Sudden Cardiac Death In Subjects Research Articles

Viral myocarditis in combination with genetic cardiomyopathy as a cause of sudden death. An autopsy series

Sudden cardiac death (SCD) is a major public health issue worldwide. In the young (< 40 years of age), genetic cardiomyopathies and viral myocarditis, sometimes in combination, are the most frequent, but underestimated, causes of SCD. Molecular autopsy is essential for prevention. Several studies have shown an association between genetic cardiomyopathies and viral myocarditis, which is probably underestimated due to insufficient post-mortem investigations. We report on four autopsy cases illustrating the pathogenesis of these combined pathologies. In two cases, a genetic hypertrophic cardiomyopathy was diagnosed in combination with Herpes Virus Type 6 (HHV6) and/or Parvovirus-B19 (PVB19) in the heart. In the third case, autopsy revealed a dilated cardiomyopathy and virological analyses revealed acute myocarditis caused by three viruses: PVB19, HHV6 and Epstein-Barr virus. Genetic analyses revealed a mutation in the gene coding for desmin. The fourth case illustrated a channelopathy and a PVB19/HHV6 coinfection. Our four cases illustrate the highly probable deleterious role of cardiotropic viruses in the occurrence of SCD in subjects with genetic cardiomyopathies. We discuss the pathogenetic link between viral myocarditis and genetic cardiomyopathy. Molecular autopsy is essential in prevention of these SCD, and a close collaboration between cardiologists, pathologists, microbiologists and geneticians is mandatory.

Interplay Between Fitness, Systolic Blood Pressure and Sudden Cardiac Death (from a Cohort Study)

Modifiable risk factors, such as blood pressure and cardiorespiratory fitness (CRF) play a role in the genesis of sudden cardiac death (SCD). However, data on their joint contributions to SCD risk are scarce. We aimed to evaluate the interplay between systolic blood pressure (SBP), CRF, and SCD risk in a cohort of men. Resting SBP was measured using a random-zero sphygmomanometer and CRF was assessed using a respiratory gas exchange analyzer during clinical exercise testing at baseline in 2,291 men aged 42 to 61years. SBP was classified as normal and high (<140 and ≥140mm Hg, respectively) and CRF as low, medium, and high. Cox regression analysis was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for SCD. A total of 262 SCDs occurred during a median follow-up of 28.2years. Comparing high versus normal SBP, the multivariable-adjusted HR (95% CI) for SCD was 1.35 (1.03 to 1.76). Comparing low versus high CRF levels, the corresponding adjusted HR (95% CI) for SCD was 1.81 (1.23 to 2.65). The HRs remained similar when SBP was further adjusted for CRF and CRF was further adjusted for SBP. Men with high SBP and low CRF compared with normal SBP and medium-high CRF, had an increased risk of SCD (HR 2.67, 95% CI 1.76 to 4.05), with no significant evidence of an association between men with high SBP and medium-high CRF and SCD risk (HR 1.38, 95% CI 0.84 to 2.26). There was modest evidence of an additive interaction between SBP and CRF in relation to SCD. In conclusion, there exists an interplay between SBP, CRF, and SCD risk in middle-aged and older men. Medium to high CRF levels may mitigate the increased risk of SCD in subjects with high SBP.

Risk stratification of sudden cardiac death in subjects with asymptomatic ventricular preexcitation: diagnostic value of non-invasive and invasive methods

Abstract Introduction In subjects with asymptomatic ventricular preexcitation (AVP) guidelines recommend follow-up by non-invasive methods. However, in some patients accessory pathways (APs) show high-risk invasive parameters and risk of sudden death. Objectives To assess the association between the non-invasive and invasive risk stratification (NIRS and IRS) in AVP patients in our center. Material and methods Retrospective and observational study in 58 patients with AVP, underwent NIRS and IRS. Association between NIRS (electrocardiogram, holter and ergometry testing) and IRS variables (AERP ≤250 msec, SPERRI ≤250 msec, atrioventricular reentrant tachycardia or AF, multiple APs) from the electrophysiological study (EPS), and sensitivity and specificity of NIRS to predict a high-risk EPS were determined. Results Of patients with high-risk EPS (n=41), 55% had a previously low-risk NIRS (n=11) while 78% (n=30) had a high-risk NIRS (p=0.05). A low-risk NIRS had a sensitivity (S) 27% and specificity (E) 47% to predict a high-risk EPS. Conclusions In our population, 1 of every 2 patients with low-risk NIRS presented a high-risk IRS. The NIRS methods present low S and E for risk stratification in AVP patients. Funding Acknowledgement Type of funding sources: None.

Poor R-wave progression as a predictor of sudden cardiac death in the general population and subjects with coronary artery disease

Poor R-wave progression (PRWP) is a common clinical finding on the standard 12-lead electrocardiogram (ECG), but its prognostic significance is unclear. The purpose of this study was to examine the prognosis associated with PRWP in terms of sudden cardiac death (SCD), cardiac death, and all-cause mortality in general population subjects with and without coronary artery disease (CAD). Data and 12-lead ECGs were collected from a Finnish general population health examination survey conducted during 1978-1980 with follow-up until 2011. The study population consisted of 6854 subjects. Main end points were SCD, cardiac death, and all-cause mortality. PRWP was defined as R-wave amplitude ≤ 0.3 mV in lead V3 and R-wave amplitude in lead V2 ≤ R-wave amplitude in lead V3. PRWP occurred in 213 subjects (3.1%). During the follow-up period of 24.3 ± 10.4 years, 3723 subjects (54.3%) died. PRWP was associated with older age, higher prevalence of heart failure and CAD, and β-blocker medication. In multivariate analyses, PRWP was associated with SCD (hazard ratio [HR] 2.13; 95% confidence interval [CI] 1.34-3.39), cardiac death (HR 1.75; 95% CI 1.35-2.15), and all-cause mortality (HR 1.29; 95% CI 1.08-1.54). In the subgroup with CAD, PRWP had a stronger association with cardiac mortality (HR 1.71; 95% CI 1.19-2.46) than in the subgroup without CAD, while the association with SCD was significant only in the subgroup with CAD (HR 2.62; 95% CI 1.38-4.98). PRWP was associated with adverse prognosis in the general population and with SCD in subjects with CAD.

Impact of age and sex on the long-term prognosis associated with early repolarization in the general population

Early repolarization (ER) has been linked to the risk of sudden cardiac death (SCD) in the general population, although controversy remains regarding risks across various subgroups. The purpose of this study was to investigate whether age and sex influence the prognostic significance of ER. We evaluated the 12-lead electrocardiograms of 6631 Finnish general population subjects age ≥30 years (mean age 50.1 ± 13.9 years; 44.5% men) for the presence of ER (J-point elevation ≥0.1 mV in ≥2 inferior/lateral leads) and followed them for 24.4 ± 10.3 years. We analyzed the association between ER and the risk of SCD, cardiac death, and all-cause mortality in subgroups according to age (<50 or ≥50 years) and sex. ER was present in 367 of the 3305 subjects age <50 years and in 426 of 3326 subjects ≥50 years. ER was not associated with any of the endpoints in the entire study population. After adjusting for clinical factors, ER was associated with SCD (hazard ratio [HR] 1.88; 95% confidence interval [CI] 1.16-3.07) in subjects <50 but not in older subjects (interaction between ER and age group, P = .048). In the younger subgroup, women with ER had a high risk of SCD (HR 4.11; 95% CI 1.41-12.03), whereas among men ER was not associated with SCD. Finally, ER was not associated with cardiac mortality or all-cause mortality in either age group. ER is associated with SCD in subjects younger than 50 years, particularly in women, but not in subjects 50 years and older.

Electrocardiogram as a predictor of sudden cardiac death in middle-aged subjects without a known cardiac disease

BackgroundAbnormal 12‑lead electrocardiogram (ECG) findings and proposing its ability for enhanced risk prediction, majority of the studies have been carried out with elderly populations with prior cardiovascular diseases. This study aims to denote the association of sudden cardiac death (SCD) and various abnormal ECG morphologies using middle-aged population without a known cardiac disease. MethodsIn total, 9511 middle-aged subjects (mean age 42 ± 8.2 years, 52% males) without a known cardiac disease were included in this study. Risk for SCD was assessed after 10 and 30-years of follow-up. ResultsAbnormal ECG was present in 16.3% (N = 1548) of subjects. The incidence of SCD was distinctly higher among those with any ECG abnormality in 10 and 30-year follow-ups (1.7/1000 years vs. 0.6/1000 years, P < 0.001; 3.4/1000 years vs. 1.9/1000 years, P < 0.001). At 10-year point, competing risk multivariate regression model showed HR of 1.62 (95% CI 1.0–2.6, P = 0.05) for SCD in subjects with abnormal ECG. QRS duration ≥ 110 ms, QRST-angle > 100°, left ventricular hypertrophy, and T-wave inversions were the most significant independent ECG risk markers for 10-year SCD prediction with up to 3-fold risk for SCD. Those with ECG abnormalities had a 1.3-fold risk (95% CI 1.07–1.57, P = 0.007) for SCD in 30-year follow-up, whereas QRST-angle > 100°, LVH, ER ≥ 0.1 mV and ≥0.2 mV were the strongest individual predictors. Subjects with multiple ECG abnormalities had up to 6.6-fold risk for SCD (P < 0.001). ConclusionSeveral ECG abnormalities are associated with the occurrence of early and late SCD events in the middle-age subjects without known history of cardiac disease.

Overexpression of miR-221 in sudden death with cardiac hypertrophy patients

BackgroundCardiac hypertrophy is a well-known risk factor for heart failure and sudden cardiac death (SCD). On the other hand, physiological cardiac hypertrophy is often observed in young healthy men, and it is difficult to predict SCD in cardiac hypertrophy subjects who do not show symptoms of heart failure. MicroRNAs (miRNAs) widely regulate biological activity and play pivotal roles in heart failure progression. In this study, we investigated whether miRNA expression is altered in SCD with cardiac hypertrophy (SCH). MethodsCardiac tissues were sampled at autopsy from SCH patients, compensated cardiac hypertrophy (CCH) subjects who died of causes other than heart failure, and control cases without cardiac hypertrophy or heart failure. After histopathological examination, we performed deep sequencing and quantitative PCR of cardiac miRNAs. Results and discussionAlthough SCH and CCH showed indistinguishable histological features, their miRNA expression signatures were distinct. Among the 240 miRNAs stably detected in the heart, 8 were differentially expressed between SCH and CCH. Specifically, miR-221 increased in SCH compared to CCH and control cases. The significant elevation of cardiac miR-221 in SCH patients is correlated with lethal outcomes. Thus, our results indicate that an elevated miR-221 level is potentially associated with an increased risk of SCD in subjects with cardiac hypertrophy.

Ten questions on Brugada syndrome

Brugada syndrome is a possible cause of sudden cardiac death in subjects with characteristic ECG pattern (type 1 Brugada ECG pattern). Brugada ECG pattern is not infrequent in the general population and the challenge is to identify within a large population those patients who are really at risk. Unfortunately, this is a partially unresolved problem and this uncertainty determines an inhomogeneous behavior among doctors. Some of them overestimate the risk extensively indicating cardioverter-defibrillator implantation, others apply restrictive indications of guidelines, many are not able to decide without doubts.In this paper we will try to clarify some doubts, to give some certain points, and to draw some perspectives for the future.

Chronic Obstructive Pulmonary Disease and Risk of Sudden Cardiac Death

ObjectivesThe purpose of this study was to determine whether chronic obstructive pulmonary disease (COPD) is associated with sudden cardiac death (SCD) in the community. BackgroundCOPD is linked to cardiovascular mortality; an association with SCD has not been systematically investigated in the general population. MethodsIn the Oregon Sudden Unexpected Death Study (approximately 1 million population), adult SCD case subjects were compared with geographic control subjects with coronary artery disease. Detailed clinical and electrocardiographic risk marker information was obtained from medical records. The association of COPD with SCD in the overall population and in a propensity score–matched dataset was assessed with logistic models. ResultsSCD case subjects (n = 728; age 69.9 ± 13.7 years) were more likely than control subjects (n = 548; age 67.2 ± 11.3 years) to have left ventricular ejection fraction ≤35% (27.5% vs. 12.0%; p < 0.0001), COPD (30.8% vs. 12.8%, p < 0.0001), diabetes mellitus (47.7% vs. 31.8%; p < 0.0001), use short-acting beta-2 agonist agents (SBAs) (22.3% vs. 12.6%; p < 0.0001), and less likely to use beta-blockers (60.6% vs. 66.4%; p = 0.03). In multivariable analysis, COPD was significantly associated with SCD (odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.4 to 3.5; p < 0.001). There was no significant interaction between COPD and medications, but an interaction was identified between SBAs and beta-blockers (p = 0.04); SBAs were strongly associated with SCD in subjects not taking beta-blockers (OR: 3.3; 95% CI: 1.4 to 7.7; p = 0.005) but not in those taking beta-blockers (OR: 1.3; 95% CI: 0.7 to 2.3; p = 0.39). The COPD-SCD association was maintained in a propensity score–matched analysis. ConclusionsCOPD is associated with SCD risk in the community independent of medications, electrocardiographic risk markers, and left ventricular ejection fraction. Among other mechanisms, pro-arrhythmogenic right ventricular remodeling and systemic inflammation warrant further investigation.

Sport und Arrhythmien

Regular exercise decreases the risk of coronary artery disease by controlling risk factors. On the other hand, vigorous exertion increases the risk of sudden cardiac death in subjects with pre-existing cardiac diseases. Long term endurance sport practice may increase the incidence of atrial fibrillation, atrial flutter and sinus node dysfunction in otherwise healthy subjects.

Uric acid is predictive of cardiovascular mortality and sudden cardiac death in subjects referred for coronary angiography

Background and aimsHigh serum uric acid (SUA) is suggested to be causally involved in the pathogenesis of vascular disease. The present study aimed to investigate whether SUA independently predicts all-cause mortality, cardiovascular mortality and sudden cardiac death in subjects scheduled for coronary angiography. Methods and resultsWe studied participants of the LUdwigshafen RIsk and Cardiovascular health (LURIC) study. A total of 3245 individuals were included in the analysis. There was a follow-up for all-cause mortality, cardiovascular mortality, and sudden cardiac death with a mean (±standard deviation) duration of 7.3 (±2.3) years. Sex-specific quartiles of SUA were established and multivariate statistical models were used. A total of 730 deaths occurred during the follow-up. Among these, 473 (64.8%) were accounted for by cardiovascular diseases. Sudden cardiac death occurred in 184 (25.2%) cases. Adjusting for sex and age subjects in the fourth SUA quartile had increased all-cause (hazard ratio (HR) = 1.68, p < 0.001) and cardiovascular (HR = 2.00, p < 0.001) mortality compared to individuals in the first quartile. Furthermore, high SUA was a risk factor for sudden cardiac death (HR = 2.27, p < 0.001). These associations remained significant including cardiovascular risk factors and the severity of coronary atherosclerosis as covariates in the models. After additional adjustment for medication use statistical significance for the association between the SUA quartiles and all-cause mortality disappeared. ConclusionHigh SUA independently indicates increased risk for cardiovascular and sudden cardiac death in subjects referred for coronary angiography.

Prolonged Tpeak-to-Tend Interval on the Resting ECG Is Associated With Increased Risk of Sudden Cardiac Death

Early studies indicate that prolongation of the interval between the peak and the end of the T wave (Tpeak to Tend [TpTe]) on the 12-lead ECG is a marker of ventricular arrhythmogenesis. However, community-based studies have not been conducted. TpTe and other ECG predictors were evaluated in the ongoing Oregon Sudden Unexpected Death Study based in the Portland, Oregon, metropolitan area using a case-control design. Cases of sudden cardiac death (SCD) (n = 353; mean age, 66.6 years; 95% CI, 65.1 to 68.1 years; 67% men) were compared with living controls with coronary artery disease (n = 342; mean age, 64.7 years; 95% CI, 63.4 to 66.0 years; 69% men) from the same region. Analysis of TpTe and selected ECG intervals was limited to sinus rhythm 12-lead ECGs. For cases, these were obtained before and unrelated to SCD. Independent-samples t tests and multiple logistic regression were used. Mean TpTe was significantly greater in cases (89.4 ms; 95% CI, 87.7 to 91.2 ms; P < 0.0001) than in controls (76.1 ms; 95% CI, 74.8 to 77.4 ms). The other ECG intervals (corrected QT interval [QTc], QRS duration [QRSD], and TpTe/QT ratio) also were significantly prolonged among cases versus controls (P ≤ 0.01). TpTe remained a significant predictor of SCD after adjusting for age, sex, QTc, QRSD, and left ventricular function. Odds of SCD increased more with a 1-SD increase in TpTe (12 ms) among subjects with prolonged QRSD (odds ratio, 3.49; 95% CI, 2.06 to 5.91) than with a 1-SD increase in TpTe among subjects with normal QRSD (odds ratio, 1.96; 95% CI, 1.65 to 2.32). TpTe remained significantly associated with SCD in subjects with normal QTc. Prolongation of the TpTe interval measured in lead V5 was independently associated with SCD, with particular utility when the QTc was normal or not measurable because of prolonged QRSD.

Relation of Atrial and/or Ventricular Premature Complexes on a Two-Minute Rhythm Strip to the Risk of Sudden Cardiac Death (the Atherosclerosis Risk in Communities [ARIC] Study)

Ventricular premature complexes (VPCs) and atrial premature complexes (APCs) are common findings on routinely obtained electrocardiograms. Despite their common occurrence, the significance of these irregular beats is unclear, especially with regard to risk of sudden cardiac death (SCD). In this study, we examined the prospective relation between baseline VPCs or APCs and SCD, myocardial infarction, and fatal coronary heart disease (CHD) in a population-based sample of subjects from the Atherosclerosis Risk in Communities (ARIC) study excluding participants with known history of CHD or stroke. Baseline examination was conducted from 1987 to 1989, with follow-up data regarding clinical cardiac events collected until December 2002. The total study population was 14,574 subjects. Kaplan-Meier curves and computed univariate and multivariate Cox proportional hazard models were employed to estimate the effect of VPC and APC occurrences on incident cardiac events. During the follow-up period, there were 130 incident cases of SCD, 1,657 incident cases of CHD cases, and 288 cases of fatal CHD. Participants with VPC were 2 times as likely to have SCD (hazard ratio [HR] 2.09, 95% confidence interval [CI] 1.22 to 3.56) compared to those without VPC. Presence of APC was not significantly associated with SCD (HR 1.15, 95% CI 0.56 to 2.39). Compared to subjects without VPC and APC, risk of SCD in subjects with VPC and APC was significantly increased (HR 6.39, 95% CI 2.58 to 15.84). In conclusion, our study shows that subjects with VPCs are significantly more likely to die from SCD, despite not having any known history of cardiovascular disease. This effect appears to be additive when APCs occur concurrently.

NT-proBNP Concentrations in Mountain Marathoners

The 76 amino acid N-terminal proB-type natriuretic peptide (NT-proBNP) is proposed for evaluating and monitoring heart pathologies characterized by myocardial wall stress. Strenuous exercise might generate transitory ischemia, myocardial stress, and diastolic left ventricular dysfunction, possibly inducing an increase of some biochemical parameter concentrations. An alert has been claimed owing to biochemical and instrumental signs of heart dysfunction in recreational athletes during marathon races. We studied the behaviour of NT-proBNP in 15 mountain marathoners before and after a race. The concentrations of the parameter were lower than that observed in controls at rest and were similar to that observed in professional soccer and rugby players. The concentrations significantly increased after the race. NT-proBNP is low at rest in professional athletes, and the increase after physical exercise is physiological. The marathoners, even when performing races in a high-altitude environment, show NT-proBNP concentrations similar to those of athletes from other sports disciplines, characterized by low levels of effort and by a mix of aerobic and anaerobic metabolism. The increase of NT-proBNP is linked to strenuous physical exercise and to heavy heart effort, testified also by an increase of troponin I. However, the role of the NT-proBNP could be important to screen recreational and professional marathoners to avoid possible heart problems and sudden cardiac death in subjects with occult heart disease. The results of the present study are relevant to the design and evaluation of training programs for improving strength and function of professional marathoners.

Asymptomatic ST-segment depression during exercise testing and the risk of sudden cardiac death in middle-aged men: a population-based follow-up study

Silent electrocardiographic ST change predicts future coronary events in patients with coronary heart disease (CHD), but the prognostic significance of asymptomatic ST-segment depression with respect to sudden cardiac death in subjects without apparent CHD is not well known. We investigated the association between silent ST-segment depression during and after maximal symptom-limited exercise test and the risk of sudden cardiac death in a population-based sample of 1769 men without evident CHD. A total of 72 sudden cardiac death occurred during the median follow-up of 18 years. The risk of sudden cardiac death was increased among men with asymptomatic ST-segment depression during exercise [hazard ratio (HR) 2.1, 95% confidence interval (CI) 1.2-3.9] as well as among those with asymptomatic ST-segment depression during recovery period (HR 3.2, 95% CI 1.7-6.0). Asymptomatic ST-depression during exercise testing was a stronger predictor for the risk of sudden cardiac death especially among smokers as well as in hypercholesterolaemic and hypertensive men than in men without these risk factors. Asymptomatic ST-segment depression was a very strong predictor of sudden cardiac death in men with any conventional risk factor but no previously diagnosed CHD, emphasizing the value of exercise testing to identify asymptomatic high-risk men who could benefit from preventive measures.

Renal insufficiency is an independent predictor of sudden cardiac death in subjects with coronary artery disease: Findings from the oregon sudden unexplained death study

Renal insufficiency is an independent predictor of sudden cardiac death in subjects with coronary artery disease: Findings from the oregon sudden unexplained death study

Bisoprolol reduces episodes of ventricular tachycardia and sudden cardiac death in subjects with chronic heart failure

Bisoprolol reduces episodes of ventricular tachycardia and sudden cardiac death in subjects with chronic heart failure

Attenuated 24-h heart rate variability in apparently healthy subjects, subsequently suffering sudden cardiac death

Attenuated cardiac parasympathetic activity appear to be an important risk factor contributing to sudden cardiac death in subjects with overt coronary disease but its predictive value in otherwise healthy normal subjects is not known. We have for 8 years followed 260 apparently healthy adult subjects who underwent Holter monitoring. Twelve died, 14 developed ischaemic heart disease and four suffered sudden cardiac death. A healthy control subject was matched, along with other risk factors, for each case. In each subject 24-h heart rate variability was calculated as the deviation of all normal R-R intervals from mean R-R (SD) and the percentage of successive R-R interval differences exceeding 6% (%DIF6%)--this was used as an index of cardiac parasympathetic activity. There were no significant differences in heart rate variability between the cases developing problems and controls. In the sudden cardiac death victims, however, there was a clear trend towards lower heart rate variability. In them waketime mean SD was 73 ms versus 85 ms for cases and controls respectively (p = 0.08), and for sleeptime 61 ms versus 76 ms (p = 0.07). Compared to normal limits for heart rate variability obtained in 140 subjects that remained healthy for 8 years, figures for both SD and %DIF6% in sudden cardiac death subjects were at or below 95% confidence limits. The results indicate that altered autonomic balance may contribute to sudden cardiac death even in apparently healthy subjects. Subjects with a low 24-h heart rate variability on Holter monitoring may be predicted at an early stage of being at greater risk.(ABSTRACT TRUNCATED AT 250 WORDS)