Prevention Of Sudden Cardiac Death Research Articles

Expanded application of wearable cardioverter defibrillators beyond current guidelines: proposal for a European register explained through single clinical scenarios

The wearable cardioverter defibrillator (WCD) is becoming a more and more widely used instrument for the prevention of sudden cardiac death of patients either with a secondary prevention implantable cardioverter...

History of the implantable cardioverter-defibrillator in Germany

The implantable cardioverter-defibrillator (ICD) was abreakthrough in the prevention of sudden cardiac death. After years of technical development in the USA, Michel Mirowski succeeded in proving reliable automatic defibrillation of ventricular tachyarrhythmias through initial human implantations in 1980, despite many obstacles. Nearly 4years later, the first patients received ICDs at multiple centers in Germany. Subsequently, outside the USA, Germany became the country with highest implantation rates. The absolute number of implantations remained small as long as implantations required epicardial defibrillation electrodes and therefore thoracotomy by cardiac surgeons. Pacemaker-like implantation using atransvenous defibrillation electrode with apectoral ICD became feasible in the early 1990s pushing implantation rates to the next level. Technical advancements were accompanied by clinical research in Germany, and often, the first-in-human studies were conducted in Germany. In 1991, the first guidelines for indications were established in the USA and Germany. Several randomized studies on indications were published between 1996 and 2009, mostly led by American teams with German participation, but also under German leadership (CASH, CAT, DINAMIT, IRIS). The DANISH study in 2016 questioned the results of these long-standing studies. Instead of providing ICDs to patients using abroad indication, future efforts aim to identify patients who, despite optimal medical therapy, cardiac resynchronization therapy (CRT), and/or catheter ablation, need protection against sudden cardiac death. Risk scores incorporating myocardial scars in magnetic resonance imaging (MRI) and genetic information are expected to contribute to more individualized and effective indications.

Whether to implant a defibrillator or not? The Possibility of Using the MADIT-ICD Benefit Score Calculator in Real Practice

To study the predictive capabilities of the MADIT-ICD Benefit Score calculator in assessing the benefit of implantable cardioverter defibrillator (ICD) placement for the primary prevention of sudden cardiac death (SCD). This study included 388 patients with NYHA II-IV functional class chronic heart failure (CHF) with a left ventricular ejection fraction (LVEF) ≤35 % who underwent ICD placement for the primary prevention of SCD. Patients were followed up for two years to record the endpoints of first-time paroxysmal sustained ventricular tachyarrhythmia (VT) or non-arrhythmic death. According to the results of calculation with the MADIT-ICD Benefit Score calculator, 276 (71 %) patients had a high risk of VT (score ≥7) and 150 (39 %) had a high risk of non-arrhythmic death (score ≥3). 336 (94%) patients would benefit from an ICD: 148 (38 %) with a high level of probability and 218 (56 %) with a medium level of probability. According to the incidence of endpoints, VT episodes predominated in the low-ICD benefit group (36%), while the high-ICD benefit group had a relatively high incidence of non-arrhythmic death (12%). The results obtained for a cohort of Russian patients with CHF and reduced LVEF indicated that the use of the MADIT-ICD Benefit Score in routine clinical practice does not improve the stratification of SCD risk compared to the traditional approach to selecting patients with CHF for ICD based on the LVEF value.

Imagenetics for Precision Medicine in Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is a common heart muscle disorder of nonischemic etiology associated with heart failure development and the risk of malignant ventricular arrhythmias and sudden cardiac death. A tailored approach to risk stratification and prevention of sudden cardiac death is required in genetic DCM given its variable presentation and phenotypic severity. Currently, advances in cardiogenetics have shed light on disease mechanisms, the complex genetic architecture of DCM, polygenic contributors to disease susceptibility and the role of environmental triggers. Parallel advances in imaging have also enhanced disease recognition and the identification of the wide spectrum of phenotypes falling under the DCM umbrella. Genotype-phenotype associations have been also established for specific subtypes of DCM, such as DSP (desmoplakin) or FLNC (filamin-C) cardiomyopathy but overall, they remain elusive and not readily identifiable. Also, despite the accumulated knowledge on disease mechanisms, certain aspects remain still unclear, such as which patients with DCM are at risk for disease progression or remission after treatment. Imagenetics, that is, the combination of imaging and genetics, is expected to further advance research in the field and contribute to precision medicine in DCM management and treatment. In the present article, we review the existing literature in the field, summarize the established knowledge and emerging data on the value of genetics and imaging in establishing genotype-phenotype associations in DCM and in clinical decision making for DCM patients.

Anti-Arrhythmic Effects of Heart Failure Guideline-Directed Medical Therapy and Their Role in the Prevention of Sudden Cardiac Death: From Beta-Blockers to Sodium-Glucose Cotransporter 2 Inhibitors and Beyond.

Sudden cardiac death (SCD) accounts for a substantial proportion of mortality in heart failure with reduced ejection fraction (HFrEF), frequently triggered by ventricular arrhythmias (VA). This review aims to analyze the pathophysiological mechanisms underlying VA and SCD in HFrEF and evaluate the effectiveness of guideline-directed medical therapy (GDMT) in reducing SCD. Beta-blockers, angiotensin receptor-neprilysin inhibitors, and mineralocorticoid receptor antagonists have shown significant efficacy in reducing SCD risk. While angiotensin-converting enzyme inhibitors and angiotensin receptor blockers exert beneficial impacts on the renin-angiotensin-aldosterone system, their direct role in SCD prevention remains less clear. Emerging treatments like sodium-glucose cotransporter 2 inhibitors show promise but necessitate further research for conclusive evidence. The favorable outcomes of those molecules on VA are notably attributable to sympathetic nervous system modulation, structural remodeling attenuation, and ion channel stabilization. A multidimensional pharmacological approach targeting those pathophysiological mechanisms offers a complete and synergy approach to reducing SCD risk, thereby highlighting the importance of optimizing GDMT for HFrEF. The current landscape of HFrEF pharmacotherapy is evolving, with ongoing research needed to clarify the full extent of the anti-arrhythmic benefits offered by both existing and new treatments.

Variable clinical expression of a novel FLNC truncating variant in a large family

BackgroundVariants in Filamin-C (FLNC) have been associated with various hereditary cardiomyopathies. Recent literature reports a prevalence of sudden cardiac death (SCD) of 13–25% among carriers of truncating-variants, with mean age of 42±15 years for first SCD event. This study reports two familial cases of SCD and the results of cascade screening of their large family. MethodsMolecular-autopsy of the SCD victims revealed a novel truncating-variant in the FLNC gene (chr 7:128496880 [hg19]; NM_001458.5; c.7467_7474del; p.(Ser2490fs)). We screened thirty-two family members following genetic counseling, and variant carriers underwent a comprehensive workup followed by consultation with a cardiologist with expertise in the genetics of cardiac diseases. ResultsSeventeen variant carriers were identified: ages between 9 and 85 (mean 47±26). Fifteen underwent clinical evaluation. To date, none of the identified carriers has had major adverse events. In evaluated patients, ECG showed right-axis deviation in 60% (n = 9). Holter recorded frequent premature ventricular contractions (PVCs) (991±2030 per 24 h) in 33% (n = 5) with 4 patients having polymorphic PVC morphology. Three carriers had echocardiographic evidence of mild left-ventricular (LV) systolic dysfunction and another with mild LV dilatation. Cardiac magnetic-resonance (CMR) exhibited late‑gadolinium-enhancement in 10 out of 11 exams, mainly in the mid-myocardium and sub-epicardium, frequently involving the septum and the inferior-lateral wall. ConclusionThis large FLNC truncating variant carrier family exhibits high cardiomyopathy penetrance, best diagnosed by CMR, with variable clinical expressions. These findings present a challenge in SCD prevention management and underscoring the imperative for better risk stratification measures.

Detection of gene mutation in the prognosis of a patient with arrhythmogenic right ventricular cardiomyopathy: a case report

BackgroundArrhythmogenic right ventricular cardiomyopathy (ARVC), or more recently known as arrhythmogenic cardiomyopathy (ACM), is an heritable disorder of the myocardium characterized by progressive fibrofatty replacement the heart muscle and risk of ventricular arrhythmias and sudden cardiac death (SCD). We report a case study to demonstrate the role of gene mutation detection in risk stratification for primary prevention of SCD in a young patient diagnosed with ARVC.Case presentationA 15-year-old Asian (Vietnamese) male patient with no history of documented tachyarrhythmia or syncope and a family history of potential SCD was admitted due to palpitations. Clinical findings and work-up including cardiac magnetic resonance imaging (MRI) were highly suggestive of ARVC. Gene sequencing was performed for SCD risk stratification, during which PKP2 gene mutation was found. Based on the individualized risk stratification, an ICD was implanted for primary prevention of SCD. At 6 months post ICD implantation, the device detected and successfully delivered an appropriate shock to terminate an episode of potentially fatal ventricular arrhythmia. ICD implantation was therefore proven to be appropriate in this patient.ConclusionsWhile gene mutations are known to be an important factor in the diagnosis of ARVC according to the 2010 Task Force Criteria and recent clinical guidelines, their role in risk stratification of SCD remains controversial. Our case demonstrated that when used with other clinical factors and family history, this information could be helpful in identifying appropriate indication for ICD implantation.

Optimizing sudden cardiac death prevention: a promise of wearable cardioverter-defibrillator.

Optimizing sudden cardiac death prevention: a promise of wearable cardioverter-defibrillator.

Primary Electrical Heart Disease-Principles of Pathophysiology and Genetics.

Primary electrical heart diseases, often considered channelopathies, are inherited genetic abnormalities of cardiomyocyte electrical behavior carrying the risk of malignant arrhythmias leading to sudden cardiac death (SCD). Approximately 54% of sudden, unexpected deaths in individuals under the age of 35 do not exhibit signs of structural heart disease during autopsy, suggesting the potential significance of channelopathies in this group of age. Channelopathies constitute a highly heterogenous group comprising various diseases such as long QT syndrome (LQTS), short QT syndrome (SQTS), idiopathic ventricular fibrillation (IVF), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and early repolarization syndromes (ERS). Although new advances in the diagnostic process of channelopathies have been made, the link between a disease and sudden cardiac death remains not fully explained. Evolving data in electrophysiology and genetic testing suggest previously described diseases as complex with multiple underlying genes and a high variety of factors associated with SCD in channelopathies. This review summarizes available, well-established information about channelopathy pathogenesis, genetic basics, and molecular aspects relative to principles of the pathophysiology of arrhythmia. In addition, general information about diagnostic approaches and management is presented. Analyzing principles of channelopathies and their underlying causes improves the understanding of genetic and molecular basics that may assist general research and improve SCD prevention.

Clinical role of triggers and modulation factors of ventricular arrhythmogenesis in stable coronary artery disease

Ventricular arrhythmias are more commonly associated with coronary artery disease. However, ventricular arrhythmogenesis can be initiated by various trigger factors against its background. The substrate of arrhythmias in various nosological forms of stable coronary heart disease is heterogeneous. The patient may have stable exertional angina without severe fibrosis or have a history of myocardial infarction with significant scarring. Therefore the predictive value and prognostic significant of ventricular arrhythmias is not always unambiguous. Thus, for the successful treatment of arrhythmias as a main component of the prevention of sudden cardiac death, an individualized pathogenetic approach is the most important. The purpose of this article is to analyze and clinically interpret the results of studies, publications for 1980-2023, in which the authors describe the etiological, pathophysiological, pathomorphological characteristics of ventricular arrhythmias and their predictive value and prognostic significant for patients with stable coronary artery disease.

Cardiac Device Therapy in Patients with Chronic Kidney Disease: An Update.

Cardiovascular diseases (CVDs) and chronic kidney disease (CKD) are frequently interconnected and their association leads to an exponential increase in the risk of both fatal and non-fatal events. In addition, the burden of arrhythmias in CKD patients is increased. On the other hand, the presence of CKD is an important factor that influences the decision to pursue cardiac device therapy. Data on CKD patients with device therapy are scarce and mostly derives from observational studies and case reports. Cardiac resynchronization therapy (CRT) is associated with decreased mortality, reduced heart failure symptoms, and improved renal function in early stages of CKD. Implantable cardioverter defibrillators (ICDs) are associated with a significant reduction in the mortality of CKD patients only for the secondary prevention of sudden cardiac death. Cardiac resynchronization therapy with defibrillator (CRT-D) is preferred in patients who meet the established criteria. The need for cardiac pacing is increased three-fold in dialysis patients. CKD is an independent risk factor for infections associated with cardiac devices.

European guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death 2022: cardiomyopathy. What’s new?

The review provides information on new indications that should be guiden the diagnosis and treatment of ventricular arrhythmias in patients with cardiomyopathy. The analysis of modern definitions and classifications of cardiomyopathy is given. The issues of ventricular arrhythmias in different cardiomyopathy phenotypes, risk stratification of sudden cardiac death and its prevention are considered in detail.

Clinical and genetic characterization of patients with catecholaminergic polymorphic ventricular tachycardia: a case series

AIM: of the study was to evaluate the clinical and genetic characteristics, including the development of adverse events and outcomes in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT).
 MATERIALS AND METHODS: The clinical phenotype of eight patients with CPVT, two of whom were relatives of probands, was observed over 4 years. The clinical and instrumental study included ECG-12, 24-hour Holter ECG monitoring, genealogical history collection and family history of sudden cardiac death (SCD), transthoracic echocardiography and cardiac magnetic resonance imaging to detect structural myocardial changes, electrophysiologic study according to indications, and ICD monitoring. High-throughput sequencing (NGS) was utilized to search for mutations in genes linked to the onset of channelopathies and other inherited rhythm disorders.
 RESULTS: In 8 patients, nucleotide variants of pathogenicity classes III-V were identified according to the ACMG (2015) criteria in the RYR2 gene associated with CPVT. Pathogenic (IV-V class) and likely pathogenic (IV class) mutations in the RYR2 gene were found in 6 (75%) probands, variants with uncertain clinical significance (VUS, class III) were found in 2 patients. At the time of diagnosis, transient QTc interval prolongation of more than 480 ms was detected in 4 (50%) patients; bradycardia less than 54 beats/min — in 2 (25%) patients, sequences of supraventricular tachycardia and ventricular tachyarrhythmia — in 2 (25%) patients. The most severe form of the disease with marked clinical manifestations and an episode of clinical death with subsequent resuscitation, as well as a transient QTc interval prolongation exceeding 500 ms was observed in patients with mutations c.11814C A (p.Ser3938Arg, rs794728704); c.463G A (p.Gly155Arg) and c.14876G A (p.Arg4959Gln, rs794728811) in the RYR2 gene. Three (37.5%) patients underwent ICD implantation; one for primary SCD prevention and two for secondary prevention.
 CONCLUSION: In this study, the spectrum of clinical manifestations in patients with genetically confirmed CPVT was examined. The findings highlight transient QTc interval extensions, significant sinus bradycardia, and sequences of supraventricular tachyarrhythmias, which can escalate into life-threatening ventricular tachyarrhythmias in CPVT patients.

Analysis of electrotherapy in patients with implantable cardioverter-defibrillator for primary prevention of sudden cardiac death according to remote monitoring data

Aim: To determine the factors associated with development of justified and inappropriate implantable cardioverter-defibrillator (ICD) activations in patients at high risk of sudden cardiac death based on the remote monitoring systemMaterial and Methods. We analyzed remote monitoring data from 2014 to 2022 in 132 patients with ICD for primary prevention of sudden cardiac death (SCD). Patients were divided into 2 groups 1 – patients with persistent paroxysmal tachyarrhythmias; 2 – patients without persistent paroxysms of ventricular tachycardia (VT) / ventricular fibrillation (VF). In case of inappropriate shocks, the causes and possible predictors of their development were analyzed.Results. Of 132 patients, 62 (46.9%) patients appeared to have persistent VT/VF. It was found that the probability of detecting persistent paroxysms of VT/VF decreased with a history of revascularization (p = 0.030) and increased in the absence of amiodarone therapy (p = 0.012), with increasing age (p = 0.035), with decreasing left ventricular ejection fraction (LVEF) less than 35% (p = 0.016). 71 arrhythmic episodes (17.9%) in 27 (20.4%) patients were considered as false detection of tachyarrhythmias. Analyzing the causes of inappropriate electrotherapy, different types of supraventricular tachyarrhythmias in the zone of VT detection (85.9%), including atrial fibrillation (25.4%), in smaller percentage of cases there was discovered T-wave detection 4.2%, noise on the electrode – 2.8%, 7.1% – double counter due to the operation of the cardiac contractility modulation device. When analyzing factors associated with the development of false detection, reliable results were obtained with regard to the presence of a history of atrial fibrillation (p = 0.036), implanted single-chamber ICD (p = 0.028).Conclusion. The development of persistent ventricular tachyarrhythmias was noted in 47% of patients with ICD as a part of primary prevention of sudden cardiac death, and 20.4% had the development of inappropriate detection and electrotherapy. Predictors of their occurrence have been identified, which can be used as development of strategies for shock minimization.

Role of genetics in inflammatory cardiomyopathy

Traditional cardiomyopathy paradigms segregate inflammatory etiologies from those caused by genetic variants. An identified or presumed trigger is implicated in acute myocarditis or chronic inflammatory cardiomyopathy but growing evidence suggests a significant proportion of patients have an underlying cardiomyopathy-associated genetic variant often even when a clear inflammatory trigger is identified. Recognizing a possible genetic contribution to inflammatory cardiomyopathy may have major downstream implications for both the patient and family. The presenting features of myocarditis (i.e. chest pain, arrhythmia, and/or heart failure) may provide insight into diagnostic considerations. One example is isolated cardiac sarcoidosis, a distinct inflammatory cardiomyopathy that carries diagnostic challenges and clinical overlap; genetic testing has increasingly reclassified cases of isolated cardiac sarcoidosis as genetic cardiomyopathy, notably altering management. On the other side, inflammatory presentations of genetic cardiomyopathies are likewise underappreciated and a growing area of investigation. Inflammation plays an important role in the pathogenesis of several familial cardiomyopathies, especially arrhythmogenic phenotypes. Given these clinical scenarios, and the implications on clinical decision making such as initiation of immunosuppression, sudden cardiac death prevention, and family screening, it is important to recognize when genetics may be playing a role.

Use of subcutaneous cardioverter-defibrillator. First cases reported from National Institute of Cardiology Ignacio Chávez-Mexico.

The transvenous implantable cardioverter defibrillator (ICD) is the treatment of choice for the prevention of sudden cardiac death (SCD). Its use could be restricted when device-related infections occurs or in the pediatric population. In the later, an ICD represents a challenge, due to the minimal dimensions of the venous system in children, the length of the electrodes, the size of the generator, as well as the anatomical complexity in cases with associated congenital heart disease. This article presents the first Mexican patients with a subcutaneous ICD (SC-ICD) implant as a therapy for the prevention of SCD. The first four cases were implanted at the Ignacio Chávez National Institute of Cardiology with a SC-ICD (Emblem, Boston Scientific, USA), three of them were pediatric patients, including the first implant of this type of device in a pediatric patient in Latin America. The 3-incision and 2-incision techniques were used under general anesthesia. A successful implantation was obtained with the 3-incision technique in the first 2 cases and the last 2 with the 2-incision technique. Proper functioning of the device was corroborated in the operating room with proof of appropriate therapy (65 J) for ventricular fibrillation induced with 50 Hz stimulation. No immediate complications were observed. One patient had appropriate shocks two months after the implant. During follow-up, one child developed skin erosion at the level of the curve of the electrode on the sternum, with no signs of infection. In the operating room, the damaged skin was resected, the barrel and the fixation silk were removed, surgical lavage was performed, and the skin was closed again, thus avoiding removal of the system. The SC-ICD is an alternative therapy to the transvenous ICD. It can be considered first choice in subjects who do not require ventricular pacing, including pediatric patients. Skin complications can occur but do not pose a threat as venous complications of conventional ICDs.

Factors Associated With Non-Uptake of Implantable Cardioverter-Defibrillator (ICD) Among Eligible Patients at a Tertiary Hospital in Kenya.

Efficacy of Implantable Cardioverter-Defibrillator (ICD) implantation in both primary and secondary prevention of Sudden Cardiac Death (SCD) in at-risk population is well established. ICD implantation rates remain low particularly in Africa with a paucity of data regarding factors associated with non-uptake. The primary study objective was to determine the factors associated with non-uptake of ICD among heart failure (HF) patients with reduced ejection fraction (EF<35%). Reasons for ICD refusal among eligible patients were reviewed as a secondary objective. This was a retrospective study among HF patients eligible for ICD implantation evaluated between 2018 to 2020. Comparison between ICD recipient and non-recipient categories was made to establish determinants of non-uptake. Of 206 eligible patients, only 69 (33.5%) had an ICD. Factors independently associated with non-uptake were lack of private insurance (42.3% vs 63.8%; p = 0.005), non-cardiology physician (16.1% vs 5.8%; p = 0.045) and non-ischemic cardiomyopathy (54.7% vs 36.4% p = 0.014). The most common (75%) reason for ICD refusal was inability to pay for the device. ICDs are underutilized among eligible HF with reduced EF patients in Kenya. The majority of patients without ICD had no private insurance, had non-ischemic cardiomyopathy and non-cardiology primary physician. Early referral of HF with reduced EF patients to HF specialists to optimize guideline-directed medical therapy and make ICD recommendation is needed.

Kiosk 4R-TC-09 - Myocardial Scar Characteristics by 3D-LGE Cannot Fully Explain Different Arrhythmic Event Rates in Primary and Secondary Prevention of Sudden Cardiac Death

Kiosk 4R-TC-09 - Myocardial Scar Characteristics by 3D-LGE Cannot Fully Explain Different Arrhythmic Event Rates in Primary and Secondary Prevention of Sudden Cardiac Death

КЛИНИЧЕСКИЙ СЛУЧАЙ БИВЕНТРИКУЛЯРНОЙ АРИТМОГЕННОЙ КАРДИОМИОПАТИИ, АССОЦИИРОВАННОЙ С МУТАЦИЕЙ В ГЕНЕ DSG2

This article describes clinical observation over a patient with a biventricular form of arrhythmogenic cardiomyopathy associated with a mutation in DSG2 gene. The morphological realization of this mutation is associated with fibrous-fat replacement of the myocardium of both ventricles of the heart, which is clinically manifested by the development of life-threatening ventricular arrhythmias and a high risk of biventricular heart failure with a tendency to a progressive decrease in myocardial contractility. The affect on young people of working age, hereditary determinism and an unfavorable prognosis of survival actualizes the importance of diagnostic alertness in the examination of young patients with a clinical picture including ventricular arrhythmias, presyncope, syncope conditions and sudden cardiac death. The main issues of diagnosis, criteria for diagnosis in accordance with the Padua criteria (2020), current principles of treatment and prevention of sudden cardiac death are considered.

Management Strategies in Arrhythmogenic Cardiomyopathy across the Spectrum of Ventricular Involvement.

Improved disease recognition through family screening and increased life expectancy with appropriate sudden cardiac death prevention has increased the burden of heart failure in arrhythmogenic cardiomyopathy (ACM). Heart failure management guidelines are well established but primarily focus on left ventricle function. A significant proportion of patients with ACM have predominant or isolated right ventricle (RV) dysfunction. Management of RV dysfunction in ACM lacks evidence but requires special considerations across the spectrum of heart failure regarding the initial diagnosis, subsequent management, monitoring for progression, and end-stage disease management. In this review, we discuss the unique aspects of heart failure management in ACM with a special focus on RV dysfunction.