Cardiovascular complications of systemic sclerosis: What to look for

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

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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.


  • 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.



Autoimmune rheumatic diseases increase the risk of cardiovascular disease. In rheumatoid arthritis and systemic lupus erythematosus, the risk is driven primarily by the inflammatory milieu, leading to accelerated coronary and cerebrovascular atherosclerosis independent of traditional atherosclerotic risk factors.1–3 The extent of cardiovascular involvement in other rheumatologic diseases has been less well characterized but is an area of growing interest.

In this review, we focus on the cardiovascular complications of systemic sclerosis and review recommendations for monitoring these patients in clinical practice.


Systemic sclerosis is an autoimmune rheumatic disease characterized by excessive extracellular matrix deposition leading to diffuse fibrosis, endothelial dysfunction, and microvascular injury. It is most common in North America, Southern Europe, and Australia,4,5 and it affects women more than men in ratios ranging from 3:1 to 14:1.6 The mean age at diagnosis is around 50.

The disease can affect the lungs (interstitial lung disease and pulmonary hypertension), the heart, the kidneys, and the gastrointestinal tract.

Systemic sclerosis has 2 main subtypes: limited cutaneous systemic sclerosis, formerly called CREST syndrome) and diffuse cutaneous systemic sclerosis. The limited cutaneous subtype is characterized by tightening of the skin of the distal extremities (below the elbows and knees) and face, while diffuse cutaneous systemic sclerosis can manifest as more extensive skin tightening also involving proximal extremities and the trunk. Both subtypes can have an effect on the cardiovascular system.

Some cardiovascular risk factors such as dyslipidemia, diabetes mellitus, and high body mass index are less common in patients with systemic sclerosis than in patients with rheumatoid arthritis, while the rates of arterial hypertension, smoking, chronic obstructive pulmonary disease, osteoporosis, and neoplasms are similar between the 2 groups.7


Overt cardiac involvement in systemic sclerosis is associated with a mortality rate of up to 70% over 5 years,8,9 and about one-fourth of deaths in patients with systemic sclerosis are from cardiac causes.10,11 Studies in Europe10,12 showed that many patients with systemic sclerosis have cardiac involvement detectable by magnetic resonance imaging even if they do not have clinical disease. Pulmonary arterial hypertension (PAH) is a complication of both subtypes of systemic sclerosis and portends a higher risk of death.8

Thus, it is critical for clinicians to understand the potential comorbid conditions associated with systemic sclerosis, particularly the cardiovascular ones, and to work closely with cardiologists to help optimize the evaluation and management.


Mechanisms of cardiac and vascular involvement in systemic sclerosis

Figure 1. Mechanisms of cardiac and vascular involvement in systemic sclerosis.

Microvascular disease in systemic sclerosis is primarily driven by endothelial cell activation and injury, leading to overexpression of adhesion molecules, recruitment of immune cells, intimal fibrosis, and fibroblast proliferation (Figure 1).13

Abnormal vasoreactivity, a consequence of an imbalance between endothelium-derived vasoconstrictors and vasodilators, defective angiogenesis, and endothelial injury, leads to tissue ischemia and vascular endothelial growth factor expression, which initiates injury and fibrosis in the myocardium and in other organs.14–17 Fibrosis involves the myocardium, pericardium, and conduction system.13,18

Myocardial involvement in systemic sclerosis is thought to be due mainly to abnormal vasoreactivity and microvascular abnormalities such as transient coronary artery spasm leading to repeated focal ischemia.19,20 Abnormal vasoreactivity has been demonstrated during cardiac catheterization21: while mean coronary sinus blood flow in systemic sclerosis patients was normal at rest, vasodilator reserve was significantly reduced in patients with diffuse cutaneous systemic sclerosis after maximal vasodilation with dipyridamole. Additionally, endomyocardial biopsy showed fibrosis and concentric intimal hypertrophy with normal epicardial coronary arteries.21

More research into other mechanisms of cardiovascular disease in systemic sclerosis is needed to allow for better preventive care for these patients.


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