Cardiovascular complications of systemic sclerosis: What to look for

Cleveland Clinic Journal of Medicine. 2019 October;86(10):685-695 | 10.3949/ccjm.86a.18109
October 1, 2019|Cleveland Clinic Journal of Medicine
Preethi Mani, MD;Danny Gonzalez, MD;Soumya Chatterjee, MD, MS, FRCP;Michael D. Faulx, MD
Author and Disclosure Information

Preethi Mani, MD
Department of Cardiovascular Medicine, Cleveland Clinic; Clinical Instructor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 

Danny Gonzalez, MD
Department of Cardiovascular Medicine, Cleveland Clinic 

Soumya Chatterjee, MD, MS, FRCP
Department of Rheumatic and Immunologic Diseases, Cleveland Clinic; Associate Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Michael D. Faulx, MD
Department of Cardiovascular Medicine, Cleveland Clinic; Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 

Address: Preethi Mani, MD, Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; manip@ccf.org; pmani87@gmail.com

Release date: October 1, 2019
Expiration date: September 30, 2020
Estimated time of completion: 1 hour

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ABSTRACT

Systemic sclerosis, an autoimmune disease characterized by fibrosis of the skin and various internal organs, is associated with cardiovascular abnormalities including pulmonary hypertension, atherosclerosis, right and left ventricular dysfunction, arrhythmias, conduction defects, pericardial disease, and valvular heart disease. Clinicians caring for patients with this disease should regularly screen for cardiac symptoms, and patients with abnormal findings should be managed in conjunction with a cardiologist to optimally modify cardiovascular risks.

KEY POINTS

  • Pulmonary hypertension is common in systemic sclerosis and carries a poor prognosis. Patients with systemic sclerosis should be screened regularly with echocardiography, followed, when necessary, by right heart catheterization to detect it early.
  • Myocardial infarction and stroke are more common in patients with systemic sclerosis, and preventive measures are the same as for the general population.
  • Right ventricular dysfunction secondary to pulmonary hypertension is common in systemic sclerosis; left ventricular dysfunction is less so. Routine echocardiography should include assessment of right and left ventricular function.
  • Electrocardiography should be performed periodically, and urgently when indicated, to look for potentially dangerous arrhythmias.

ARRHYTHMIAS AND CONDUCTION DEFECTS

Patients with systemic sclerosis are prone to arrhythmias due to both conduction system fibrosis and myocardial damage.

Arrhythmias accounted for 6% of the deaths in the EULAR Scleroderma Trials and Research (EUSTAR) database.11

In the Genetics Versus Environment in Scleroderma Outcome Study (GENISOS),70  250 patients who had had systemic sclerosis for at least 3 years were studied during a period of approximately 6 years, during which there were 52 deaths, 29 of which were directly attributable to systemic sclerosis. Multivariable Cox modeling showed that 7 variables predicted mortality:

,
  • Body mass index < 18.5 kg/m2
  • Age ≥ 65
  • Forced vital capacity < 50% predicted
  • Systolic blood pressure ≥ 140 or diastolic blood pressure ≥ 90 mm Hg
  • Pulmonary fibrosis
  • Positive anticentromere antibodies
  • Cardiac arrhythmias.

The hazard ratio for death in patients with arrhythmias in this model was 2.18 (95% CI 1.05–4.50, P = .035). Thus, finding arrhythmias in systemic sclerosis patients can provide important prognostic information.

While resting electrocardiography in patients with systemic sclerosis  most commonly shows sinus rhythm, 24-hour electrocardiographic monitoring has revealed nonsustained supraventricular and ventricular arrhythmias in a significant percentage.71,72 Although difficult to quantify in routine practice, parameters controlled by the autonomic nervous system including heart rate variability and heart rate turbulence have been shown to be impaired in systemic sclerosis, and these measures are associated with an increased risk of malignant arrhythmias and sudden cardiac death.73,74

Conduction abnormalities

Conduction abnormalities occur in one-fifth to one-third of patients with systemic sclerosis.75,76 The most common abnormal conduction finding is left bundle branch block, followed by first-degree atrioventricular block. High-degree atrioventricular block is uncommon,76 though a few case reports of complete heart block thought to be related to systemic sclerosis have been published.77–79 An autopsy study showed that the conduction system is relatively spared from myocardial changes seen in systemic sclerosis patients, and thus it is speculated that the conduction disturbances are a consequence of damaged myocardium rather than damage to conduction tissue.80

Given the array of electrophysiologic abnormalities that systemic sclerosis patients can have, it is critical to monitor all patients with routine (annual or biannual) electrocardiography; to take possible arrhythmia-related symptoms seriously; and to evaluate them with further workup such as Holter monitoring for 24 hours or even longer, event monitoring, exercise testing, or tilt-table testing.

PERICARDIAL DISEASE

Pericardial disease is clinically apparent in 5% to 16% of patients with systemic sclerosis81; patients with limited cutaneous systemic sclerosis have more pericardial disease than those with diffuse cutaneous systemic sclerosis (30% vs 16%).82 Forty-one percent of systemic sclerosis patients have been shown to have pericardial effusion by echocardiography,81 but the effusions are typically small and rarely cause tamponade, though tamponade is associated with a poor prognosis.

Large pericardial effusions can develop before skin thickening and diagnosis of systemic sclerosis.81,83,84 Thus, systemic sclerosis should be considered in patients with pericardial effusions of unknown etiology.

In a small study,85 the pericardial fluid in systemic sclerosis was typically exudative, with lactate dehydrogenase greater than 200 U/L, a fluid-serum lactate dehydrogenase ratio greater than 0.6, and a fluid-serum total protein ratio greater than 0.5.

Pericardial effusion can be a sign of impending scleroderma renal crisis,86 and thus renal function should be carefully monitored in systemic sclerosis patients with pericardial effusion. Constrictive pericarditis and restrictive cardiomyopathy can rarely occur in systemic sclerosis and may more commonly present with symptoms.

Pericardial disease in systemic sclerosis should be treated in a standard fashion with nonsteroidal anti-inflammatory drugs. Corticosteroids are generally of limited benefit and should be avoided, especially in the setting of scleroderma renal crisis.81

VALVULAR HEART DISEASE

Based on limited studies, the prevalence of significant valvular heart disease in systemic sclerosis patients does not seem to be higher than that in the general population. While patients with systemic sclerosis and CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) have been shown to have a higher frequency of mitral valve prolapse and mild mitral regurgitation,87,88 these abnormalities do not often progress in severity, and thus their clinical significance is limited.