BACKGROUND:Cardiac Resynchronisation Therapy (CRT) has demonstrated short and long-term benefit in heart failure with reduced ejection fraction (HFrEF), including ischaemic (ICM) and non-ischaemic cardiomyopathy. However, there is a paucity of evidence regarding its role in cardiac sarcoidosis (CS). METHODS:Consecutive CS patients with CRT and baseline left ventricle ejection fraction (LVEF)≤40 referred to one specialist hospital in London between November 2008-March 2023 were retrospectively reviewed. The baseline characteristics, short-term echocardiographic, clinical parameters and long-term primary and secondary outcomes were compared against a cohort of ICM patients with CRT and baseline LVEF≤40. Patients with incomplete follow-up were excluded. The primary endpoint was a composite of all-cause mortality, cardiac transplantation or heart failure hospitalisation. Secondary endpoint included ventricular arrhythmic events. RESULTS:63 CS and 93 ICM patients were analysed. A greater proportion of ICM patients male with older ages overall (both p < 0.01), whereas a larger proportion of CS patients had atrioventricular block and heart failure hospitalisations (both p < 0.01). Both cohorts demonstrated significant serial increase in left ventricular (LV) ejection fraction and reduction in LV end-systolic and end-diastolic volumes (p < 0.01). After a mean follow up of 40.9 (±32.0) months, the primary and secondary endpoint was reached by significantly more CS patients (log-rank p = 0.008 and log-rank p = 0.004). Age (HR: 1.12 (95 %CI 1.06-1.17, p < 0.001) and presence of CS (HR: 8.33 (95 %CI 3.03-22.93, p < 0.001) were independent predictors of the primary endpoint on multivariable analysis. CONCLUSION:CS patients with CRT demonstrated reverse remodelling, but had adverse long-term primary and secondary outcomes when compared to ICM patients.

AbstractAimsIn cardiac sarcoidosis (CS) patients, the benefit of cardiac resynchronization therapy (CRT) remains unclear. We sought to assess the short‐term and long‐term effects of CRT in CS patients with a range of left ventricular (LV) ejection fractions (LVEFs).MethodsConsecutive CS patients with heart failure with reduced ejection fraction (HFrEF; LVEF ≤ 40%), mildly reduced ejection fraction (HFmrEF; LVEF 41%–49%) and preserved ejection fraction (HFpEF; LVEF ≥ 50) treated with CRT under the care of a tertiary UK centre between 2008 and 2023 were reviewed. CRT response was defined by >5% improvement in serial LVEF. The primary endpoint was a composite of all‐cause mortality, cardiac transplantation or unplanned hospitalization for decompensated heart failure. The secondary endpoint included ventricular arrhythmic events.ResultsOf the 100 patients enrolled (age 58 ± 10 years; 71% male), 63 had HFrEF, 17 had HFmrEF and 20 had HFpEF. After short‐term follow‐up (9.8 ± 5.4 months), HFrEF patients demonstrated significant LVEF response (P < 0.01). On Kaplan–Meier analysis (follow‐up 38 ± 32 months), HFrEF non‐responders had significantly worse event‐free survival compared with HFrEF responders for the primary (P < 0.001) and secondary (P = 0.001) endpoints. Despite short‐term LV function improvement, CRT responders still had worse event‐free survival compared with HFmrEF/HFpEF patients for the primary endpoint (P < 0.001). On multivariable Cox analysis, age [hazard ratio (HR) 1.05, 95% confidence interval (CI) 1.01–1.10, P = 0.008] and HFrEF CRT non‐response (HR 12.33, 95% CI 2.45–61.87, P = 0.002) were associated with the primary endpoint.ConclusionsIn CS patients with HFrEF, CRT response is associated with a better long‐term prognosis than non‐response. However, HFrEF CRT responders still have worse long‐term prognosis than HFmrEF/HFpEF patients.

Introduction: In patients with cardiac sarcoidosis (CS), implantable cardioverter-defibrillators (ICDs) are important for preventing sudden cardiac death. This study aimed to investigate sex disparities in CS patients undergoing ICD implantation. Methods: The 2016-2020 National Inpatient Sample (NIS) database compared the characteristics and outcomes of males and females with CS receiving ICDs. Results: Among 760 CS patients who underwent inpatient ICD implantation, 66.4% were male. Males were younger (55.0 vs. 56.9 years, p < .01), had higher rates of diabetes (31.7% vs. 21.6%, p < .01) and chronic kidney disease (CKD) (16.8% vs. 7.8%, p < .01) but lower prevalence of atrial fibrillation (AF) (11.9% vs. 23.5%, p < .01), sick sinus syndrome (4.0% vs. 7.8%, p = .024), ventricular fibrillation (VF) (9.9% vs. 15.7%, p = .02), and black ancestry (31.9% vs. 58.0%, p < .01). Unadjusted major adverse cardiovascular events (MACE), defined as a composite of in-hospital death, myocardial infarction (MI), and ischemic stroke, was higher in females (11.8% vs. 6.9%, p = .024), but when adjusted for age and tCharlson Comorbidity Index (CCI), females demonstrated significantly lower odds of experiencing MACE (aOR: 0.048, 95% CI: 0.006-0.395, p = .005). Incidence of acute kidney injury (AKI) post-ICD was significantly lower in females (15.7% vs. 23.8%, p = .01) as was the adjusted odds (aOR: 0.282, 95% CI: 0.146-0.546, p < .01). There was comparable mean length of stay and hospital charges. ConclusionI: CD utilization in CS patients is more common among males, who have a higher prevalence of diabetes and CKD but a lower prevalence of AF, sick sinus syndrome, and VF. Adjusted MACE and AKI were significantly lower in females.

Background: Cardiac sarcoidosis (CS) may vary in its clinical presentation and outcome. This study aimed to evaluate the mode of presentation, prognosis and predictors of outcome among a contemporary cohort of CS patients.Methods and Results: This was a retrospective study of consecutive patients with CS based on Heart Rhythm Society criteria. Patients were divided into those with new cardiac involvement of previously diagnosed extra-cardiac sarcoidosis (Group A) and those with cardiac disease as the first manifestation of previously undetected systemic sarcoidosis (Group B). The composite endpoint consisted of all-cause mortality, aborted sudden cardiac death, ventricular arrhythmia, heart failure hospitalisation and cardiac transplantation. A total of 319 CS patients were studied (67% male, 55.4±12 years old); Group B patients had a 3-fold higher prevalence of ventricular arrhythmias, higher brain natriuretic peptide (BNP), lower left ventricular ejection fraction (LVEF) and higher proportion of abnormal cardiac magnetic resonance and fluorodeoxyglucose positron emission tomography (FDG-PET) scans than group A patients. During follow-up of 3.0±2.4 years, group B patients had a similar mortality rate, but higher annualized composite event rate of 13.9% compared to 6% for group A (p<0.0001). Multivariate analysis of the whole cohort showed BNP (HR:2.41, [95%CI 1.34–4.31] p=0.003), LVEF (HR:0.96, [95%CI 0.94-0.98] p<0.0001) and SUVmax (HR:1.11, [95%CI 1.04-1.19] p=0.001) to be independent predictors of adverse outcome.Conclusion: Cardiac sarcoidosis is associated with significant morbidity and mortality, particularly in those with cardiac involvement as the first manifestation. Higher BNP, lower LVEF and more intense myocardial inflammation were predictors of poor outcome.

Introduction: Risk stratification in cardiac sarcoidosis (CS) remains challenging, especially in those with preserved left ventricular ejection fraction (LVEF). Myocardial strain parameters are more sensitive than LVEF for detecting early sub-clinical myocardial dysfunction, but their prognostic value in CS is not known. Methods: We investigated consecutive newly diagnosed CS patients between 2015 and 2018. All patients underwent 2D echocardiography including global longitudinal strain (GLS) and global circumferential strain (GCS) measurement, cardiac magnetic resonance (CMR) for late gadolinium enhancement (LGE) and FDG-PET imaging to derive the maximum standard uptake value (SUVmax). The LGE score was quantified as the number of myocardial segments with LGE. Major adverse cardiac events (MACE) were all-cause death, sustained ventricular arrhythmia (VA), device implantation and new onset heart failure (HF) admission. Results: A total of 120 patients were included with age of 55±12 years; 87% were Caucasian, 43% had hypertension and 13% had diabetes. Mean LVEF was 55±12.3%, GLS was -13.4±4.2%, GCS was -16.0±5.6% and regional wall motion abnormalities (RWMA) occurred in 36% of cases. During median follow-up of 4.3 years, 43 patients experienced MACE consisting of 15 deaths, 19 VAs, 7 devices and 2 HF admissions. In multivariate analysis syncope, ethnicity, echo-derived left atrial volume and RWMA were independent predictors of MACE along with CMR-derived right ventricular EF and LGE score. Although GLS and GCS were lower in those with MACE, neither had independent prognostic value. SUVmax was also not predictive of events. In a subgroup analysis of the 86 patients with LVEF ≥50%, 20 patients experienced MACE. Multivariate analysis showed non-Caucasian ethnicity (HR 3.18 [95% CI 1.02-9.88]; P = 0.04), RWMA (HR 3.76 [95% CI 1.29-10.98]; P = 0.02), LGE-score (HR 1.26 95% CI 1.05-1.51]; P = 0.01 and GCS (HR 1.18 [95% CI 1.04-1.36]; P = 0.01) were independent predictors of MACE. A GCS value above the optimal cut-off of -16.4% was associated with a worse outcome (log-rank P = 0.005). Conclusion Ethnicity, RWMA and LGE-score are robust markers of outcome in newly diagnosed CS. Reduced GCS provides additional prognostic information in those with preserved LVEF.

Introduction: Sacubitril/Valsartan is an established treatment for heart failure patients with reduced ejection fraction (HFrEF). However, there is a paucity of data on its use in patients with cardiac sarcoidosis (CS). Hypothesis To establish the beneficial role of Sacubitril/Valsartan in cardiac sarcoidosis. Methods All consecutive CS patients taking Sacubitril/Valsartan were identified from our database from 2016 to 2022. They were followed up for at least 6 months with serial echocardiography. Data regarding symptoms and echocardiographic parameters were compared using Wilcoxon signed rank test. Results A total of 30 CS patients taking Sacubitril/Valsartan were identified (mean age: 56.73±11.63 years old). The diagnosis of CS was determined in all patients by a multi-disciplinary team. Patients were male predominant (73.3%). The prevalence of smoking, diabetes, hypertension and ischaemic heart disease was 20%, 10%, 10% and 3.3% respectively. Beta-blockers, mineralocorticoid receptor antagonists, prednisolone, implantable cardioverter defibrillator and cardiac resynchronisation therapy (defibrillator) were present in 93.3%, 96.7%, 53.3%, 16.7% and 56.7% patients respectively. At the time of diagnosis, 24 (80%) patients were found to have active cardiac sarcoidosis on cardiac PET. At 6-months following the commencement of Sacubitril/Valsartan, there was a significant improvement in LV ejection fraction (38.77±10.26% vs 32.87±9.30%, p<0.001), LV end-systolic diameter (4.89±1.06cm vs 5.14±1.07cm, p=0.013) and New York Heart Association class (1.6±0.55 vs 2.0±0.52, p=0.001). During the median follow up of 24.9 months, the composite end-point of death and cardiac transplantation was reached in 3 (10%) patients (3 deaths and 0 cardiac transplantation). The patients experiencing at least one sustained ventricular arrhythmia (or aborted sudden cardiac death) decreased from 9 to 7 (p=0.21), the mean prednisolone dose was also comparable (11.56±4.42 vs 10.28±3.71, p=0.50) and none of the patients stopped Sacubitril/Valsartan. Conclusions Sacubitril/Valsartan in cardiac sarcoidosis patients with HFrEF is associated with at least short-term improvements in LV remodelling and functional status.