Sudden cardiac death, arrhythmias and abnormal electrocardiography in systemic sclerosis: A systematic review and meta-analysis

Objective: To calculate the frequency of sudden cardiac death(SCD), arrhythmia and conduction defects in SSc. Methods: MEDLINE/EMBASE were searched to January 2023. English-language studies reporting the incidence/frequency of SCD, arrhythmia and electrocardiography(ECG) abnormalities in SSc were included. Odds ratios(OR), estimations of annual incidence or pooled frequencies were calculated. Results: Seventy-nine studies(n = 13,609 participants with SSc) were included in the meta-analysis. Methodology and outcomes were heterogeneous. Ten studies included cohorts with known/suspected SSc-associated heart involvement(SHI), generally defined as clinically-manifest cardiac disease/abnormal cardiac investigations. The incidence of SCD in SHI was estimated to be 3.3% annually(n = 4 studies, 301PY follow-up). On ambulatory ECG, 18% of SHI cohorts had non-sustained ventricular tachycardia(NSVT; n = 4, 95%CI3.2–39.3%), 70% frequent premature ventricular complexes (PVCs; n = 1, 95%CI34.8–93.3%), and 8% atrial fibrillation (AF; n = 1, 95%CI4.2–13.6%). Nineteen studies included participants without SHI, defined as normal cardiac investigations/absence of cardiac disease. The estimated incidence of SCD was approximately 2.9% annually (n = 1, 67.5PY). Compared to healthy controls, individuals without SHI demonstrated NSVT 13.3-times more frequently (n = 2, 95%CI2–102), and paroxysmal supraventricular tachycardia 7-times more frequently (n = 4, 95%CI3–15). Other ambulatory ECG abnormalities included NSVT in 9% (n = 7, 95%CI6–14%), >1000 PVCs/24 h in 6% (n = 2, 95%CI1–13%), and AF in 7% (n = 5, 0–21%). Fifty studies included general SSc cohorts unselected for cardiac disease. The incidence of SCD was estimated to be 2.0% annually(n = 4 studies, 1646PY). Unselected SSc cohorts were 10.5-times more likely to demonstrate frequent PVCs (n = 2, 95%CI 2–59) and 2.5-times more likely to have an abnormal electrocardiography (n = 2, 95%CI1–4). Conclusions: The incidence of SCD in SSc is estimated to be 1.0–3.3% annually, at least 10-fold higher than general population estimates. Arrhythmias including NSVT and frequent PVCs appear common, including amongst those without known/suspected SHI.