Abstract: HomeCirculationVol. 114, No. 11Sudden Cardiac Death Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBSudden Cardiac DeathBetter Understanding of Risks, Mechanisms, and Treatment John C. Lopshire and Douglas P. Zipes John C. LopshireJohn C. Lopshire From the Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Ind. and Douglas P. ZipesDouglas P. Zipes From the Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Ind. Originally published12 Sep 2006https://doi.org/10.1161/CIRCULATIONAHA.106.647933Circulation. 2006;114:1134–1136Sudden cardiac death (SCD) is generally defined as unexpected death as the result of cardiovascular causes in a person with or without preexisting heart disease, within 1 hour of onset of change in clinical status.1 Most instances of SCD are thought to involve ventricular tachycardia degenerating to ventricular fibrillation (VF) and subsequent asystole, although the percent of ventricular tachyarrhythmias found as the first rhythm at the time of collapse appears to be decreasing.2 In 60% to 80% of cases, SCD occurs in the setting of coronary artery disease. Nonischemic cardiomyopathy and infiltrative, inflammatory, and acquired valvular diseases account for most other SCD events.3 A small percentage of SCDs occur in the setting of ion channel mutations responsible for inherited abnormalities such as the long/short QT syndromes, Brugada syndrome, and catecholaminergic ventricular tachycardia. Although accounting for a small number of SCDs overall, these fascinating syndromes provide mechanistic insights never before available. In addition, other genetic abnormalities such as hypertrophic cardiomyopathy and congenital heart defects such as anomalous coronary arteries are responsible for SCD.Articles p 1140 and 1146Despite widespread advances in the treatment of ischemic heart disease with early recognition and revascularization therapies and the growing use of automated external defibrillators and implantable cardioverter-defibrillators to detect and treat ventricular arrhythmias, SCD remains a major cause of death in industrialized countries, exceeding 300 000 events per year in the United States, or about 20% of all deaths annually.3 The only pharmacological advances have been achieved with drugs that affect "upstream" regulatory events, such as statins, angiotensin-converting enzyme inhibitors, fish oil, aspirin, β-blockers, and aldosterone inhibitors, rather than with "traditional" ion channel–blocking antiarrhythmic agents.4A frequently observed and notable aspect of SCD is its unpredictable and seemingly random nature of onset. Accordingly, one of the most vexing issues remains early identification of individuals at highest risk, especially the subset of patients with SCD without overt signs, symptoms, or evidence of heart disease. Although clinical studies have been largely unsuccessful at identifying global and specific markers of SCD risk in the general population, certain clinical and diagnostic findings are associated with increased risk of SCD, generally found in patients with established disease. These include markers such as abnormal left ventricular systolic function or ejection fraction, scalar electrical abnormalities such as microvolt T-wave alternans, increased QRS duration, and repolarization abnormalities, abnormal electrical activity during invasive electrophysiological testing, disordered autonomic nervous system function manifested by alteration and variability in resting and exercising heart rate and baroreflex sensitivity, and the presence of occult ventricular arrhythmias. Interestingly, some studies have reported circadian and seasonal variations on the rate of SCD.5–7 Despite these advances, the biomarkers presently used have insufficient predictive accuracy to identify the at-risk individual but instead identify groups of people at risk.1,3,8 Major advances in this area are needed to identify predisposing risks.We also still lack fundamental understanding of the precipitating factors that underlie initiation of ventricular tachycardia/VF causing SCD at a specific time, hence the question we have raised, "Why did he die on Tuesday and not on Monday?"1 If we can identify the factors that probably represent interplay between a receptive substrate and a transient initiating event,8 we can begin to develop more effective strategies for prevention of SCD. The challenge is to determine the nature of the receptive substrate and how it interacts with the transient trigger. Moreover, we cannot forget that both the substrate and the trigger may change over time, so that an "ice pick" evaluation at 1 reference point may not provide useful information a few months later because short-term changes occur in a long-term disease. For example, recent studies have shown that the neural substrate, through nerve sprouting, can change over weeks9 as can the trigger, with T-wave alternans increasing before the development of ventricular tachyarrhythmias.10We can also rephrase the question of why some patients fibrillate to ask why some individuals at risk do not fibrillate. Do they have some sort of an "antifibrillatory reserve" that protects them? Do they require a double hit,11 that is, a confluence of events necessary to trigger the cascade leading to ventricular fibrillation, with the latter being the final common pathway in response to multiple and different inputs? We have learned that there are different mechanisms that can initiate and perpetuate atrial fibrillation. The same probably applies to ventricular fibrillation.In this issue of Circulation, 2 articles attempt to identify risk factors for susceptibility to malignant ventricular arrhythmias and SCD. Müller and coworkers12 investigated the conditions preceding cardiac arrest that occurred in the Berlin, Germany, emergency response network. Information on medical history, medications, first-registered arrhythmia, and signs or symptoms present for up to 24 hours before out-of-hospital cardiac arrest in 406 patients was collected by an emergency physician on the scene after successful resuscitation or declaration of death. The location of the events was at home in 72% of cases. This is consistent with previous data from the United States.13 Notably, nearly two thirds of the episodes were witnessed, but bystander cardiopulmonary resuscitation (CPR) was performed in only 20% of these patients. Moreover, patients were more likely to receive bystander CPR in public than at home. Still, patients who received bystander CPR had significantly higher rates of successful resuscitation and eventual hospital discharge. Earlier studies have reported similar findings.14 Preexisting cardiac disease was present in 67% of patients. Accordingly, the most frequently reported symptom was angina, followed by dyspnea, nausea/vomiting, and dizziness/syncope. No symptoms were reported in 25% of patients. Interestingly, patients tolerated symptoms longer at home (75 minutes) than in public (20 minutes). The authors concluded that in the study population, signs and symptoms are present, often for a significant period of time, which could herald the onset of cardiac arrest. This observation suggests that symptoms are often present before cardiac arrest and draws attention to the important fact that patient and family education of the warning signs of cardiovascular disease and lay person interventions such as CPR might dramatically improve survival in cardiac arrest. Reports many years ago noted similar symptoms before cardiac arrest, but, in general, the symptoms were too nonspecific to trigger emergency action.15Also reported in this issue of Circulation, Dekker and coworkers16 conducted a case-control study in survivors of primary VF that occurred in the setting of acute ST-segment elevation myocardial infarction (STEMI) with the goal of identifying risk factors for primary VF. Control patients were age- and sex-matched patients with STEMI with no primary VF. Both groups had no history of primary VF, myocardial infarction, or structural heart disease, and all participants underwent subsequent percutaneous coronary intervention. Baseline characteristics, including electrocardiographic parameters (heart rate, axis, PQ interval, QRS duration, and QTc), infarct size, culprit vessel, and presence of angina were similar between groups. Interestingly, atrial fibrillation was diagnosed in 21% of cases and 0% of control subjects who received prior cardiac care. For unknown reasons, atrial fibrillation has been shown to be a risk factor for sudden cardiac death in other studies as well.17 A major finding of the study was that cases had a significantly higher percentage of family history of SCD or aborted SCD (43% versus 25% in control subjects). Two prior studies have also noted an association between family history and SCD risk,18,19 but this is the first study to specifically study patients with STEMI. Additionally, cases had significantly increased ST-segment deviation, even on ECGs obtained before cardioversion, perhaps reflecting inherited repolarization "sensitivity" to ischemia and ventricular arrhythmias.20,21 The authors conclude that complex and multifactorial genetic and environmental factors may underlie the finding that family history predicted primary VF in this study and advocate using the family history as an integrating tool for risk stratification of patients with STEMI. Since a greater percentage of cases compared with control subjects sought cardiac care before having primary VF, perhaps a more thorough history taking might have changed the patients' initial cardiac management, thus leading to further diagnostic testing and additional or different pharmacotherapy. Dekker and coworkers provide additional compelling evidence that a genetic mechanism may increase a patient's propensity to have lethal arrhythmias and SCD. Recent studies support the notion that subtle genetic variations such as single nucleotide polymorphisms can influence the phenotypic expression of low penetrance ion channel mutations and increase propensity to ventricular arrhythmias and SCD.22 In the future, techniques such as genome-wide linkage analysis may allow the detection of polymorphisms and mutations that confer increased SCD risk in the general population without overt evidence of cardiovascular abnormalities.23It is clear from these and other studies that better understanding of the contribution of molecular and genetic/proteomic influences on the risk for developing, or for not developing, ventricular tachyarrhythmias, as well as understanding the mechanisms responsible for the onset and maintenance of arrhythmias in a variety of animal models, including human beings, is essential to both identify individuals at risk and to develop specific therapies to mitigate that risk. However, the future holds great promise, with advances in imaging capabilities and genetics, pharmacotherapy, and device technology, all playing increasing roles.The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.DisclosuresDrs Lopshire and Zipes receive research support from Medtronic, Inc. Dr Zipes is also a consultant to Medtronic.FootnotesCorrespondence to Douglas P. Zipes, MD, Krannert Institute of Cardiology, 1800 North Capitol Ave, Suite E315, Indianapolis, IN 46202. E-mail [email protected] References 1 Zipes DP, Rubart M. Neural modulation of cardiac arrhythmias and sudden death. Heart Rhythm. 2006; 3: 108–113.CrossrefMedlineGoogle Scholar2 Cobb LA, Fahrenbruch CE, Olsufka M, Copass MK. Changing incidence of out-of-hospital ventricular fibrillation, 1980–2000. JAMA. 2002; 288: 3008–3013.CrossrefMedlineGoogle Scholar3 Myerburg RJ, Interian A, Simmons J, Castellanos A. Sudden cardiac death. In: Zipes DP, ed. Cardiac Electrophysiology: From Cell to Bedside. 4th ed. Philadelphia: WB Saunders; 2004: 720–731.Google Scholar4 Alberte C, Zipes DP. Use of nonantiarrhythmic drugs for prevention of sudden cardiac death. J Cardiovasc Electrophysiol. 2003; 14: S87–S95.CrossrefMedlineGoogle Scholar5 Page RL, Zipes DP, Powell JL, Luceri RM, Gold MR, Peters R, Russo AM, Bigger JT, Sung RJ, McBurnie MA, AVID Investigators. Seasonal variation of mortality in the antiarrhythmics versus implantable defibrillators (AVID) study registry. Heart Rhythm. 2004; 1: 435–440.CrossrefMedlineGoogle Scholar6 Muller D, Lampe F, Wegscheider K, Schultheiss HP, Behrens S. Annual distribution of ventricular tachycardias and ventricular fibrillation. Am Heart J. 2003; 146: 1061–1065.CrossrefMedlineGoogle Scholar7 Willich SN, Goldberg RJ, Maclure M, Perriello L, Muller JE. Increased onset of sudden cardiac death in the first three hours after awakening. Am J Cardiol. 1992; 70: 65–68.CrossrefMedlineGoogle Scholar8 Zipes DP, Wellens HJJ. Sudden cardiac death. Circulation. 1998; 98: 2334–2351.CrossrefMedlineGoogle Scholar9 Oh Y, Jong A, Kim DT, Li H, Wang C, Zemljic A, Ross RS, Fishbein MC, Chen PS, Chen LS. Spatial distribution of nerve sprouting after myocardial infarction in mice. Heart Rhythm. 2006; 6: 728–736.Google Scholar10 Paz O, Zhou X, Gillberg J, Tseng HJ, Gang E, Swerdlow C. Detection of T-wave alternans using an implantable cardioverter-defibrillator. Heart Rhythm. 2006; 3: 791–797.CrossrefMedlineGoogle Scholar11 Tomaselli GF, Zipes DP. What causes sudden death in heart failure? Circ Res. 2004; 95: 754–763.LinkGoogle Scholar12 Müller D, Agrawal R, Arntz HR. How sudden is sudden cardiac death? Circulation. 2006; 114: 1146–1150.LinkGoogle Scholar13 Weaver WD, Peberdy MA. Defibrillators in public places: one step closer to home. N Engl J Med. 2002; 347: 1223–1224.CrossrefMedlineGoogle Scholar14 de Vreede-Swagemakers JJ, Gorgels AP, Dubois-Arbouw WI, Dalstra J, Daemen MJAP, van Ree JW, Stijns RE, Wellens HJJ. Circumstances and causes of out-of-hospital cardiac arrest in sudden death survivors. Heart. 1998; 79: 356–361.CrossrefMedlineGoogle Scholar15 Goldstein S, Medendorp SV, Landis JR, Wolfe RA, Leighton R, Ritter G, Vasu CM, Acheson A. Analysis of cardiac symptoms preceding cardiac arrest. Am J Cardiol. 1986; 58: 1195–1198.CrossrefMedlineGoogle Scholar16 Dekker LRC, Bezzina CR, Henriques JPS, Tanck MW, Koch KT, Alings MW, Arnold AER, de Boer M-J, Gorgels APM, Michels HR, Verkerk A, Verheugt FWA, Zijlstra F, Wilde AAM. Familial sudden death is an important risk factor for primary ventricular fibrillation: a case-control study in acute myocardial infarction patients. Circulation. 2006; 114: 1140–1145.LinkGoogle Scholar17 Gronefeld GC, Mauss O, Li YG, Klingenheben T, Hohnloser SH. Association between atrial fibrillation and appropriate implantable cardioverter defibrillator therapy: results from a prospective study. J Cardiovasc Electrophysiol. 2000; 11: 1208–1214.CrossrefMedlineGoogle Scholar18 Friedlander Y, Siscovick DS, Weinmann S, Austin MA, Psaty BM, Lemaitre RN, Arbogast P, Raghunathan TE, Cobb LA. Family history as a risk factor for primary cardiac arrest. Circulation. 1998; 97: 155–160.CrossrefMedlineGoogle Scholar19 Jouven X, Desnos M, Guerot C, Ducimetière P. Predicting sudden death in the population: the Paris prospective study I. Circulation. 1999; 99: 1978–1983.CrossrefMedlineGoogle Scholar20 Roden DM. Pharmacogenetics and drug-induced arrhythmias. Cardiovasc Res. 2001; 50: 224–231.CrossrefMedlineGoogle Scholar21 Ueda N, Zipes DP, Wu J. Coronary occlusion and reperfusion promote afterdepolarizations and ventricular tachycardia in a canine tissue model of long QT3. Am J Physiol Heart Circ Physiol. 2006; 290: H607–H612.CrossrefMedlineGoogle Scholar22 Crotti L, Lundquist AL, Insolia R, Pedrazzini M, Ferrandi C, De Ferrari GM, Vicentini A, Yang P, Roden DM, George AL Jr, Schwartz PJ. KCNH2-K897T is a genetic modifier of latent congenital long-QT syndrome Circulation. 2005; 112: 1251–1258.LinkGoogle Scholar23 Rubart M, Zipes DP. Genes and cardiac repolarization: the challenge ahead. Circulation. 2005; 112: 1242–1244.LinkGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. 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Harms P, Elders P, Rutters F, Lissenberg-Witte B, Tan H, Beulens J, Nijpels G and van der Heijden A (2023) Longitudinal association of electrocardiogram abnormalities with major adverse cardiac events in people with Type 2 diabetes: the Hoorn Diabetes Care System cohort, European Journal of Preventive Cardiology, 10.1093/eurjpc/zwac314 Mazumdar H, Bhowmik R, Shaharyar M, Mandal A, Anand K, Patra S, Kumari R, Jana S, Haldar P and Karmakar S (2023) Mechanism of action of antiarrhythmic drugs How Synthetic Drugs Work, 10.1016/B978-0-323-99855-0.00013-0, (289-327), . Mada P, Parmar P, S Y and Pannala D (2022) A review on role of autopsy in the diagnosis of sudden arrhythmic deaths, IP International Journal of Forensic Medicine and Toxicological Sciences, 10.18231/j.ijfmts.2022.009, 7:2, (39-42), Online publication date: 28-Jul-2022. Varotsos P, Sarlis N and Skordas E (2022) Order Parameter and Entropy of Seismicity in Natural Time before Major Earthquakes: Recent Results, Geosciences, 10.3390/geosciences12060225, 12:6, (225) Wu C, Lin Y, Lee I, Lo M, Hsieh Y, Chen A, Wang W, Chang S, Lo L, Hu Y, Chung F, Tuan T, Chao T, Liao J, Hsieh W, Chang T, Lin C, Feng A, How C, Chen S and Tolkacheva E (2022) Using QRS loop descriptors to characterize the risk of sudden cardiac death in patients with structurally normal hearts, PLOS ONE, 10.1371/journal.pone.0263894, 17:2, (e0263894) Zimmerman D and Tan H (2021) Epidemiology and risk factors of sudden cardiac arrest, Current Opinion in Critical Care, 10.1097/MCC.0000000000000896, 27:6, (613-616), Online publication date: 1-Dec-2021. Yamakawa H, Kato T, Noh J, Yuasa S, Kawamura A, Fukuda K and Aizawa Y (2021) Thyroid Hormone Plays an Important Role in Cardiac Function: From Bench to Bedside, Frontiers in Physiology, 10.3389/fphys.2021.606931, 12 Xie D, Wu J, Wu Q, Zhang X, Zhou D, Dai W, Zhu M and Wang D (2021) Integrating proteomic, lipidomic and metabolomic data to construct a global metabolic network of lethal ventricular tachyarrhythmias (LVTA) induced by aconitine, Journal of Proteomics, 10.1016/j.jprot.2020.104043, 232, (104043), Online publication date: 1-Feb-2021. Ben Ahmed H, Ben Khelil M, Bellali M, Shimi M, Belhaj A, Allouche M, Allouche E, Razghallah R, Banasr A, Benzarti A and Hamdoun M (2021) La mort subite cardiaque chez la femme, registre du nord de la Tunisie, Annales de Cardiologie et d'Angéiologie, 10.1016/j.ancard.2020.10.005, 70:1, (1-6), Online publication date: 1-Feb-2021. Shimizu A, Zankov D, Sato A, Komeno M, Toyoda F, Yamazaki S, Makita T, Noda T, Ikawa M, Asano Y, Miyashita Y, Takashima S, Morita H, Ishikawa T, Makita N, Hitosugi M, Matsuura H, Ohno S, Horie M and Ogita H (2020) Identification of transmembrane protein 168 mutation in familial Brugada syndrome, The FASEB Journal, 10.1096/fj.201902991R, 34:5, (6399-6417), Online publication date: 1-May-2020. Ohlsson M, Kennedy L, Juhlin T and Melander O (2020) Risk prediction of future cardiac arrest by evaluation of a genetic risk score alone and in combination with traditional risk factors, Resuscitation, 10.1016/j.resuscitation.2019.11.005, 146, (74-79), Online publication date: 1-Jan-2020. Hussein A and Wilkoff B (2019) Cardiac Implantable Electronic Device Therapy in Heart Failure, Circulation Research, 124:11, (1584-1597), Online publication date: 24-May-2019. Lai D, Zhang Y, Zhang X, Su Y and Bin Heyat M An Automated Strategy for Early Risk Identification of Sudden Cardiac Death by Using Machine Learning Approach on Measurable Arrhythmic Risk Markers, IEEE Access, 10.1109/ACCESS.2019.2925847, 7, (94701-94716) Cooke M and Brewer R (2019) Medical Emergencies Pediatric Dentistry, 10.1016/B978-0-323-60826-8.00010-9, (142-158), . Bisi A, Micucci M, Gobbi S, Belluti F, Budriesi R and Rampa A (2018) Cardiovascular Profile of Xanthone-Based 1,4 Dihydropyridines Bearing a Lidoflazine Pharmacophore Fragment, Molecules, 10.3390/molecules23123088, 23:12, (3088) Sarlis N, Skordas E and Varotsos P (2018) A remarkable change of the entropy of seismicity in natural time under time reversal before the super-giant M9 Tohoku earthquake on 11 March 2011, EPL (Europhysics Letters), 10.1209/0295-5075/124/29001, 124:2, (29001) Sarlis N, Skordas E, Varotsos P, Ramírez-Rojas A and Flores-Márquez E (2018) Natural time analysis: On the deadly Mexico M8.2 earthquake on 7 September 2017, Physica A: Statistical Mechanics and its Applications, 10.1016/j.physa.2018.04.098, 506, (625-634), Online publication date: 1-Sep-2018. Leonard C, Brensinger C, Aquilante C, Bilker W, Boudreau D, Deo R, Flory J, Gagne J, Mangaali M and Hennessy S (2018) Comparative Safety of Sulfonylureas and the Risk of Sudden Cardiac Arrest and Ventricular Arrhythmia, Diabetes Care, 10.2337/dc17-0294, 41:4, (713-722), Online publication date: 1-Apr-2018. Braysh K, Zerbe R, Zein R, Oueidat D, Hawi J, Oke L and Jurjus A (2018) The Advancement of Postmortem Investigations in Sudden Cardiac Death Post Mortem Examination and Autopsy - Current Issues From Death to Laboratory Analysis, 10.5772/intechopen.71555 Khazaei M, Raeisi K, Goshvarpour A and Ahmadzadeh M (2018) Early detection of sudden cardiac death using nonlinear analysis of heart rate variability, Biocybernetics and Biomedical Engineering, 10.1016/j.bbe.2018.06.003, 38:4, (931-940), . Hussein A and Chung M (2018) Prevention of Sudden Cardiac Death Chronic Coronary Artery Disease, 10.1016/B978-0-323-42880-4.00022-4, (321-336), . Petrović D, Ilić M, Ilić B, Stojanović S, Stojanović M and Simonović D Case Report of the Patient with Acute Myocardial Infarction: "From Flatline to Stent Implantation", Acta Facultatis Medicae Naissensis, 10.1515/afmnai-2017-0036, 34:4, (329-337) Ding Z, Yang M, Wang Y, Wu S, Qiu X and Liu Q (2017) Retrospective analysis of 769 cases of sudden cardiac death from 2006 to 2015: a forensic experience in China, Forensic Science, Medicine and Pathology, 10.1007/s12024-017-9888-z, 13:3, (336-341), Online publication date: 1-Sep-2017. Leonard C, Hennessy S, Han X, Siscovick D, Flory J and Deo R (2017) Pro- and Antiarrhythmic Actions of Sulfonylureas: Mechanistic and Clinical Evidence, Trends in Endocrinology & Metabolism, 10.1016/j.tem.2017.04.003, 28:8, (561-586), Online publication date: 1-Aug-2017. Karam N, Marijon E, Bougouin W, Spaulding C and Jouven X (2016) Mort subite : y a-t-il une spécificité féminine ?, Annales de Cardiologie et d'Angéiologie, 10.1016/j.ancard.2016.10.004, 65:6, (390-394), Online publication date: 1-Dec-2016. Roselli M, Carocci A, Budriesi R, Micucci M, Toma M, Di Cesare Mannelli L, Lovece A, Catalano A, Cavalluzzi M, Bruno C, De Palma A, Contino M, Perrone M, Colabufo N, Chiarini A, Franchini C, Ghelardini C, Habtemariam S and Lentini G (2016) Synthesis, antiarrhythmic activity, and toxicological evaluation of mexiletine analogues, European Journal of Medicinal Chemistry, 10.1016/j.ejmech.2016.05.046, 121, (300-307), Online publication date: 1-Oct-2016. NAGIBIN V, EGAN BENOVA T, VICZENCZOVA C, SZEIFFOVA BACOVA B, DOVINOVA I, BARANCIK M and TRIBULOVA N (2016) Ageing Related Down-Regulation of Myocardial Connexin-43 and Up-Regulation of MMP-2 May Predict Propensity to Atrial Fibrillation in Experimental Animals, Physiological Research, 10.33549/physiolres.933389, (S91-S100), Online publication date: 29-Sep-2016. Fujita H, Acharya U, Sudarshan V, Ghista D, Sree S, Eugene L and Koh J (2016) Sudden cardiac death (SCD) prediction based on nonlinear heart rate variability features and SCD index, Applied Soft Computing, 10.1016/j.asoc.2016.02.049, 43, (510-519), Online publication date: 1-Jun-2016. Scorza F, Scorza C and Ferraz H (2016) Domperidone, Parkinson disease and sudden cardiac death: Mice and men show the way, Clinics, 10.6061/clinics/2016(02)01, 71:2, (59-61), Online publication date: 1-Feb-2016. Connolly A and Bishop M (2016) Computational Representations of Myocardial Infarct Scars and Implications for Arrhythmogenesis, Clinical Medicine Insights: Cardiology, 10.4137/CMC.S39708, 10s1, (CMC.S39708), Online publication date: 1-Jan-2016. Zhao P, Wang J, Gao P, Li X and Brewer R (2016) Sudden unexpected death from natural diseases: Fifteen years' experience with 484 cases in Seychelles, Journal of Forensic and Legal Medicine, 10.1016/j.jflm.2015.10.004, 37, (33-38), Online publication date: 1-Jan-2016. Bernotiene G, Radisauskas R, Tamosiunas A and Milasauskiene Z (2015) Trends in out-of-hospital ischemic heart disease mortality for the 25–64 year old population of Kaunas, Lithuania, based on data from the 1988–2012 Ischemic Heart Disease Registry, Scandinavian Journal of Public Health, 10.1177/1403494815586294, 43:6, (648-656), Online publication date: 1-Aug-2015. Child N, Bishop M, Hanson B, Coronel R, Opthof T, Boukens B, Walton R, Efimov I, Bostock J, Hill Y, Rinaldi C, Razavi R, Gill J and Taggart P (2015) An activation-repolarization time metric to predict localized regions of high susceptibility to reentry, Heart Rhythm, 10.1016/j.hrthm.2015.04.013, 12:7, (1644-1653), Online publication date: 1-Jul-2015. Hayashi M, Shimizu W and Albert C (2015) The Spectrum of Epidemiology Underlying Sudden Cardiac Death, Circulation Research, 116:12, (1887-1906), Online publication date: 5-Jun-2015. Baris O, Ederer S, Neuhaus J, von Kleist-Retzow J, Wunderlich C, Pal M, Wunderlich F, Peeva V, Zsurka G, Kunz W, Hickethier T, Bunck A, Stöckigt F, Schrickel J and Wiesner R (2015) Mosaic Deficiency in Mitochondrial Oxidative Metabolism Promotes Cardiac Arrhythmia during Aging, Cell Metabolism, 10.1016/j.cmet.2015.04.005, 21:5, (667-677), Online publication date: 1-May-2015. Wang M, Shan J, Yang Q, Ma X, Jin S, Guo X, You Q and Tang Y (2014) Antiarrhythmic efficacy of CPUY102122, a multiple ion channel blocker, on rabbits with ischemia/reperfusion injury, Pharmacological Reports, 10.1016/j.pharep.2014.06.017, 66:6, (1022-1030), Online publication date: 1-Dec-2014. Ramírez J, Laguna P, Bayés de Luna A, Malik M and Pueyo E (2014) QT/RR and T-peak-to-end/RR curvatures and slopes in chronic heart failure: Relation to sudden cardiac death, Journal of Electrocardiology, 10.1016/j.jelectrocard.2014.08.013, 47:6, (842-848), Online publication date: 1-Nov-2014. Lewek J, Kaczmarek K, Cygankiewicz I, Wranicz J and Ptaszynski P (2014) Inflammation and arrhythmias: potential mechanisms and clinical implications, Expert Review of Cardiovascular Therapy, 10.1586/14779072.2014.942286, 12:9, (1077-1085), Online publication date: 1-Sep-2014. Mehta P, Polk D, Zhang X, Li N, Painovich J, Kothawade K, Kirschner J, Qiao Y, Ma X, Chen Y, Brantman A, Shufelt C, Minissian M and Bairey Merz C (2014) A randomized controlled trial of acupuncture in stable ischemic heart disease patients, International Journal of Cardiology, 10.1016/j.ijcard.2014.07.011, 176:2, (367-374), Online publication date: 1-Sep-2014. Colquitt J, Mendes D, Clegg A, Harris P, Cooper K, Picot J and Bryant J (2014) Implantable cardioverter defibrillators for the treatment of arrhythmias and cardiac resynchronisation therapy for the treatment of heart failure: systematic review and economic evaluation, Health Technology Assessment, 10.3310/hta18560, 18:56, (1-560) Reyes J (2014) Successful extended cerebrocardiopulmonary resuscitation of a sudden death patient: A case report, Colombian Journal of Anesthesiology, 10.1016/j.rcae.2014.04.008, 42:3, (229-233), Online publication date: 1-Jul-2014. García Reyes J (2014) Reanimación cerebrocardiopulmonar prolongada exitosa en un paciente con muerte súbita: un reporte de caso, Revista Colombiana de Anestesiología, 10.1016/j.rca.2014.03.006, 42:3, (229-233), Online publication date: 1-Jul-2014. Morillo C (2014) Sudden cardiac death: improving our pathological diagnosis--are we there yet?, Europace, 10.1093/europace/eut433, 16:6, (785-786), Online publication date: 1-Jun-2014. Anzai T, Frey M and Nogami A (2014) Cardiac arrhythmias during long-duration spaceflights, Journal of Arrhythmia, 10.1016/j.joa.2013.07.009, 30:3, (139-149), Online publication date: 1-Jun-20