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1.
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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2.
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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3.
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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4.
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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5.
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.
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6.
Ion Channel Disorders and Sudden Cardiac Death.
Garcia-Elias, A, Benito, B
International journal of molecular sciences. 2018;(3)
Abstract
Long QT syndrome, short QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia are inherited primary electrical disorders that predispose to sudden cardiac death in the absence of structural heart disease. Also known as cardiac channelopathies, primary electrical disorders respond to mutations in genes encoding cardiac ion channels and/or their regulatory proteins, which result in modifications in the cardiac action potential or in the intracellular calcium handling that lead to electrical instability and life-threatening ventricular arrhythmias. These disorders may have low penetrance and expressivity, making clinical diagnosis often challenging. However, because sudden cardiac death might be the first presenting symptom of the disease, early diagnosis becomes essential. Genetic testing might be helpful in this regard, providing a definite diagnosis in some patients. Yet important limitations still exist, with a significant proportion of patients remaining with no causative mutation identifiable after genetic testing. This review aims to provide the latest knowledge on the genetic basis of cardiac channelopathies and discuss the role of the affected proteins in the pathophysiology of each one of these diseases.
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7.
Combined Effect of Sauna Bathing and Cardiorespiratory Fitness on the Risk of Sudden Cardiac Deaths in Caucasian Men: A Long-term Prospective Cohort Study.
Laukkanen, JA, Laukkanen, T, Khan, H, Babar, M, Kunutsor, SK
Progress in cardiovascular diseases. 2018;(6):635-641
Abstract
Both cardiorespiratory fitness (CRF) and frequency of sauna bathing (FSB) are each strongly and independently associated with sudden cardiac death (SCD) risk. However, the combined effect of CRF and FSB on SCD risk has not been previously investigated. We evaluated the joint impact of CRF and FSB on the risk of SCD in the Kuopio Ischemic Heart Disease prospective cohort study of 2291 men aged 42-61 years at recruitment. Objectively measured CRF and self-reported sauna bathing habits were assessed at baseline. CRF was categorized as low and high (median cutoffs) and FSB as low and high (defined as ≤2 and 3-7 sessions/week respectively). Multivariable adjusted hazard ratios (HRs) with confidence intervals (CIs) were calculated for SCD. During a median follow-up of 26.1 years, 226 SCDs occurred. Comparing high vs low CRF, the HR (95% CIs) for SCD in analysis adjusted for several established risk factors was 0.48 (0.34-0.67). Comparing high vs low FSB, the corresponding HR was 0.67 (0.46-0.98). Compared to men with low CRF & low FSB, the multivariate-adjusted HRs of SCD for the following groups: high CRF & high FSB; high CRF & low FSB; and low CRF & high FSB were 0.31 (0.16-0.63), 0.49 (0.34-0.70), and 0.71 (0.45-1.10) respectively. In a general male Caucasian population, the combined effect of high aerobic fitness (as measured by CRF) and frequent sauna baths is associated with a substantially lowered risk of future SCD compared with high CRF or frequent sauna bathing alone.
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8.
Drugs to prevent sudden cardiac death.
Erath, JW, Hohnloser, SH
International journal of cardiology. 2017;:22-24
Abstract
Sudden cardiac death (SCD) remains a major public health burden despite enormous advances in post-resuscitation care, management of structural heart diseases, and antiarrhythmic treatment modalities. Primary and secondary prevention of sudden cardiac death require understanding of the underlying substrate causing ventricular arrhythmias and its modification by pharmacological (i.e. heart failure therapy) or interventional (catheter ablation) methods. Antiarrhythmic drug therapy has experienced ups and downs during the last 30years balancing high antiarrhythmic potential, toxic side effects and pro-arrhythmic potency. Therefore, the implantable cardioverter-defibrillator (ICD) remains irreplaceable in primary and secondary prevention of SCD. Hybrid therapy combing antiarrhythmic drugs (predominantly amiodarone) with ICD therapy represents an often-used treatment option. This short review provides an overview of current pharmacological therapy aiming to prevent SCD.
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9.
Usefulness of Cardiac Sympathetic Nerve Imaging Using (123)Iodine-Metaiodobenzylguanidine Scintigraphy for Predicting Sudden Cardiac Death in Patients With Heart Failure.
Kasama, S, Toyama, T, Kurabayashi, M
International heart journal. 2016;(2):140-4
Abstract
The autonomic nervous system plays an important role in the human heart. Activation of the cardiac sympathetic nervous system is a cardinal pathophysiological abnormality associated with the failing human heart. Myocardial imaging using (123)I-metaiodobenzylguanidine (MIBG), an analog of norepinephrine, can be used to investigate the activity of norepinephrine, the predominant neurotransmitter of the sympathetic nervous system. Many clinical trials have demonstrated that (123)I-MIBG scintigraphic parameters predict cardiac adverse events, especially sudden cardiac death, in patients with heart failure. In this review, we summarize results from published studies that have focused on the use of cardiac sympathetic nerve imaging using (123)I-MIBG scintigraphy for risk stratification of sudden cardiac death in patients with heart failure.
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10.
Sudden cardiac death and chronic kidney disease: From pathophysiology to treatment strategies.
Di Lullo, L, Rivera, R, Barbera, V, Bellasi, A, Cozzolino, M, Russo, D, De Pascalis, A, Banerjee, D, Floccari, F, Ronco, C
International journal of cardiology. 2016;:16-27
Abstract
Chronic kidney disease (CKD) patients demonstrate higher rates of cardiovascular mortality and morbidity; and increased incidence of sudden cardiac death (SCD) with declining kidney failure. Coronary artery disease (CAD) associated risk factors are the major determinants of SCD in the general population. However, current evidence suggests that in CKD patients, traditional cardiovascular risk factors may play a lesser role. Complex relationships between CKD-specific risk factors, structural heart disease, and ventricular arrhythmias (VA) contribute to the high risk of SCD. In dialysis patients, the occurrence of VA and SCD could be exacerbated by electrolyte shifts, divalent ion abnormalities, sympathetic overactivity, inflammation and iron toxicity. As outcomes in CKD patients after cardiac arrest are poor, primary and secondary prevention of SCD and cardiac arrest could reduce cardiovascular mortality in patients with CKD.