Cardiac involvement in systemic sclerosis: Getting to the heart of the matter

New Insights into Profibrotic Myofibroblast Formation in Systemic Sclerosis: When the Vascular Wall Becomes the Enemy

“…Cardiovascular disease is the cause of death in 14–36% of all SSc cases with a wide range of pathologic manifestations including microvascular disease, atherosclerotic coronary artery disease, myocardial fibrosis and pericarditis [ 31 , 32 ]. Microvascular disease manifests with nonocclusive concentric intimal hyperplasia of myocardial arterioles and unique myocardial lesions known as “contraction band necrosis”, which is due to a sort of cardiac Raynaud’s phenomenon, i.e., a sequelae of perfusion and reperfusion injuries (microvascular coronary vasospasm) resulting in ischemic events finally leading to arrhythmias and cardiac dysfunction [ 4 , 7 , 33 , 34 ]. Moreover, different vascular abnormalities such as fibrinoid necrosis, mural fibrosis, intimal proliferation and medial hyperplasia have been detected in in coronary arteries of <1 mm in size [ 24 ].…”

“…Moreover, different vascular abnormalities such as fibrinoid necrosis, mural fibrosis, intimal proliferation and medial hyperplasia have been detected in in coronary arteries of <1 mm in size [ 24 ]. Strikingly, intermittent vascular spasm, reperfusion injury and ischemic necrosis are considered to play a pivotal role in inducing myocardial fibrosis, histologically manifesting as a patchy replacement of cardiac myocytes with acellular collagenous material throughout the myocardium [ 4 , 24 , 33 , 34 ]. As far as macrovascular involvement is concerned, arterial intimal thickening and occlusion by atheromatous plaques characterized by a plenty of foamy macrophages and cholesterol clefts with an overlying fibrous cap have been demonstrated in some SSc patients [ 6 , 35 , 36 , 37 ].…”

Primary systemic sclerosis heart involvement: A systematic literature review and preliminary data-driven, consensus-based WSF/HFA definition

“…15 The most frequent clinical cardiac features may include impaired contractility and relaxation, arrhythmias, myocarditis and pericardial disease. 16 Despite the plethora of possible different manifestations, primary cardiac involvement shares the main overall disease pathogenetic features, with variable combination of inflammatory, fibrotic and vasculopathic changes. 17 These may explain why certain demographic or SSc features may act as risk factors for specific SSc cardiac manifestations, such as older age at disease onset, 18,19 male gender, 20 auto-antibodies positivity, 19,21 diffuse cutaneous subset 22 and musculoskeletal involvement 22 for more inflammatory involvements including myocarditis, while history of digital ulcers 23 may increase the risk of vasculopathic and subsequent fibrotic and dysfunctional changes.…”

Serum Organ-Specific Anti-Heart and Anti-Intercalated Disk Autoantibodies as New Autoimmune Markers of Cardiac Involvement in Systemic Sclerosis: Frequency, Clinical and Prognostic Correlates

“…It is often clinically silent, and when symptomatic, carries a poor prognosis, accounting for one third of total deaths [2]. Primary HInv is associated with a variable phenotype: clinical presentations include dyspnoea, palpitations, arrhythmias, chest pain, heart failure (HF) with depressed left ventricular ejection fraction (LVEF), and diastolic dysfunction, although most patients are asymptomatic at early stages [3,4]. SSc may have a high arrhythmic burden [5], with a 5% sudden death rate in patients with both skeletal and cardiac muscle diseases [6].…”