Predictors of Poor Long-Term Outcomes in Patients with Newly Diagnosed Asymptomatic Cardiac Sarcoidosis: A Cardiovascular Magnetic Resonance Study

Abstract

Background: The prevalence of patients with cardiac sarcoidosis (CS) diagnosed at a subclinical stage has increased; however, their long-term outcomes are not well known. Objectives: To investigate the incidence and predictors of adverse long-term outcomes in newly diagnosed patients with asymptomatic CS. Methods: Forty-three patients with newly diagnosed asymptomatic CS and comprehensive baseline evaluation with cardiovascular magnetic resonance (CMR) were studied. Asymptomatic CS was defined as CS in patients with biopsy-proven extracardiac sarcoidosis without cardiac symptoms but with abnormalities on CMR or positron emission tomography according to Heart Rhythm Society criteria. The primary endpoint was a composite of all-cause mortality, new ventricular arrhythmia or an atrioventricular block requiring cardiac device implantation, and hospitalization for heart failure. Results: Patients had a mean age of 56 ± 11 years and presented with normal left ventricular (LV) ejection fraction (58 ± 4%). A total of 44.2% of patients reached the composite endpoint during 5 years of follow-up. Patients with the primary endpoint were predominantly female (73.7%) and had a significantly higher prevalence of right ventricular (RV) involvement compared to patients without the primary endpoint (RV late gadolinium enhancement (LGE) in 26.3% vs. 4.2%, p = 0.037). In multivariate regression analysis, extensive LV LGE (HR 1.61, 95% CI 1.16-2.04, p = 0.004) and impaired RV global longitudinal strain (GLS) at baseline (HR 0.46, 95% CI 0.24-0.68, p = 0.015) were significantly predictive of the primary endpoint, whereas treatment with corticosteroids after CS diagnosis was significantly associated with improved outcomes (HR 7.69, 95% CI 1.11-11.11, p = 0.044). Conclusions: Newly diagnosed patients with asymptomatic CS have a significant incidence of adverse outcomes after 5 years of follow-up. The extent of LV LGE and impaired RV GLS at baseline predict poor long-term outcomes in asymptomatic CS.

Keywords: cardiac magnetic resonance in cardiac sarcoidosis; cardiac sarcoidosis; left ventricular late gadolinium enhancement in cardiac sarcoidosis; outcomes in cardiac sarcoidosis; right ventricular longitudinal strain in cardiac sarcoidosis; silent cardiac sarcoidosis.

Figure 1

CMR-LGE findings in asymptomatic patients with cardiac sarcoidosis and histological confirmation: (A) Patient with hypertrophic phenotype and patchy distribution of LGE in the LV (blue arrow) and inferior wall of the RV (orange arrow). (B) Asymptomatic patient with extensive LV LGE (14% of LV mass). CMR = cardiovascular magnetic resonance; LGE = late gadolinium enhancement; LV = left ventricle; RV = right ventricle.

Figure 2

Receiver-operating characteristic curves to detect patients with major adverse cardiovascular events. LV LGE extent and RVFW GLS showed the highest areas under the curve among the CMR markers of ventricular function at baseline. LV GLS was not predictive of outcomes. CMR = cardiovascular magnetic resonance; LV GLS = left ventricular global longitudinal strain; LV LGE = left ventricular late gadolinium extent; RVFW GLS = right ventricular free wall global longitudinal strain.

Figure 3

Cumulative incidence of adverse events in patients with asymptomatic CS. Kaplan–Meier Curves stratified using cortison therapy after CS diagnosis (A), extent of LV LGE (B), and RVFW-GLS (C). LV LGE = left ventricular late gadolinium enhancement; RVFW GLS = right ventricular free wall global longitudinal strain.