Medical Therapy and Clinical Outcomes in Cardiac Sarcoidosis Patients With Systolic Heart Failure.

BACKGROUND: Cardiac sarcoidosis (CS) may result in systolic heart failure (heart failure with reduced ejection fraction [HFrEF]), but its response to guideline-directed medical therapy (GDMT) remains uncertain. METHODS AND RESULTS: We investigated 881 patients evaluated for CS to identify those with diagnosed CS, left ventricular ejection fraction (LVEF) ≤40% at diagnosis, and follow-up echocardiogram within 11-24 months. Demographics, LVEF, GDMT as quantified by Kansas City Medical Optimization (KCMO) score, and immunosuppressive treatment were recorded. The primary outcome was a composite of event-free survival (unplanned heart failure hospitalization, left ventricular assist device [LVAD]/heart transplant, or death). Seventy-nine (9%) CS patients met the inclusion criteria (35% female, median age 57 years, mean LVEF 30.9%, median New York Heart Association class II [46%], mean number of GDMT agents 1.7, and mean KCMO score 31.8). Most (87%) were treated with immunosuppressive treatment. At follow-up (median 16 months), the mean number of GDMT agents increased to 2.2 (P=0.02), and the mean KCMO score to 70.1 (P<0.001). Mean LVEF improved to 39.9% (excluding LVAD/transplant; P<0.001) and the change in LVEF was correlated with follow-up KCMO score (P<0.001). The primary outcome occurred in 13 (16%) patients and differed by KCMO score (log-rank P<0.001), but not by immunosuppressive treatment (log-rank P=0.36). CONCLUSIONS: GDMT optimization is associated with better cardiac remodeling and clinical outcomes in CS patients with HFrEF.

An magnetic resonance imaging-pathology correlation case report of cardiac sarcoidosis mimicking arrhythmogenic biventricular cardiomyopathy.

Background: Cardiac sarcoidosis (CS) is a granulomatous disease that can manifest as conduction defects, ventricular arrhythmias, and heart failure. The diagnosis of CS is inherently difficult due to variable presentations; as such, endomyocardial biopsy is often required but lacks sensitivity due to patchy myocardial involvement. Moreover, the diagnostic criteria of CS and arrhythmogenic cardiomyopathy overlap, particularly in right-side dominant or biventricular presentations, which further complicates an already challenging differential diagnosis. Case summary: A 53-year-old man with no prior chronic medical conditions presented with ventricular tachycardia (VT) and heart failure with reduced ejection fraction. He was found to have biventricular cardiomyopathy and late gadolinium enhancement on cardiac magnetic resonance imaging, resulting in an initial diagnosis of arrhythmogenic cardiomyopathy. Implantable cardioverter-defibrillator was placed, but he was readmitted for recurrent VT 2 months later. Despite an aggressive VT therapy (combination of antiarrhythmic drugs, epicardial and endocardial ablation, and stellate ganglion block), he continued with refractory VT and developed cardiogenic shock. Extra-corporeal membrane oxygenation was initiated as a bridge to heart transplantation. Pathology of the explanted heart revealed the underlying disease to be CS. Discussion: Cardiac sarcoidosis can mimic arrhythmogenic biventricular cardiomyopathy and may be difficult to distinguish by the proposed diagnostic criteria. High clinical suspicion and thorough investigation are necessary for an earlier diagnosis and initiation of treatment.

Arrhythmic manifestations and outcomes of definite and probable cardiac sarcoidosis.

BACKGROUND: The 2014 Heart Rhythm Society consensus statement defines histological (definite) and clinical (probable) diagnostic categories of cardiac sarcoidosis (CS), but few studies have compared their arrhythmic phenotypes and outcomes. OBJECTIVE: The purpose of this study was to evaluate the electrophysiological/arrhythmic phenotype and outcomes of patients with definite and probable CS. METHODS: We analyzed the arrhythmic/electrophysiological phenotype in a single-center North American cohort of 388 patients (median age 56 years; 39% female, n = 151) diagnosed with definite (n = 58) or probable (n = 330) CS (2000-2022). The primary composite outcome was survival to first ventricular tachycardia/fibrillation (VT/VF) event or sudden cardiac death. Key secondary outcomes were also assessed. RESULTS: At index evaluation, in situ cardiac implantable electronic devices and antiarrhythmic drug use were more common in definite CS. At a median follow-up of 3.1 years, the primary outcome occurred in 22 patients with definite CS (38%) and 127 patients with probable CS (38%) (log-rank, P = .55). In multivariable analysis, only a higher ratio of the 18F-fluorodeoxyglucose maximum standardized uptake value of the myocardium to the maximum standardized uptake value of the blood pool (hazard ratio 1.09; 95% confidence interval 1.03-1.15; P = .003, per 1 unit increase) was associated with the primary outcome. During follow-up, patients with definite CS had a higher burden of device-treated VT/VF events (mean 2.86 events per patient-year vs 1.56 events per patient-year) and a higher rate of progression to heart transplant/left ventricular assist device implantation but no difference in all-cause mortality compared with patients with probable CS. CONCLUSION: Patients with definite and probable CS had similarly high risks of first sustained VT/VF/sudden cardiac death and all-cause mortality, though patients with definite CS had a higher overall arrhythmia burden. Both CS diagnostic groups as defined by the 2014 Heart Rhythm Society criteria require an aggressive approach to prevent arrhythmic complications.

Arrhythmic Prognosis According to Left Ventricular Systolic Dysfunction Severity in Cardiac Sarcoidosis.

BACKGROUND: Current guidelines present varying classes of recommendations for implantable cardioverter-defibrillator (ICD) utilization in patients with cardiac sarcoidosis (CS) and left ventricular ejection fraction (LVEF) <50%. OBJECTIVE: To investigate the ventricular arrhythmia risk in CS patients with ICDs and varying degrees of LV systolic dysfunction. METHODS: We included CS patients with an ICD and LVEF <50% at index evaluation. The primary outcome was survival free of sustained ventricular tachycardia/fibrillation (VT/VF) after ICD implantation and was assessed comparatively for LVEF ≤35 vs 36-49% and for primary vs secondary prevention ICD indication. RESULTS: We included 61 patients (median age 57 years, 61% male) with LVEF 36-49% (n=23) or LVEF ≤35% (n=38). An ICD was implanted for secondary prevention in 24% and 44% of the LVEF ≤35% and 36-49% groups, respectively (p=0.11). The primary outcome did not differ between the two groups in univariable analysis (LVEF ≤35% vs 36-49% HR 0.85 [95% CI 0.39, 1.82], p=0.67). In multivariable analysis, secondary prevention ICD indication was the only significant predictor of incident sustained VT/VF (HR 2.86 [95% CI 1.23, 6.67], p=0.015). The mean sustained VT/VF event burden was higher in the secondary as compared with the primary prevention ICD patients (0.47 vs 0.11 events/patient-year, p=0.005) but did not differ significantly between LVEF ≤35% and 36-49% patients. CONCLUSIONS: CS patients with ICD indications and LVEF 36-49% carry similarly high arrhythmic risk as those with LVEF ≤35%. Patients with secondary prevention ICDs have the highest overall risk.