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Sarcoidosis is a multisystem disorder of unknown etiology. The leading hypothesis involves an antigen-triggered dysregulated T-cell-driven immunologic response leading to non-necrotic granulomas. In cardiac sarcoidosis (CS), the inflammatory response can lead to fibrosis, culminating in clinical manifestations such as atrioventricular block and ventricular arrhythmias. Cardiac manifestations frequently present as first and isolated signs or may appear in conjunction with extracardiac manifestations. The incidence of sudden cardiac death (SCD) is high. Diagnosis remains a challenge. For a definite diagnosis, endomyocardial biopsy (EMB) is suggested. In clinical practice, compatible findings in advanced imaging using cardiovascular magnetic resonance (CMR) and/or positron emission tomography (PET) in combination with extracardiac histological proof is considered sufficient. Management revolves around the control of myocardial inflammation by employing immunosuppression. However, data regarding efficacy are merely based on observational evidence. Prevention of SCD is of particular importance and several guidelines provide recommendations regarding device therapy. In patients with manifest CS, outcome data indicate a 5-year survival of around 90% and a 10-year survival in the range of 80%. Data for patients with silent CS are conflicting; some studies suggest an overall benign course of disease while others reported contrasting observations. Future research challenges involve better understanding of the immunologic pathogenesis of the disease for a targeted therapy, improving imaging to aid early diagnosis, assessing the need for screening of asymptomatic patients and randomized trials. [ABSTRACT FROM AUTHOR]

Background: Decision-making in primary prevention is not always trivial and many clinical scenarios are not reflected in current guidelines. To help evaluate a patient's individual risk, a new score to predict the benefit of an implantable defibrillator (ICD) for primary prevention, the MADIT-ICD benefit score, has recently been proposed. The score tries to predict occurrence of ventricular arrhythmias and non-arrhythmic death based on data from four previous MADIT trials. We aimed at examining its usefulness in a large single-center register of S-ICD patients with various underlying cardiomyopathies. Methods and results: All S-ICD patients with a primary preventive indication for ICD implantation from our large single-center database were included in the analysis (n = 173). During a follow-up of 1227 ± 978 days, 27 patients developed sustained ventricular arrhythmias, while 6 patients died for non-arrhythmic reasons. There was a significant correlation for patients with ischemic cardiomyopathy (ICM) (n = 29, p = 0.04) to the occurrence of ventricular arrhythmia. However, the occurrence of ventricular arrhythmias could not sufficiently be predicted by the MADIT-ICD VT/VF score (p = 0.3) in patients with (n = 142, p = 0.19) as well as patients without structural heart disease (n = 31, p = 0.88) and patients with LV-EF < 35%. Of the risk factors included in the risk score calculation, only non-sustained ventricular tachycardias were significantly associated with sustained ventricular arrhythmias (p = 0.02). Of note, non-arrhythmic death could effectively be predicted by the proposed non-arrhythmic mortality score as part of the benefit score (p = 0.001, r = 0.3) also mainly driven by ICM patients. Age, diabetes mellitus, and a BMI < 23 kg/m2 were key predictors of non-arrhythmic death implemented in the score. Conclusion: The MADIT-ICD benefit score adds a new option to evaluate expected benefit of ICD implantation for primary prevention. In a large S-ICD cohort of primary prevention, the value of the score was limited to patients with ischemic cardiomyopathy. Future research should evaluate the performance of the score in different subgroups and compare it to other risk scores to assess its value for daily clinical practice. [ABSTRACT FROM AUTHOR]

Syncopes are a very common phenomenon and have a high recurrence rate. The differentiation between the psychogenic and physical, especially of arrhythmic origin, remains difficult. In many cases, an implantable loop recorder is used for the detection of possible arrhythmias, leading to syncopes. Yet, the existing literature suggests that psychological factors may play a significant role in recurrent syncopes. We aimed at analyzing the potential role of several psychological factors on the recurrence of arrhythmic or non-arrhythmic syncopes. Methods and results: A total of 119 patients, who had received an implantable loop recorder for recurrent syncopes at our center between 01/2018 and 12/2021, participated in this retrospective cohort study. Anxiety, depression and quality of life were assessed using extensively validated questionnaires (GAD-7, PHQ-9 and SF-12). The mean follow-up after loop recorder implantation was 710 ± 430 days and 50% of patients were female. The mean patient age was 54.8 ± 18.6 years. Most patients had no evidence of structural heart disease (84%), and normal LV function (92%). A statistical analysis revealed that the presence of structural heart disease was the strongest predictor for arrhythmic syncope during follow-up. In patients with non-arrhythmic syncopes, we found significantly higher levels of anxiety (GAD-7 score: 2.5 ± 2.6 vs. 4.8 ± 4.3) and depression (PHQ-9 score: 3.9 ± 3.6 vs. 6.8 ± 5.1), and a lower quality of life (SF-12 score: 33.7 ± 6.4 vs. 29.6 ± 7.8). Discussion: We identified factors as contributors to a better identification of patients at risk for arrhythmic as well as non-arrhythmic syncopes. Especially anxious or depressive symptoms may hinted at non-arrhythmic causes of syncope. However, the study was limited by its retrospective design and low patient number. Further trials should likewise combine the diagnostic yield of loop recorders with psychometric evaluations before implantation and combine it with additional diagnostic measures, such as video monitoring, to further examine the role of psychological factors in the pathomechanism and treatment of syncope. [ABSTRACT FROM AUTHOR]

Introduction: Transesophageal echocardiography (TEE) is routinely performed before catheter ablation of atrial tachyarrhythmias to rule out the presence of left atrial thrombi. However, data to support this practice are inconsistent. Methods: We analyzed consecutive pre-procedural TEE in a high-volume electrophysiology center for the presence of left atrial thrombi and a relevant flow reduction in the left atrial appendage (LAA) defined as LAA sludge or LAA emptying velocity (LAAEV) < 20 cm/s. The possible predictors of reduced flow were recorded and compared in a multivariate logistic regression analysis. Results: 1676 TEE were included (1122 before pulmonary vein isolation, 436 before atrial flutter ablation, 166 before other ablations). 543 patients (32%) were female and 991 (59%) were on DOAC. Nine patients (0.5%) had an LAA thrombus on pre-procedural TEE. Ninety-five further patients (5.7%) had a relevant reduction in LAA flow. The underlying rhythm showed a significant association with the presence of LAA thrombus or reduced LAA flow (p = 0.003). Patients in sinus rhythm and cavotricuspid isthmus-dependent atrial flutter exhibited the lowest risk. Additionally, reduced kidney function was associated with a reduction in LAA flow velocities (p = 0.04). Of note, two LAA thrombi occurred in patients in sinus rhythm and six out of nine patients with an LAA thrombus were on vitamin-K antagonists. Conclusions: LAA thrombus is a rare occurrence before an elective catheter ablation. The underlying rhythm and kidney function may serve as markers of a higher likelihood of significantly reduced LAAEV and LAA thrombus. [ABSTRACT FROM AUTHOR]

Background: Different electrocardiogram (ECG) findings are known to be independent predictors of clinical response to cardiac resynchronization therapy (CRT). It remains unknown how these findings influence very long-term prognosis. Methods and Results: A total of 102 consecutive patients (75 males, mean age 65 ± 10 years) referred to our center for CRT implantation had previously been included in this prospective observational study. The same patient group was now re-evaluated for death from all causes over a prolonged median follow-up of 10.3 years (interquartile range 9.4–12.5 years). During follow-up, 55 patients died, and 82% of the clinical non-responders (n = 23) and 44% of the responders (n = 79) were deceased. We screened for univariate associations and found QRS width during biventricular (BIV) pacing (p = 0.02), left ventricular (LV) pacing (p < 0.01), Δ LV paced–right ventricular (RV) paced (p = 0.03), age (p = 0.03), New York Heart Association (NYHA) class (p < 0.01), CHA2DS2-Vasc score (p < 0.01), glomerular filtration rate (p < 0.01), coronary artery disease (p < 0.01), non-ischemic cardiomyopathy (NICM) (p = 0.01), arterial hypertension (p < 0.01), NT-proBNP (p < 0.01), and clinical response to CRT (p < 0.01) to be significantly associated with mortality. In the multivariate analysis, NICM, the lower NYHA class, and smaller QRS width during BIV pacing were independent predictors of better outcomes. Conclusion: Our data show that QRS width duration during biventricular pacing, an ECG parameter easily obtainable during LV lead placement, is an independent predictor of mortality in a long-term follow-up. Our data add further evidence that NICM and lower NYHA class are independent predictors for better outcome after CRT implantation. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of a combination of ranolazine with different selective inhibitors of the Na+/Ca2+-exchanger (NCX) in an established experimental model of atrial fibrillation (AF). Eighteen hearts of New Zealand white rabbits were retrogradely perfused. Atrial catheters were used to record monophasic action potentials (aPRR). Hearts were paced at three different cycle lengths. Thereby, atrial action potential durations (aAPD90), atrial effective refractory periods (aERP) and atrial post-repolarization refractoriness were obtained. Isoproterenol and acetylcholine were employed to increase the occurrence of AF. Thereafter, the hearts were assigned to two groups (n = 9 each group) and additionally perfused with a combination of 10 µM ranolazine and 1 µM of the selective NCX-inhibitor ORM-10103 (group A: Rano-ORM) or 10 µM ranolazine and 1 µM of another NCX-inhibitor, SEA0400 (group B: Rano-SEA). The infusion of Iso/ACh led to a shortening of aAPD90, aERP, aPRR and the occurrence of AF episodes was significantly increased. Additional perfusion with ranolazine and ORM-10103 (group A) significantly prolonged the refractory periods and aPRR and AF episodes were effectively reduced. In group B, Rano-SEA led to a slight decrease in aAPD90 while aERP and aPRR were prolonged. The occurrence of AF episodes was consecutively reduced. To our knowledge, this is the first study investigating the effect of ranolazine combined with different selective NCX-inhibitors in an isolated whole-heart model of AF. Both combinations prolonged aERP and aPRR and thereby suppressed the induction of AF. [ABSTRACT FROM AUTHOR]