Primary heart involvement in systemic sclerosis, from conventional to innovative targeted therapeutic strategies

Abstract

Primary heart involvement is frequent in systemic sclerosis, even though often sub-clinical, and includes cardiac abnormalities that are predominantly attributable to systemic sclerosis rather than other causes and/or complications. A timely diagnosis is crucial to promptly start the appropriate therapy and to prevent the potential life-threatening early and late complications. There is little evidence on how to best manage systemic sclerosis-primary heart involvement as no specific treatment recommendations for heart disease are available, and a shared treatment approach is still lacking. The objective of this review is to summarize the state of the art of current literature and the overall management strategies and therapeutic approaches for systemic sclerosis-primary heart involvement. Novel insights into pathogenic mechanisms of systemic sclerosis-primary heart involvement are presented to facilitate the comprehension of therapeutic targets and novel treatment strategies.

Diagnosis and management of primary heart involvement in systemic sclerosis

“…Once diagnosed, there is little evidence on how to best manage SSc-pHI because no specific recommendations are available for SSc-pHI, and a shared treatment approach is still lacking [9 ▪ ].…”

“…SSc-pHI can occur with a broad clinical spectrum potentially involving all cardiac structures. In fact, in SSc pericardial disease, arrhythmias, valvular disease, myocardial ischemia/coronary microvascular disease (CMD), diastolic dysfunction, myocarditis, myocardial fibrosis and heart failure may be observed [2,3,9 ▪ ]. Therefore, signs and symptoms of SSc-pHI are heterogeneous as SSc-pHI may clinically present as acute heart failure or fulminant myocarditis, asymptomatic conduction defects and ventricular arrhythmias, and diastolic dysfunction [3,9 ▪ ].…”

“…In fact, in SSc pericardial disease, arrhythmias, valvular disease, myocardial ischemia/coronary microvascular disease (CMD), diastolic dysfunction, myocarditis, myocardial fibrosis and heart failure may be observed [2,3,9 ▪ ]. Therefore, signs and symptoms of SSc-pHI are heterogeneous as SSc-pHI may clinically present as acute heart failure or fulminant myocarditis, asymptomatic conduction defects and ventricular arrhythmias, and diastolic dysfunction [3,9 ▪ ]. At early stages, SSc-pHI could even be asymptomatic [2,3,9 ▪ ], and once clinically evident, the most common complaint is dyspnoea with exertion [2,10,11].…”

“…Therefore, signs and symptoms of SSc-pHI are heterogeneous as SSc-pHI may clinically present as acute heart failure or fulminant myocarditis, asymptomatic conduction defects and ventricular arrhythmias, and diastolic dysfunction [3,9 ▪ ]. At early stages, SSc-pHI could even be asymptomatic [2,3,9 ▪ ], and once clinically evident, the most common complaint is dyspnoea with exertion [2,10,11]. However, dyspnoea is not specific for SSc-pHI, since it could be also related to lung (ILD and PAH) and skeletal (myositis) involvement or to other causes of cardiac damage.…”

“…The recently emerged role of inflammation underlying the SSc-pHI has led to important therapeutic implications: treatment interventions effectively dampening the acute inflammatory process at an early stage, preventing the cardiac remodelling and improving patients’ outcome. In SSc myocarditis, the use of immunosuppressive drugs (steroids, cyclophosphamide, azathioprine and mycophenolate mofetil) has been used to target the pro-inflammatory mediators of the disease [9 ▪ ,10–13,23,24,28 ▪▪ ,120–124]. Pulse corticosteroids can ameliorate myocardial oedema, detected by CMR, [10,125,126] and have been successfully used in virus-negative EMB-proven myocarditis and pericarditis, with beneficial effects on clinical status and cardiac enzymes [10,23], but not with a definite benefit on left ventricular systolic function [127].…”