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Relative peak exercise oxygen pulse is related to sudden cardiac death, cardiovascular and all-cause mortality in middle-aged men.
Laukkanen, JA, Araújo, CGS, Kurl, S, Khan, H, Jae, SY, Guazzi, M, Kunutsor, SK
European journal of preventive cardiology. 2018;(7):772-782
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Abstract
Background Preliminary evidence suggests that peak exercise oxygen pulse - peak oxygen uptake/heart rate-, a variable obtained during maximal cardiopulmonary exercise testing and a surrogate of stroke volume, is a predictor of mortality. We aimed to assess the associations of peak exercise oxygen pulse with sudden cardiac death, fatal coronary heart disease and cardiovascular disease and all-cause mortality. Design A prospective study. Methods Peak exercise oxygen pulse was assessed in a maximal cycling test at baseline in 2227 middle-aged men of the Kuopio Ischaemic Heart Disease cohort study using expired gas variables and electrocardiograms. Relative peak exercise oxygen pulse was obtained by dividing the absolute value by body weight. Results During a median follow-up of 26.1 years 1097 subjects died; there were 220 sudden cardiac deaths, 336 fatal coronary heart diseases and 505 fatal cardiovascular diseases. Relative peak exercise oxygen pulse (mean 19.5 (4.1) mL per beat/kg/102) was approximately linearly associated with each outcome. Comparing extreme quartiles of relative peak exercise oxygen pulse, hazard ratios (95% confidence intervals) for sudden cardiac death, fatal coronary heart disease and cardiovascular disease, and all-cause mortality on adjustment for cardiovascular risk factors were 0.55 (0.36-0.83), 0.58 (0.42-0.81), 0.60 (0.46-0.79) and 0.59 (0.49-0.70), respectively ( P < 0.001 for all). The hazard ratios were unchanged on further adjustment for C-reactive protein and the use of beta-blockers. The addition of relative peak exercise oxygen pulse to a cardiovascular disease mortality risk prediction model significantly improved risk discrimination (C-index change 0.0112; P = 0.030). Conclusion Relative peak exercise oxygen pulse measured during maximal exercise was linearly and inversely associated with fatal cardiovascular and all-cause mortality events in middle-aged men. In addition, relative peak exercise oxygen pulse provided significant improvement in cardiovascular disease mortality risk assessment beyond conventional risk factors.
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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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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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Reappraisal of Reported Genes for Sudden Arrhythmic Death: Evidence-Based Evaluation of Gene Validity for Brugada Syndrome.
Hosseini, SM, Kim, R, Udupa, S, Costain, G, Jobling, R, Liston, E, Jamal, SM, Szybowska, M, Morel, CF, Bowdin, S, et al
Circulation. 2018;(12):1195-1205
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Abstract
BACKGROUND Implicit in the genetic evaluation of patients with suspected genetic diseases is the assumption that the genes evaluated are causative for the disease based on robust scientific and statistical evidence. However, in the past 20 years, considerable variability has existed in the study design and quality of evidence supporting reported gene-disease associations, raising concerns of the validity of many published disease-causing genes. Brugada syndrome (BrS) is an arrhythmia syndrome with a risk of sudden death. More than 20 genes have been reported to cause BrS and are assessed routinely on genetic testing panels in the absence of a systematic, evidence-based evaluation of the evidence supporting the causality of these genes. METHODS We evaluated the clinical validity of genes tested by diagnostic laboratories for BrS by assembling 3 gene curation teams. Using an evidence-based semiquantitative scoring system of genetic and experimental evidence for gene-disease associations, curation teams independently classified genes as demonstrating limited, moderate, strong, or definitive evidence for disease causation in BrS. The classification of curator teams was reviewed by a clinical domain expert panel that could modify the classifications based on their independent review and consensus. RESULTS Of 21 genes curated for clinical validity, biocurators classified only 1 gene ( SCN5A) as definitive evidence, whereas all other genes were classified as limited evidence. After comprehensive review by the clinical domain Expert panel, all 20 genes classified as limited evidence were reclassified as disputed with regard to any assertions of disease causality for BrS. CONCLUSIONS Our results contest the clinical validity of all but 1 gene clinically tested and reported to be associated with BrS. These findings warrant a systematic, evidence-based evaluation for reported gene-disease associations before use in patient care.
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Combined effect of renal function and serum potassium level in sudden cardiac death in aging hypertensive subjects.
Fauvel, JP, Gueyffier, F, Thijs, L, Ducher, M
Hypertension research : official journal of the Japanese Society of Hypertension. 2018;(6):469-474
Abstract
In patients with chronic kidney disease, serum potassium level is a factor influencing sudden cardiac death (SCD). The aim of our analysis was to study the combined effect of serum potassium level and renal function on the onset of SCD in elderly hypertensive subjects. Data from the 3620 hypertensive patients aged over 70 years were extracted from three randomized clinical trials included in the INDANA database. During a mean follow up of 4.5 years, 81 patients (2.24%) died from SCD. Mean serum potassium levels and prevalence of chronic kidney disease were not different in patients who died from SCD. In addition to serum potassium and creatinine levels, 14 clinical and biological variables linked to cardiovascular diseases recorded at baseline were analyzed using a Bayesian network. The area under the receiver operating characteristic curve of the Bayesian model reached 0.91. Bayesian inference was used to simulate the combined effects of serum potassium and creatinine levels on SCD. Our analysis, using simulated data from Bayesian model, showed that the estimated probabilities of SCD was significantly increased in case of hyperkalemia (>5.0 mmol/l) and in case of hypokalemia (<3.5 mmol/l) and in case of chronic kidney disease. Combined effects of serum potassium level and renal function revealed that chronic kidney disease increased the probability of SCD whatever the serum potassium level. Our results using a Bayesian model confirm the deleterious effects of hypokalemia, hyperkalemia and chronic kidney disease on SCD in elderly hypertensive patients.
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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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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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Leptin predicts short-term major adverse cardiac events in patients with coronary artery disease.
Puurunen, VP, Kiviniemi, A, Lepojärvi, S, Piira, OP, Hedberg, P, Junttila, J, Ukkola, O, Huikuri, H
Annals of medicine. 2017;(5):448-454
Abstract
INTRODUCTION Leptin is an adipose tissue-derived hormone associated with cardiovascular risk factors. We examined whether leptin predicts major adverse cardiac events (MACE) in coronary artery disease (CAD) patients. METHODS Fasting plasma leptin levels were measured in 1327 male and 619 female CAD patients. The patients were followed up for two years. The primary endpoint (MACE) was the composite of a hospitalisation for congestive heart failure (CHF) or a cardiac death. The secondary endpoint was the composite of an acute coronary syndrome (ACS) or a stroke. RESULTS In regression analysis including established risk variables, high leptin levels were associated with a significantly increased risk of MACE (HR 3.37; 95%CI 1.64-6.90; p = 0.001) and ACS or stroke (HR 1.95; 95%CI 1.29-2.96; p = 0.002). Adding leptin to the risk model for MACE increased the C-index from 0.78 (95%CI 0.71-0.85) to 0.81 (0.74-0.88) and improved classification (NRI 0.36; 95%CI 0.13-0.60; p = 0.002) and discrimination of the patients (IDI 0.016; 95%CI 0.001-0.030; p = 0.031). CONCLUSIONS High plasma leptin levels predict short-term occurrence of CHF or cardiac death and ACS or stroke in patients with CAD independently of established risk factors. The possible harmful effects of leptin should be thoroughly investigated. Key messages Leptin is a peptide hormone secreted mainly by adipose tissue. It has been associated with several cardiovascular risk factors. High leptin levels predict the short-term occurrence of congestive heart failure or cardiac death and ACS or stroke in patients with CAD independently of established risk factors. The possible detrimental effects of leptin on the cardiovascular system should be thoroughly investigated.
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Genotype-phenotype dilemma in a case of sudden cardiac death with the E1053K mutation and a deletion in the SCN5A gene.
Jenewein, T, Beckmann, BM, Rose, S, Osterhues, HH, Schmidt, U, Wolpert, C, Miny, P, Marschall, C, Alders, M, Bezzina, CR, et al
Forensic science international. 2017;:187-194
Abstract
Mutations in the cardiac sodium channel gene SCN5A may result in various arrhythmia syndromes such as long QT syndrome type 3 (LQTS), Brugada syndrome (BrS), sick sinus syndrome (SSS), cardiac conduction diseases (CCD) and possibly dilated cardiomyopathy (DCM). In most of these inherited cardiac arrhythmia syndromes the phenotypical expression may range from asymptomatic phenotypes to sudden cardiac death (SCD). A 16-year-old female died during sleep. Autopsy did not reveal any explanation for her death and a genetic analysis was performed. A variant in the SCN5A gene (E1053K) that was previously described as disease causing was detected. Family members are carriers of the same E1053K variant, some even in a homozygous state, but surprisingly did not exhibit any pathological cardiac phenotype. Due to the lack of genotype-phenotype correlation further genetic studies were performed. A novel deletion in the promoter region of SCN5A was identified in the sudden death victim but was absent in other family members. These findings demonstrate the difficulties in interpreting the results of a family-based genetic screening and underline the phenotypic variability of SCN5A mutations.
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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.