 1.5% per year. Post mortem studies show atherosclerotic lesions in more than 50% of SLE patients, regardless of the cause of death. Coronary atherosclerotic plaques in patients with SLE were composed ofmacrophages, foam cells, inflammatory cells and extracellular lipids. Thickening of themediawas also described. More rarely reported coronary lesions include vasculitic changes and aneurysms. Neutrophil aggregates, lymphocytic infiltrates, fibrinoid necrosis, immune complex deposits, and vessel wall edema have been reported in inflamed coronary arteries. The etiology of early atherosclerosis in SLE involves other risk factors than those in the general population. The most important risk factors include endothelial cell inflammation and dysfunction, the presence of anticardiolipin antibodies, and the duration of glucocorticoid use. Treatment with azathioprine and cyclosporinAhas also been related to the risk of early atherogenesis, while hydroxychloroquine and chloroquine exert a beneficial effect on the lipid profile and have anticoagulant properties. Even in SLE patientswithout atherosclerotic lesions, coronary microcirculation abnormalities and coronary vasospasmhave been noted thatmay result inmyocardial infarction. Due to often young age of patients with SLE complicated by coronary artery disease, classical symptoms of the latter are frequently attributed to pericarditis or pleuritis, leading to a delay in diagnosis and treatment. In some patients, coronary artery disease remains asymptomatic, and myocardial infarction is often catastrophic. Pulmonary arterial hypertension develops in 4-9%of SLE patients, often with coexisting cardiomegaly. One cause of pulmonary arterial hypertension in these patients may be chronic pulmonary embolism which is usually related to the presence of antiphospholipid antibodies (aPL), primarily lupus anticoagulant or anticardiolipin antibodies.
Antiphospholipid antibody syndrome or antiphospholipid syndrome (APS) is an acquired autoimmune disease inwhich the presence of aPL (lupus anticoagulant [LA], anticardiolipin antibodies [aCL], or anti-beta2-glycoprotein I antibodies [aβ2GPI]) is associated with arterial or venous thrombotic events, which are often multiple, and recurrent fetal loss.APSmay be idiopathic (primary APS, PAPS) or related to other disease (secondary APS, SAPS), most commonly connective tissue disease such as systemic lupus erythematosus, cancer, and infections. Mortality in these patients is strongly related to cardiovascular complications. For example,myocardial infarction is responsible for 18.9% of all deaths among patients with APS. Cardiovascular system involvement may occur in 40-70% of patients with APS and include:
- Valve thickening/dysfunction;
- Myocardial infarction;
- Angina pectoris;
- Intracardiac thrombi;
- Myocardial microthrombi and related ventricular dysfunction;
- Pulmonary hypertension.
The most common alterations are cardiac valvular changes (present in 32-38% of patients with PAPS vs. 0-5%in the general population). Aseptic vegetations or valve leaflet thickening are usually noted. Valvular changes associated with the presence of aPL were defined during the 11th International Congress on Antiphospholipid Antibodies.Mitral is themost commonly affected valve, followed by aortic valve and tricuspid valve.
Valvular regurgitation is significantly more common than valvular stenosis. Pathologic valvular changes include localised thickening >3mmof the proximal or middle part of a leaflet, and irregular nodules on the surface ofmitral or aortic valve (Fig. 3-6). Valvular abnormalities in patients with coexisting SLEmay be confirmed by histological examination of Libman-Sacks lesions (Fig. 3). In all cases, infective endocarditis and a history of rheumatic fever should be excluded. Valvular abnormalities are usually asymptomatic and valve replacement is necessary in only 4-6% of cases. However, patients with valvular involvement related to APS are at significantly increased risk of arterial embolic events. A close association has been observed between valvular abnormalities and stroke incidence. In addition, valvular changes are significantly more common in patients with peripheral vascular events (i.e., thrombosis) than in patients with obstetrical complications of APS. The first report suggesting that aPL are related to atherosclerosis was published in 1993. In that study, a cross-reaction was found to occur between aPL and antibodies against oxidized low-density lipoproteins (ox-LDL). Since that time, there has been increasing evidence indicating an association between aPL and the risk ofmyocardial infarction. In a prospective multicenter clinical study of 1000 patients with APS, myocardial infarction occurred in 2.8% of patients, and the 5-year incidence was 5.5%. Anticardiolipin antibodies were present in 15% of these patients but their prevalence increased to 21% among patients with incident myocardial infarction below 45 years of age. Coronary artery disease in young patients (<45 years of age) is currently considered an indication for aPL testing. Intracardiac thrombi have been documented in patients with aPL. Their presence is usually associated with embolic complications. They are mostly localised in the right heart chambers, and the diagnostic method of choice is transesophageal echocardiography. Myocardial microthrombi are mostly found in patients with multiorgan thrombosis in the course of catastrophic APS, and they are rare in patients with PAPS. Patients usually present with symptoms of myocardial infarction but no lesions are found at coronary angiography. Chronic thrombosis in cardiac microcirculation leads to systolic and diastolic ventricular dysfunction. The most recent guidelines on the management of patients with cardiac involvement in APS were published in 2011. Anticoagulation is indicated in patients with documented changes in the valvular apparatus and at least one thromboembolic event. In contrast, prophylactic anticoagulationwas not found to be effective in limiting the development of valvular abnormalities. The optimal management of an acutemyocardial infarction in patients with APS is still under debate. As intravascular interventions in patients with aPL are associated with a high risk of thrombotic complications, they should be kept to a necessary minimum. The rates of complications following percutaneous coronary angioplasty and coronary artery bypass grafting in patients with APS are high. Recurrent thrombosis has been reported after coronary stenting. Oral anticoagulation, e.g.with warfarin, is indicated in the secondary prevention of myocardial infarction in patients with APS. Addition of a small dose of acetylsalicylic acidmay also be considered. APS patients with a high thrombotic risk (aCL+/LA+/aβ2GPI+) who underwent percutaneous coronary intervention with stenting, should be treated with oral anticoagulants (target international normalized ratio [INR] 2-3) combined with clopidogrel (75mg/day) and aspirin (100mg/day).
FIGURE 3. A female patient with antiphospholipid syndrome and a history of cerebral embolic events. Transthoracic echocardiography (A) in the apical four-chamber view shows marked thickening of mitral leaflets (arrows), with slightly limited valve opening. Transesophageal echocardiography (B) in the same patient shows mobile, moderately echogenic masses on the atrial surface of mitral leaflets (arrows) that resemble small vegetations. Their localization on the inflow surface is typical for Libman-Sacks vegetations.
In patients with intracardiac thrombi, aggressive anticoagulation or even surgical thrombus removal is indicated. Even operated patients, however, require chronic anticoagulation after the surgical treatment.
Ankylosing spondylitis, previously known as Bechterew disease, is a form of seronegative inflammatory spondyloarthropathy. It is a chronic arthritis affecting sacroiliac joints, joints of the spine, and peripheral joints, characterised by entheseal inflammation or enthesitis. Extra-articular manifestations of ankylosing spondylitis may also develop, including uveitis, cardiovascular alterations, and gastointestinal lesions. Cardiovascular abnormalities are noted in nearly 80%of patients with ankylosing spondylitis, but they result in significant clinical symptoms in only 10% of patients. An analysis ofmortality causes in ankylosing spondylitis showed that cardiovascular disease was the cause of death in 40-50% of patients. Cardiovascular involvement is more common with longer duration of ankylosing spondylitis. The disease processmay affect all cardiac structures, large vessels, and the conduction system. In the majority of cases, cardiac changes in ankylosing spondylitis remain asymptomatic for a long time and are usually diagnosed when cardiac conduction block or aortic regurgitation develops. Chest pain in these patients is often attributed to disease progression in the skeletal systemand not to cardiovascular abnormalities. The latter, however, progress with longer duration of the disease but may also precede other symptoms. Patients with ankylosing spondylitis with cardiovascular involvement are also much more likely to develop concomitant peripheral joint inflammation. The most commonly found cardiovascular manifestation of ankylosing spondylitis is aortic regurgitation due to aortic inflammation and dilatation, as well as fibrosis of the aortic valve itself. Adiastolic murmur over the aortic valve can be heard in 5% of patients, and splitting of the second heart sound is found in 2% of patients. Echocardiography shows aortic regurgitation in about 4% of patients with disease duration of <15 years, but this proportion increases to 10% among patients with disease duration of >30 years. Aortic inflammatory changes were first described by Mallory in 1936, and their association with ankylosing spondylitis was confirmed by Bauer in 1951. Inflammation usually involves the proximal portion of the aorta butmay bemore extensive, involving even the abdominal aorta. The inflammatory process results in intimal proliferation in the vasa vasorum, infiltrates of plasmocytes and lymphocytes, hyalinization, and calcification, along with focal necrosis, elastic fiber decomposition and fibrosis within the aortic intima. Inflammatory infiltrates and obliterating changes develop inthe adventitia, resulting in vessel lumen obstruction. The inflammatory process may subsequently involve aortic or mitral valve leaflets which become thickened and distorted, with rolled-up edges (Fig. 7).
In some cases, leaflet involvement is less severe but the disease process affects the annulus, resulting in valvular regurgitation. Changes seen in ankylosing spondylitis include aortic dilatation and the presence of a subaortic bump, or localised fibrotic thickening at the base of the anterior mitral leaflet. Aortic dilatation is noted in nearly 60% of patients, more frequently in men. Subacute bacterial endocarditis involving the aortic valve has also been reported in patients with newly diagnosed ankylosing spondylitis. Aortic changes becomemore frequent with more advanced patient age, longer duration of the disease, and more severe disease. Valvular changes may be the initial presentation of ankylosing spondylitis.
Mitral valve abnormalities, including mitral regurgitation and mitral valve prolapse, are reported much less frequently. Cardiac auscultation may reveal a systolic murmur over the mitral valve in 10% of patients, and a systolic click is present in 5% of patients. Echocardiography shows mitral regurgitation in 1-6% of patients and mitral valve prolapse in 10% of patients. In the subset with juvenile ankylosing spondylitis, mild mitral regurgitation has been noted in 5-10% of patients. Pericarditis in patients with ankylosing spondylitis is usually of the fibrinous type but occurs infrequently. Pericardial thickening has been noted in 7.5% of patients, and pericardial effusion in 5% of patients. Interventricular septal thickening has been reported in 2.5% of patients Left ventricular diastolic dysfunction usually precedes systolic dysfunction and is an early manifestation of cardiac involvement in the course of many diseases. In patients with ankylosing spondylitis, left ventricular diastolic dysfunction has been reported much more frequently compared to the control group. Echocardiography showed early left ventricular diastolic dysfunction in 20-50% of patients with ankylosing spondylitis. No relation was found between diastolic dysfunction and patient age, duration of the disease, and clinical and radiological markers of disease activity.
Another major cardiac problem in patients with ankylosing spondylitis are conduction disturbances, likely resulting from subaortic fibrosis that damages the atrioventricular node, the proximal part of His and bundle branches. Histological examinations of the myocardium and autopsy studies of patients with ankylosing spondylitis showed mild, diffuse growth of intramuscular connective tissue, consisting primarily of reticular fibers.
Finally, it should be noted that 20% of patients with ankylosing spondylitis are diagnosedwith hypertension, and 17.5% with ischemic heart disease.
Psoriatic arthritis is a seronegative inflammatory spondyloarthropathy characterised by joint inflammation accompanying psoriasis. The disease may also lead to extra-articular involvement, including ocular, cardiovascular, and gastrointestinal manifestations. Despite cardiovascular diseases are themajor cause of mortality in patients with psoriatic arthritis, few papers have been published in the literature regarding cardiovascular changes in the patients. The risk of cardiovascular death in patients with psoriatic arthritis is increased 1.3-fold compared to the general population. An increased incidence of atherosclerosis, ischemic heart disease, congestive heart failure, lipid abnormalities, and hypertension has been reported. Diastolic dysfunction with restrictive filling pattern has a significantly higher prevalence in echocardiographic examinations in patients with psoriatic arthritis. Similarly to ankylosing spondylitis, aortic regurgitation may develop (Fig. 8). Data regarding the incidence of mitral regurgitation in patients with psoriatic arthritis have been inconsistent, with reported estimates ranging from 4.5% to 56%. In some patients, echocardiography reveals fibrosing pericarditis andmyocarditis. Secondary amyloidosis may sometimes develop in psoriatic arthritis, resulting in coronary lesions, secondary myocardial ischemia, and damage to the cardiac conduction system.
FIGURE 8. A female patient with psoriatic arthritis and HLA-B27 positive spondyloarthropathy. A. Moderate aortic regurgitation with regurgitant jet visualized using color Doppler (arrow) in the parasternal long-axis view. B. Aortic regurgitation in the same patient, assessed using continuous wave Doppler in the apical five-chamber view.
Rheumatoid arthritis (RA) is a systemic connective tissue disease characterised by symmetric joint inflammation. In addition, both extra-articular changes and systemic complicationsmay develop in RA. Increased mortality in RA is primarily due to cardiovascular systeminvolvement.RAcontributes to premature atherosclerosis and myocardial infarction. Increased risk of ischemic heart disease in RAis related to duration of the disease, and the use of glucocorticoids and disease-modifying antirheumatic drugs, including biologic agents. The risk of atherosclerotic plaque development in patients with RAis increased threefold compared to the control group. Myocardial infarction occursmore frequently in patientswith rheumatoid factor, and ST segment depression is significantly more common in RA patients with rheumatoid nodules compared to the patients without rheumatoid nodules. Finally, coronary vasculitis was observed in patients with active inflammation before introduction of anti-inflammatory drugs and biologic agents to the therapy of RA. The most common cardiovascular manifestation of RA is pericarditis, found in 30-50% of patients in echocardiographic and postmortem studies (Fig. 9). The proportion of patients with clinical symptoms of pericarditis ismuch smaller (10%). Pericarditis usually develops in patients with severe RA, mostly in men with advanced joint destruction, rheumatoid nodules, and extra-articularmanifestations of RA. Both obliterative pericarditis and acute progressing effusive pericarditis are associated with increased mortality. In most cases, pericarditis develops in patients with established RA, although it may occasionally precede the diagnosis of arthritis. Rheumatoid nodules may be located in various cardiac structures, leading to myocardial dysfunction, arrhythmias, and valvular abnormalities. Currently, valvular changes resulting from RA have become less frequent, with mitral regurgitation being most commonly reported (Figs. 10-12).
FIGURE 12. A female patient with rheumatoid arthritis. A. Mitral inflow pattern showing impaired relaxation (mild diastolic dysfunction), with the E/A ratio of <0.5. Evaluation of septal mitral annulus excursion with Doppler tissue imaging (B) confirmed left ventricular diastolic dysfunction with a very low e’ wave velocity.
Systemic sclerosis (SS) is a connective tissue disease characterised by diffuse microangiopathy and excessive collagen deposition in skin and internal organs. Cardiac involvement is frequent in SS, although clinically it is often mild or asymptomatic. Overt cardiac disease is diagnosed in 20-25% of patients, while in autopsy studies it is currently found in about 80% of cases. Cardiac involvement is significantlymore common in patients with generalised SS. However, the diagnosis ofmild or subclinical cardiac involvement in SS is of major clinical and therapeutic importance.
Cardiac involvement in SS mostly manifests with:
- Congestive heart failure;
- Pericarditis; or
- Sudden cardiac death.
During the last 30 years, introduction of angiotensin converting enzyme inhibitors to the therapy of SS has resulted in a dramatic reduction of mortality related to scleroderma renal crisis, with more deaths occurring due to pulmonary fibrosis and pulmonary hypertension (accounting for 50% of deaths) or congestive heart failure. The inflammatory process and vascular changes in SS result in myocardial fibrosis with morphological characteristics that are significantly different fromthose of fibrosis due to atherosclerosis. Echocardiography reveals multi-segment myocardial hypokinesis secondary to diffuse inflammation, as evidenced by the lack of coronary lesions. In 10 to 50% of patients with SS, echocardiographic examination shows asymptomatic increase in left ventricularmass, increased thickness of the posterior wall of the left ventricle, asymetric interventricular septal hypertrophy, prolonged isovolumetricrelaxation time, or impaired right ventricular filling (Figs. 13 and 14). Recent studies evaluating early cardiac damage in SS have revealed that the predominant echocardiographic finding is right ventricular dysfunction, resulting from extensive myocardial damage or increased afterload (due to pulmonary fibrosis or pulmonary hypertension) (Fig. 15). Impaired right ventricular diastolic filling and increased right ventricular end-diastolic dimension may be noted in a significant proportion of patients. Thallium scintigraphy studies revealed myocardial perfusion defects, associated with impaired myocardial contractility, in nearly all patients with SS. Early subclinical myocardial dysfunction in SS has also been confirmed with dobutamine stress echocardiography.
Pericarditis is a frequent finding in SS, observed in up to 50% of patients undergoing echocardiographic examination (Figs. 16 and 17).Clinical manifestations of pericardial involvement are noted in 5-15% of patients. Pericardial involvement in SS is also a predictor of interstitial lung disease and pulmonary hypertension. Diffuse scarring and fibrosis involving myocardium of all four cardiac chambers may be responsible for electrocardiographic abnormalities seen in precordial leads, including myocardial infarction pattern and bundle branch blocks (in 35% of patients), and PR interval prolongation. Conduction disturbances are noted in about 25-75% of patients with SS.
Pulmonary arterial hypertension and lung fibrosis are currently considered the most common causes of mortality in SS. Pulmonary arterial hypertension is present in 8-12% of patients with limited SS, particularly often in patients with the CREST syndrome (calcinosis, Raynaud’s syndrome, esophageal dysmotility, sclerodactyly, telangiectasia) and the presence of anticentromere antibodies. Pulmonary hypertension in patients with SS includes:
- Pulmonary arterial hypertension;
- Pulmonary hypertension due to left heart disease;
- Pulmonary hypertension associated with lung diseases and/or hypoxia.
Three-year survival was reported in 64% of SS patients with concomitant pulmonary arterial hypertension and only 39% of SS patients with interstitial lung disease and pulmonary hypertension. Pulmonary hypertension in SS is a unique phenotype characterised by the worst outcomes as compared to idiopathic pulmonary arterial hypertension and pulmonary hypertension associated with other connective tissue diseases. Evaluation for pulmonary arterial hypertension should be prompted by the presence of some clinical features and serologic markers (Raynaud’s phenomenon, multiple telangiectasias, high serumuric acid level, LA+, aCL+, elevated B-type natriuretic peptide [BNP] level, reduced diffusion capacity [DLCO]) in patients with connective tissue diseases. Echocardiography with measurements of right ventricular and pulmonary arterial pressures is currently considered a standard screening procedure in all patients with SS. Early diagnosis of pulmonary hypertension (confirmed by the right heart catheterisation) and implementation of appropriate treatment (particularly with prostanoids under specific therapeutic programmes) may improve survival in this patient group (Figs. 18-22). Cardiac arrhythmias are also common in these patients. Supraventricular arrhythmias are most frequently observed, such as atrial fibrillation, atrial flutter and paroxysmal supraventricular tachycardia (in 20-30% of patients).Ventricular arrhythmias, including multifocal and coupled premature ventricular beats, are less frequent (in 7-13% of patients). Their presence is associated with a risk of sudden cardiac death (5-21%).
Systemic connective tissue diseases are associated with the following cardiac abnormalities:
- Cardiac valvular changes, including nonbacterial vegetations and leaflet fibrosis and thickening, are seen in systemic lupus erythematosus, antiphospholipid syndrome, and rheumatoid arthritis. When cardiac valves are affected, infective endocarditis and rheumatoid fever should always be excluded.
- Increased risk of an early development of atherosclerosis and coronary artery disease is particularly often seen in systemic lupus erythematosus and rheumatoid arthritis.
- Intracardiac thrombi are typical for antiphospholipid syndrome.
- Early left ventricular diastolic dysfunction is most frequently reported in patients with systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis.
- Pericarditis is common in systemic lupus erythematosus and rheumatoid arthritis, while asymptomatic pericardial effusion is also a frequent finding in systemic sclerosis.
- Pulmonary hypertension is typical for systemic sclerosis and systemic lupus erythematosus. Pulmonary hypertension is an important but still often underestimated component of the clinical picture of systemic connective tissue diseases. The pathogenesis of pulmonary hypertension in systemic connective tissue diseases is mediated by immunologic mechanisms, which calls for a combined treatment approach in this patient group. Associated pulmonary hypertension in systemic connective tissue disease is an adverse prognostic factor regarding both the clinical course of the disease and the duration of patient survival, particularlywhen combinedwith interstitial lung disease.
- Inflammation involving the proximal part of the aorta and the aortic valve, with the presence of a characteristic subaortic bump, andcardiac conduction disturbances are typical features of ankylosing spondylitis.
- Haque S, Gordon C, Isenberg D, et al: Risk factors for clinical coronary heart disease in systemic lupus erythematosus: the lupus and atherosclerosis evaluation of risk (LASER) study. Rheumatol. 2010,37(2):322-9.
- IshimoriML,Martin R, Berman DS, et al:Myocardial ischemia in the absence of obstructive coronary artery disease in systemic lupus erythematosus. JACC Cardiovasc Imaging. 2011,4(1):27-33.
- NikpourM, UrowitzMB, Ibañez D, et al:. Relationship between cardiac symptoms,myocardial perfusion defects and coronary angiography findings in systemic lupus erythematosus. Lupus. 2011, 20(3):299-304.
- Cervera R, TektonidouMG, Espinosa G, et al: Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APSManifestations (I): catastrophic APS, APS nephropathy and heart valve lesions. Lupus. 2011;20(2):165-73.