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Background Cardiac sarcoidosis (CS) is a major cause of morbidity and mortality in patients with systemic sarcoidosis. Steroid-sparing agents are increasingly used, despite a lack of randomized trials or published guidelines to direct treatment. Methods and Results This retrospective study included 77 patients with CS treated with prednisone monotherapy (n = 32) or a combination with mycophenolate mofetil (n = 45) between 2003 and 2018. Baseline characteristics and clinical outcomes were evaluated. The mean patient age was 53 ± 11 years at CS diagnosis, 66.2% were male, and 35.1% were Black. The total exposure to maximum prednisone dose (initial prednisone dose × days at dose) was lower in the combination therapy group (1440 mg [interquartile range (IQR), 1200–2760 mg] vs 2710 mg [IQR, 1200–5080 mg]; P = .06). On 18F-fluorodeoxyglucose positron emission tomography scans, both groups demonstrated a significant decrease in the cardiac maximum standardized uptake value after treatment: a median decrease of 3.9 (IQR 2.7–9.0, P = .002) and 2.9 (IQR 0–5.0, P = .001) for prednisone monotherapy and combination therapy, respectively. Most patients experienced improvement or complete resolution in qualitative cardiac 18F-fluorodeoxyglucose uptake (92.3% and 70.4% for the prednisone and combination therapy groups, respectively). Mycophenolate mofetil was well tolerated. Conclusions Mycophenolate mofetil in combination with prednisone for the treatment of CS may minimize corticosteroid exposure and decrease cardiac inflammation without significant adverse effects.

Background Patients with end-stage cardiomyopathy due to cardiac sarcoidosis (CS) may be referred for mechanical circulatory support (MCS) and heart transplantation (HT). We describe outcomes of patients with CS undergoing HT, focusing on the use of MCS as a bridge to transplant (BTT). Methods Using the United Network for Organ Sharing Scientific Registry of Transplant Recipients, we identified all adult waitlisted patients and isolated HT recipients from 2006 to 2015. These were divided into those with and without CS and further divided into those who did or did not receive MCS as BTT. Outcomes included 1- and 5-year post-transplantation freedom from mortality and 5-year freedom from primary graft failure. Results Over the study period, 31,528 patients were listed for HT, 148 (0.4%) of whom had CS. Among the CS patients, 34 (23%) received MCS as BTT. 18,348 patients (58%) eventually underwent HT, including 67 (0.4%) with CS, 20 (30%) of whom had received BTT MCS. Compared with non-CS diagnoses, CS patients had similar 1-year (91% vs 90%; log rank P = .88) and 5-year (83% vs 77%; log rank P = .46) freedom from mortality. Survival was also similar between CS BTT and non-CS BTT groups at 1 year (89% vs 89%; log-rank P = .92) and 5 years (72% vs 75%; log-rank P = .77). Conclusions Survivals after HT were similar between CS and non-CS patients out to 5 years, and were also similar between CS and non-CS BTT cohorts. Both HT and BTT MCS should be considered in patients with CS.

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It is 35 years since the first description of arrhythmogenic right ventricular cardiomyopathy (ARVC) and more than 20 years since the first reports establishing desmosomal gene mutations as a major cause of the disease. Early advances in the understanding of the clinical, pathological and genetic architecture of ARVC resulted in consensus diagnostic criteria, which proved to be sensitive but not entirely specific for the disease. In more recent years, clinical and genetic data from families and the recognition of a much broader spectrum of structural disorders affecting both ventricles and associated with a propensity to ventricular arrhythmia have raised many questions about pathogenesis, disease terminology and clinical management. In this paper, we present the conclusions of an expert round table that aimed to summarise the current state of the art in arrhythmogenic cardiomyopathies and to define future research priorities.

Introduction Cardiac sarcoidosis (CS) is characterized histologically by the presence of noncaseating granulomas and manifests as conduction abnormality, ventricular arrhythmia and progressive heart failure. With advances in imaging techniques, CS is being increasingly recognized as an underlying cause of cardiomyopathy. To date, there are no randomized trials or published guidelines to direct treatment strategies in CS, specifically in regards to optimal immunosuppressive therapy. We sought to describe our experience using a combination of prednisone and mycophenolate mofetil (MMF) in the treatment of patients (pts) with CS. Methods We retrospectively identified pts with CS who received either prednisone monotherapy or combination therapy with MMF. Outcomes assessed were response to immunosuppression based on occurrence of post-treatment ventricular arrhythmias, change in left ventricular ejection fraction (LVEF) on echocardiogram (recovery defined as LVEF ≥ 50%, improvement defined as any increase in LVEF) and change in inflammation on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). Results Thirty-seven pts with CS were identified, 9 of whom were classified as having isolated CS. A total of 25 pts (51.5 ± 11.4 yrs old, 40% female, 40% African American (AA)) were treated with combination therapy: 16 were initiated on MMF within 60 days of prednisone and 9 greater than 60 days after prednisone. Twelve pts (57.2 ± 8.8 yrs old, 50% female, 42% AA) were treated with prednisone only. The combination therapy group, when compared to the prednisone only group, were sicker at presentation and more commonly presented with ventricular tachycardia (VT) (8/25, 32% vs 1/12, 8% respectively), advanced AV block (7/25, 28% vs 2/12, 16.7%) and EF Conclusion We found that patients with severe CS appear to respond well to combination therapy with prednisone and MMF, with more than half having improvement in LV function and two-thirds showing improvement in FDG uptake. Those with severe LV dysfunction at treatment initiation however, are less likely to recover LV function. Our experience suggests that MMF is an effective steroid-sparing therapy in patients with CS.

Sex hormones are linked to right ventricular (RV) function, but the relationship between genetic variation in these pathways and RV function is unknown.We performed a cross-sectional study of 2761 genotyped adults without cardiovascular disease. The relationships between RV measures and single nucleotide polymorphisms (SNPs) in 10 candidate genes were assessed. Urinary oestradiol (E2) metabolites produced by cytochrome P4501B1 (CYP1B1) and serum testosterone were measured in women and men respectively.In African-American (AA) women, the CYP1B1 SNP rs162561 was associated with RV ejection fraction (RVEF), such that each copy of the A allele was associated with a 2.0% increase in RVEF. Haplotype analysis revealed associations with RVEF in AA (global p−6) and white (global p=0.05) women. In white subjects, higher E2 metabolite levels were associated with significantly higher RVEF. In men, androgen receptors SNPs (rs1337080; rs5918764) were significantly associated with all RV measures and modified the relationship between testosterone and RVEF.Genetic variation in E2 metabolism and androgen signalling was associated with RV morphology in a sex-specific manner. The CYP1B1 SNP identified is in tight linkage disequilibrium with SNPs associated with pulmonary hypertension and oncogenesis, suggesting these pathways may underpin sexual dimorphism in RV failure.

We are grateful for the 2 thoughtful letters concerning our recent article1 on the ECG features of arrhythmogenic right ventricular dysfunction (ARVD). Because ECGs are widely available and inexpensive, it important for those interested in this field to fully explore the diagnostic and prognostic potential of 12-lead ECGs. There were 3 main issues raised in these letters. The first concerned whether our control population was appropriate. As noted in our article, our study included 2 control populations. The first was a series of 27 patients who were evaluated in the ARVD clinic because of a first- or second-degree relative with ARVD. Each of these patients underwent a comprehensive evaluation to screen for ARVD, including an ECG, signal-averaged ECG, Holter, magnetic resonance imaging, and stress testing. The second control population was a series of 30 patients with a right bundle-branch block ECG pattern who did not have relatives with ARVD and were not being evaluated in our ARVD clinic. …

Background— The purpose of this study was to reevaluate the ECG features of arrhythmogenic right ventricular dysplasia (ARVD). The second objective was to evaluate the sensitivity and specificity of the standard and newly proposed diagnostic ECG markers in the presence of a right bundle-branch block (RBBB). Methods and Results— One hundred patients with ARVD (57 men; aged 39±15 years) and 57 controls (21 men; aged 40±17 years) were included. Among the 100 patients with ARVD, a complete RBBB was present in 17 patients, and 15 patients had an incomplete RBBB. T-wave inversion through V 3 demonstrated optimal sensitivity and specificity in both ARVD patients without a complete RBBB or incomplete RBBB (71% [95% confidence interval, 58% to 81%] and 96% [95% confidence interval, 81% to 100%], respectively) and in ARVD patients with incomplete RBBB (73% [95% confidence interval, 45% to 92%] and 95% [95% confidence interval, 77% to 100%], respectively). Between ARVD patients and controls with a complete RBBB, the only 2 parameters that differed were the prevalence of T-wave inversion through V 4 (59% versus 12%, respectively; P 1 P Conclusions— We evaluated comprehensively the diagnostic value of ECG markers for ARVD. On the basis of the findings, we propose an algorithm, with examination of QRS morphology being the first step, for ECG evaluation of ARVD patients. Definite criteria are then applied on the basis of the presence of no RBBB, incomplete RBBB, and complete RBBB to obtain the best diagnostic utility of the ECG.