Sudden Cardiac Death In Individuals Research Articles

Common Variants in Cardiac Ion Channel Genes Are Associated With Sudden Cardiac Death

Rare variants in cardiac ion channel genes are associated with sudden cardiac death in rare primary arrhythmic syndromes; however, it is unknown whether common variation in these same genes may contribute to sudden cardiac death risk at the population level. We examined the association between 147 single nucleotide polymorphisms (SNPs) (137 tag, 5 noncoding SNPs associated with QT interval duration, and 5 nonsynonymous SNPs) in 5 cardiac ion channel genes, KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2, and sudden and/or arrhythmic death in a combined nested case-control analysis among 516 cases and 1522 matched control subjects of European ancestry enrolled in 6 prospective cohort studies. After accounting for multiple testing, 2 SNPs (rs2283222 located in intron 11 in KCNQ1 and rs11720524 located in intron 1 in SCN5A) remained significantly associated with sudden/arrhythmic death (false discovery rate=0.01 and 0.03, respectively). Each increasing copy of the major T-allele of rs2283222 or the major C-allele of rs1172052 was associated with an odds ratio of 1.36 (95% confidence interval, 1.16 to 1.60; P=0.0002) and 1.30 (95% confidence interval, 1.12 to 1.51; P=0.0005), respectively. Control for cardiovascular risk factors and/or limiting the analysis to definite sudden cardiac death did not significantly alter these relationships. In this combined analysis of 6 prospective cohort studies, 2 common intronic variants in KCNQ1 and SCN5A were associated with sudden cardiac death in individuals of European ancestry. Further study in other populations and investigation into the functional abnormalities associated with noncoding variation in these genes may lead to important insights into predisposition to lethal arrhythmias.

Cardiac amyloidosis and Brugada-like ECG pattern

The Brugada syndrome is an inherited channelopathy associated with a high propensity of ventricular tachyarrhythmias and sudden cardiac death in individuals with structurally normal hearts. Recent data are indicative of mild structural changes, mainly involving the right ventricle, in patients with Brugada syndrome. We present the case of a patient with cardiac amyloidosis due to multiple myeloma who presented with pre-syncopal episodes and intermittent Brugada-like ECG pattern.

Drugs and Brugada syndrome patients: Review of the literature, recommendations, and an up-to-date website (www.brugadadrugs.org)

Worldwide, the Brugada syndrome has been recognized as an important cause of sudden cardiac death in individuals at a relatively young age. Importantly, many drugs have been reported to induce the characteristic Brugada syndrome-linked ECG abnormalities and/or (fatal) ventricular tachyarrhythmias. The purpose of this study was to review the literature on the use of drugs in Brugada syndrome patients, to make recommendations based on the literature and on expert opinion regarding drug safety, and to ensure worldwide online and up-to-date availability of this information to all physicians who treat Brugada syndrome patients. We performed an extensive review of the literature, formed an international expert panel to produce a consensus recommendation to each drug, and initiated a website (www.brugadadrugs.org). The literature search yielded 506 reports for consideration. Drugs were categorized into one of four categories: (1) drugs to be avoided (n = 18); (2) drugs preferably avoided (n = 23); (3) antiarrhythmic drugs (n = 4); and (4) diagnostic drugs (n = 4). Level of evidence for most associations was C (only consensus opinion of experts, case studies, or standard-of-care) as there are no randomized studies and few nonrandomized studies in Brugada syndrome patients. Many drugs have been associated with adverse events in Brugada syndrome patients. We have initiated a website (www.brugadadrugs.org) to ensure worldwide availability of information on safe drug use in Brugada syndrome patients.

Vitamin D Deficiency and Risk for Cardiovascular Disease

Vitamin D is an important prohormone for optimal intestinal calcium absorption for mineralization of bone. Because the vitamin D receptor is present in multiple tissues, there has been interest in evaluating other potential functions of vitamin D, particularly, in cardiovascular diseases (CVD). Cross-sectional studies have reported that vitamin D deficiency is associated with increased risk of CVD, including hypertension, heart failure, and ischemic heart disease. Initial prospective studies have also demonstrated that vitamin D deficiency increases the risk of developing incident hypertension or sudden cardiac death in individuals with preexisting CVD. Very few prospective clinical studies have been conducted to examine the effect of vitamin D supplementation on cardiovascular outcomes. The mechanism for how vitamin D may improve CVD outcomes remains obscure; however, potential hypotheses include the downregulation of the reninangiotensin-aldosterone system, direct effects on the heart, and vasculature or improvement of glycemic control. This review will examine the epidemiologic and clinical evidence for vitamin D deficiency as a cardiovascular risk factor and explore potential mechanisms for the cardioprotective effect of vitamin D.

Is ICD necessary for primary prevention of sudden cardiac death in individuals with asymptomatic Brugada-type ECG?

Is ICD necessary for primary prevention of sudden cardiac death in individuals with asymptomatic Brugada-type ECG?

Noxious arousal induces T-wave changes in healthy subjects

Background Sudden arousal has been associated with sudden cardiac death in individuals with ischemic heart disease, cardiac arrhythmias, and the congenital long QT syndrome. This study aimed to determine the effects of arousal on ventricular repolarization in normal individuals by examining the dynamic QT interval–heart rate relationship and T-wave morphology changes under various “arousal” scenarios. Methods Eighteen healthy subjects (6 women and 12 men; median age, 22 years) underwent 4 separate 24-hour electrocardiogram recordings using 2-channel Holter recorders. The protocol contained 5 different arousal events: (1) natural waking (woke naturally, then stood up), (2) morning alarm (woken by alarm in the morning, then stood up); (3) night alarm (woken by alarm during the night, then stood up), (4) morning alarm–remain lying (woken by alarm in the morning but remained supine), and (5) lying to standing (stood up from a supine position during the day). Holter recordings were analyzed using a commercial package for dynamic assessment of the QT/RR relationship. Results In the 20 minutes after arousal, no changes were seen in overall QT/RR relationship in any of the groups. However, marked T-wave morphology changes, including T-wave inversion, were observed in all the arousal events. Postural changes only accounted for a small proportion of change in T-wave morphology. Conclusions In healthy subjects, noxious arousal causes marked changes in the morphology of the T wave. This may reflect abnormal adaptation of repolarization to sudden changes in heart rate and autonomic tone.

Noxious Arousal Induces T Wave Abnormalities in Healthy Subjects

Background Sudden arousal has been associated with sudden cardiac death in individuals with ischaemic heart disease, cardiac arrhythmias and the congenital long QT syndrome. This study aimed to determine the effects of arousal on ventricular repolarisation in normal individuals by examining the dynamic QT-interval-heart rate relationship and T-wave morphology changes under various ‘arousal’ scenarios. Methods 18 healthy subjects (6 female, 12 male, median age 22) underwent four separate 24-hour ECG recordings using 2-channel Holter recorders. The protocol contained five different arousal events: Natural Waking (woke naturally, then stood up); Morning Alarm (woken by alarm in the morning, then stood up); Night Alarm (woken by alarm during the night, then stood up); Morning Alarm-Remain Lying (woken by alarm in the morning but remained supine) and Lying to Standing (stood up from a supine position during the day). Holter recordings were analysed using a commercial package for dynamic assessment of the QT-RR relationship. Results In the twenty minutes after arousal no changes were seen in overall QT-RR relationship in any of the groups. However, marked T-wave morphology changes, including T wave inversion, were observed in all the arousal events. Postural changes only accounted for a small proportion of change in T wave morphology. Conclusions In healthy subjects noxious arousal causes marked changes in the morphology of the T wave. This may reflect abnormal adaptation of repolarisation to sudden changes in heart rate and autonomic tone.

Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of brugada syndrome and no previous cardiac arrest

Background— Patients with Brugada syndrome who were resuscitated from an episode of ventricular fibrillation are at high risk for recurrent sudden death. There is general agreement about the therapeutic strategy for these patients. Conversely, the prognosis and approach in patients with a diagnostic ECG but without a previous history of sudden cardiac death is controversial. We analyzed a large cohort of patients with Brugada syndrome without previous cardiac arrest to understand the determinants of prognosis. Methods and Results— A total of 547 patients with an ECG diagnostic of Brugada syndrome and no previous cardiac arrest were studied. The mean age was 41±15 years, and 408 were male. The diagnostic ECG was present spontaneously in 391 patients. In the remaining 156 individuals, the abnormal ECG was noted only after the administration of an antiarrhythmic drug. One hundred twenty-four patients had suffered from at least 1 episode of syncope. During programmed ventricular stimulation, a sustained ventr...

Sudden death prevented in hypertrophic cardiomyopathy

The most common cause of sudden cardiac death in individuals aged less than 35 years, including competitive athletes, is the inherited disorder hypertrophic cardiomyopathy (HCM). Until recently, no therapeutic intervention had been identified to prevent sudden death in HCM. This case report highlights the role of the implantable cardioverter defibrillator (ICD) in preventing sudden death in patients with HCM. The report highlights the importance of risk stratification in patients with HCM in order to identify those individuals who would most likely benefit from ICD therapy. The ICD implantation is now the treatment of choice in preventing sudden death in selected (highest risk) populations with HCM. In the future, understanding the molecular basis of sudden death in HCM may identify potential new gene-based therapeutic strategies.

Cocaethylene and heart disease during murine AIDS

Cocaethylene is an active cocaine metabolite believed to play a causative role in the increased incidence of sudden cardiac death in individuals who co-administer alcohol and cocaine. Prolonged and excessive abuse of cocaine and alcohol will result in marked alteration of host immunity to increased susceptibility to infection. To test the chronic direct effect of cocaethylene on the heart function, a conductance catheter system (CCS) was used in vivo in this study. To test whether cocaethylene injection exacerbates coxsackievirus B3 (CVB3) or cytomegalovirus (CMV) cardiomyopathy during murine AIDS, female C57BL/6 mice were infected with LP-BM5 retrovirus and superinfected with CVB3 or CMV. Daily, mice were injected intraperitoneally with cocaethylene in 0.9% saline solution (concentration increased gradually from 15 to 25 mg/ml). Histopathology of heart tissue was analyzed in all groups, and cytokines of spleen were measured in the CMV-infected groups. Results showed there was little effect on the cardiovascular system after cocaethylene injection. Cocaethylene injection during murine retrovirus infection greatly exacerbated the pathogenesis of CVB3 or CMV infection, whereas CMV-infected mice showed relatively moderate cardiac pathology compared with CVB3 infection. Both CMV and retrovirus infection suppressed the Th1 response. Our data suggest that cocaethylene treatment shifts the cytokine balance and suppresses Th1 response particularly, facilitating increased CVB3- or CMV-induced myocarditis.

Sports-related and non-sports-related sudden cardiac death in young adults

Sports-related sudden cardiac deaths were compared with non-sports-related sudden cardiac death in individuals (14 to 40 years old) who were autopsied from 1981 to 1988 at the Maryland Medical Examiner's Office. Thirty-four of 690 total cases of sudden cardiac death were sports-related, which represents 5% of sudden cardiac death in this age group. Causes of death were severe atherosclerosis (nine), hypertrophic cardiomyopathy with asymmetry (eight), coronary artery anomalies (four), idiopathic concentric left ventricular hypertrophy (three), myocarditis (two), arrhythmogenic right ventricle (one), Kawasaki disease (one), and unknown (six); two of the cases with unknown causes had tunnel arteries. Exercise-related deaths were more likely due to hypertrophic cardiomyopathy (p = 0.0007) compared with 102 age-, sex-, and race-matched controls in the nonexercise group; there was no difference in the incidence of severe atherosclerosis (p = 0.4). The mean age of individuals with hypertrophic cardiomyopathy with asymmetry was less than that of those with severe atherosclerosis (24 vs 32 years, p = 0.03). Thus exercise precipitates sudden cardiac death in younger individuals with hypertrophic cardiomyopathy.

Quantitation of human interleukin-6 in peripheral blood mononuclear cell culture supernatants by ELISA: [formula omitted] Genzyme Corp., Boston, MA 02111

Cocaethylene is an active cocaine metabolite believed to play a causative role in the increased incidence of sudden cardiac death in individuals who co-administer alcohol and cocaine. Prolonged and excessive abuse of cocaine and alcohol will result in marked alteration of host immunity to increased susceptibility to infection. To test the chronic direct effect of cocaethylene on the heart function, a conductance catheter system (CCS) was used in vivo in this study. To test whether cocaethylene injection exacerbates coxsackievirus B3 (CVB3) or cytomegalovirus (CMV) cardiomyopathy during murine AIDS, female C57BL/6 mice were infected with LP-BM5 retrovirus and superinfected with CVB3 or CMV. Daily, mice were injected intraperitoneally with cocaethylene in 0.9% saline solution (concentration increased gradually from 15 to 25 mg/ml). Histopathology of heart tissue was analyzed in all groups, and cytokines of spleen were measured in the CMV-infected groups. Results showed there was little effect on the cardiovascular system after cocaethylene injection. Cocaethylene injection during murine retrovirus infection greatly exacerbated the pathogenesis of CVB3 or CMV infection, whereas CMV-infected mice showed relatively moderate cardiac pathology compared with CVB3 infection. Both CMV and retrovirus infection suppressed the Th1 response. Our data suggest that cocaethylene treatment shifts the cytokine balance and suppresses Th1 response particularly, facilitating increased CVB3- or CMV-induced myocarditis.

Fibronectin and the spontaneous growth of scleroderma lung fibroblasts cultured from bronchoalveolar lavage fluid: [formula omitted]. Med Univ of South Carolina, Charleston, SC 29425

Cocaethylene is an active cocaine metabolite believed to play a causative role in the increased incidence of sudden cardiac death in individuals who co-administer alcohol and cocaine. Prolonged and excessive abuse of cocaine and alcohol will result in marked alteration of host immunity to increased susceptibility to infection. To test the chronic direct effect of cocaethylene on the heart function, a conductance catheter system (CCS) was used in vivo in this study. To test whether cocaethylene injection exacerbates coxsackievirus B3 (CVB3) or cytomegalovirus (CMV) cardiomyopathy during murine AIDS, female C57BL/6 mice were infected with LP-BM5 retrovirus and superinfected with CVB3 or CMV. Daily, mice were injected intraperitoneally with cocaethylene in 0.9% saline solution (concentration increased gradually from 15 to 25 mg/ml). Histopathology of heart tissue was analyzed in all groups, and cytokines of spleen were measured in the CMV-infected groups. Results showed there was little effect on the cardiovascular system after cocaethylene injection. Cocaethylene injection during murine retrovirus infection greatly exacerbated the pathogenesis of CVB3 or CMV infection, whereas CMV-infected mice showed relatively moderate cardiac pathology compared with CVB3 infection. Both CMV and retrovirus infection suppressed the Th1 response. Our data suggest that cocaethylene treatment shifts the cytokine balance and suppresses Th1 response particularly, facilitating increased CVB3- or CMV-induced myocarditis.

Ventricular Tachyarrhythmia Associated With Psychological Stress

Psychological stress has been reported to be a risk factor for sudden cardiac death in individuals both with and without underlying structural heart disease. From a group of 80 patients presenting with life-threatening ventricular tachyarrhythmia, six were identified without underlying structural heart disease. Five of these six patients experienced marked psychological stress. Each of these five patients underwent arrhythmia evaluation, demonstrating recurrent rapid monomorphic ventricular tachycardia related to changes in tone of the sympathetic nervous system. Subsequently, solitary beta-adrenergic blocker therapy was given to each patient. During therapy, four of the five patients had a marked reduction of both arrhythmia and symptoms during a follow-up ranging from 29 to 49 (mean, 38) months.