Background An enhanced inflammatory response predicts worse outcomes in heart failure (HF). We hypothesized that administration of Interleukin-1 (IL-1) receptor antagonist (anakinra) could inhibit the inflammatory response and improve peak aerobic exercise capacity in patients with recently decompensated systolic HF. Methods and Results We randomly assigned 60 patients with reduced left ventricular ejection fraction (<50%) and elevated C-reactive protein (CRP) levels (>2 mg/L), within 14 days of hospital discharge, to daily subcutaneous injections with anakinra 100 mg for 2 weeks, 12 weeks, or placebo. Patients underwent measurement of peak oxygen consumption (VO2 [mL•kg−1•min−1]) and ventilatory efficiency (the VE/VCO2 slope). Treatment with anakinra did not affect peak VO2 or VE/VCO2 slope at 2 weeks. At 12 weeks, patients continued on anakinra showed an improvement in peak VO2 from 14.5 [10.5–16.6] to 16.1 [13.2–18.6] mL•kg−1•min−1 (P=0.009 for within-group changes), whereas no significant changes occurred within the anakinra 2-week or placebo groups. The between groups differences, however, were not statistically significant. The incidence of death or re-hospitalization for HF at 24 weeks was 6%, 31%, and 30%, in the anakinra 12-week, anakinra 2-week and placebo groups, respectively (Log-rank test P=0.10). Conclusions No change in peak VO2 occurred at 2 weeks in patients with recently decompensated systolic HF treated with anakinra, whereas an improvement was seen in those patients in whom anakinra was continued for 12 weeks. Additional larger studies are needed to validate the effects of prolonged anakinra on peak VO2 and re-hospitalization for HF.

Purpose of Review-In this state-of-the-art review, we highlight our current understanding of diagnosis, assessment, and management of cardiac sarcoidosis (CS), focusing on recently published data and expert consensus statement guidelines. Recent Findings-Academic interest in cardiac sarcoidosis research has increased over the past decade along with increased clinical awareness among clinicians. In 2014, the Heart Rhythm Society published the first expert consensus statement on diagnosing and managing arrhythmias associated with CS. Cardiac magnetic resonance has emerged as a valuable tool both for diagnosing CS and predicting risk of life-threatening ventricular arrhythmias based on burden of late gadolinium enhancement. Cardiac fluorodeoxyglucose-positron emission tomography now plays a role in diagnosis, risk stratification, and assessing response to immunosuppressive therapy. Summary-Collaborative, multidisciplinary research efforts are needed to further our understanding of this rare, complex disease. Two large multicenter prospective registries-the international Cardiac Sarcoidosis Consortium and the Canadian Cardiac Sarcoidosis Research Group-are enrolling patients to help provide insights into the natural history of the disease and current treatment strategies. Future research should focus on randomized controlled trials comparing different treatment strategies and identifying and testing novel therapeutic agents.

IMPORTANCE Ventricular tachycardia (VT) is associated with high mortality in patients with cardiac sarcoidosis (CS), and medical management of CS-associated VT is limited by high failure rates. The role of catheter ablation has been investigated in small, single-center studies.OBJECTIVE To investigate outcomes associated with VT ablation in patients with CS. DESIGN, SETTING, AND PARTICIPANTSThis cohort study from the Cardiac Sarcoidosis Consortium registry (2003-2019) included 16 tertiary referral centers in the US, Europe, and Asia. A total of 158 consecutive patients with CS and VT were included (33% female; mean [SD] age, 52 [11] years; 53% with ejection fraction [EF] <50%).EXPOSURES Catheter ablation of CS-associated VT and, as appropriate, medical treatment. MAIN OUTCOMES AND MEASURESImmediate and short-term outcomes included procedural success, elimination of VT storm, and reduction in defibrillator shocks. The primary long-term outcome was the composite of VT recurrence, heart transplant (HT), or death. RESULTSComplete procedural success (no inducible VT postablation) was achieved in 85 patients (54%). Sixty-five patients (41%) had preablation VT storm that did not recur postablation in 53 (82%). Defibrillator shocks were significantly reduced from a median (IQR) of 2 (1-5) to 0 (0-0) in the 30 days before and after ablation (P < .001). During median (IQR) follow-up of 2.5 (1.1-4.9) years, 73 patients (46%) experienced VT recurrence and 81 (51%) experienced the composite primary outcome. One-and 2-year rates of survival free of VT recurrence, HT, or death were 60% and 52%, respectively. EF less than 50% and myocardial inflammation on preprocedural 18 F-fluorodeoxyglucose positron emission tomography were significantly associated with adverse prognosis in multivariable analysis for the primary outcome (HR, 2.24; 95% CI, 1.37-3.64; P = .001 and HR, 2.93; 95% CI, 1.31-6.55; P = .009, respectively). History of hypertension was associated with a favorable long-term outcome (adjusted HR, 0.51; 95% CI, 0.28-0.92; P = .02). CONCLUSIONS AND RELEVANCEIn this observational study of selected patients with CS and VT, catheter ablation was associated with reductions in defibrillator shocks and recurrent VT storm. Preablation LV dysfunction and myocardial inflammation were associated with adverse long-term prognosis. These data support the role of catheter ablation in conjunction with medical therapy in the management of CS-associated VT.

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Hospital admission for decompensated heart failure (HF) marks a critical inflection point in a patient’s health. Despite the improvement in signs/symptoms during hospitalization, patients have a high likelihood of readmission, reflecting a lack of resolution of the underlying condition. Surprisingly no studies have characterized the cardiorespiratory fitness (CRF) of such patients. Fifty-two patients (38 [73%] male, age 57 [52–65] years, left-ventricular ejection fraction 31% [24–38]) underwent cardiopulmonary exercise testing (CPX) 4 (1–10) days after hospital discharge, when stable and without overt signs of volume overload. Transthoracic Doppler echocardiography, measurement of N-terminal pro-B-natriuretic peptide (NT-proBNP), and quality of life were also assessed. Aerobic exercise capacity was severely reduced: peak oxygen consumption (pVO2) was 14.1 (11.2–16.3) mL•kg−1•min−1. Ventilatory inefficiency as indicated by the minute ventilation carbon dioxide production relationship (VE/VCO2 slope) >30 and oxygen uptake efficiency slope (OUES) <2.0 was noted in 41 (77%) and 39 (75%) patients, respectively. Forty-five (87%) of patients had one of two high-risk features (pVO2 <14 mL•kg−1•min−1 or VE/VCO2 >30). Perceived functional capacity, measured by the Duke Activity Status Index (DASI) was also severely reduced, and correlated with pVO2. NT-proBNP levels and early transmitral velocity/early mitral annulus velocity (E/e′) ratio at echocardiography showed a modest correlation with lower pVO2. In conclusion, patients with recently decompensated systolic HF demonstrate severe impairment in cardiorespiratory fitness severely limiting quality of life.