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Aims: Biomarkers have shown promising results in risk assessment of cardiovascular events. Their role in predicting the risk of sudden cardiac death (SCD) is not well established. We tested the performance of several biomarkers in risk assessment for SCD in patients with coronary artery disease (CAD) and preserved left ventricular function. Methods and results: The study population consisted of 1,946 CAD patients (68% male; mean age 66.9±8.6 yrs; type 2 diabetes (T2D) 43%) enrolled in the ARTEMIS study. The study subjects underwent examinations with echocardiography and measurement of several biomarkers. The primary endpoint of the study was SCD. During the mean follow up of 76±20 months 50 patients experienced SCD. Elevated high sensitive CRP (hs-CRP, p = 0.001), soluble ST2 (sST2, p<0.001), B-type natriuretic peptide (BNP, p<0.001), and highly sensitive TroponinT (hs-TnT, p<0.001) predicted the occurrence of SCD in univariate analysis. Using the optimal cutoff points, elevated sST2 (≥27.45ng/mL; hazard ratio [HR] 2.7; 95%CI 1.4–5.1, p = 0.003) and hs-TnT (≥15 ng/mL; HR 2.9; 95% CI 1.5–5.6, p = 0.002) were the strongest predictors of SCD followed by hs-CRP (HR 2.4; 95% CI 1.3–4.4, p = 0.004) and BNP (HR 1.9; 95% CI 1.0–3.7, p = 0.046) in adjusted analysis. Combination of elevated hs-TnT and sST2 resulted in adjusted HR of 6.4 (95% CI 2.6–15.5, p<0.001). Conclusion: Elevated sST2 and hs-TnT predict the occurrence of SCD among patients with CAD and preserved left ventricular function. The association between sST2, hs-TnT and SCD may be explained by an ongoing myocardial apoptosis followed by fibrosis leading to vulnerability to malignant arrhythmias. [ABSTRACT FROM AUTHOR]

Presence of J-point elevation with rapidly ascending ST segment in the anterior leads of the 12-lead electrocardiogram has been generally considered a benign phenomenon. The concept of benign nature of J-waves has changed as data emerged on variants of J-waves that were associated with the increased risk of sudden cardiac death. Two specific inherited arrhythmia syndromes, such as Brugada syndrome and early repolarization syndrome, have been recognized that carry an increased risk for ventricular fibrillation. The current review is aimed at discussing the clinical aspects of these syndromes and the implications of incidental recognition of the J-waves in a randomly recorded electrocardiogram of asymptomatic subjects. [ABSTRACT FROM AUTHOR]

Abstract: The incidence of adverse cardiovascular events is higher among spectators of exciting sports events, but the mechanistic link between the events is not known. We assessed the heart rate (HR) and blood pressure (BP) dynamics of enthusiastic male ice hockey spectators (60±9years) with coronary artery disease (CAD) during Finnish national league ice hockey play-off final matches. Twenty-four-hour ambulatory ECG (n =55) and BP (n =17) were recorded at the time of the match and on a control day. Beat-to-beat R–R intervals and BP were recorded during the match and a bicycle exercise at equal HR levels (n =21). Systolic and diastolic BP were significantly higher 1h before, during, and 1h after the match than on the control day, e.g., the highest systolic BP was 180±14 vs. 145±15 and diastolic 103±13 vs. 82±11mmHg (p <0.001 for both). HR was higher throughout the match (p <0.05) and remained elevated 2h after the match (p <0001), and measures of HR variability were decreased during the match (p <0.01). Low-frequency variability in BP was higher during the match than during the exercise test (p <0.01). The results show that cardiac vagal outflow is attenuated and vasomotor sympathetic activity elevated during exciting sports events and BP dynamics differ from those occurring during physical exercise at equal HRs. The autonomic reactions may partly explain the vulnerability to cardiovascular events caused by this type of leisure-time emotional excitement. [Copyright &y& Elsevier]

• The design of PREDESTINATION study is elegant. • 5 factors were associated with an increased risk of ventricular fibrillation during the first myocardial infarction. • Future genetic studies may reveal genetic variants that predispose to sudden cardiac death. [ABSTRACT FROM AUTHOR]

: ObjectivesThis study assessed the predictive power of arrhythmia risk markers after an acute myocardial infarction (AMI).: BackgroundSeveral 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.: MethodsA 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.: ResultsDuring 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).: ConclusionsThe 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. [Copyright &y& Elsevier]

Type 2 diabetes is a strong risk factor for coronary heart disease and sudden cardiac death. It is associated with reduced baroreflex sensitivity (BRS) and heart rate variability (HRV), which are indicators of increased risk for mortality and morbidity in various patient populations. This study was designed to assess the effects of exercise training on BRS, HRV, and hemodynamics in patients with type 2 diabetes. Subjects (50 men, mean age 53.3 +/- 5.1 years) with type 2 diabetes were randomized into either a control group, in which they received conventional treatment only, or an exercise group, in which they received conventional treatment together with heart rate-controlled endurance training twice a week and supervised muscle strength training twice a week for 12 months. Measurements taken at baseline and follow-up included VO(2max), standard time and frequency domain measures of HRV during 24-h recording, and BRS by the phenylephrine method. Cardiac index, systemic vascular resistance index, stroke index, and pulse wave velocity were measured by whole-body impedance cardiography. Significant improvements in VO(2max) (exercise group: +2.3 ml x kg(-1) x min(-1); P < 0.005 vs. control group), muscle strength, and glycemic control (exercise group: HbA(1c) -0.9%; P < 0.001 vs. control group) were observed in the exercise group. BRS increased in the exercise group, from 6.8 to 8.6 ms/mmHg, and decreased in the control group, from 7.5 to 6.4 ms/mmHg (95% CI for the difference between 0.05 and 4.36 ms/mmHg; P < 0.05). No significant changes in the time or frequency domain measures of HRV or in systemic hemodynamics were observed. We concluded that exercise training improves BRS sensitivity in type 2 diabetes subjects in addition to increasing the exercise capacity and muscle strength and improving glucose control. These beneficial effects in reflectory autonomic regulation and glucose control caused by exercise may be associated with improved prognosis of type 2 diabetes patients. [ABSTRACT FROM AUTHOR]

HUIKURI, H.V.,et al.: Cardiac Arrhythmias and Risk Stratification After Myocardial Infarction: Results of the CARISMA Pilot Study.CARISMA is a multicenter study enrolling patients with a left ventricular ejection fraction ≤40% after acute myocardial infarction (AMI), in whom an electrocardiogram (ECG) loop recorder (ILR) is implanted to measure the incidence of tachyarrythmia 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. (PACE 2003; 26[Pt. II]:416–419). [ABSTRACT FROM AUTHOR]

Compares traditional with nonlinear indexes of heart rate (HR) variability in a variety of cases of appropriate sinus tachycardia and congestive heart failure (CHF). Specificity of the changes in HR dynamics among patients with CHF; Fractal measures of HR dynamics; Correlation between HR and HR variability measures.

The mortality benefit of implantable cardioverter defibrillator (ICD) therapy in primary and secondary prevention has been shown in various studies in patients with depressed left ventricular systolic function. This study determined the association between the mortality benefit of ICD therapy and the use of β-blocking medication in randomized ICD trials. Eligible studies were randomized controlled trials of ICD therapy compared with conventional medical treatment reporting mortality as an outcome (Medline from May 1995 to May 2005). Ten randomized trials were included. Included studies were reviewed to determine the number of patients, follow-up, and the mortality of ICD and control groups. The analysis of these trials showed a strong negative association between the use of β-blocking medication and the 2-year mortality benefit of ICD therapy (r = −0.81, p <0.01). In conclusion, the use of β-blocking medication is associated with a reduced absolute mortality benefit of ICD therapy in reported randomized trials. [Copyright &y& Elsevier]

The aim of this study was to cross-sectionally examine whether hemoglobin (Hb) levels within the normal variation associate with heart rate variability (HRV) measures and baroreflex sensitivity (BRS). The study population included 733 Finnish subjects of the OPERA cohort (aged 41-59 yr, 53% males, 51.7% treated for hypertension) of whom HRV was measured from a standardized 45-min period and whose Hb levels were within the Finnish reference intervals. The low Hb tertile (mean Hb, 135 g/L) had an overall healthier metabolic profile compared with the high Hb tertile (mean Hb, 152 g/L). BRS was higher in the low Hb tertile compared with the high Hb tertile (P < 0.05). R-R interval (RRi) and standard deviation (SD) of the RRi (SDNN)index were the longest in the low Hb tertile regardless of posture. Of the spectral components of HRV, HF power was the highest in the low Hb tertile regardless of posture (P < 0.05). In a stepwise logistic regression model, BRS associated negatively with Hb levels after adjusting for covariates (B = -0.160 [-0.285; -0.035]). Similar associations were observed for SDNNindex when lying down (B = -0.105 [-0.207; -0.003]) and walking (B = -0.154 [-0.224; -0.083]). For HF power negative associations with Hb levels were observed when lying down (B = -0.110 [-0.180; -0.040]), sitting (B = -0.150 [-0.221; -0.079]), and in total analysis (B = -0.124 [-0.196; -0.053]). Overall, lower Hb levels associated independently with healthier cardiac autonomic function. [ABSTRACT FROM AUTHOR]

The editor discusses the need for selecting patients for prophylactic treatment with implantable cardioverter-defibrillator (ICD) by citing reference to an article by J.P. Amlie and colleagues within the issue. He mentions that in their study Amlie has elaborated the results of a prospective study that assessed the utility of Wedensky Modulation (WM) in predicting the device therapy of the recipients of the ICD.

The article highlights the association of heart rate variability (HRV) with autonomic nervous system (ANS). Topics discussed include study on the ANS control of sinus node periodicity; long-term HRV that provide powerful risk prediction mainly in cardiac patients; and the function of ANS to maintain the homeostasis of organism.

The author discusses a study by K. Reinier and colleagues which investigated the connection of socioeconomic status to the incidence of sudden cardiac arrest. The author says that the study's results, which reveal that there is higher sudden cardiac arrest incidence in poorer neighbourhoods in metropolitan areas in North America, are not surprising. The author notes that the decisions by health care managers and politicians in instituting health care reforms should be informed by this study.

The article discusses the common factors which lead to vulnerability to atrial fibrillation (AF). The role of autonomic nervous system in predicting the onset of AF is also discussed. Heart rate behavior was analyzed in relation to onset of AF. It is stated that preoperative analysis of fractal heart rate behavior and entropy can predict the AF occurrence after cardiac surgery.

Presents a response by M. J. Pekka Raatikainen et al to a letter to the editor about their article "Microvolt T-Wave Alternans During Exercise and Pacing in Patients With Acute Myocardial Infarction," in a 2005 issue.

Introduction: The risk for sudden cardiac death (SCD) increases with ageing. Methods: We evaluated causes and characteristics of unexpected SCD in SCD victims aged ≥ 80 years in a consecutive series of 5,869 SCD victims in Northern Finland. All the victims underwent medico-legal autopsy as medico-legal autopsy is mandatory in cases of unexpected sudden death in Finland. All the non-cardiac deaths such as pulmonary embolism and cerebral hemorrhage were excluded from the study, as were unnatural deaths such as intoxications. Results: Among SCD victims ≥ 80 years, 91.0% of SCDs were due to ischemic heart disease (IHD) determined in autopsy and 9.0% due to non-ischemic heart disease (NIHD), whereas among those < 80 years, only 72.6% of SCDs were due to IHD and 27.4% due to NIHD (P <.001). Severe fibrosis in myocardium was more common whereas heart weight and liver weight, body mass index and abdominal fat thickness, were lower among SCD victims aged ≥ 80 years than among victims aged < 80 years. In those with IHD as etiology of SCD, at least 75% stenosis in one or more major coronary vessels was more common in SCD victims aged ≥ 80 years than among victims aged < 80 years (P =.001). SCD victims 80 years or older were less likely to die during physical activity than those under 80 years old (5.6% vs. 15.9%, P <.001). Dying in sauna was more common among those ≥ 80 years than among those < 80 years (5.5% vs. 2.6%, P <.001). Conclusion: In victims of unexpected SCD aged ≥ 80 years, the autopsy-based etiology of SCD was more commonly IHD than in those aged < 80 years. In SCD victims aged ≥ 80 years, severe fibrosis in myocardium, representing arrhythmic substrate, was more common than in the younger ones. [ABSTRACT FROM AUTHOR]

Background: Nonischemic heart disease (NIHD) is the underlying pathology in about 20% of sudden cardiac deaths (SCDs). Psychotropic medication has been reported as a risk factor for SCD among patients with coronary artery disease, but similar information concerning NIHD is scarce. Objectives: We evaluated the use of psychotropic medication in victims of SCD due to NIHD and compared it to the general medication use in Finland. Method: Study population was derived from the Finnish Genetic Study of Arrhythmic Events (Fingesture) (n = 5,869, mean age: 65 ± 12, 79% males; 1,404 victims of SCD due to NIHD, mean age: 57 ± 13, 77% males). All deaths occurred in Northern Finland during 1998–2017. All victims underwent a medicolegal autopsy. Data on use of medication were defined using postmortem toxicology results and patient records. Subjects with neither toxicological analysis nor information of medication use available were excluded. Information on general medication use was derived from Finnish Statistics on Medicines 2018 and presented as defined daily dose/1,000 inhabitants/day. Results: Psychotropic medication was used by 579 (41%) subjects with NIHD, whereas in the general population, only 12% were estimated to use psychotropics. The results were similar in subgroups of psychotropic medication: 27% versus 2.3% for benzodiazepines, 19% versus 7.5% for antidepressants, and 18% versus 2.2% for antipsychotics. Conclusions: Use of psychotropic medication is common in victims of SCD due to NIHD compared to the general population. [ABSTRACT FROM AUTHOR]

A response by Heikki V. Huikuri and Jani T. Tikkanen to a letter to the editor about their article "Long-term Outcome Associated With Early Repolarization on Electrocardiography," by J. T. Tikkanen et al. in the December 24, 2009 issue is presented.

A response by Heikki V. Huikuri and colleagues to several letters to the editor about their article "Sudden Death Due to Cardiac Arrhythmias" in the November 15, 2001 issue is presented.

Focuses on sudden death due to cardiac arrhythmias. Rates of death from cardiovascular causes in developed countries; Mechanisms of sudden death from arrhythmia, including ventricular tachycardia degeneration; Epidemiology; Risk factors, including cardiovascular dysfunction and ambient ventricular arrhythmias; Prevention.

Fragmented QRS (fQRS) is an electrocardiographic (ECG) marker of myocardial conduction abnormality, characterized by additional notches in the QRS complex. The presence of fQRS has been associated with an increased risk of all-cause mortality and arrhythmia in patients with cardiovascular disease. However, current binary visual analysis is prone to intra- and inter-observer variability and different definitions are problematic in clinical practice. Therefore, objective quantification of fQRS is needed and could further improve risk stratification of these patients. We present an automated method for fQRS detection and quantification. First, a novel robust QRS complex segmentation strategy is proposed, which combines multi-lead information and excludes abnormal heartbeats automatically. Afterwards extracted features, based on variational mode decomposition (VMD), phase-rectified signal averaging (PRSA) and the number of baseline-crossings of the ECG, were used to train a machine learning classifier (Support Vector Machine) to discriminate fragmented from non-fragmented ECG-traces using multi-center data and combining different fQRS criteria used in clinical settings. The best model was trained on the combination of two independent previously annotated datasets and, compared to these visual fQRS annotations, achieved Kappa scores of 0.68 and 0.44, respectively. We also show that the algorithm might be used in both regular sinus rhythm and irregular beats during atrial fibrillation. These results demonstrate that the proposed approach could be relevant for clinical practice by objectively assessing and quantifying fQRS. The study sets the path for further clinical application of the developed automated fQRS algorithm. [ABSTRACT FROM AUTHOR]

Abstract: Attenuated cardiac vagal regulation indicates an increased risk of cardiac events, but the reasons for this impaired regulation are not well known. Cardiac vagal regulation was measured in 5.408 subjects (2627 men and 2781 women) who underwent short term (100s) ECG recordings during controlled deep respiration (0.1Hz). Under these conditions, the power in the low frequency (LF) spectral band (0.05 to 0.15Hz) predominantly reflects cardiac vagal outflow. There was a strong inverse relationship between LF power and age in both genders (β=−0.033 in men and −0.035 in women; P<0.0005). There was a more rapid decline in women in the second and third decade in which LF power was significantly lower than in men (P=0.004). In both genders, there was an association between impaired cardiac vagal outflow and fibrinogen level. Altogether, the factors studied explained nearly 20% of the interindividual variation of LF power. In conclusion, in a general population, impaired cardiac vagal regulation is associated with many cardiovascular risk factors, including fibrinogen. Women have a more rapid decline of vagal regulation in the second and third decades. [Copyright &y& Elsevier]

Heart rate variability has been analyzed conventionally with time and frequency domain methods, which measure the overall magnitude of RR interval fluctuations around its mean value or the magnitude of fluctuations in some predetermined frequencies. Analysis of heart rate dynamics by methods based on chaos theory and nonlinear system theory has gained recent interest. This interest is based on observations suggesting that the mechanisms involved in cardiovascular regulation likely interact with each other in a nonlinear way. Furthermore, recent observational studies suggest that some indexes describing nonlinear heart rate dynamics, such as fractal scaling exponents, may provide more powerful prognostic information than the traditional heart rate variability indexes. In particular, the short-term fractal scaling exponent measured by the detrended fluctuation analysis method has predicted fatal cardiovascular events in various populations. Approximate entropy, a nonlinear index of heart rate dynamics, that describes the complexity of RR interval behavior, has provided information on the vulnerability to atrial fibrillation. Many other nonlinear indexes, e.g., Lyapunov exponent and correlation dimensions, also give information on the characteristics of heart rate dynamics, but their clinical utility is not well established. Although concepts of chaos theory, fractal mathematics, and complexity measures of heart rate behavior in relation to cardiovascular physiology or various cardiovascular events are still far away from clinical medicine, they are a fruitful area for future research to expand our knowledge concerning the behavior of cardiovascular oscillations in normal healthy conditions as well as in disease states. [ABSTRACT FROM AUTHOR]

Traditional and Nonlinear HRV and Mortality. Introduction:Decreased heart rate variability (HRV) and abnormal nonlinear HRV shortly after myocardial infarction (MI) are risk factors for mortality. Traditional HRV predicts mortality in patients with a range of times post-MI, but the association of nonlinear HRV and outcome in this population is unknown.Methods and Results:HRV was determined from 740 tapes recorded before antiarrhythmic therapy in Cardiac Arrhythmia Suppression Trial patients with ventricular premature contractions (VPCs) suppressed on the first randomized treatment. Patients were 70± 121 days post-MI. Follow up was 362± 241 days (70 deaths). The association between traditional time and frequency-domain HRV and mortality and nonlinear HRV and mortality were compared for the entire population (ALL), those without coronary artery bypass graft post-MI (no CABG), and those without CABG or diabetes (no CABG, no DIAB) using univariate and multivariate Cox regression analysis. Strength of association was compared by P values and Wald Chi-square values. Nonlinear HRV included short-term fractal scaling exponent, power law slope, and SD12 (Poincaré dimension). For ALL and for no CABG, increased daytime SD12 had the strongest association with mortality (P= 0.002 ALL and P<0.001 no CABG). For no CABG, no DIAB increased 24-hour SD12 hours had the strongest association (P<0.001) with mortality. Upon multivariate analysis, increased SD12, decreased ln ULF (ultra low frequency), and history of prior MI and history of congestive heart failure each remained in the model.Conclusion:Nonlinear HRV is associated with mortality post-MI. However, as with traditional HRV, this is diluted by CABG surgery post-MI and by diabetes. Results suggest that decreased long-term HRV and increased randomness of heart rate are each independent risk factors for mortality post-MI.(J Cardiovasc Electrophysiol, Vol. 16, pp. 13-20, January 2005) [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) mortality has declined substantially over the past decades thanks to advancing medical and interventional/surgical treatments; therefore, the prognostic value of the heart rate variability in CAD in the current treatment era is not well established. We evaluated the prognostic significance of baseline heart rate variability in 1,757 ARTEMIS study patients with angiographically verified CAD. During an average follow-up time of 8.7 ± 2.2 years, a total of 285 (16.2%) patients died. Of the patients, 63 (3.6%) suffered sudden cardiac death or were resuscitated from sudden cardiac arrest (SCD/SCA), 60 (3.4%) experienced non-sudden cardiac death (NSCD), and death attributable to non-cardiac causes (NCD) occurred in 162 (9.2%) patients. For every 10 ms decrease in standard deviation of normal to normal intervals the risk for SCD/SCA, NSCD and NCD increased significantly: HR 1.153 (95% CI 1.075–1.236, p<0.001), HR 1.187 (95% CI 1.102–1.278, p<0.001) and HR 1.080 (95% CI 1.037–1.125, p<0.001), respectively. The natural logarithm of the low-frequency component of the power spectrum and the short-term scaling exponent of the detrended fluctuation analysis also had significant association with all modes of death (p<0.001). After relevant adjustment, standard deviation of normal-to-normal intervals retained its association with NSCD and NCD (p<0.01), the natural logarithm of the low-frequency component of the power spectrum with all modes of death (p from <0.05 to <0.01), and the short-term scaling exponent of the detrended fluctuation analysis with SCD/SCA (p<0.05) and NCD (p<0.001). In conclusion, impairment of many measures of heart rate variability predicts mortality but is not associated with any specific mode of death in patients with stable CAD during the current treatment era, limiting the clinical applicability of heart rate variability to targeting therapy. [ABSTRACT FROM AUTHOR]

Postoperative myocardial ischemia is a common finding after coronary artery bypass grafting (CABG) and is associated with an adverse short-term clinical outcome. The reasons and pathophysiologic background for the occurrence of ischemia after CABG are not well established. We tested the hypothesis that altered heart rate (HR) behavior precedes the onset of myocardial ischemic episodes in patients after CABG. Time-domain HR variability measurements, along with analysis of Poincare´ plots and fractal scaling analysis were assessed in 40 CABG patients from 48-hour postoperative Holter recordings. Twenty patients experienced 195 ischemic episodes during the postoperative course. In the univariate analysis of HR variability measurements of the first postoperative day (POD), the increased ratio between the short-term (SD1) and long-term (SD2) HR variability analyzed from the Poincare´ plot and the decreased short- and intermediate-term fractal scaling exponents α1 and α2 were significantly associated with ischemia during the study period (p <0.01, p <0.05, and p <0.05, respectively). In the multivariate model, the increased SD1/SD2 ratio of the first POD was the most powerful independent predictor of all possible confounding variables for the occurrence of postoperative ischemia (corresponding to a change of 0.15 U; odds ratio 2.2 and 95% confidence interval 1.2 to 5.7; p <0.01). Altered HR dynamics have been associated with myocardial ischemic episodes in patients after CABG, suggesting that the autonomic nervous system has an important role in the pathogenesis of myocardial ischemia in the postoperative phase of CABG. [Copyright &y& Elsevier]

Studies the heart rate dynamics before the spontaneous onset of ventricular tachyarrhythmias in Chagas' heart disease. Study design and patients; Factor preceding the spontaneous onset of ventricular fibrillation (VF) in chronic Chagas' cardiomyopathy; Changes in the correlation dimension of RR intervals.

The contribution of genetic variants to non-ischemic sudden cardiac death (SCD) due to acquired myocardial diseases is unclear. We studied whether SCD victims with hypertension/obesity related hypertrophic myocardial disease harbor potentially disease associated gene variants. The Fingesture study has collected data from 5869 autopsy-verified SCD victims in Northern Finland. Among SCD victims, 740 (13%) had hypertension and/or obesity as the most likely explanation for myocardial disease with hypertrophy and fibrosis. We performed next generation sequencing using a panel of 174 cardiac genes for 151 such victims with the best quality of DNA. We used 48 patients with hypertension and hypertrophic heart as controls. Likely pathogenic variants were identified in 15 SCD victims (10%) and variants of uncertain significance (VUS) were observed in additional 43 SCD victims (28%). In controls, likely pathogenic variants were present in two subjects (4%; p = 0.21) and VUSs in 12 subjects (25%; p = 0.64). Among SCD victims, presence of potentially disease-related variants was associated with lower mean BMI and heart weight. Potentially disease related gene variants are common in non-ischemic SCD but further studies are required to determine specific contribution of rare genetic variants to the extent of acquired myocardial diseases leading to SCD. [ABSTRACT FROM AUTHOR]

The article highlights the association between heart rate variability (HRV) and the autonomic nervous system (ANS). Topics discussed include estimating ANS responses to provocations by assessment of ANS responsiveness; SDNN which is a measure of total heartbeat interval variance; and absolute measurements of low (LF) and high (HF) frequency HRV components from their proportions or normalized expressions.

Abnormal 12-lead electrocardiogram (ECG) can predict cardiovascular events, including sudden cardiac death. We tested the hypothesis that ECG provides useful information on guiding implantable cardioverter defibrillator (ICD) therapy into individuals with impaired left ventricular ejection fraction (LVEF). Retrospective data of primary prevention ICD implantations from 14 European centers were gathered. The registry included 5111 subjects of whom 1687 patients had an interpretable pre-implantation ECG available (80.0% male, 63.3 ± 11.4 years). Primary outcome was survival without appropriate ICD shocks or heart transplantation. A low-risk ECG was defined as a combination of ECG variables that were associated with the primary outcome. A total of 1224 (72.6%) patients survived the follow-up (2.9 ± 1.7 years) without an ICD shock, 224 (13.3%) received an appropriate shock and 260 (15.4%) died. Low-risk ECG defined as QRS duration <120 ms, QTc interval <450 ms for men and <470 ms for women, and sinus rhythm, were met by 515 patients (30.5%). Multivariable Cox regression showed that the hazard (HR) for death, heart transplantation or appropriate shock were reduced by 42.5% in the low-risk group (HR 0.575; 95% CI 0.45–0.74; p < 0.001), compared to the high-risk group. The HR for the first appropriate shock was 42.1% lower (HR 0.58; 95% CI 0.41–0.82; p = 0.002) and the HR for death was 48.0% lower (HR 0.52; 95% CI 0.386–0.72; p < 0.001) in the low-risk group. Sinus rhythm, QRS <120 ms and normal QTc in standard 12-lead ECG provides information about survival without appropriate ICD shocks and might improve patient selection for primary prevention ICD therapy. • 12-lead ECG identifies the patients who may not benefit from primary prophylactic ICD patients. • Low risk ECG is defined as QRS duration <120 ms, sinus rhythm, and normal QTc duration. • 12-lead ECG can be used together with other risk variables in identifying the candidate for prophylactic ICD therapy. [ABSTRACT FROM AUTHOR]

Objective: Diabetes increases the risk of all-cause mortality and sudden cardiac death (SCD). The exact mechanisms leading to sudden death in diabetes are not well known. We compared the incidence of appropriate shocks and mortality in patients with versus without diabetes with a prophylactic implantable cardioverter defibrillator (ICD) included in the retrospective EU-CERT-ICD registry.Research Design and Methods and Results: A total of 3,535 patients from 12 European EU-CERT-ICD centers with a mean age of 63.7 ± 11.2 years (82% males) at the time of ICD implantation were included in the analysis. A total of 995 patients (28%) had a history of diabetes. All patients had an ICD implanted for primary SCD prevention. End points were appropriate shock and all-cause mortality. Mean follow-up time was 3.2 ± 2.3 years. Diabetes was associated with a lower risk of appropriate shocks (adjusted hazard ratio [HR] 0.77 [95% CI 0.62-0.96], P = 0.02). However, patients with diabetes had significantly higher mortality (adjusted HR 1.30 [95% CI 1.11-1.53], P = 0.001).Conclusions: All-cause mortality is higher in patients with diabetes than in patients without diabetes with primary prophylactic ICDs. Subsequently, patients with diabetes have a lower incidence of appropriate ICD shocks, indicating that the excess mortality might not be caused primarily by ventricular tachyarrhythmias. These findings suggest a limitation of the potential of prophylactic ICD therapy to improve survival in patients with diabetes with impaired left ventricular function. [ABSTRACT FROM AUTHOR]

Introduction: The prognostic significance of P‐wave morphology in patients with coronary artery disease (CAD) is not well‐known. Methods: A total of 1946 patients with angiographically verified CAD were included in the Innovation to reduce Cardiovascular Complications of Diabetes at the Intersection (ARTEMIS) study. The P‐wave morphology could be analyzed in 1797 patients. Results: During 7.4 ± 2.0 years, a total of 168 (9.3%) patients died or experienced resuscitation from sudden cardiac arrest (SCA), 43 (2.4%) patients experienced sudden cardiac death (SCD) or were resuscitated from SCA, 37 (2.1%) patients succumbed to non‐SCD (NSCD), and 88 (4.9%) patients to noncardiac death (NCD). Of the P‐wave parameters, the absolute P‐wave residuum (PWR), the heterogeneity of the P‐wave morphology (PWH), and the P‐wave duration (Pdur) had the closest univariate association with the risk of SCD/SCA (0.0038 ± 0.0026 vs 0.0022 ± 0.0017, P < .001; 11.0 ± 5.2 vs 8.6 ± 3.6, P < .01; 142.7 ± 16.9 vs 134.8 ± 14.3 milliseconds, P < .01; SCD/SCA vs no SCD/SCA, respectively). After adjustments with factors that were associated with the risk of SCD/SCA, such as diabetes, smoking, left bundle branch block, high‐sensitivity C‐reactive protein, and high‐sensitivity troponin T, PWR (P < .001), PWH (P < .05), and Pdur (P < 0.01) still predicted SCD/SCA but not non‐sudden cardiac death. When these parameters were added to the SCD/SCA clinical risk model, the discrimination and reclassification accuracy of the risk model increased significantly (P < .05, P < .001) and the C‐index increased from 0.745 to 0.787. Conclusion: The P‐wave morphology parameters independently predict SCD/SCA in patients with CAD. [ABSTRACT FROM AUTHOR]

Objective: To compare cardiac mortality in patients with CAD and prediabetes with that in CAD patients with normal glycemic status and type 2 diabetes.Research Design and Methods: The Innovation to Reduce Cardiovascular Complications of Diabetes at the Intersection (ARTEMIS) study included patients with CAD after revascularization (79%), optimal medical therapy, or both. Patients had type 2 diabetes (n = 834), impaired glucose tolerance (IGT; n = 314), impaired fasting glucose (IFG; n = 103), or normal glycemic status (n = 697) as defined on the basis of the results of an oral glucose tolerance test. The primary end point was cardiac death. Major adverse cardiac event (MACE: cardiac death, heart failure, or acute coronary syndrome) and all-cause mortality were secondary end points.Results: During a mean ± SD follow-up of 6.3 ± 1.6 years, 101 cardiac deaths, 385 MACEs, and 208 deaths occurred. Patients with IGT tended to have 49% lower adjusted risk for cardiac death (P = 0.069), 32% lower adjusted risk for all-cause mortality (P = 0.076), and 36% lower adjusted risk for MACE (P = 0.011) than patients with type 2 diabetes. The patients with IFG had 82% lower adjusted risk for all-cause mortality (P = 0.015) than the patients with type 2 diabetes, whereas risks for cardiac death and MACE did not differ significantly between the two groups. The adjusted risks for cardiac death, MACE, and all-cause mortality among patients with IGT and IFG did not significantly differ from those risks among patients with normal glycemic status.Conclusions: Cardiac mortality or incidence of MACE in patients with CAD with prediabetes (i.e., IGT or IFG after revascularization, optimal medical therapy, or both) does not differ from those values in patients with normal glycemic status. [ABSTRACT FROM AUTHOR]

Cardiorespiratory fitness (CRF) and physical activity (PA) are associated with autonomic function, but their associations to orthostatic autonomic responses are unclear in epidemiological setting. We hypothesized that higher CRF and PA would associate with higher immediate vagal responses and lower incidence of adverse findings during orthostatic test. At age of 46, 787 men and 938 women without cardiorespiratory diseases and diabetes underwent an orthostatic test (3‐minutes sitting, 3‐minutes standing) with recording of RR intervals (RRi) and blood pressure (BP) by finger plethysmography. Acute responses of RRi (30:15 ratio) and BP were calculated. CRF was measured by a submaximal step test and daily amount of moderate‐to‐vigorous PA (MVPA) for 2 weeks by wrist‐worn accelerometer. Lifelong PA was based on questionnaires at ages of 14, 31, and 46. High CRF was significantly associated with higher RRi 30:15 ratio (adjusted standardized β = 0.17, P < 0.001) and milder acute decrease of systolic BP while standing (β = 0.10, P = 0.001), while MVPA was not (β = 0.04 for RRi 30:15 ratio and β = 0.05 for systolic BP acute response). High lifelong PA was significantly associated with higher RRi 30:15 ratio (β = 0.08, P = 0.002) but not with acute systolic BP response. Those in the lowest tertile of CRF had 9.2‐fold risk (P = 0.002) of having postural orthostatic tachycardia syndrome compared to more fit. Cardiorespiratory fitness and lifelong physical activity, but not current physical activity, were independently associated with higher cardiac vagal response to orthostasis. The present results underscore the importance fitness and lifelong physical activity in prevention of abnormal autonomic function and related cardiovascular risk. [ABSTRACT FROM AUTHOR]

The debate whether an elevated level of serum uric acid (SUA) is an independent marker of cardiovascular risk is still going on. We examined morbidity and mortality related to SUA and hyperuricemia in a well-characterized population with very long follow-up. Study included 4696 participants (aged 30-59 years at baseline) of the coronary heart disease (CHD) Study of the Finnish Mobile Clinic Health Examination Survey. Adjusted hazard ratios (HRs) of hyperuricemia (defined as ≥360 µmol/l and ≥420 µmol/l) and SUA quintiles for mortality and adverse cardiovascular outcomes are reported. During the mean follow up of 30.6 years there were 2723 deaths, 887 deaths for CHD of which 340 were classified as sudden cardiac deaths, 1642 hospitalizations due to CHD and 798 hospitalizations due to congestive heart failure. After adjusting to baseline risk factors and presence of cardiovascular diseases as well as the use of diuretics there were no significant differences in the risk of any of the outcomes when analyzed either according to quintiles of SUA or using a cut-off point SUA ≥360 µmol/l for hyperuricemia. Only a rare finding of hyperuricemia SUA ≥420 µmol/l among women (n = 17, 0.9%) was independently associated with significantly higher risk of mortality (adjusted HR: 2.59, 95% CI: 1.54-4.34) and a combination end-point of major adverse cardiac events (MACEs) (HR: 2.69; 95% CI: 1.56-4.66). SUA was not an independent indicator of morbidity and mortality, with the exception of particularly high levels of SUA among women. [ABSTRACT FROM AUTHOR]

Aims: To investigate prognostic significance of post-exercise recovery of rate-pressure product (RPP) in patients with stable coronary artery disease (CAD) and type 2 diabetes (T2D).Methods: Patients with angiographically documented CAD and T2D (n = 697) underwent symptom-limited bicycle exercise test. Exercise capacity (EC), heart rate, blood pressure and RPP responses to peak exercise and recovery (2' and 5' after cessation of exercise) were analyzed. Cardiac death was the primary and sudden cardiac death (SCD) secondary endpoint.Results: During a median follow-up of 76 months, 49 cardiac deaths (7.0%) and 28 SCDs (4.0%) were observed. The recovery of RPP at 5' was the strongest univariate predictor of cardiac death (hazard ratio [HR]: 2.55 per SD decrease, 95%CI: 1.82-3.58, p < 0.001) and SCD (HR: 2.34, 95%CI: 1.51-3.62, p < 0.001). In multivariate analysis, it remained significantly associated to cardiac death and SCD without (HR: 1.66, 95%CI: 1.14-2.41, p < 0.01 and HR: 1.75, 95%CI: 1.08-2.85, p < 0.05, respectively) and with additional adjustment for EC and peak RPP (HR: 1.45, 95%CI: 1.09-1.92, p < 0.05 and HR: 1.52, 95%CI: 1.01-2.27, p < 0.05, respectively).Conclusions: The recovery of RPP after exercise is a potent predictor of cardiac death in patients with CAD and T2D. It provides significant prognostic information beyond EC and peak RPP. [ABSTRACT FROM AUTHOR]

Abstract Background Electrocardiographic (ECG) left ventricular hypertrophy (LVH) is an established risk factor for cardiovascular events. However, limited data is available on the prognostic values of different ECG LVH criteria specifically to sudden cardiac death (SCD). Our goal was to assess relationships of different ECG LVH criteria to SCD. Methods Three traditional and clinically useful (Sokolow–Lyon, Cornell, R aVL) and a recently proposed (Peguero–Lo Presti) ECG LVH voltage criteria were measured in 5730 subjects in the Health 2000 Survey, a national general population cohort study. Relationships between LVH criteria, as well as their selected composites, to SCD were analyzed with Cox regression models. In addition, population-attributable fractions for LVH criteria were calculated. Results After a mean follow-up of 12.5 ± 2.2 years, 134 SCDs had occurred. When used as continuous variables, all LVH criteria except for R aVL were associated with SCD in multivariable analyses. When single LVH criteria were used as dichotomous variables, only Cornell was significant after adjustments. The dichotomous composite of Sokolow–Lyon and Cornell was also significant after adjustments (hazard ratio for SCD 1.82, 95% confidence interval 1.20–2.70, P = 0.006) and was the only LVH measure that showed statistically significant population-attributable fraction (11.0%, 95% confidence interval 1.9–19.2%, P = 0.019). Conclusions Sokolow–Lyon, Cornell, and Peguero–Lo Presti ECG, but not R aVL voltage, are associated with SCD risk as continuous ECG voltage LVH variables. When SCD risk assessment/adjustment is performed using a dichotomous ECG LVH measure, composite of Sokolow–Lyon and Cornell voltages is the preferred option. Highlights • There has been limited data on relationship of ECG LVH measures to sudden cardiac death. • Sokolow–Lyon, Cornell, and Peguero–Lo Presti are associated with sudden cardiac death risk as continuous LVH variables. • R aVL is not associated with sudden cardiac death risk. • Composite of Sokolow–Lyon and Cornell voltages is the preferred dichotomous ECG measure to adjust for SCD risk. [ABSTRACT FROM AUTHOR]

Regular year-round exercise is recommended for patients with coronary artery disease (CAD). However, the combined effects of cold and moderate sustained exercise, both known to increase cardiac workload, on cardiovascular responses are not known. We tested the hypothesis that cardiac workload is increased, and evidence of ischemia would be observed during exercise in the cold in patients with CAD. Sixteen men (59.3 ± 7.0 yr, means ± SD) with stable CAD each underwent 4, 30 min exposures in a randomized order: seated rest and moderate-intensity exercise [walking, 60%-70% of max heart rate (HR)] performed at +22°C and -15°C. Systolic brachial blood pressure (SBP), HR, electrocardiogram (ECG), and skin temperatures were recorded throughout the intervention. Rate pressure product (RPP) and ECG parameters were obtained. The combined effects of cold and submaximal exercise were additive for SBP and RPP and synergistic for HR when compared with rest in a neutral environment. RPP (mmHg·beats/min) was 17% higher during exercise in the cold (18,080 ± 3540) compared with neutral (15,490 ± 2,940) conditions (P = 0.001). Only a few ST depressions were detected during exercise but without an effect of ambient temperature. The corrected QT interval increased while exercising in the cold compared with neutral temperature (P = 0.023). Recovery of postexercise blood pressure was similar regardless of temperature. Whole body exposure to cold during submaximal exercise results in higher cardiac workload compared with a neutral environment. Despite the higher RPP, no signs of myocardial ischemia or abnormal ECG responses were observed. The results of this study are useful for planning year-round exercise-based rehabilitation programs for stable CAD patients. [ABSTRACT FROM AUTHOR]

Background: Myocardial fibrosis is a common postmortem finding among young individuals with sudden cardiac death. Because there is no known single cause, we tested the hypothesis that some cases of myocardial fibrosis in the absence of identifiable causes (primary myocardial fibrosis [PMF]) are associated with genetic variants.Methods: Tissue was obtained at autopsy from 4031 consecutive individuals with sudden cardiac death in Northern Finland, among whom PMF was the only structural finding in 145 subjects with sudden cardiac death. We performed targeted next-generation sequencing using a panel of 174 genes associated with myocardial structure and ion channel function when autopsies did not identify a secondary basis for myocardial fibrosis. All variants with an effect on protein and with a minor allele frequency <0.01 were classified as pathogenic or variants of uncertain significance on the basis of American College of Medical Genetics consensus guidelines.Results: Among the 96 specimens with DNA passing quality control (66%), postmortem genetic tests identified 24 variants of known or uncertain significance in 26 subjects (27%). Ten were pathogenic/likely pathogenic variants in 10 subjects (10%), and 14 were variants of uncertain significance in 11 genes among 16 subjects (17%). Five variants were in genes associated with arrhythmogenic right ventricular cardiomyopathy, 6 in hypertrophic cardiomyopathy-associated genes, and 11 in dilated cardiomyopathy-associated genes; 2 were not associated with these disorders. Four unique variants of uncertain significance cosegregated among multiple unrelated subjects with PMF. No pathogenic/likely pathogenic variants were detected in ion channel-encoding genes.Conclusions: A large proportion of subjects with PMF at autopsy had variants in genes associated with arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy without autopsy findings of those diseases, suggesting that PMF can be an alternative phenotypic expression of structural disease-associated genetic variants or that risk-associated fibrosis was expressing before the primary disease. These findings have clinical implications for postmortem genetic testing and family risk profiling. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Little is known about the association between electrocardiographic abnormalities and exercise‐related sudden cardiac death. Therefore, our aim was to identify possible electrocardiographic findings related to exercise‐induced sudden cardiac death. Methods and results: The FinGesture study includes 3,989 consecutive sudden cardiac deaths in northern Finland between 1998 and 2012, out of whom a total of 647 subjects had a previously recorded electrocardiography acquired from the archives of Oulu University Hospital. In 276 of these cases the death was witnessed, and the activity at the time of death was either rest or physical exercise (PE); in 40 (14%) cases sudden cardiac death was exercise‐related and in 236 (86%) cases death took place at rest. Fragmented QRS complex in at least two consecutive leads within anterior leads (V1‐V3) was more common in the exercise‐group compared to rest‐group (17 of 40, 43% vs. 51 of 236, 22%, P  =  0.005). Pathologic Q wave in anterior leads was more common in the PE group (9 of 40, 23% vs. 26 of 236, 11%; P  =  0.044). Median QRS duration was prolonged in the exercise‐group compared to the rest‐group (100 milliseconds vs. 94 milliseconds, P = 0.047). QTc interval, the prevalence of inverted T‐waves, or other electrocardiographic abnormalities did not differ significantly between the two groups. Conclusions: As a conclusion, fragmented QRS complex in the anterior leads is associated with an increased risk of sudden cardiac death during PE. [ABSTRACT FROM AUTHOR]