Search

Background: Previous data have shown that various nonischemic cardiac diseases account for about 20% of sudden cardiac deaths (SCDs) and that dilated and hypertrophic cardiomyopathy (CM) are major causes of nonischemic SCD.Objective: The purpose of this study was to define the prevalence and causes of SCD due to nonischemic CM in the current era given the substantial change in the diagnosis and treatment of cardiac diseases and in lifestyle patterns.Methods: A total of 2661 consecutive victims of SCD from among a population of approximately 470,000 inhabitants in the Province of Oulu, Northern Finland, were included in the study. The causes of deaths were determined from the uniformly required autopsies of SCD victims in Finland, plus available medical records and standardized questionnaires.Results: Nonischemic cause of SCD was found in 579 victims (21.8% of all the SCDs). Mean age (± SD) was 55 (±12) years; 78% were males. After subgrouping the nonischemic SCDs into various categories, SCDs associated most closely with obesity (23.7%), followed by alcoholic CM (19.0%), hypertensive CM (15.5%), and fibrotic CM (13.6%). Fibrotic CM was the most common association with SCD in subjects younger than 40 years (28.3%), whereas alcoholic CM was the most common cause of death in subjects between 40 and 59 years of age (25.8%).Conclusion: CM related to obesity, fibrotic CM, and alcoholic CM are commonly associated with nonischemic SCD in the current era. The association of SCD with fibrotic CM is notably frequent among victims younger than 40 years. [ABSTRACT FROM AUTHOR]

Background and Methods: In order to study fractal HR dynamics in Chagas disease, we performed detrended fluctuation analysis (DFA)-along with analysis of power-law beta slope (beta index) and standard deviation of N-N intervals (SDNN)-in edited and unedited (with ventricular premature beats - VPBs, only in DFA analysis) series of R-R intervals from Holter monitoring of healthy controls (Group 0, n = 27) and Chagas disease patients with left ventricular (LV) ejection fraction >50% (Group 1, n = 137) and with LV ejection fraction <50% (Group 2, n = 23).Results: When analyzed from the edited R-R interval data, the long-term scaling exponent alpha(2) is altered both among the Chagas patients with and without LV dysfunction. The short-term scaling exponent alpha(1) was higher in Group 1 Chagas patients as compared to controls (P < 0.01) and did not differ between Group 2 and controls. In unedited R-R interval series, alpha(1) was significantly reduced in Group 2 Chagas patients (0.55 +/- 0.002) as compared to controls (0.90 +/- 0.002) and Group 1 (0.91 +/- 0.003) (P < 0.001), but did not differ between Group 1 and controls. Similarly alpha(2) was lower in Group 2 compared to other groups (P < 0.001). SDNN did not differ between the groups, but the beta index derived from 1/f model was reduced both in Group 1 and 2 Chagas patients as compared to controls (P < 0.01). There was strong correlation (rs = 0.82; P < 0.001) between the beta and alpha(2) index from edited series. There was an inverse correlation (rs =-0.63, P < 0.01) between the number of VPBs and alpha(1) index of unedited series.Conclusions: The long-term fractal HR dynamics altered in chagasic patients with and without LV dysfunction could be an early sign of autonomic dysfunction. Patients with impaired LV function show marked alterations in short-term fractal HR dynamics toward more random behavior, mainly due to frequent ectopy. Prospective studies are necessary to define the value of these indices as predictors of death in Chagas disease. [ABSTRACT FROM AUTHOR]

Background: Although KCNH2 (HERG) K897T polymorphism has been shown to be associated with the QT interval measured from 12-lead electrocardiogram (ECG), the functional significance of K897T polymorphism has been debated. The aim of this study was to test whether the K897T polymorphism of the KCNH2 (HERG) gene coding for the rapidly activating delayed rectifier K+ channel influences cardiac repolarization assessed by principal component analysis (PCA) of T-wave morphology.Methods: Twelve-lead ECGs were digitized and T-wave morphology was analyzed with a PCA method in a population consisting of 228 healthy middle-aged subjects (121 women and 107 men). DNA samples were genotyped for the nucleotide 2690 A>C variation of the KCNH2 gene, corresponding to the KCNH2 K(lysine)897T(threonine) amino acid polymorphism.Results: The allele frequencies were 0.86 (K) and 0.14 (T). The KCNH2 K897T polymorphism was associated with the total cosine R-to-T (TCRT), which reflects the wave front direction between depolarization and repolarization. TCRT was 0.421 in the genotype KK and 0.300 in the genotypes KT and TT (P = 0.04). The difference of TCRT was more marked between the KCNH2 K897T genotypes in women (P = 0.03) than in men (P = 0.52).Conclusions: The common K897T polymorphism of the cardiac potassium channel KCNH2 has functional significance for cardiac electrical properties. Subjects with a less common genotype, KT or TT, have smaller TCRT, which reflects dyssynchrony between depolarization and repolarization and is associated with an increased risk of cardiac mortality. [ABSTRACT FROM AUTHOR]

Background: Premature beats (PBs) have been considered as artifacts producing a bias in the traditional analysis of heart rate (HR) variability. We assessed the effects and significance of PBs on fractal scaling exponents in healthy subjects and patients with a recent myocardial infarction (AMI).Methods: Artificial PBs were first generated into a time series of pure sinus beats in 20 healthy subjects and 20 post-AMI patients. Thereafter, a case-control approach was used to compare the prognostic significance of edited and nonedited fractal scaling exponents in a random elderly population and in a post-AMI population. Detrended fluctuation analysis (DFA) was used to measure the short-term (alpha1) and long-term (alpha2) fractal scaling exponents.Results: Artificial PBs caused a more pronounced reduction of alpha1 value among the post-AMI patients than the healthy subjects, for example, if > 0.25% of the beats were premature a > 25% decrease in the alpha1 was observed in post-AMI patients, but 4% of the premature beats were needed to cause a 25% reduction in alpha1 in healthy subjects. Both edited (1.01 +/- 0.31 vs 1.19 +/- 0.27, P < 0.01) and unedited alpha1 (0.71 +/- 0.33 vs 0.89 +/- 0.36, P < 0.05) differed between the patients who died (n = 42) and those who survived (n = 42) after an AMI. In the general population, only unedited alpha1 differed significantly between survivors and those who died (0.96 +/- 0.19 vs 0.83 +/- 0.27, P < 0.05).Conclusions: Unedited premature beats result in an increase in the randomness of short-term R-R interval dynamics, particularly in post-AMI patients. Premature beats must not necessarily be edited when fractal analysis is used for risk stratification. [ABSTRACT FROM AUTHOR]

Objectives: This study assessed the predictive power of arrhythmia risk markers after an acute myocardial infarction (AMI).Background: Several risk variables have been suggested to predict the occurrence of sudden cardiac death (SCD), but the utility of these variables has not been well established among patients using medical therapy according to contemporary guidelines.Methods: A consecutive series of 700 patients with AMI was studied. The end points were total mortality, SCD, and nonsudden cardiac death (non-SCD). Nonsustained ventricular tachycardia (nsVT), ejection fraction (EF), heart rate variability, baroreflex sensitivity, signal-averaged electrocardiogram (SAECG), QT dispersion, and QRS duration were analyzed (n = 675). Beta-blocking therapy was used by 97% of the patients at discharge and by 95% at one and two years after AMI.Results: During a mean (+/-SD) follow-up of 43 +/- 15 months, 37 non-SCDs (5.5%) and 22 SCDs (3.2%) occurred. All arrhythmia risk variables differed between the survivors and those with non-SCD (e.g., the standard deviation of N-N intervals was 98 +/- 32 vs. 74 +/- 21 ms [p < 0.001] and the QRS duration was 103 +/- 22 vs.89 +/- 16 ms [p < 0.001]). Sudden cardiac death was weakly predicted only by reduced EF (<0.40; p < 0.05), nsVT (p < 0.05), and abnormal SAECG (p < 0.05), but not by autonomic markers or standard ECG variables. The positive predictive accuracy of EF, nsVT, and abnormal SAECG as predictors of SCD was relatively low (8%, 12%, and 13%, respectively).Conclusions: The common arrhythmia risk variables, particularly the autonomic and standard ECG markers, have limited predictive power in identifying patients at risk of SCD after AMI in the beta-blocking era. [ABSTRACT FROM AUTHOR]

Background: The vast majority of reports of inappropriate sinus tachycardia (IST) had included predominantly young females with ages ranging between 15 and 46 years. In contrast, the present study presents the findings in four elderly females (aged 61-71 years) with long-standing symptoms of palpitations, more than 15 years, in whom IST was diagnosed in their 6th or 7th decade.Methods: Clinical and laboratory examinations including electrocardiograms, echocardiograms, and heart rate variability studies were retrospectively reviewed in four of the nine elderly female patients with long-standing cardiac symptoms. Indices of heart rate variability were compared to four age-matched asymptomatic elderly females with no structural heart disease.Results: The resting electrocardiograms were normal but one had voltage criteria for left ventricular hypertrophy. All traditional time- and frequency-domain indices were significantly decreased in the symptomatic elderly females as compared to the controls. Echocardiograms showed normal ejection fraction, and in three patients evidence of diastolic dysfunction and mild left ventricular hypertrophy. Blood pressures were elevated, with systolic blood pressure ranging from 170 to 190 and diastolic blood pressure ranging from 94 to 106. Anxiety disorders were diagnosed in all patients.Conclusions: This study demonstrates that IST can be present in a wide spectrum of patient populations, including elderly populations. It seems that some cases of IST can become chronic if not treated adequately. Apparently, earlier identification and treatment could have improved the quality of life of the patients. Traditional HRV indices may not be valuable to support either a sympathetic or parasympathetic mechanism. Therefore, further studies should consider the potential usefulness of the nonlinear method such as, for example, approximate entropy and detrended fluctuation analysis. [ABSTRACT FROM AUTHOR]

CARISMA is a multicenter study enrolling patients with a left ventricular ejection fraction < or = 40% after acute myocardial infarction (AMI), in whom an electrocardiogram (ECG) loop recorder (ILR) is implanted to measure the incidence of tachyarrhythmia and bradyarrhythmia episodes. The value of 24 hour ambulatory ECG, signal-averaged ECG late potentials, QT dispersion, T wave alternans, and electrophysiologic testing as predictors of life-threatening arrhythmias is examined. The study tested the automatic documentation of arrhythmias by the ILR in 30 post-AMI patients. RESULTS: At a mean follow-up of 47 days, the ILR had detected atrial tachyarrhythmias in 8 of 28 patients, nonsustained ventricular tachycardias in 2, and transient third degree atrioventricular block in 3. An indication for implantation of an implantable cardioverter defibrillator (ICD) or permanent pacemaker (PM) was observed in 9 out of 29 patients (31%). An average of 2.3 events stored by the ILR were due to inappropriate triggering. Because its memory size is limited to a maximum of 14 episodes, the ILR was unable to store arrhythmias 28% of the follow-up time. False events rate and monitoring time were improved by suturing the device within its pocket. CONCLUSIONS: The ILR allowed the automatic detection of brady- and tachyarrhythmias in post-AMI patients, though a high incidence of false activations were observed. Clinically significant arrhythmias were recorded in a large number of patients with depressed left ventricular function early after AMI. This prompted the implantation of ICD or PM in nearly one third of patients. [ABSTRACT FROM AUTHOR]

Background: Patients with congestive heart failure (CHF) have alterations in the traditional and nonlinear indices of heart rate (HR) dynamics, which have been associated with an increased risk of mortality. This study was designed to test the effects of carvedilol, a nonselective beta-blocker with alpha-1 blocking properties, on HR dynamics in patients with CHF.Methods: We studied 15 patients with CHF secondary to ischemic or idiopathic cardiomyopathy who met the following inclusion criteria: NYHA functional class II-III, optimal conventional medical therapy, normal sinus rhythm, left ventricular ejection fraction (LVEF) of < 40%, and resting systolic blood pressure greater than 100 mmHg. The 6-minute corridor walk test, estimation of LVEF, and 24-hour Holter recording were performed at baseline and after 12 weeks of therapy with carvedilol. Traditional time and frequency domain measures and short-term fractal scaling exponent of HR dynamics were analyzed.Results: After 12 weeks of therapy with carvedilol, the mean LVEF improved significantly (from 0.27 +/- 0.08 to 0.38 +/- 0.08, P < 0.001). The average HR decreased significantly (from 86 +/- 11 to 70 +/- 8 beats/min, P < 0.001). The mean distance traveled in the 6-minute walk test increased significantly (from 177 +/- 44 to 273 +/- 55 m, P < 0.01). The frequency-domain indices (HF and LF), the time domain indices (rMSSD and PNN5 ), and the short-term fractal scaling exponent increased significantly. The scaling exponent increased particularly among the patients with the lowest initial values (< 1.0), and the change in the fractal scaling exponent correlated with the change in ejection fraction (r = 0.63, P < 0.01).Conclusion: Carvedilol improves time and frequency domain indices of HR variability and corrects the altered scaling properties of HR dynamics in patients with CHF. It also improves LVEF and functional capacity. These specific changes in HR behavior caused by carvedilol treatment may reflect the normalization of impaired cardiovascular neural regulation of patients with CHF. [ABSTRACT FROM AUTHOR]

Background: Various methods can be used to edit biological and technical artefacts in heart rate variability (HRV), but there is relatively little information on the effects of such editing methods on HRV.Methods: The effects of editing on HRV analysis were studied using R-R interval data of 10 healthy subjects and 10 patients with a previous myocardial infarction (MI). R-R interval tachograms of verified sinus beats were analyzed from short-term ( approximately 5 min) and long-term ( approximately 24 hours) recordings by eliminating different amounts of real R-R intervals. Three editing methods were applied to these segments: (1) interpolation of degree zero, (2) interpolation of degree one, and (3) deletion without replacement.Results: In time domain analysis of short-term data, the standard deviation of normal-to-normal intervals (SDANN) was least affected by editing, and 30%-50% of the data could be edited by all the three methods without a significant error (< 5%). In the frequency domain analysis, the method of editing resulted in remarkably different changes and errors for both the high-frequency (HF) and the low-frequency (LF) spectral components. The editing methods also yielded in different results in healthy subjects and AMI patients. In 24-hour HRV analysis, up to 50% could be edited by all methods without an error larger than 5% in the analysis of the standard deviation of normal to normal intervals (SDNN). Both interpolation methods also performed well in the editing of the long-term power spectral components for 24-hour data, but with the deletion method, only 5% of the data could be edited without a significant error.Conclusions: The amount and type of editing R-R interval data have remarkably different effects on various HRV indices. There is no universal method for editing ectopic beats that could be used in both the time-domain and the frequency-domain analysis of HRV. [ABSTRACT FROM AUTHOR]

Previous studies have shown that indexes describing heart rate (HR) dynamics may predict subsequent deaths of patients after an acute myocardial infarction (AMI). Because beta-blocking (BB) drugs affect both mortality and HR dynamics, the prognostic power of measurements of HR dynamics may have changed in the current era of BB therapy. This study assessed the temporal changes and prognostic significance of time-domain, spectral, and fractal indexes of HR variability along with HR turbulence after an AMI among patients with optimized BB medication. SD of NN intervals, spectral indexes, the short-term fractal scaling exponent (alpha(1)), power-law slope (beta), and turbulence onset and slope were measured in 600 patients at 5 to 7 days after AMI and in 416 patients at 12 months after AMI. In the multivariate analysis, after adjusting for clinical variables, only reduced fractal HR indexes, alpha1 and beta (p <0.01 for both), turbulence onset, and slope (p <0.05 for both), measured at the convalescent phase after AMI, predicted subsequent cardiac death. All time-domain and spectral HR variability indexes and turbulence onset increased significantly during the 12-month period after AMI (p <0.001 for all), whereas the fractal indexes and turbulence slope remained unchanged. Late after AMI, reduced beta (p <0.05) and turbulence slope (p <0.01) were the only independent predictors of cardiac mortality. Traditional time-domain and spectral measurements of HR variability and turbulence onset improved significantly after AMI, whereas the fractal HR dynamics and turbulence slope remained stable. Fractal HR variability and HR turbulence retain their prognostic power in the BB era, when measured either at the convalescent or late phase after AMI. [ABSTRACT FROM AUTHOR]

Background: Hypertrophic cardiomyopathy is a common cause of non-ischaemic sudden cardiac death (SCD). Left ventricular hypertrophy (LVH) without cardiomyopathy-related myocardial disarray is a common autopsy finding and is often associated with prior hypertension in SCD subjects. Our aim was to investigate novel rare gene variants among SCD subjects with presumably hypertension-related LVH and myocardial fibrosis at autopsy., Methods: Whole exome sequencing was used to study rare variants (minor allele frequency<0.005) estimated to be deleterious in 96 non-ischaemic SCD subjects with presumably hypertension-related LVH and myocardial fibrosis. Associations of the identified variants with cardiac disease endpoints were replicated in the Finnish national genetic study (FinnGen) dataset., Results: 18 variants were estimated likely to affect protein function and 14 of these were associated with cardiomyopathies, heart failure, conduction abnormalities, hypertension and/or cardiac arrest in Finnish population (FinnGen). Three of the variants were classified as pathogenic or likely pathogenic. These include the splice site variant NM&#95;000449.3:c.234-1G>A in regulatory factor X5 and frameshift variants NM&#95;000449.3:c.234-1G>A in dehydrogenase/reductase 7C and NM&#95;015873.3:c.1164del in villin like., Conclusions: We identified rare deleterious variants associated with LVH in SCD subjects. Several of the identified rare variants associated with cardiovascular endpoints including heart failure, cardiomyopathies, cardiac arrest and hypertension in general population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The aim of this study was to investigate the clinical implication of incidentally induced atrial fibrillation (AF) during programmed electrical stimulation (PES) in patients with left ventricular systolic dysfunction (≤40%) after an acute myocardial infarction (MI)., Methods: In this study, we included 231 patients from the Cardiac Arrhythmias and RIsk Stratification after Myocardial InfArction (CARISMA) study with left ventricular ejection fraction ≤40% and no prior history of AF. These patients underwent PES 6 weeks post-MI as part of the study protocol. Patients all received an implantable cardiac monitor (ICM) 3-21 days post-MI and were continuously monitored for cardiac arrhythmias for 2 years. Induction of AF was unwanted but reported if this incidentally occurred., Results: A total of 61 patients (26%) developed AF within 2 years of follow-up, in which n = 10 (29%) had incidental AF during PES at baseline. The overall risk of AF was not significantly increased in patients with incidental AF (n = 34) during PES compared to patients without incidental AF (n = 197) (HR 1.6 [0.9-3.0], p = 0.14). The risk of bradyarrhythmia (HR = 0.2 [0.0-1.2], p = 0.07), ventricular arrhythmias (HR = 0.7 [0.1-5.8], p = 0.77), and major cardiovascular events (MACE) (HR 0.5 [0.2-1.7], p = 0.28) was not significantly different in patients with versus without incidental AF., Conclusions: Incidentally induced AF during PES in post-MI patients with reduced LVEF was not significantly associated with a higher risk of long-term atrial fibrillation, other cardiac arrhythmias, or major cardiac events., Trial Registration: NCT00145119., (© 2024 The Author(s). Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Smartwatches and home-based blood pressure (BP) devices have permitted easy use of heart rate variability (HRV) and BP to identify the recovery status of users after acute exercise training. The reproducibility of HRV and BP after exercise in healthy young participants is not well known. Eighteen participants (age 27 ± 6 years, female n = 8) performed test and retest aerobic exercises (cycling, 30 min, 60% of peak workload, W) and a control session in randomized order. RMSSD, high and low-frequency power of RR intervals, and BP were measured at rest and 30-60 min after interventions. The relative reproducibility was assessed by the intraclass correlation coefficient (ICC) and 95% confidence interval (95% CI). The absolute reproducibility was evaluated using the coefficient of variation (CV%). HRV indices revealed moderate-to-excellent reproducibility at rest (ICC 0.81-0.86; 95% CI 0.53-0.95) but not after exercise (ICC -0.06 to 0.60; 95% CI -1.85 to 0.85). Systolic BP had a good-to-excellent reproducibility before (ICC 0.93; 95% CI 0.81-0.98, CV% 4.2) and after exercise (ICC 0.93; 95% CI 0.81-0.97, CV% 4.2). The reproducibility of HRV indices is poor after exercise in young participants. However, the reproducibility of BP is excellent at rest and after aerobic exercise., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Data on the prognostic significance of temporal variability of spatial heterogeneity of electrocardiographic repolarization in coronary artery disease (CAD) are limited., Objective: The purpose of this study was to evaluate the prognostic value of temporal variability of T-wave morphology analyzed from a 5-minute resting electrocardiogram in CAD., Methods: The standard deviation (SD) of T-wave morphology dispersion (TMD-SD) and the SD of total cosine R-to-T were analyzed on a beat-to-beat basis from a 5-minute period of the standard resting 12-lead electrocardiogram obtained before the clinical stress test in 1702 patients with angiographically verified CAD and well-preserved left ventricular function., Results: During an average of 8.7 ± 2.2 years of follow-up, 60 patients experienced sudden cardiac death/arrest (SCD/SCA) (3.5%), 69 patients nonsudden cardiac death (NSCD) (4.1%), and 161 patients noncardiac death (9.5%). TMD-SD was significantly higher in patients who experienced SCD/SCA than in other patients (1.72 ± 2.00 vs 1.12 ± 1.75; P = .01) and higher in patients who succumbed to NSCD than in other patients (1.57 ± 1.74 vs 1.12 ± 1.76; P = .04), but it did not differ significantly between patients who experienced noncardiac death and those without such an event (1.16 ± 1.42 vs 1.14 ± 1.79; P = .86). In the Cox multivariable hazards model, TMD-SD retained its significant association with the risk of SCD/SCA (hazard ratio 1.119; 95% confidence interval 1.015-1.233; P = .024) but not with the risk of NSCD (hazard ratio 1.089; 95% confidence interval 0.983-1.206; P = .103)., Conclusion: TMD-SD is independently associated with the long-term risk of SCD/SCA in patients with CAD., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Myocardial fibrosis is a common finding in victims of sudden cardiac death (SCD). Whole exome sequencing was performed in 127 victims of SCD with primary myocardial fibrosis as the only pathological finding. These cases are derived from the Fingesture study which has collected data from autopsy-verified SCD victims in Northern Finland. A computational approach was used to identify protein interactions in cardiomyocytes. Associations of the identified variants with cardiac disease endpoints were investigated in the Finnish national genetic study (FinnGen) dataset. We identified 21 missense and one nonsense variant. Four variants were estimated to affect protein function, significantly associated with SCD/primary myocardial fibrosis (Fingesture) and associated with cardiac diseases in Finnish population (FinnGen). These variants locate in cartilage acidic protein 1 (CRATC1), calpain 1 (CAPN1), unc-45 myosin chaperone A (UNC45A) and unc-45 myosin chaperone B (UNC45B). The variants identified contribute to function of extracellular matrix and cardiomyocytes., (© 2024. The Author(s).)

Background: New methods to identify patients who benefit from a primary prophylactic implantable cardioverter-defibrillator (ICD) are needed. T-wave alternans (TWA) has been shown to associate with arrhythmogenesis of the heart and sudden cardiac death. We hypothesized that TWA might be associated with benefit from ICD implantation in primary prevention., Methods and Results: In the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter-Defibrillators) study, we prospectively enrolled 2327 candidates for primary prophylactic ICD. A 24-hour Holter monitor reading was taken from all recruited patients at enrollment. TWA was assessed from Holter monitoring using the modified moving average method. Study outcomes were all-cause death, appropriate shock, and survival benefit. TWA was assessed both as a contiguous variable and as a dichotomized variable with cutoff points <47 μV and <60 μV. The final cohort included 1734 valid T-wave alternans samples, 1211 patients with ICD, and 523 control patients with conservative treatment, with a mean follow-up time of 2.3 years. TWA ≥60 μV was a predicter for a higher all-cause death in patients with an ICD on the basis of a univariate Cox regression model (hazard ratio, 1.484 [95% CI, 1.024-2.151]; P =0.0374; concordance statistic, 0.51). In multivariable models, TWA was not prognostic of death or appropriate shocks in patients with an ICD. In addition, TWA was not prognostic of death in control patients. In a propensity score-adjusted Cox regression model, TWA was not a predictor of ICD benefit., Conclusions: T-wave alternans is poorly prognostic in patients with a primary prophylactic ICD. Although it may be prognostic of life-threatening arrhythmias and sudden cardiac death in several patient populations, it does not seem to be useful in assessing benefit from ICD therapy in primary prevention among patients with an ejection fraction of ≤35%.

Background: Regardless of progress in treatment of coronary artery disease (CAD), there is still a significant residual risk of death in patients with CAD, highlighting the need for additional risk stratification markers. Our previous study provided evidence for a novel blood pressure-regulating mechanism involving 4β-hydroxycholesterol (4βHC), an agonist for liver X receptors, as a hypotensive factor. The aim was to determine the role of 4βHC as a prognostic factor in CAD., Methods and Results: The ARTEMIS (Innovation to Reduce Cardiovascular Complications of Diabetes at the Intersection) cohort consists of 1946 patients with CAD. Men and women were analyzed separately in quartiles according to plasma 4βHC. Basic characteristics, medications, ECG, and echocardiography parameters as well as mortality rate were analyzed. At baseline, subjects with a beneficial cardiovascular profile, as assessed with traditional markers such as body mass index, exercise capacity, prevalence of diabetes, and use of antihypertensives, had the highest plasma 4βHC concentrations. However, in men, high plasma 4βHC was associated with all-cause death, cardiac death, and especially sudden cardiac death (SCD) in a median follow-up of 8.8 years. Univariate and comprehensively adjusted hazard ratios for SCD in the highest quartile were 3.76 (95% CI, 1.6-8.7; P =0.002) and 4.18 (95% CI, 1.5-11.4; P =0.005), respectively. In contrast, the association of cardiac death and SCD in women showed the lowest risk in the highest 4βHC quartile., Conclusions: High plasma 4βHC concentration was associated with death and especially SCD in men, while an inverse association was detected in women. Our results suggest 4βHC as a novel sex-specific risk marker of cardiac death and especially SCD in chronic CAD., Registration Information: clinicaltrials.gov. Identifier NCT01426685.

Background: There has been some controversy about the day-of-the-week (septadian) variation of unexpected sudden cardiac death (SCD)., Methods: We evaluated the incidence of unexpected SCD on different days of the week in a consecutive series of 5869 SCD victims from Northern Finland [the FINGESTURE study (Finnish Genetic Study of Arrhythmic Events)]. As it is mandatory in Finland, a medico-legal autopsy was performed on all unexpected sudden death victims. The autopsies were performed between the years 1998-2017., Results: The mean incidence of unexpected SCD was higher at weekends (during the days from Friday to Sunday, peaking on Saturday) than during the days from Monday to Thursday (8.54 ± 0.72 vs. 7.22 ± 0.19 SCDs per day of the week per 100,000 inhabitants per year, p < 0.001). Regardless of sex or ischemic versus non-ischemic etiology of SCD, the distribution of the occurrence of SCD among the days of the week was similar compared with the whole SCD cohort., Conclusion: The incidence of unexpected SCD was highest at weekends (during the days from Friday to Sunday, peaking on Saturday)., Competing Interests: None declared., (© 2024 The Authors.)

The association between lifestyle and cardiac structure and function measures, such as global longitudinal strain and diastolic function in a healthy midlife general population, is not well known. A subpopulation of the Northern Finland Birth Cohort 1966 took part in follow-up, including echocardiography (n = 1,155) at the age of 46. All antihypertensive medication users (n = 164), patients with diabetes (n = 70), subjects with any cardiac diseases (n = 24), and subjects with echocardiography abnormalities (n = 21) were excluded. Moderate to vigorous physical activity (MVPA) was recorded with a wrist-worn accelerometer over 14 days and categorized into high, moderate, and low MVPA groups. Similarly, alcohol consumption was categorized as low, moderate, and high-dose users of alcohol and smoking as nonsmokers, former, and current smokers. The total number of healthy subjects included in the study was 715 (44% males). Left ventricular mass index and left atrial end-systolic volume index were significantly higher in the high MVPA group compared with the low MVPA group (adjusted main effect p = 0.002 and p <0.001, respectively). Cardiac function did not differ among the physical activity groups. High alcohol consumption was associated with impaired global longitudinal strain and diastolic function (adjusted main effect p = 0.002 and p = 0.004, respectively) but not with any cardiac structure variables. Smoking was not associated with cardiac structure or function. In healthy middle-aged adults, MVPA was independently associated with structural changes in the heart but not with cardiac function. High alcohol consumption was associated with impaired modern cardiac function measures but not with cardiac structure., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To test the hypothesis that in recipients of primary prophylactic implantable cardioverter-defibrillators (ICDs), the non-planarity of ECG vector loops predicts (a) deaths despite ICD protection and (b) appropriate ICD shocks., Methods: Digital pre-implant ECGs were collected in 1948 ICD recipients: 21.4% females, median age 65 years, 61.5% ischaemic heart disease (IHD). QRS and T wave three-dimensional loops were constructed using singular value decomposition that allowed to measure the vector loop planarity. The non-planarity, that is, the twist of the three-dimensional loops out of a single plane, was related to all-cause mortality (n=294; 15.3% females; 68.7% IHD) and appropriate ICD shocks (n=162; 10.5% females; 87.7% IHD) during 5-year follow-up after device implantation. Using multivariable Cox regression, the predictive power of QRS and T wave non-planarity was compared with that of age, heart rate, left ventricular ejection fraction, QRS duration, spatial QRS-T angle, QTc interval and T-peak to T-end interval., Results: QRS non-planarity was significantly (p<0.001) associated with follow-up deaths despite ICD protection with HR of 1.339 (95% CI 1.165 to 1.540) but was only univariably associated with appropriate ICD shocks. Non-planarity of the T wave loop was the only ECG-derived index significantly (p<0.001) associated with appropriate ICD shocks with multivariable Cox regression HR of 1.364 (1.180 to 1.576) but was not associated with follow-up mortality., Conclusions: The analysed data suggest that QRS and T wave non-planarity might offer distinction between patients who are at greater risk of death despite ICD protection and those who are likely to use the defibrillator protection., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)