Cardiac Sarcoidosis-Diagnostic and Therapeutic Challenges.

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.

Relevance of mexiletine in the era of evolving antiarrhythmic therapy of ventricular arrhythmias.

Despite impressive developments in the field of ventricular arrhythmias, there is still a relevant number of patients with ventricular arrhythmias who require antiarrhythmic drug therapy and may, e.g., in otherwise drug and/or ablation refractory situations, benefit from agents known for decades, such as mexiletine. Through its capability of blocking fast sodium channels in cardiomyocytes, it has played a minor to moderate antiarrhythmic role throughout the recent decades. Nevertheless, certain patients with structural heart disease suffering from drug-refractory, i.e., mainly amiodarone refractory ventricular arrhythmias, as well as those with selected forms of congenital long QT syndrome (LQTS) may nowadays still benefit from mexiletine. Here, we outline mexiletine's cellular and clinical electrophysiological properties. In addition, the application of mexiletine may be accompanied by various potential side effects, e.g., nausea and tremor, and is limited by several drug-drug interactions. Thus, we shed light on the current therapeutic role of mexiletine for therapy of ventricular arrhythmias and discuss clinically relevant aspects of its indications based on current evidence.

Antiarrhythmic Treatment in Heart Failure.

PURPOSE OF REVIEW: Arrhythmias are common in patients with heart failure (HF) and are associated with a significant risk of mortality and morbidity. Optimal antiarrhythmic treatment is therefore essential. Here, we review current approaches to antiarrhythmic treatment in patients with HF. RECENT FINDINGS: In atrial fibrillation, rhythm control and ventricular rate control are accepted therapeutic strategies. In recent years, clinical trials have demonstrated a prognostic benefit of early rhythm control strategies and AF catheter ablation, especially in patients with HF with reduced ejection fraction. Prevention of sudden cardiac death with ICD therapy is essential, but optimal risk stratification is challenging. For ventricular tachycardias, recent data support early consideration of catheter ablation. Antiarrhythmic drug therapy is an adjunctive therapy in symptomatic patients but has no prognostic benefit and well-recognized (proarrhythmic) adverse effects. Antiarrhythmic therapy in HF requires a systematic, multimodal approach, starting with guideline-directed medical therapy for HF and integrating pharmacological, device, and interventional therapy.

Lidocaine as an anti-arrhythmic drug: Are there any indications left?

Lidocaine is classified as a class Ib anti-arrhythmic that blocks voltage- and pH-dependent sodium channels. It exhibits well investigated anti-arrhythmic effects and has been the anti-arrhythmic of choice for the treatment of ventricular arrhythmias for several decades. Lidocaine binds primarily to inactivated sodium channels, decreases the action potential duration, and increases the refractory period. It increases the ventricular fibrillatory threshold and can interrupt life-threatening tachycardias caused by re-entrant mechanisms, especially in ischemic tissue. Its use was pushed into the background in the era of amiodarone and modern electric device therapy. Recently, lidocaine has come back into focus for the treatment of acute sustained ventricular tachyarrhythmias. In this brief overview, we review the clinical pharmacology including possible side effects, the historical course, possible indications, and current Guideline recommendations for the use of lidocaine.

Predictors for major in-hospital complications after catheter ablation of ventricular arrhythmias: validation and modification of the Risk in Ventricular Ablation (RIVA) Score.

OBJECTIVE AND BACKGROUND: Catheter-based treatment of patients with ventricular arrhythmias (VA) reduces VA and mortality in selected patients. With regard to potential risks of catheter ablation, a benefit-risk assessment should be carried out. This can be performed with risk scores such as the recently published "Risk in Ventricular Ablation (RIVA) Score". We sought to validate this score and to test for possible additional predictors in a large database of VT ablations. METHODS AND RESULTS: We analyzed 1964 catheter ablations for VA in patients with (1069; 54.4%) and without (893, 45.6%) structural heart disease (SHD) and observed an overall major adverse event rate of 4.0% with an in-hospital mortality of 1.3% with significantly less complications occurring in patients without structural heart disease (6.5% vs. 1.1%; p ≤ 0.01). The RIVA Score demonstrated to be a valid predictive tool for major in-hospital complications (OR 1.18; 95% CI 1.12, 1.25; p ≤ 0.001). NYHA Class ≥ III (OR 2.5; 95% CI 1.5, 4.2; p < 0.001) and age (OR 1.04; 95% CI 1.02, 1.07; p ≤ 0.001) proved to be additional predictive parameters. Hence, a modified RIVA Score (mRIVA) model was analyzed with a subset of established predictors (SHD, eGFR, epicardial puncture) as well as new predictive parameters (age, NYHA Class ≥ III), that achieved a higher predictive value for major complications compared with the model based on all RIVA variables. CONCLUSION: Adding age and functional heart failure status (NYHA class) as simple clinical parameters to the recently published RIVA Score increases the predictive value for ablation-associated complications in a large VT ablations registry.

Management of Ventricular Arrhythmias Worldwide: Comparison of the Latest ESC, AHA/ACC/HRS, and CCS/CHRS Guidelines.

A new guideline for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death has been published by the European Society of Cardiology (ESC). Beside the 2017 American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guideline and the 2020 Canadian Cardiovascular Society/Canadian Heart Rhythm Society (CCS/CHRS) position statement, this guideline provides evidence-based recommendations for clinical practice. As these recommendations are periodically updated integrating the latest scientific evidence, there are similarities in many aspects. Nevertheless, notable differences in the recommendations can be found resulting from different scopes and publication years, differences in data selection, interpretation, and weighing, and regional factors such as differing drug availability. The aim of this paper is to compare specific recommendations to identify differences while acknowledging the commonalities and to provide an overview of the status of current recommendations with a special emphasis on gaps in evidence and future directions of research. Overall, the recent ESC guideline places a greater emphasis on the value of cardiac magnetic resonance, genetic testing in cardiomyopathies and arrhythmia syndromes, and the use of risk calculators for risk stratification. Further significant differences can be found regarding diagnostic criteria for genetic arrhythmia syndromes, the management of hemodynamically well-tolerated ventricular tachycardia, and primary preventive implantable cardioverter-defibrillator therapy.

Spotlight on the 2022 ESC guideline management of ventricular arrhythmias and prevention of sudden cardiac death: 10 novel key aspects.

Sudden cardiac death and ventricular arrhythmias are a global health issue. Recently, a new guideline for the management of ventricular arrhythmias and prevention of sudden cardiac death has been published by the European Society of Cardiology that serves as an update to the 2015 guideline on this topic. This review focuses on 10 novel key aspects of the current guideline: As new aspects, public basic life support and access to defibrillators are guideline topics. Recommendations for the diagnostic evaluation of patients with ventricular arrhythmias are structured according to frequently encountered clinical scenarios. Management of electrical storm has become a new focus. In addition, genetic testing and cardiac magnetic resonance imaging significantly gained relevance for both diagnostic evaluation and risk stratification. New algorithms for antiarrhythmic drug therapy aim at improving safe drug use. The new recommendations reflect increasing relevance of catheter ablation of ventricular arrhythmias, especially in patients without structural heart disease or stable coronary artery disease with only mildly impaired ejection fraction and haemodynamically tolerated ventricular tachycardias. Regarding sudden cardiac death risk stratification, risk calculators for laminopathies, and long QT syndrome are now considered besides the already established risk calculator for hypertrophic cardiomyopathy. Generally, 'new' risk markers beyond left ventricular ejection fraction are increasingly considered for recommendations on primary preventive implantable cardioverter defibrillator therapy. Furthermore, new recommendations for diagnosis of Brugada syndrome and management of primary electrical disease have been included. With many comprehensive flowcharts and practical algorithms, the new guideline takes a step towards a user-oriented reference book.

[ESC guideline 2022: management of ventricular arrhythmias in clinical practice]. / ESC-Leitlinie 2022: Management ventrikulärer Arrhythmien in der klinischen Praxis.

The recently published guideline of the European Society of Cardiology for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death updates the guideline from 2015. Overall, the current guideline is characterised by a great practical relevance: Illustrative algorithms, e.g., for diagnostic evaluation, and tables make the guideline a user-friendly reference book. In the diagnostic evaluation and risk stratification of sudden cardiac death, cardiac magnetic resonance imaging and genetic testing are significantly upgraded. In long-term management, the optimal treatment of the underlying disease is essential, and recommendations for heart failure therapy are adapted to current international guidelines. Catheter ablation is upgraded especially for patients with ischaemic cardiomyopathy and recurrent ventricular tachycardia, as well as in the management of symptomatic idiopathic ventricular arrhythmias. Criteria for primary prophylactic defibrillator therapy remain controversial. In the context of dilated cardiomyopathy, imaging, genetic testing, and clinical factors are given special weight in addition to left ventricular function. Additionally, revised diagnostic criteria for a large number of primary electrical diseases are provided.

[The new ESC guidelines on the management of ventricular tachyarrhythmias : Implications for daily practice]. / Die neue ESC-Leitlinie zum Management ventrikulärer Tachyarrhythmien : Was ist für die Praxis relevant?

The recently published guidelines of the European Society of Cardiology (ESC) on the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death is an update of the 2015 guideline. For the first time a new section is dedicated to public basic life support. In the acute treatment of ventricular arrhythmias electrical cardioversion is upgraded, and there is a new focus on the management of electrical storm. Recommendations for the comprehensive diagnostic evaluation of patients with first manifestations of ventricular arrhythmias structured according to common clinical scenarios are also new. Both genetic testing and cardiac magnetic resonance imaging are upgraded, not only for diagnostic evaluation but also for risk stratification. In the long-term management, recommendations for pharmacotherapy are aligned with current heart failure guidelines. Catheter ablation has gained relevance not only for recurrent ventricular tachycardia under amiodarone treatment and as an alternative to implantable cardioverter defibrillation (ICD) implantation in selected patients with coronary artery disease but also particularly in the treatment of idiopathic ventricular extrasystoles and tachycardia. The ICD treatment remains an essential component of primary and secondary prevention of sudden cardiac death. Of note, the recommendation on primary preventive ICD treatment for patients with dilated cardiomyopathy and left ventricular ejection fraction (LVEF) ≤ 35% has been downgraded. In addition to LVEF a combination of risk factors and risk calculators is included in the recommendations on primary prophylactic ICD implantation. Overall, due to numerous tables and practical algorithms, the guidelines have become a user-oriented reference book.

[From premature ventricular complexes to sustained ventricular tachycardia : An overview of innovations in the 2022 ESC Guideline on the therapy of ventricular arrhythmias]. / Von der Extrasystole zur anhaltenden Kammertachykardie : Neuerungen der ESC-Leitlinie 2022 zur Therapie ventrikulärer Arrhythmien im Überblick.

The recent 2022 European Society of Cardiology Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death are an update of the former 2015 European guidelines. With multiple tables, algorithms, and comprehensive integration of underlying study data, the new guideline is a user-oriented reference book for clinical practice that also covers special clinical situations such as cardiac arrhythmias in pregnancy or in the context of sports. Regarding the acute treatment of ventricular arrhythmias, cardioversion is now recommended in case of hemodynamically tolerated arrhythmias. Beyond that, the guideline places special emphasis on the management of the electrical storm. In long-term therapy, recommendations for drug therapy have been aligned with current heart failure guidelines. Catheter ablation of ventricular arrhythmias has gained importance not only for recurrent ventricular tachycardia under chronic amiodarone therapy and as an alternative to implantable cardioverter-defibrillators (ICDs) in selected patients with coronary artery disease, but especially for the treatment of idiopathic premature ventricular contractions and tachycardias. Risk stratification and criteria for primary preventive ICDs are still controversial topics, which are discussed in detail based on the specific disease entities.

Propofol abolishes torsade de pointes in different models of acquired long QT syndrome.

There is conflicting evidence regarding the impact of propofol on cardiac repolarization and the risk of torsade de pointes (TdP). The purpose of this study was to elucidate the risk of propofol-induced TdP and to investigate the impact of propofol in drug-induced long QT syndrome. 35 rabbit hearts were perfused employing a Langendorff-setup. 10 hearts were perfused with increasing concentrations of propofol (50, 75, 100 µM). Propofol abbreviated action potential duration (APD90) in a concentration-dependent manner without altering spatial dispersion of repolarization (SDR). Consequently, no proarrhythmic effects of propofol were observed. In 12 further hearts, erythromycin was employed to induce prolongation of cardiac repolarization. Erythromycin led to an amplification of SDR and triggered 36 episodes of TdP. Additional infusion of propofol abbreviated repolarization and reduced SDR. No episodes of TdP were observed with propofol. Similarly, ondansetron prolonged cardiac repolarization in another 13 hearts. SDR was increased and 36 episodes of TdP occurred. With additional propofol infusion, repolarization was abbreviated, SDR reduced and triggered activity abolished. In this experimental whole-heart study, propofol abbreviated repolarization without triggering TdP. On the contrary, propofol reversed prolongation of repolarization caused by erythromycin or ondansetron, reduced SDR and thereby eliminated drug-induced TdP.