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1.
The Optimal Timing of Primary Prevention Implantable Cardioverter-Defibrillator Referral in the Rapidly Changing Medical Landscape.
Wong, JA, Roberts, JD, Healey, JS
The Canadian journal of cardiology. 2021;(4):644-654
Abstract
The use of implantable cardioverter-defibrillators (ICDs) significantly reduces the risk of mortality in patients with heart failure with reduced ejection fraction (HFrEF). Current guidelines, which are based on seminal clinical trials published nearly 2 decades ago, recommend that patients be on optimal medical therapy for HF for a minimum of 3 months before referral for prophylactic ICD. This waiting period allows for left ventricular reverse remodelling and improvement in HF symptoms, which may render primary prevention ICD implantation unnecessary. However, medical therapy for HFrEF has significantly evolved since the publication of these landmark trials. Given the plethora of medical therapy options now available for HFrEF, it is appropriate to reassess the duration of this waiting period. In the present review, we examine the landmark randomised trials in primary prevention of sudden cardiac death in patients with HFrEF, summarise the novel medical therapies (sacubitril-valsartan, sodium-glucose cotransporter 2 inhibitors, ivabradine, vericiguat, and omecamtiv mecarbil) that have emerged since the publication of those trials, discuss the optimal timing of ICD referral, and review subtypes of nonischemic cardiomyopathy where timing of ICD insertion is guided by alternative criteria. With the steps now needed to optimise medical therapy for HFrEF, in terms of both classes of drugs and doses of each agent, it can easily take up to 6 months to achieve optimisation. Following that, waiting periods of 3 months for ischemic cardiomyopathy and 6 months for nonischemic cardiomyopathy may be required to allow adequate reverse remodelling before reevaluating for ICD implantation.
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2.
Cardiac involvement in Wilson disease: Review of the literature and description of three cases of sudden death.
Chevalier, K, Benyounes, N, Obadia, MA, Van Der Vynckt, C, Morvan, E, Tibi, T, Poujois, A
Journal of inherited metabolic disease. 2021;(5):1099-1112
Abstract
Wilson disease (WD) is a rare genetic condition that results from a build-up of copper in the body. It requires life-long treatment and is mainly characterized by hepatic and neurological features. Copper accumulation has been reported to be related to the occurrence of heart disease, although little is known regarding this association. We have conducted a systematic review of the literature to document the association between WD and cardiac involvement. Thirty-two articles were retained. We also described three cases of sudden death. Cardiac manifestations in WD include cardiomyopathy (mainly left ventricular (LV) remodeling, hypertrophy, and LV diastolic dysfunction, and less frequently LV systolic dysfunction), increased levels of troponin, and/or brain natriuretic peptide, electrocardiogram (ECG) abnormalities, and rhythm or conduction abnormalities, which can be life-threatening. Dysautonomia has also been reported. The mechanism of cardiac damage in WD has not been elucidated. It may be the result of copper accumulation in the heart, and/or it could be due to a toxic effect of copper, resulting in the release of free oxygen radicals. Patients with signs and/or symptoms of cardiac involvement or who have cardiovascular risk factors should be examined by a cardiologist in addition to being assessed by their interdisciplinary treating team. Furthermore, ECG, cardiac biomarkers, echocardiography, and 24-hours or more of Holter monitoring at the diagnosis and/or during the follow-up of patients with WD need to be evaluated. Cardiac magnetic resonance imaging, although not always available, could also be a useful diagnostic tool, allowing assessment of the risk of ventricular arrhythmias and further guidance of the cardiac workup.
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3.
Sudden Cardiac Death in Brugada Syndrome.
Kabra, N, Gupta, R, Aronow, WS, Frishman, WH
Cardiology in review. 2020;(4):203-207
Abstract
The Brugada syndrome is an inherited channelopathy that alters the main transmembrane ion currents that constitute the cardiac action potential. These changes not only modify the resting electrocardiogram but also predispose patients to develop malignant ventricular tachyarrhythmias that can lead to syncope, cardiac arrest, and sudden cardiac death. This syndrome is responsible for nearly 20% of all sudden cardiac deaths in patients with structurally normal hearts and up to 12% of all sudden cardiac deaths. Brugada syndrome is diagnosed by its characteristic electrocardiogram consisting of a coved-type ST-segment elevation of at least 2 mm followed by a negative T wave in either one of the right precordial leads. These changes can be observed spontaneously or after administration of a sodium channel blocker. While our understanding of this disease has increased tremendously since its first description in 1992, the primary therapeutic option remains implantation of an implantable cardioverter-defibrillator to avoid sudden cardiac death. Therefore, tremendous effort is being made to effectively risk stratify patients to determine who would benefit from implantable cardioverter-defibrillator implantation.
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4.
Role of Oxidative Stress in the Genesis of Ventricular Arrhythmias.
Adameova, A, Shah, AK, Dhalla, NS
International journal of molecular sciences. 2020;(12)
Abstract
Ventricular arrhythmias, mainly lethal arrhythmias, such as ventricular tachycardia and fibrillation, may lead to sudden cardiac death. These are triggered as a result of cardiac injury due to chronic ischemia, acute myocardial infarction and various stressful conditions associated with increased levels of circulating catecholamines and angiotensin II. Several mechanisms have been proposed to underlie electrical instability of the heart promoting ventricular arrhythmias; however, oxidative stress which adversely affects ion homeostasis due to changes in the ion channel structure and function, seems to play a critical role in eliciting different types of ventricular arrhythmias. Prevention or mitigation of the severity of ventricular arrhythmias due to antioxidants has been indicated as the fundamental contribution in the field of preventive cardiology; however, novel interventions have to be developed for greater effectiveness and specificity in attenuating the adverse effects of oxidative stress. In this review, we have attempted to discuss proarrhythmic effects of oxidative stress differing in time and concentration dependence and highlight a molecular and cellular concept how it alters cardiac cell automaticity and conduction velocity sensitizing the probability of ventricular arrhythmias with resultant sudden cardiac death due to ischemic heart disease and other stressful situations. It is concluded that pharmacological approaches targeting multiple mechanisms besides oxidative stress might be more effective in the treatment of ventricular arrhythmias than current antiarrhythmic therapy.
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5.
Ketogenesis in arrhythmogenic cardiomyopathy.
Huynh, K
Nature reviews. Cardiology. 2020;(5):266
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6.
Channelopathies That Lead to Sudden Cardiac Death: Clinical and Genetic Aspects.
Skinner, JR, Winbo, A, Abrams, D, Vohra, J, Wilde, AA
Heart, lung & circulation. 2019;(1):22-30
Abstract
Forty per cent (40%) of sudden unexpected natural deaths in people under 35 years of age are associated with a negative autopsy, and the cardiac ion channelopathies are the prime suspects in such cases. Long QT syndrome (LQTS), Brugada syndrome (BrS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) are the most commonly identified with genetic testing. The cellular action potential driving the heart cycle is shaped by a specific series of depolarising and repolarising ion currents mediated by ion channels. Alterations in any of these currents, and in the availability of intracellular free calcium, leaves the myocardium vulnerable to polymorphic ventricular tachycardia or ventricular fibrillation. Each channelopathy has its own electrocardiogram (ECG) signature, typical mode of presentation, and most commonly related gene. Long QT type 1 (gene, KCNQ1) and CPVT (gene, RyR2) typically present with cardiac events (ie syncope or cardiac arrest) during or immediately after exercise in young males; long QT type 2 (gene, KCNH2) after startle or during the night in adult females-particularly early post-partum, and long QT type 3 and Brugada syndrome (gene, SCN5A) during the night in young adult males. They are commonly misdiagnosed as seizure disorders. Fever-triggered cardiac events should also raise the suspicion of BrS. This review summarises genetics, cellular mechanisms, risk stratification and treatments. Beta blockers are the mainstay of treatment for long QT syndrome and CPVT, and flecainide is remarkably effective in CPVT. Brugada syndrome is genetically a more complex disease than the others, and risk stratification and management is more difficult.
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7.
Diagnostic evaluation and arrhythmia mechanisms in survivors of unexplained cardiac arrest.
Deif, B, Roberts, JD
Pacing and clinical electrophysiology : PACE. 2019;(10):1320-1330
Abstract
Identifying the cause of unexplained cardiac arrest is critical for appropriate management of both survivors and their family members. Aborted cardiac arrests whose cause remains unknown following investigation with a surface ECG, echocardiogram, and coronary angiogram are deemed unexplained. Many of these unexplained arrests are felt to be secondary to concealed forms of cardiac channelopathies and latent or subtle cardiomyopathies. This recognition has led to evaluating a diagnostic role for a series of additional investigations, including advanced imaging, genetic testing, and provocative forms of testing, including sodium channel blockade and treadmill testing. Despite evidence of an improved diagnostic yield through their systematic usage, clinical guidelines have yet to endorse a formal algorithm delineating investigations that must be performed before assigning a label of idiopathic ventricular fibrillation, which has resulted in markedly variables thresholds for concluding this diagnosis. Debate remains regarding the need for an invasive electrophysiology study among these patients, though identification of arrhythmic culprits requiring intracardiac electrograms for diagnostic confirmation have suggested a potential role when an initial comprehensive evaluation is unrevealing. Although progress is being made, the sizeable portion of arrests that remain unexplained despite completion of a comprehensive evaluation highlights an ongoing need for further research and additional tools to help unravel the ongoing mysteries of these near fatal events.
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8.
Predictors of cardiac arrhythmic events in non coronary artery disease patients.
Balla, C, Vitali, F, Brieda, A, Gualandi, F, Ferlini, A, Bertini, M, Ferrari, R
BMC cardiovascular disorders. 2019;(1):104
Abstract
Arrhythmic sudden cardiac death (SCD) represents a major worldwide public health problem accounting for 15-20% of deaths. Risk stratification to identify patients at risk of SCD is crucial in order to implement preventive measures in the general population. Several biomarkers have been tested exploring different pathophysiological mechanisms of cardiac conditions. Conflicting results have been described limiting so far their use in clinical practice. The use of new biomarkers such as microRNAs and sex hormones and the emerging role of genetic on risk prediction of SCD is a current research topic showing promising results.This review outlines the role of plasma biomarkers to predict ventricular arrhythmias and SCD in non coronary artery disease with a special focus on their relationship with the genetic biomarkers.
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9.
BASIC AND CLINICAL INSIGHTS IN CATECHOLAMINERGIC (FAMILIAL) POLYMORPHIC VENTRICULAR TACHYCARDIA.
Márquez, MF, Totomoch-Serra, A, Rueda, A, Avelino-Cruz, JE, Gallegos-Cortez, A
Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion. 2019;(4):226-236
Abstract
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal disease, whose characteristic ventricular tachycardias are adrenergic-dependent. Although rare, CPVT should be considered in the differential diagnosis of young individuals with exercise-induced syncope. Mutations in five different genes (RYR2, CASQ2, CALM1, TRDN, and TECRL) are associated with the CPVT phenotype, although RYR2 missense mutations are implicated in up to 60 % of all CPVT cases. Genetic testing has an essential role in the diagnosis, management, pre-symptomatic diagnosis, counseling, and treatment of the proband; furthermore, genetic information can be useful for offspring and relatives. By expert consensus, CPVT gene testing is a Class I recommendation for patients with suspected CPVT. Beta-adrenergic and calcium-channel blockers are the cornerstones of treatment due to the catecholaminergic dependence of the arrhythmias. Unresponsive patients are treated with an implantable cardioverter-defibrillator to reduce the risk of sudden cardiac death. In the present article, a brief review of the genetic and molecular mechanisms of this intriguing disease is provided.
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10.
Cardiac imaging to detect coronary artery disease in athletes aged 35 years and older. A scoping review.
Braber, TL, Reitsma, JB, Mosterd, A, Willemink, MJ, Prakken, NHJ, Halle, M, Sharma, S, Velthuis, BK
Scandinavian journal of medicine & science in sports. 2018;(3):1036-1047
Abstract
Sudden cardiac death (SCD) is a devastating event in athletes. Screening efforts that were first directed at athletes younger than 35 years are now focusing on the rapidly growing group of older sportspersons. Athletes aged ≥35 years have a 10-fold increased risk of exercise-related cardiac arrest, mostly due to coronary artery disease (CAD). Although cardiac imaging is pivotal in identifying CAD, the role of imaging modalities in screening asymptomatic older sportspersons remains unclear. We performed a scoping review to identify the role of cardiac imaging to detect CAD in older sportspersons and to identify gaps in the existing literature. We searched MEDLINE, EMBASE and the Cochrane library for studies reporting data on cardiac imaging of CAD in sportspersons ≥35 years. The systematic search yielded 1737 articles, and 14 were included in this scoping review. Imaging modalities included two echocardiography, one unenhanced computed tomography (CT) for coronary artery calcium scoring (CACS), three CACS and contrast-enhanced CT angiography (CCTA), two CACS and cardiac magnetic resonance (CMR), one CCTA with CMR and echocardiography, two CCTA, two CMR, and one myocardial perfusion imaging article. The low number of relevant articles and the selection bias introduced by studying specific groups, like veteran marathon runners, indicate the need for future research. Cardiac CT (CACS and CCTA) probably has the highest potential for pre-participation screening, with high diagnostic value to detect CAD and low radiation dose. However, currently there is insufficient evidence for incorporating routine cardiac imaging in the pre-participation screening of asymptomatic sportspersons over 35 years.