Prognosis and Outcomes of Clinically Diagnosed Cardiac Sarcoidosis Without Positive Endomyocardial Biopsy Findings

Abstract

Background: Diagnosis of cardiac sarcoidosis (CS) is sometimes difficult due to a low positive rate of epithelioid granulomas by endomyocardial biopsy (EMB). Accordingly, Japanese guidelines can allow the CS diagnosis using clinical data alone without EMB results (clinical CS) since 2006. However, little is known about prognosis and outcome of clinical CS.

Objectives: Purpose of this study was to analyze the prognosis, outcomes, and response to corticosteroid of clinical CS using large-scale cohort survey.

Methods: Overall, 422 CS patients (mean age 60 ± 13 years, 68% female, median follow-up period of 5 years), including 345 clinical CS and 77 EMB-positive patients, histologically diagnosed CS (histological CS) by Japanese guidelines, were enrolled and examined.

Results: Clinical profile (age, sex, initial cardiac arrhythmias, and abnormal uptake of gallium-67 scintigraphy or ¹⁸F-fluorodeoxyglucose positron emission tomography in heart) was similar in both groups. Although clinical CS had better prognosis (P = 0.018) and outcome (all-cause death, appropriate defibrillator therapy, and heart transplantation; P = 0.008), multivariate Cox hazard analysis revealed that left ventricular ejection fraction (LVEF) and sustained ventricular tachycardia history were independently associated with outcome (P < 0.001 and P = 0.002, respectively), but not with the diagnosed CS category. Moreover, similar LVEF recovery after corticosteroid was observed in both groups with low LVEF (≤35%) at the 1-year follow-up period (P < 0.001).

Conclusions: In clinical CS according to the Japanese guideline, prophylactic implantable-cardioverter-defibrillator and immunosuppressive therapy are important in patients with low LVEF or ventricular tachycardia history, similar to histological CS.

Keywords: 18F-FDG, 18F-fluorodeoxyglucose; 67Ga, gallium-67; AVB, atrioventricular block; BAL, bronchoalveolar lavage; CMR, cardiac magnetic resonance; CRT, cardiac resynchronization therapy; CS, cardiac sarcoidosis; EMB, endomyocardial biopsy; HRS, Heart Rhythm Society; ICD, implantable cardioverter-defibrillator; JCS, Japanese Circulation Society; JSSOG, Japanese Society of Sarcoidosis and Other Granulomatous diseases; LV, left ventricular; LVEF, left ventricular ejection fraction; PET, positron emission tomography; RFCA, radiofrequency catheter ablation; RV, right ventricle/ventricular; VT, ventricular tachycardia; cardiac sarcoidosis; clinical diagnosis; histological diagnosis; prognosis.

Graphical abstract

Figure 1

Study Population CS = cardiac sarcoidosis; JCS = Japanese Circulation Society.

Figure 2

Initial Cardiac Arrhythmias at the Time of CS Diagnosis AVB = atrioventricular block; CS = cardiac sarcoidosis; VT = ventricular tachycardia.

Figure 3

Comparison of Prognosis Between Histological and Clinical CS Patients The Kaplan-Meier curves reveal the frequency of (A) all-cause death–free and (B) adverse event–free survival between histological and clinical cardiac sarcoidosis (CS). The red line indicates histological CS, blue line indicates clinical CS.

Figure 4

The Prognosis of Clinical CS During Each Cardiac Function The Kaplan-Meier curves reveal the frequency of (A) all-cause death–free and (B) adverse event–free survival in clinical cardiac sarcoidosis (CS) patients during each cardiac function. The Kaplan-Meier curves reveal the frequency of (C) all-cause death–free and (D) adverse event–free survival in histological CS patients during each cardiac function. The blue line indicates left ventricular ejection fraction (LVEF) ≥50%, the green line indicates 35% < LVEF <50%, and the red line indicates LVEF ≤35%).

Figure 5

The Prognosis Among the 3 Types of CS Classified According to HRS 2014 The Kaplan-Meier curves reveal the frequency of (A) all-cause death–free and (B) adverse event–free survival for the 3 types of cardiac sarcoidosis (CS) classified according to the Heart Rhythm Society (HRS) 2014 guideline. The blue line indicates CS, the green line indicates probable CS, and the red line indicates undefined CS.

Central Illustration

Prognostic Predictors of CS and Effect of Corticosteroid Therapy in CS With Low LVEF AVB = atrioventricular block; CI = confidence interval; CS = cardiac sarcoidosis; HR = hazard ratio; LVEF = left ventricular ejection fraction; VT = ventricular tachycardia.