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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.)

Introduction: Non-ischaemic heart disease (NIHD) is the underlying pathology in∼20% of all sudden cardiac deaths (SCDs). Heavy drinking is known to be associated with SCD due to ischaemic heart disease, but studies on association of recent alcohol consumption and SCD in patients with NIHD are scarce. We evaluated the blood alcohol levels of autopsy verified non-ischaemic SCD victims., Methods: Study population was derived from the Finnish Genetic Study of Arrhythmic Events (Fingesture) ( n  = 5869, mean age 65 ± 12, 79% males). All deaths occurred in Northern Finland during 1998-2017. All victims underwent a medico-legal autopsy. Subjects of SCD due to ischaemic heart disease were excluded., Results: A total of 1301 (mean age 57 ± 12, 78% males) victims of SCD due to NIHD were included in the study. The blood ethanol level was elevated in 543 (42%) subjects, out of which the blood alcohol level was ≥0.10%in 339 (62%) subjects and ≥0.15%in 252 (46%) subjects. Male SCD victims had alcohol in blood more frequently compared to females (45% versus 31%, p  < .001)., Conclusion: Elevated blood alcohol level is common in SCD victims due to NIHD, especially in males. Recent alcohol consumption might contribute to the subsequent SCD in many non-ischaemic SCD victims.KEY MESSAGESElevated blood alcohol level is common in victims of sudden cardiac death due to non-ischaemic heart disease, especially in males.Recent alcohol consumption may contribute to the subsequent death in many nonischemic sudden cardiac death victims.

Aims: The Cardiac Arrhythmias and RIsk Stratification after Myocardial infArction (CARISMA) study was an observational trial including 312 patients with acute myocardial infarction (MI) and left ventricular ejection fraction (LVEF) <40%. Primary percutaneous intervention (pPCI) was introduced 2 years after start of the enrolment, dividing the population into two groups: pre- and post-pPCI. This substudy sought to describe the influence of the mode of revascularization on long-term risk of new-onset atrial fibrillation (AF), bradyarrhythmia, and ventricular tachycardia and the subsequent risk of relevant major cardiovascular events (MACE)., Methods and Results: The study included the 268 patients without a history of AF. All patients received an implantable cardiac monitor (ICM) and were followed for 2 years. The choice of revascularization was made by the treating team independently of the trial and retrospectively divided into pPCI, subacute PCI, primary thrombolysis, or no revascularization. Endpoints were new-onset arrhythmia and MACE.A total of 77 patients received no revascularization, whereas 49 received thrombolysis only and 142 received any PCI. The adjusted hazard ratio (HR) for developing any arrhythmia and the subsequently risk of MACE were increased in non-revascularized or thrombolysed patients compared with PCI-patients (any arrhythmia, non-revascularization: HR = 1.7, P = 0.01 and thrombolysis: HR = 1.6, P = 0.05; MACE, non-revascularization: HR = 3.1, P = 0.05 and thrombolysis: HR = 3.1, P = 0.08). All HRs were adjusted for significant baseline and clinically considered covariates and stratified for calendar year., Conclusion: This study is the first to demonstrate that the long-term risk of arrhythmia documented by an ICM and the subsequent risk of MACE were increased in non-revascularized or thrombolysed patients compared with PCI-patients in a post-MI population with LVEF <40%., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Importance: Myocardial infarction in the absence of major or unrecognized symptoms are characterized as silent (SMI). The prevalence of SMI among individuals who experience sudden cardiac death (SCD), with or without concomitant electrocardiographic (ECG) changes, has not previously been described in detail from large studies to our knowledge., Objective: To determine the prevalence of SMI in individuals who experience SCD without a prior diagnosis of coronary artery disease (CAD) and to detect ECG abnormalities associated with SMI-associated SCD., Design, Setting, and Participants: This case-control study compared autopsy findings, clinical characteristics, and ECG markers associated with SMI in a consecutive cohort of individuals in the Finnish Genetic Study of Arrhythmic Events (Fingesture) study population who were verified to have had SCD. The Fingesture study consists of individuals who had autopsy-verified SCD in Northern Finland between 1998 and 2017. Individuals who had SCD with CAD and evidence of SMI were regarded as having had cases; those who had SCD with CAD without SMI were considered control participants. Analyses of ECG tests were carried out by investigators blinded to the SMI data. Data analysis was completed from October 2018 through November 2018., Main Outcomes and Measures: Silent MI was defined as a scar detected by macroscopic and microscopic evaluation of myocardium without previously diagnosed CAD. Clinical history was obtained from medical records, previously recorded ECGs, and a standardized questionnaire provided to the next of kin. The hypothesis tested was that SMI would be prevalent in the population who had had SCD with CAD, and it might be detected or suspected from findings on ECGs prior to death in many individuals., Results: A total of 5869 individuals were included (2459 males [78.8%]; mean [SD] age, 64.9 [12.4] years). The cause of SCD was CAD in 4392 individuals (74.8%), among whom 3122 had no history of previously diagnosed CAD. Two individuals were excluded owing to incomplete autopsy information. An ECG recorded prior to SCD was available in 438 individuals. Silent MI was detected in 1322 individuals (42.4%) who experienced SCD without a clinical history of CAD. The participants with SMI were older than participants without MI scarring (mean [SD] age, 66.9 [11.1] years; 65.5 [11.6] years; P < .001) and were more often men (1102 of 1322 [83.4%] vs 1357 of 1798 [75.5%]; P < .001). Heart weight was higher in participants with SMI (mean [SD] weight, 483 [109] g vs 438 [106] g; P < .001). In participants with SMI, SCD occurred more often during physical activity (241 of 1322 [18.2%] vs 223 of 1798 [12.4%]; P < .001). A prior ECG was abnormal in 125 of the 187 individuals (66.8%) who had SCD after SMI compared with 139 of 251 (55.4%) of those who had SCD without SMI (P = .02)., Conclusions and Relevance: Many individuals who experienced SCD associated with CAD had a previously undetected MI at autopsy. Previous SMI was associated with myocardial hypertrophy and SCD during physical activity. Premortem ECGs in a subset with available data were abnormal in 67% of the individuals who had had a SCD after an SMI.

Aims: Delayed QRS transition zone in the precordial leads of the 12-lead electrocardiogram (ECG) has been recently associated with increased risk of sudden cardiac death (SCD), but the underlying mechanisms are unknown. We correlated echocardiographic findings with ECG and clinical characteristics to investigate how alterations in cardiac structure and function contribute to this risk marker., Methods and Results: From the ongoing population-based Oregon Sudden Unexpected Death Study (catchment population ∼1 million), SCD cases with prior ECG available (n = 627) were compared with controls (n = 801). Subjects with delayed transition at V5 or later were identified, and clinical and echocardiographic patterns associated with delayed transition were analysed. Delayed transition was present in 31% of the SCD cases and 17% of the controls. These subjects were older and more likely to have cardiovascular risk factors and history of myocardial infarction. Delayed transition was associated with increased left ventricular (LV) mass (122.7 ± 40.2 vs. 102.9 ± 33.7 g/m2; P < 0.001), larger LV diameter (53.3 ± 10.4 vs. 49.2 ± 8.0 mm; P < 0.001), and lower LV ejection fraction (LVEF) (46.4 ± 15.7 vs. 55.6 ± 12.5%; P < 0.001). In multivariate analysis, delayed transition was independently associated with myocardial infarction, reduced LVEF, and LV hypertrophy. The association between delayed transition and SCD was independent of the LVEF (OR 1.57; 95% CI 1.04-2.38; P = 0.032)., Conclusion: The underpinnings of delayed QRS transition zone extend beyond previous myocardial infarction and reduced LVEF. Since the association with sudden death is independent of these factors, this novel marker of myocardial electrical remodelling should be explored as a potential risk predictor of SCD., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Aims: Dyx is a new heart rate variability (HRV) density analysis specifically designed to identify patients at high risk for malignant ventricular arrhythmias. The aim of this study was to test if Dyx can improve risk stratification for malignant ventricular tachyarrhythmias and to test if the previously identified cut-off can be reproduced., Methods and Results: This study included 248 patients from the CARISMA study with ejection fraction ≤40% after an acute myocardial infarction and an analysable 24 h Holter recording. All patients received an implantable cardiac monitor, which was used to diagnose the primary endpoint of near-fatal or fatal ventricular tachyarrhythmias likely preventable by an implantable cardioverter defibrillator (ICD), during a period of 2 years. A Dyx ≤ 1.96 was considered abnormal. The secondary endpoint was cardiovascular death. At enrolment 59 patients (24%) had a Dyx ≤ 1.96 and 20 experienced a primary endpoint. A Dyx ≤ 1.96 was associated with a significantly increased risk for malignant arrhythmias [hazards ratio (HR) = 4.36 (1.81-10.52), P = 0.001] and cardiovascular death [HR = 3.47 (1.38-8.74), P = 0.008]. Compared with important clinical risk parameters (age >70 years and QRS > 120 ms), Dyx ≤ 1.96 significantly added predictive value (P = 0.0066)., Conclusions: Dyx was a better predictor of ventricular tachyarrhythmias than the traditional measures of HRV and heart rate turbulence, particularly in the elderly. Dyx might be a useful tool for better selection of ICD candidates in the elderly population, since a normal Dyx in this group was associated with a very low risk for malignant ventricular arrhythmias.ClinicalTrials.gov Identifier NCT00145119., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: Previous studies have shown substantially increased risk of cardiac arrhythmias and sudden cardiac death in post-myocardial infarction (MI) patients. However it remains difficult to identify the patients who are at highest risk of arrhythmias in the post-MI setting. The purpose of this study was to investigate if CHADS₂ score (congestive heart failure, hypertension, age ≥75 years, diabetes and previous stroke/TCI [doubled]) can be used as a risk tool for predicting cardiac arrhythmias after MI., Methods: The study included 297 post-MI patients from the CARISMA study with left ventricular ejection fraction (LVEF) ≤40%. All patients were implanted with an implantable cardiac monitor (ICM) within 5 to 21 days post-MI and followed every three months for two years. Atrial fibrillation, bradyarrhythmias and ventricular tachycardias were diagnosed using the ICM, pacemaker or ICD. Patients were stratified according to CHADS₂ score at enrollment. Congestive heart failure was defined as LVEF ≤40% and NYHA class II, III or IV., Results: We found significantly increased risk of an arrhythmic event with increasing CHADS₂ score (CHADS₂ score=1-2: HR=2.1 [1.1-3.9], p=0.021, CHADS₂ score ≥ 3: HR=3.7 [1.9-7.1], p<0.001). This pattern was identical when dividing the arrhythmias into subgroups of atrial fibrillation, ventricular tachycardias and bradyarrhythmias. CHADS₂ score was similarly associated with the development of major cardiovascular events defined as reinfarction, stroke, and hospitalization for heart failure or cardiovascular death., Conclusion: In the post-MI setting, CHADS₂ score efficiently identifies populations at high risk for cardiac arrhythmias., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Aims: The objective of the present analysis was to systematically examine the effect of intracoronary bone marrow cell (BMC) therapy on left ventricular (LV) function after ST-segment elevation myocardial infarction in various subgroups of patients by performing a collaborative meta-analysis of randomized controlled trials., Methods and Results: We identified all randomized controlled trials comparing intracoronary BMC infusion as treatment for ST-segment elevation myocardial infarction. We contacted the principal investigator for each participating trial to provide summary data with regard to different pre-specified subgroups [age, diabetes mellitus, time from symptoms to percutaneous coronary intervention, infarct-related artery, LV end-diastolic volume index (EDVI), LV ejection fraction (EF), infarct size, presence of microvascular obstruction, timing of cell infusion, and injected cell number] and three different endpoints [change in LVEF, LVEDVI, and LV end-systolic volume index (ESVI)]. Data from 16 studies were combined including 1641 patients (984 cell therapy, 657 controls). The absolute improvement in LVEF was greater among BMC-treated patients compared with controls: [2.55% increase, 95% confidence interval (CI) 1.83-3.26, P < 0.001]. Cell therapy significantly reduced LVEDVI and LVESVI (-3.17 mL/m², 95% CI: -4.86 to -1.47, P < 0.001; -2.60 mL/m², 95% CI -3.84 to -1.35, P < 0.001, respectively). Treatment benefit in terms of LVEF improvement was more pronounced in younger patients (age <55, 3.38%, 95% CI: 2.36-4.39) compared with older patients (age ≥ 55 years, 1.77%, 95% CI: 0.80-2.74, P = 0.03). This heterogeneity in treatment effect was also observed with respect to the reduction in LVEDVI and LVESVI. Moreover, patients with baseline LVEF <40% derived more benefit from intracoronary BMC therapy. LVEF improvement was 5.30%, 95% CI: 4.27-6.33 in patients with LVEF <40% compared with 1.45%, 95% CI: 0.60 to 2.31 in LVEF ≥ 40%, P < 0.001. No clear interaction was observed between other subgroups and outcomes., Conclusion: Intracoronary BMC infusion is associated with improvement of LV function and remodelling in patients after ST-segment elevation myocardial infarction. Younger patients and patients with a more severely depressed LVEF at baseline derived most benefit from this adjunctive therapy.

Background: After myocardial infarction (MI) the risk of sudden cardiac death due to arrhythmias is substantial., Objective: The purpose of this study was to investigate if new-onset atrial fibrillation (AF) is associated with development of potential malignant brady- and tachyarrhythmias after an acute MI., Methods: The study included 277 post-MI patients from the CARISMA study with left ventricular ejection fraction ≤ 40%, New York Heart Association class I, II, or III and no history of AF. All patients were implanted with an implantable cardiac monitor within 4 to 27 days after an acute MI and followed every 3 months for 2 years. Time-dependent association between new-onset AF > 30 s and the development of bradyarrhythmias and/or ventricular tachyarrhythmias were investigated using Cox proportional hazard regressions., Results: New-onset AF was associated with an increased risk of bradyarrhythmias when adjusting for male gender and baseline age, left ventricular ejection fraction and QRS width (HR = 2.8 [1.3-5.8], P = .006). Similarly, new-onset AF predicted ventricular tachyarrhythmias when adjusting for New York Heart Association class ≥ II and baseline QRS width (HR = 2.3 [1.2-4.4], P = .019). After dividing ventricular tachyarrhythmias into subgroups of non-sustained ventricular tachycardia (VT), sustained VT and ventricular fibrillation (VF), new-onset AF was significantly associated with an increased risk of non-sustained- and sustained VT but not VF (non-sustained VT: HR = 3.5 [1.7-7.2], P < .001, sustained VT: HR = 4.2 [1.1-15.7], P = .035, VF: HR = 1.1 [0.2-5.8], P = .877)., Conclusion: In patients surviving a MI with reduced left ventricular systolic function, new-onset AF is associated with a significantly increased risk of developing ventricular brady- and tachyarrhythmias., (© 2013.)

Aims: To identify potential new markers for assessing the risk of sudden arrhythmic events based on a method that captures features of premature ventricular complexes (PVCs) in relation to sinus RR intervals in Holter recordings (heartprint)., Methods and Results: Holter recordings obtained 6 weeks after acute myocardial infarction from 227 patients with reduced ventricular function (left ventricular ejection fraction ≤ 40%) were used to produce heartprints. Measured indices were: PVCs per hour, standard deviation of coupling interval (SDCI), and the number of occurrences of the most prevalent form of PVCs (SNIB). Predictive values, survival analysis, and Cox regression with adjustment for clinical variables were performed based on primary endpoint, defined as an electrocardiogram-documented fatal or near-fatal arrhythmic event, death from any cause, and cardiac death. High ectopy (PVCs per hour ≥10) was a predictor of all endpoints. Repeating forms of PVCs (SNIB ≥ 83) was a predictor of primary endpoint, hazard ratio = 3.5 (1.3-9.5), and all-cause death, hazard ratio = 2.8 (1.1-7.3), but not cardiac death. SDCI ≤ 80 ms was a predictor of all-cause death and cardiac death, but not of primary endpoint., Conclusion: High ectopy, prevalence of repeating forms of PVCs, and low coupling interval variability are potentially useful risk markers of fatal or near-fatal arrhythmias after myocardial infarction.

Heart rate (HR) variability has been extensively studied in cardiac patients, especially in patients surviving an acute myocardial infarction (AMI) and also in patients with congestive heart failure (CHF) or left ventricular (LV) dysfunction. The majority of studies have shown that patients with reduced or abnormal HR variability have an increased risk of mortality within a few years after an AMI or after a diagnosis of CHF/LV dysfunction. Various measures of HR dynamics, such as time-domain, spectral, and non-linear measures of HR variability have been used in risk stratification. The prognostic power of various measures, except of those reflecting rapid R-R interval oscillations, has been almost identical, albeit some non-linear HR variability measures, such as short-term fractal scaling exponent have provided somewhat better prognostic information than the others. Abnormal HR variability predicts both sudden and non-sudden cardiac death. Because of remodeling of the arrhythmia substrate after AMI, early measurement of HR variability to identify those at high risk should likely be repeated later in order to assess the risk of fatal arrhythmia events. Future randomized trials using HR variability/turbulence as one of the pre-defined inclusion criteria will show whether routine measurement of HR variability/turbulence will become a routine clinical tool for risk stratification of cardiac patients., (© 2013.)

The annual incidence of sudden cardiac death (SCD) is estimated at 1 per 1,000 for adults over the age of 35 years, and 1 per 100,000 for adolescents and young adults. Although the overall incidence of unexpected SCD among previously healthy persons is small, the emotional impact of these events is devastating. The 12-lead electrocardiogram (ECG) has been used as a risk assessment tool from healthy occupational applicants and athletes to patients with cardiovascular disorders. The ECG is also routinely recorded in the majority of patients hospitalized for non-cardiovascular causes. Thus, it is a widely used tool intended for identification of unsuspected heart disease generally, as well as for diagnosing specific disorders predisposing to fatal arrhythmias in subjects who have not experienced such events but who are at increased risk. Recognition of specific ECG features is of importance for prevention of SCD in asymptomatic persons. The purpose of this review is to catalog the disorders associated with SCD that may be reflected in 12-lead ECGs seen in office or hospital practices and to discuss their prevalence and the magnitude of risks. The focus is on ECG findings suggesting increased SCD risk among the asymptomatic subjects without previously diagnosed cardiac disease.

Background: Treatment of acute myocardial infarction with stem cell transplantation has achieved beneficial effects in many clinical trials. The bone marrow microenvironment of ST-elevation myocardial infarction (STEMI) patients has never been studied even though myocardial infarction is known to cause an imbalance in the acid-base status of these patients. The aim of this study was to assess if the blood gas levels in the bone marrow of STEMI patients affect the characteristics of the bone marrow cells (BMCs) and, furthermore, do they influence the change in cardiac function after autologous BMC transplantation. The arterial, venous and bone marrow blood gas concentrations were also compared., Methods: Blood gas analysis of the bone marrow aspirate and peripheral blood was performed for 27 STEMI patients receiving autologous stem cell therapy after percutaneous coronary intervention. Cells from the bone marrow aspirate were further cultured and the bone marrow mesenchymal stem cell (MSC) proliferation rate was determined by MTT assay and the MSC osteogenic differentiation capacity by alkaline phosphatase (ALP) activity assay. All the patients underwent a 2D-echocardiography at baseline and 4 months after STEMI., Results: As expected, the levels of pO(2), pCO(2), base excess and HCO(3) were similar in venous blood and bone marrow. Surprisingly, bone marrow showed significantly lower pH and Na(+) and elevated K(+) levels compared to arterial and venous blood. There was a positive correlation between the bone marrow pCO(2) and HCO(3) levels and MSC osteogenic differentiation capacity. In contrast, bone marrow pCO(2) and HCO(3) levels displayed a negative correlation with the proliferation rate of MSCs. Patients with the HCO(3) level below the median value exhibited a more marked change in LVEF after BMC treatment than patients with HCO(3) level above the median (11.13 ± 8.07% vs. 2.67 ± 11.89%, P = 0.014)., Conclusions: Low bone marrow pCO(2) and HCO(3) levels may represent the optimal environment for BMCs in terms of their efficacy in autologous stem cell therapy in STEMI patients.

Aims: The present study aimed to assess whether there are differences in risk indicators for perpetuating ventricular tachyarrhythmias (pVT) and self-terminating ventricular tachyarrhythmias (stVT)., Methods and Results: Patients with acute myocardial infarction (AMI) and baseline left ventricular ejection fraction ≤ 40% (n = 292) received an implantable electrocardiogram loop recorder from 5 to 21 days after AMI and were followed up for 24 months to document arrhythmic events in the Cardiac Arrhythmias and Risk Stratification after Acute Myocardial Infarction (CARISMA) study. Several risk markers, such as the inducibility to sustained ventricular tachycardia during programmed electrical stimulation (PES), the signal-averaged ECG QRS duration (SAECG-QRS), heart rate variability (HRV) and turbulence (HRT), T-wave alternans, and non-sustained ventricular tachycardia on Holter were analysed at 6 weeks after the AMI. During the follow-up, 26 patients (9%) experienced an stVT (≥ 16 beats and < 30 s), and 21 patients (7%) a pVT. The occurrence of non-sustained ventricular tachycardia on Holter significantly predicted stVT [hazard ratio (HR) = 2.90, 1.26-6.67, 95% confidence interval (CI), P = 0.01], but not pVT during the follow-up. The inducibility during PES (HR = 5.02, 1.85-13.60, 95% CI, P = 0.001), SAECG-QRS ≥ 130 ms (HR = 8.73, 3.38-22.56, 95% CI, P < 0.001), the short-term scaling exponent HRV parameter ≤ 0.77 (HR = 5.65, 2.12-15.10, 95% CI, P = 0.001), and HRT slope ≤ 1.75 ms/NN (HR = 4.57, 1.80-11.59, 95% CI, P = 0.001) were significant predictors of pVT, even after adjustments with relevant clinical parameters (P from < 0.01 to < 0.001), but did not significantly predict the occurrence of stVT (P from 0.35 to 0.75)., Conclusion: Self-terminating ventricular tachyarrhythmia and pVT have differences in electrophysiological substrate and arrhythmia modifiers in post-AMI patients with moderate left ventricular dysfunction.

Aims: High-degree atrioventricular block (HAVB) after acute myocardial infarction (AMI) is associated with increased risk of mortality. Risk markers and predictors of HAVB occurring after AMI are largely unknown. The aim of this study was to assess the predictive value of risk markers derived from a series of non-invasive and invasive tests for the development of HAVB documented by an implantable loop recorder (ILR) in late convalescent phases of an AMI., Methods and Results: The study included 292 patients with AMI and subsequent left ventricular dysfunction without prior HAVB or implanted pacemaker. An ILR was implanted for continuous arrhythmia surveillance. Risk stratification testing was performed at inclusion and 6 weeks after AMI. The tests included echocardiography, electrocardiogram (ECG), 24 h Holter monitoring, and an invasive electrophysiological study. High-degree atrioventricular block was documented in 28 (10%) patients during a median follow-up of 2.0 (0.4-2.0) years. Heart rate variability (HRV) measures and non-sustained ventricular tachycardia occurring at the week 6 Holter monitoring were highly predictive of HAVB. Power law slope <-1.5 ms(2)/Hz was the most powerful HRV parameter (HR = 6.02 [2.08-17.41], P < 0.001)., Conclusion: Late HAVB development in post-AMI patients with left ventricular dysfunction can be predicted by risk stratification tests. Measures of HRV reflecting autonomic dysfunction revealed the highest predictive capabilities.

Background: High-degree atrioventricular block (HAVB) is a frequent complication in the acute stages of a myocardial infarction associated with an increased rate of mortality. However, the incidence and clinical significance of HAVB in late convalescent phases of an AMI is largely unknown. The aim of this study was to assess the incidence and prognostic value of late HAVB documented by continuous electrocardiogram (ECG) monitoring in post-AMI patients with reduced left ventricular function., Methods: The study included 286 patients from the CARISMA study with AMI and left ventricular ejection fraction of 40% or less. An insertable loop recorder was implanted 5 to 21 days after AMI for incessant arrhythmia surveillance. Furthermore, ECG documentation was supplemented by a 24-hour Holter monitoring conducted at week 6 post-AMI. The clinical significance of HAVB occurring more than 21 days after AMI was examined with respect to development of major heart failure events and major ventricular tachyarrhythmic events., Results: During a median follow-up of 1.9 years (interquartile range 0.9-2.0), late HAVB was documented in 30 patients. The risk of major heart failure events (hazard ratio [HR] 4.08 [1.38-12.09], P = .01) and major ventricular tachyarrhythmic events (HR = 5.41 [1.88-15.58], P = .002) were significantly increased in patients who developed late HAVB., Conclusion: High-degree atrioventricular block documented by continuous ECG monitoring occurring more than 3 weeks after AMI is a frequent complication in post-AMI patients with left ventricular dysfunction. Furthermore, HAVB is associated with ominous prognostic implications of both potentially lethal arrhythmias and heart failure., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Intracoronary administration of autologous bone marrow stem cells (BMC) has been shown to result in a subtle improvement of global left ventricular ejection fraction after ST-elevation myocardial infarction (STEMI), but the overall benefits of BMC therapy are still unclear. We studied the influence of intracoronary injections of BMC on levels of natriuretic peptides and inflammatory mediators, which are well established prognostic biomarkers, in patients with STEMI., Methods: In this randomized, double-blind study, consecutive patients with an acute STEMI treated with thrombolysis followed by PCI 2-6 days after STEMI, were randomly assigned to receive either intracoronary BMC or placebo medium into the infarct-related artery. Blood samples were drawn for biochemical determinations., Results: From baseline to 6 months, there was a significant decrease in the levels of N-terminal probrain natriuretic peptide (NT-proBNP), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) in the whole patient population (P < 0.001 for all). However, no difference was observed between the BMC group (n = 39) and the placebo group (n = 39) in the change of the levels of NT-proANP (median -54 vs. +112 pmol/L), NT-proBNP (-88 vs. -115 pmol/L) or inflammatory markers IL-6 (-3.86 vs. -5.61 pg/mL), hsCRP (-20.29 vs. -22.36 mg/L) and tumor necrosis factor α (-0.12 vs. -0.80 pg/mL) between baseline and 6 months., Conclusion: Intracoronary BMC therapy does not appear to exert any significant effects on the secretion of natriuretic peptides or inflammatory biomarkers in STEMI patients.

Background: Heart rate (HR) turbulence lasting up to 15 beats after ventricular premature beats (VPBs) may have profound effects on HR variability measures. Aim of this study was to examine the effects of HR turbulence on HR variability measures., Methods: We developed an algorithm, which deletes 15 consecutive RR intervals after VPBs and examined the effects of the HR turbulence removal on the HR variability measures in patients after an acute myocardial infarction (AMI). Two hundred and sixty seven patients with left ventricular ejection fraction (LVEF) ≤ 0.40 and occurrence of VPBs were included in the study. Differences (%) between original HR data and HR turbulence edited data were compared., Results: HR turbulence editing had variable effects on different HR variability indexes. Ultra low (ULF) and very low frequency (VLF) spectral components were mostly affected by the HR turbulence removal. Both ULF and VLF decreased significantly both at baseline Holter recordings (ULF: P = 0.006, VLF: P = 0.031) and at 6 weeks from AMI (ULF: P < 0.001, VLF: P = 0.001). The number of VPBs had a marked influence on results, e.g., when the number of VPBs exceeded the highest decile (≈50 VPBs/hour), the ULF and VLF spectral component were >30% lower after removal of turbulence. In addition, the prediction of arrhythmic events by ULF component improved after turbulence removal (AUC: 0.69 ->0.74)., Conclusions: HR turbulence affects HR variability measures, especially the ULF and VFL spectral components. Editing of the HR turbulence should be considered when HR variability is measured from Holter recordings., (©2011, Wiley Periodicals, Inc.)

Background and Aim: chronotropic incompetence is risk marker of mortality in various populations, but its value in risk stratification of patients with a recent myocardial infarction (MI) is not known., Methods: a consecutive series of 494 patients with a recent MI underwent a symptom-limited bicycle ergometer test and echocardiography before discharge from the hospital. Cardiac death was the primary end-point and sudden cardiac death (SCD) the secondary end-point. Heart rate (HR) response to exercise was evaluated using maximal chronotropic response index (CRI = 100 × (peak HR - resting HR) × (220 - age - resting HR)(-1))., Results: during 8 years of follow-up, 40 patients (8.1%) experienced cardiac death, of whom 18 died suddenly (3.6%). Abnormal CRI (<39) was the most powerful predictor of the primary end-point with adjusted relative risk (RR) of 5.4 (95% CI 2.9-11.2; P < 0.001) and also a potent risk marker for SCD (adjusted RR 7.3; 95% CI 2.6-20.0; P < 0.001). Adjusted RR of decreased left ventricular ejection fraction (LVEF) (<45%) was 3.4 (95% CI 1.8-6.6; P < 0.001) for cardiac death. In the final predictive model of cardiac death, the removal of CRI decreased c-index from 0.817 to 0.778, whereas c-index was 0.791 after removal of LVEF., Conclusions: chronotropic incompetence is a powerful predictor of cardiac mortality among post-MI patients.

Background: Type 2 diabetes mellitus is a well-established risk factor for atherosclerosis, but its contribution to sudden cardiac death (SCD) risk after myocardial infarction (MI) is not well defined., Objective: The purpose of this study was to compare the incidence and time-dependent risk of SCD in diabetic patients versus nondiabetic patients during 5-year follow-up after acute MI., Methods: A total of 3,276 patients were enrolled at the time of acute MI between 1996 and 2005. Mean age at entry was 60 ± 11 years, and the cohort was followed until 2009. At entry into the study, diabetes was present in 629 (19.2%) patients. The primary endpoint was SCD, and the secondary endpoints were non-SCD and all-cause mortality., Results: Among diabetic patients, the incidence of SCD was higher (5.9%) than in nondiabetic patients (1.7%), with a hazard ratio (HR) of 3.8 (95% confidence interval [CI] 2.4-5.8; P <.001) and adjusted HR of 2.3 (95% CI 1.4-3.8; P <.01). In diabetic patients with left ventricular ejection fraction >35%, the incidence of SCD was nearly identical to that of nondiabetic patients with ventricular ejection fraction ≤35% (4.1% vs 4.9%; P = .48). An excess in the incidence of non-SCD began to appear among diabetic patients within the first 6 months of follow-up (P <.001) but not in the incidence of SCD (P = .09). The excess in SCD among diabetic patients began to appear more than 6 months after the index event., Conclusion: Patients with type 2 diabetes are at higher risk for SCD after MI than are nondiabetic patients. The incidence of SCD in post-MI type 2 diabetic patients with left ventricular ejection fraction >35% is equal to that of nondiabetic patients with left ventricular ejection fraction <35%., (Copyright © 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Knowledge about the incidence of cardiac arrhythmias after acute myocardial infarction has been limited by the lack of traditional ECG recording systems to document and confirm asymptomatic and symptomatic arrhythmias. The Cardiac Arrhythmias and Risk Stratification After Myocardial Infarction (CARISMA) trial was designed to study the incidence and prognostic significance of arrhythmias documented by an implantable cardiac monitor among patients with acute myocardial infarction and reduced left ventricular ejection fraction., Methods and Results: A total of 1393 of 5869 patients (24%) screened in the acute phase (3 to 21 days) of an acute myocardial infarction had left ventricular ejection fraction ≤40%. After exclusions, 297 patients (21%) (mean±SD age, 64.0±11.0 years; left ventricular ejection fraction, 31±7%) received an implantable cardiac monitor within 11±5 days of the acute myocardial infarction and were followed up every 3 months for an average of 1.9±0.5 years. Predefined bradyarrhythmias and tachyarrhythmias were recorded in 137 patients (46%); 86% of these were asymptomatic. The implantable cardiac monitor documented a 28% incidence of new-onset atrial fibrillation with fast ventricular response (≥125 bpm), a 13% incidence of nonsustained ventricular tachycardia (≥16 beats), a 10% incidence of high-degree atrioventricular block (≤30 bpm lasting ≥8 seconds), a 7% incidence of sinus bradycardia (≤30 bpm lasting ≥8 seconds), a 5% incidence of sinus arrest (≥5 seconds), a 3% incidence of sustained ventricular tachycardia, and a 3% incidence of ventricular fibrillation. Cox regression analysis with time-dependent covariates revealed that high-degree atrioventricular block was the most powerful predictor of cardiac death (hazard ratio, 6.75; 95% confidence interval, 2.55 to 17.84; P<0.001)., Conclusions: This is the first study to report on long-term cardiac arrhythmias recorded by an implantable loop recorder in patients with left ventricular ejection fraction ≤40% after myocardial infarction. Clinically significant bradyarrhythmias and tachyarrhythmias were documented in a substantial proportion of patients with depressed left ventricular ejection fraction after acute myocardial infarction. Intermittent high-degree atrioventricular block was associated with a very high risk of cardiac death. Clinical Trial Registration- URL: http://www.ClinicalTrials.gov, Unique identifier: NCT00145119.

Background: Atrial fibrillation (AF) increases morbidity and mortality in patients with previous myocardial infarction and left ventricular systolic dysfunction. The purpose of this study was to identify patients with a high risk for new-onset AF in this population using invasive and noninvasive electrophysiological tests., Methods: The study included 271 patients from the Cardiac Arrhythmias and RIsk Stratification after Myocardial InfArction (CARISMA) study with an acute myocardial infarction (AMI) and left ventricular ejection fraction ≤40% without previous AF at enrollment. Within 21 days after the AMI, an implantable loop recorder was inserted and used to diagnose AF over the 2-year study duration. The following tests were performed: heart rate variability (HRV) and turbulence (HRT) analyses from repeated 24-hour Holter recordings, 2-dimensional (2D)-echocardiograms, exercise test, and programmed electrophysiologic stimulation., Results: A total of 101 patients (37%) developed AF during the study. Predictive measures included several indexes of HRV including reduced low-frequency (LF) power from spectral HRV analysis (adjusted HR = 1.6, P = 0.034), HRT slope ≤2.5 (HR = 1.6, P = 0.032) and Detrended Fluctuation Analysis (DFA1) from HRV analysis (HR = 1.8, P = 0.011); all are measures of cardiac autonomic nervous system dysfunction. Combined with age >60 years, low values for LF, HRT slope, and DFA1 provided a powerful risk score for prediction of new-onset AF (1-2 points: HR = 4.3, P = 0.001, 3-4 points: HR = 7.0, P < 0.001)., Conclusion: Abnormal HRV and HRT parameters, which are associated with disturbances in the cardiac autonomic regulation, are associated with increased risk of new-onset AF independently of conventional clinical risk variables., (© 2010 Wiley Periodicals, Inc.)

Background: The beta-1 adrenergic receptor (beta1AR) plays a fundamental role in the regulation of cardiovascular functions. It carries a nonsynonymous single nucleotide polymorphism in its carboxyl terminal tail (Arg389Gly), which has been shown to associate with various echocardiographic parameters linked to left ventricular hypertrophy (LVH). Diabetes mellitus (DM), on the other hand, represents a risk factor for LVH. We investigated the possible association between the Arg389Gly polymorphism and LVH among non-diabetic and diabetic acute myocardial infarction (AMI) survivors., Methods: The study population consisted of 452 AMI survivors, 20.6% of whom had diagnosed DM. Left ventricular parameters were measured with two-dimensional guided M-mode echocardiography 2-7 days after AMI, and the Arg389Gly polymorphism was determined using a polymerase chain reaction-restriction fragment length polymorphism assay., Results: The Arg389 homozygotes in the whole study population had a significantly increased left ventricular mass index (LVMI) when compared to the Gly389 carriers (either Gly389 homozygotes or Arg389/Gly389 heterozygotes) [62.7 vs. 58.4, respectively (p = 0.023)]. In particular, the Arg389 homozygotes displayed thicker diastolic interventricular septal (IVSd) measures when compared to the Gly389 carriers [13.2 vs. 12.3 mm, respectively (p = 0.004)]. When the euglycemic and diabetic patients were analyzed separately, the latter had significantly increased LVMI and diastolic left ventricular posterior wall (LVPWd) values compared to the euglycemic patients [LVMI = 69.1 vs. 58.8 (p = 0.001) and LVPWd = 14.2 vs. 12.3 mm (p < 0.001), respectively]. Furthermore, among the euglycemic patients, the Arg389 homozygotes displayed increased LVMI and IVSd values compared to the Gly389 carriers [LVMI = 60.6 vs. 56.3, respectively (p = 0.028) and IVSd = 13.1 vs. 12.0 mm, respectively (p = 0.001)]. There was no difference in the LVMI and IVSd values between the diabetic Arg389 homozygotes and Gly389 carriers., Conclusions: The data suggest an association between the beta1AR Arg389Gly polymorphism and LVH, particularly the septal hypertrophy. The Arg389 variant appears to confer a higher risk of developing LVH than the corresponding Gly389 variant among patients who have suffered AMI. This association cannot be considered to be universal, however, since it does not appear to exist among diabetic AMI survivors.

Aims: The aim of this study was to investigate the association between diastolic dysfunction and long-term occurrence of new-onset atrial fibrillation (AF) and cardiac events in patients with acute myocardial infarction (AMI) and left ventricular (LV) systolic dysfunction., Methods and Results: The study was performed as a substudy on the CARISMA study population. The CARISMA study enrolled 312 patients with an AMI and LV ejection fraction

Background: Data on the value of baseline brain natriuretic peptide (BNP) and autonomic markers in predicting heart failure (HF) hospitalization after an acute myocardial infarction (AMI) are limited., Methods: A consecutive series of patients with AMI without a previous history of HF (n = 569) were followed up for 8 years. At baseline, the patients had a blood sample for determination of BNP, a 24-hour Holter recording for evaluating heart rate variability (HRV) and heart rate turbulence (HRT), and an assessment of baroreflex sensitivity (BRS) using phenylephrine test., Results: During the follow-up, 79 (14%) patients were hospitalized due to HF. Increased baseline BNP, decreased HRV, HRT, and BRS had a significant association with HF hospitalization in univariate comparisons (P < 0.001 for all). After adjusting with all the relevant clinical parameters, BNP, HRV, and HRT still significantly predicted HF hospitalization (P < 0.001 for BNP and for the short-term scaling exponent alpha(1), P < 0.01 for turbulence slope). In the receiver operator characteristics curve analysis, the area under the curve for BNP was 0.77, for the short-term scaling exponent alpha(1) 0.69, for turbulence slope 0.71, and for BNP/standard deviation of all N-N intervals ratio 0.80., Conclusion: Baseline increased BNP and impaired autonomic function after AMI yield significant information on the long-term risk for HF hospitalization.

Objective: To assess the determinants of functional recovery in patients with ST-elevation myocardial infarction (STEMI) treated initially with thrombolysis, followed by percutaneous coronary intervention and intracoronary injection of bone marrow-derived stem cells (BMC)., Design: A randomised, placebo-controlled, double-blind study (substudy of FINCELL)., Setting: Two tertiary cardiac centres., Participants: 78 patients with STEMI randomly assigned to receive either intracoronary BMC (n=39) or placebo (n=39) into the infarct-related artery., Interventions: Thrombolysis a few hours after symptom onset, percutaneous coronary intervention and intracoronary injection of BMC 2-6 days later., Main Outcome Measures: Efficacy of the BMC treatment was assessed by measurement of the change of global left ventricular ejection fraction (LVEF) from baseline to 6 months after STEMI. Various predefined variables (eg, the levels of certain natriuretic peptides and inflammatory cytokines) were analysed as determinants of improvement of LVEF., Results: In the BMC group, the most powerful determinant of the change in LVEF was the baseline LVEF (r=-0.58, p<0.001). Patients with baseline LVEF at or below the median (< or = 62.5%) experienced a more marked improvement in LVEF (+12.7 + or - 12.5 %units, p<0.001) than those above the median (-0.8 + or - 6.3 %units, p=0.10). Elevated N-terminal probrain natriuretic peptide (p<0.001) and N-terminal proatrial natriuretic peptide (p=0.052) levels were also associated with improvement in LVEF in the BMC group but not in the placebo group., Conclusions: The global LVEF recovers most significantly after intracoronary infusion of BMC in patients with the most severe impairment of LVEF on admission. The baseline levels of natriuretic peptides seem also to be associated with LVEF recovery after BMC treatment. Trial registration ClinicalTrials.gov number, NCT00363324.

Aims: To assess the association of electrocardiographic repolarization and depolarization patterns to vulnerability to ventricular tachyarrhythmias., Methods: In the present case-control study, a 12-lead ECG, signal-averaged ECG (SAECG), T-wave and QRS morphology, and T-wave alternans (TWA) were analyzed in post-MI patients with and without documented sustained ventricular tachycardia (VT) or fibrillation (VF) (VT/VF group, n=40, Non-VT/VF group, n=37, respectively) and healthy subjects (n=41)., Results: The QRS complex duration, measured from standard ECG (128 +/- 32 ms vs. 102 +/- 21 ms, p<0.001) or SAECG (125 +/- 25 ms vs. 99 +/- 20 ms, p<0.001), was significantly longer in the VT/VF than Non-VT/VF group. Several T-wave morphology variables, e.g., the total cosine of the angle between the main vectors of T-wave and QRS loops (TCRT), were different in the VT/VF (-0.13 +/- 0.58) and Non-VT/VF group (-0.11 +/- 0.48) compared to the healthy controls (0.47 +/- 0.50, p<0.001). However, there were no significant differences in any of the T-wave morphology variables including TWA between the two post-MI groups., Conclusion: Abnormalities in ventricular depolarization are more common among post-MI patients with prior VT/VF than in those without documented ventricular tachyarrhythmias. Abnormal T-wave morphology and TWA seem to reflect the heart disease rather than specifically vulnerability to VT/VF.

Background: Autonomic dysfunction tends to improve over time after acute myocardial infarction (MI), but the clinical significance of autonomic remodeling is not well known., Objective: The purpose of this study was to test the hypothesis that the amount of recovery of autonomic function early after MI is associated with a risk for serious arrhythmias., Methods: The prognostic significance of autonomic remodeling after MI was assessed in one post-MI cohort [Cardiac Arrhythmia and Risk Stratification after Myocardial Infarction (CARISMA)] and validated in a second cohort [Risk Estimation After Infarction, Noninvasive Evaluation (REFINE)]. Changes in heart rate variability (DeltaHRV) and heart rate turbulence (DeltaHRT) were measured from 24-hour ECG recordings performed early (5-21 days) and later (6 weeks) after MI in CARISMA (n = 312). DeltaHRV and DeltaHRT were similarly measured from early (2-4 weeks) and later (10-14 weeks) post-MI recordings in REFINE (n = 322)., Results: HRV and HRT increased over time in both cohorts. Attenuated recovery of autonomic function, defined as DeltaHRT slope <2.0 ms/RR, was associated with a 9.4-fold (95% confidence interval 1.2-71.6; P = .03) higher risk of ECG-documented sustained ventricular tachycardia or ventricular fibrillation in CARISMA and a 7.0-fold (95% confidence interval 1.6-29.6; P = .009) higher risk of fatal or near-fatal events in REFINE. Changes in HRV and HRT were not predictive of nonarrhythmic death in either cohort., Conclusion: Attenuated recovery of autonomic function early after MI consistently predicts a higher risk of fatal or near-fatal arrhythmic events. A lack of improvement in HRT early after MI appears to be a specific marker for serious arrhythmic events.

Aims: To determine whether risk stratification tests can predict serious arrhythmic events after acute myocardial infarction (AMI) in patients with reduced left ventricular ejection fraction (LVEF < or = 0.40)., Methods and Results: A total of 5869 consecutive patients were screened in 10 European centres, and 312 patients (age 65 +/- 11 years) with a mean LVEF of 31 +/- 6% were included in the study. Heart rate variability/turbulence, ambient arrhythmias, signal-averaged electrocardiogram (SAECG), T-wave alternans, and programmed electrical stimulation (PES) were performed 6 weeks after AMI. The primary endpoint was ECG-documented ventricular fibrillation or symptomatic sustained ventricular tachycardia (VT). To document these arrhythmic events, the patients received an implantable ECG loop-recorder. There were 25 primary endpoints (8.0%) during the follow-up of 2 years. The strongest predictors of primary endpoint were measures of heart rate variability, e.g. hazard ratio (HR) for reduced very-low frequency component (<5.7 ln ms(2)) adjusted for clinical variables was 7.0 (95% CI: 2.4-20.3, P < 0.001). Induction of sustained monomorphic VT during PES (adjusted HR = 4.8, 95% CI, 1.7-13.4, P = 0.003) also predicted the primary endpoint., Conclusion: Fatal or near-fatal arrhythmias can be predicted by many risk stratification methods, especially by heart rate variability, in patients with reduced LVEF after AMI.

Background and Aims: We aimed to replicate the previously observed association between acetylcholine receptor subtype M2 (CHRM2) gene polymorphisms and heart rate recovery (HRR) after exercise in patients with a recent acute myocardial infarction (AMI) and assess the prognostic significance of CHRM2 gene variants after AMI., Methods: HRR was determined as the difference between maximal heart rate and heart rate at 1 minute after the symptom-limited bicycle exercise test in 192 post-AMI patients. Genetic variants at the CHRM2 locus in intron 5 (rs324640) and the 3'-UTR of exon 6 (rs8191992) were assessed., Results: The rs324640 C/C and rs8191992 A/A homozygotes had more than a 3-fold risk of being in the lowest HRR quartile (< or = 8 bpm) compared to the T/T homozygotes (odds ratio (OR) 3.2, 95% confidence interval (CI) 1.2-8.6, P=0.017 and OR 3.8, 95% CI 1.3-11.1, P=0.016, respectively). In a larger sample of post-AMI patients (n=491), both C/C and A/A genotypes predicted cardiac mortality (11%) (adjusted relative risk (RR) 2.5, 95% CI 1.4-4.3, P=0.002 and RR 2.1, 95% CI 1.1-3.8, P=0.017, respectively) during a follow-up of 7.7+/-2.2 years., Conclusions: DNA sequence variation at the CHRM2 locus is a determinant of cardiac autonomic function in the postexercise early recovery phase and predicts cardiac mortality after AMI.

Aims: To assess the efficacy and safety of bone marrow cell (BMC) therapy after thrombolytic therapy of an acute ST-elevation myocardial infarction (STEMI)., Methods and Results: Patients with STEMI treated with thrombolysis followed by percutaneous coronary intervention (PCI) 2-6 days after STEMI were randomly assigned to receive intracoronary BMCs (n = 40) or placebo medium (n = 40), collected and prepared 3-6 h prior PCI and injected into the infarct artery immediately after stenting. Efficacy was assessed by the measurement of global left ventricular ejection fraction (LVEF) by left ventricular angiography and 2-D echocardiography, and safety by measuring arrhythmia risk variables and restenosis of the stented vessel by intravascular ultrasound. At 6 months, BMC group had a greater absolute increase of global LVEF than placebo group, measured either by angiography (mean +/- SD increase 7.1 +/- 12.3 vs. 1.2 +/- 11.5%, P = 0.05) or by 2-D echocardiography (mean +/- SD increase 4.0 +/- 11.2 vs. -1.4 +/- 10.2%, P = 0.03). No differences were observed between the groups in the adverse clinical events, arrhythmia risk variables, or the minimal lumen diameter of the stented coronary lesion., Conclusion: Intracoronary BMC therapy is associated with an improvement of global LVEF and neutral effects on arrhythmia risk profile and restenosis of the stented coronary lesions in patients after thrombolytic therapy of STEMI.

Background: Autonomic markers, such as heart rate variability (HRV), heart rate turbulence (HRT), and baroreflex sensitivity (BRS) provide information on the risk of all-cause mortality after an acute myocardial infarction (AMI), but their value in predicting nonfatal cardiac events is not well known., Methods: A consecutive series of 675 patients with an AMI were followed up to 30 months. At baseline, the patients underwent a 24-hour Holter recording, and assessment of BRS using phenylephrine test. Several parameters of HRV and HRT were determined., Results: After the follow-up, 98 patients (15%) had a nonfatal acute coronary event. Among the studied variables, the short-term scaling exponent alpha1 (P = 0.002), power-law slope beta (P = 0.008), low-frequency component of HRV power spectrum (P < 0.001), turbulence slope (P < 0.001), and BRS (P < 0.001) had the strongest association with the occurrence of nonfatal acute coronary events in univariate comparisons. After adjustment with relevant clinical variables (such as age, gender, ejection fraction, functional class, medication, diabetes) in the Cox proportional hazards model, alpha1 and beta remained as statistically significant predictors of nonfatal acute coronary events (HR = 2.0 [1.2-3.2, 95% CIs, P = 0.006] for alpha1 < or = 1.025), (HR = 1.9 [1.2-3.1, P = 0.008] for beta < or =-1.507)., Conclusion: Several autonomic markers provide information on the risk of recurrent nonfatal coronary events after an AMI. Altered fractal heart rate behavior seems to be the strongest independent predictor of such events.

Background: Measurement of high-frequency (HF) spectral power of heart rate (HR) variability has not been able to identify the patients at risk of sudden cardiac death (SCD) despite the experimental evidence of protective role of vagal activity for fatal arrhythmias., Aim: We developed a novel respiratory sinus arrhythmia (RSA) analysis method and tested its ability to predict SCD after an acute myocardial infarction., Method: The RSA analysis method was developed in 13 subjects from simultaneous recordings of respiration and R-R intervals. An adaptive threshold was computed based on the zero-phase forward and reverse digital filtering in the analysis of RSA. With this method, only respiration-related R-R interval fluctuations are included. The prognostic power of RSA, analyzed from 24-hour electrocardiographic recordings, was subsequently assessed in a large postinfarction population including 1631 patients with mean follow-up of 40 +/- 17 months., Results: Depressed RSA was a strong predictor of SCD (hazard ratio 7.4; 95% CI 3.6-15.1; P 0.0001) but only a weak predictor of non-SCD. The RSA index remained an independent predictor of SCD after adjustments for ejection fraction and other clinical risk variables (RR 4.7; 95% CI 2.28-9.85)., Conclusions: Reduced respiratory-related HR dynamics, detected by RSA index, are a specific marker of an increased risk of SCD among postinfarction patients.

Background: Various indexes of 24-hour heart rate variability (HRV) have been able to predict all-cause mortality after an acute myocardial infarction (AMI), but their value in predicting specific modes of cardiac death has been limited., Aim: The aim of this study was to assess the role of two novel spectral indexes of HRV as predictors of either sudden (SCD) or non-sudden cardiac death after an AMI. Method. We used two novel methods of spectral analysis of HRV: 1) the high-frequency (HF) spectral component, V(index), calculated as an average HF power from the most linear portion of HF power versus the R-R interval regression curve, and 2) the prevalent low-frequency oscillation of heart rate (PLF). V(index), conventional HRV measures, and PLF were analyzed from 24-hour Holter recordings of 590 patients with a recent AMI., Results: During the mean follow-up of 39+/-14 months, SCD occurred in 3% (n = 17) and non-sudden cardiac death in 5% (n = 28) of the patients. In univariate analysis, V(index) was the most potent predictor of SCD (RR: 6.0, 95% CI: 1.7-20.7, P<0.01), also remaining the most powerful predictor of SCD after adjustment for clinical variables and ejection fraction (RR: 4.2, 95% CI: 1.2-15.2, P<0.05). PLF was a potent predictor of non-sudden cardiac death (RR: 13.9, 95% CI: 5.9-32.5, P<0.001), but it did not predict SCD., Conclusions: Novel spectral HRV analysis methods, V(index) and PLF, provide significant information of the risk of the specific mode of death after an AMI.

Background: Observational studies have suggested that a parental history of sudden death increases one's risk of dying suddenly. This study tested the hypothesis that a family history of sudden cardiac death (SCD) is a risk factor for SCD caused by an acute coronary event., Methods and Results: A retrospective case-control study included (1) consecutive victims of SCD (n=138) whose deaths were verified to be due to an acute coronary event without a history of prior myocardial infarction at medicolegal autopsy, (2) consecutive patients surviving an acute myocardial infarction (AMI; n=254), and (3) healthy control subjects (n=470). Family history of AMI and SCD among the first-degree relatives was ascertained in each study group. The incidence of SCD in the 1223 first-degree relatives of SCD victims was higher (5.2%) than that in the 2326 relatives of AMI survivors (3.3%; odds ration [OR] 1.6, 95% confidence interval [CI] 1.2 to 2.2, P<0.01) or the 3748 relatives of controls (OR 2.2; 95% CI 1.6 to 3.0, P<0.001). The history of SCD in 2 or more first-degree relatives was also higher (10.9%) among SCD victims than among AMI survivors (3.5%; OR 3.3, 95% CI 1.4 to 7.8, P<0.01) or controls (1.1%; OR 11.3, 95% CI 4.0 to 31.8, P<0.001). The family history of AMI did not differ between the SCD and AMI groups. Male gender and current smoking were the only coronary risk factors that were more prevalent among SCD victims than among AMI survivors (P<0.001 for both)., Conclusions: Subjects with a family history of SCD have an increased risk of dying suddenly during an acute coronary event.

The epidemiologic pattern of sudden cardiac death (SCD) may have changed in the modern treatment era of patients after an acute myocardial infarction (AMI). We evaluated the effect of optimized medical and revascularization therapy on the incidence of SCD after an AMI. A total of 2,130 consecutive patients (mean age 59 +/- 10 years) with an AMI from 2 European centers (Germany and Finland) was included in the study. In this population, 1,004 patients (47%) were treated with an optimized medical and revascularization strategy (defined as treatment with revascularization, beta blockers, aspirin, statins, and angiotensin-converting enzyme inhibitors). Nonoptimized treatment, defined as a lack of any optimized treatment, was received by 1,126 patients (53%). During the mean follow-up of 2.9 +/- 1.3 years, the incidence of SCD was very low among patients who received optimized treatment (1.2%, annual incidence 0.4%) compared with those who did not (3.6%, annual incidence 1.4%, p <0.01). The treatment strategy that had the greatest effect on differences in the SCD rate was revascularization therapy, with the hazard ratio of SCD being 2.1 (95% confidence interval 1.2 to 3.7, p <0.01) for SCD among nonrevascularized patients. Nonoptimized treatment was more often received by older patients, women, diabetic patients, and those with depressed left ventricular function. In conclusion, the incidence of SCD is low in the modern treatment era of patients after an AMI. Coronary revascularization seems to have a great effect on altered the epidemiologic pattern of SCD.

The aim of the study was to assess whether parameters based on the T-wave loop and QRS loop predict mortality, and cardiac mortality in particular, during follow-up of consecutive survivors of acute myocardial infarction (AMI). Patients with AMI (n = 437), treated according to contemporary guidelines, underwent digital high-resolution electrocardiography in orthogonal Frank leads (X, Y, Z) 5 to 14 days after AMI. Several T-wave and QRS loop parameters, such as the width and height of the loops and their ratio, T-wave loop dispersion (TWLD), QRS loop dispersion, and co-sine of the angle between the main vectors of the T-wave and QRS loops (TCRT), were calculated using a custom-made software package. During an average follow-up period of 43 +/- 14 months, 53 patients (12%) died. Of these 53 deaths, 35 were cardiac. TWLD and TCRT were the T-wave loop/QRS loop parameters that best predicted for cardiac mortality on univariate comparison (35.4 +/- 5.62 vs 32.8 +/- 2.87 for TWLD, p < 0.001 and -0.135 +/- 0.665 vs -0.657 +/- 0.518 for TCRT, p < 0.001, alive vs cardiac death, respectively). After adjustment for clinical risk markers in the Cox regression analysis, TWLD still significantly predicted for cardiac mortality (p < 0.05); however, TCRT had lost its predictive power. TWLD did not have significant univariate or multivariate association with noncardiac mortality. In conclusion, TWLD that describes the shape of the T-wave loop is a specific predictor of cardiac death and independent of the clinical risk markers in the current treatment era of patients with AMI.

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 (Poincare 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.

Cardiac Arrhythmias and Risk Stratification after Myocardial infarction (CARISMA) is a prospective multicenter trial designed to document the incidence of cardiac arrhythmias after acute myocardial infarction (AMI), and to assess the predictive accuracy of various arrhythmic risk markers. In this substudy of the CARISMA trial, microvolt T-wave alternans (TWA) was assessed with specific equipment 6 weeks after AMI during bicycle exercise, atrial (A) pacing, and simultaneous ventricular and atrial (V + A) pacing in 80 patients with left ventricular ejection fraction (LVEF) <40%. The agreement between the acute test results was determined by overall proportion of concordance and the kappa statistic. Sustained TWA was observed in 24, 45, and 50% of the patients during the exercise test, A pacing, and V + A pacing, respectively. The number of indeterminate TWA was significantly lower during V + A pacing (n = 7) than exercise test (n = 34). The TWA concordance rate was 71% between exercise and V + A pacing (kappa= 0.53, P = 0.001), 79% between exercise and A pacing (kappa= 0.54, P < 0.001), and 95% between the two pacing modes (kappa= 0.89, P < 0.001). Patients with positive TWA in all tests had lower LVEF (28 +/- 7% vs 35 +/- 9%, P < 0.01) and wider QT dispersion (99 +/- 44 ms vs 67 +/- 38 ms, P < 0.01) than those with inconsistent test result. The low number of indeterminate tests and high concordance between the test results indicate that V + A pacing may provide a valuable means to assess TWA in patients who cannot complete the exercise test.

This study was designed to assess the relationship between R-R interval length and heart rate (HR) variability in healthy subjects and patients after an acute myocardial infarction (AMI). Twenty-four-hour ambulatory ECG recordings were obtained for 76 healthy subjects and 82 post-AMI patients. The high-frequency (HF, 0.15-0.4 Hz) spectral power of R-R intervals was analyzed in 5-min sequences over 24 h and plotted as a function of the corresponding mean R-R interval length. Quadratic regression model was used to study the relationship between R-R interval length and HF power. If a distinct deflection point (R-R0) occurred in the quadratic regression (r >0.50) model before maximum R-R interval, indicating the plateau of HF power, the relationship between R-R interval and HF power was defined as saturated. Otherwise, the relationship was defined as linear (r >0.50) or low correlated (r >0.50). The relationship was saturated in 35, linear in 38, and low correlated in 3 healthy subjects. In post-AMI patients, the relationship was saturated in 9 subjects, linear in 44 subjects, and low correlated in 29 patients. The HF power analyzed from the 24-h period did not differ between the saturated and linear groups, but when analyzed from the linear portion only, HF spectral power was smaller in the linear than the saturated group both among healthy subjects (P <0.05) and post-AMI patients (P <0.05). Saturation of the HF oscillations of R-R intervals is a common phenomenon in healthy subjects and also present in post-AMI patients during ambulatory conditions. This saturation effect may bias the quantification of cardiac vagal function when HR variability is analyzed from Holter recordings.

Objectives: This prospective study tested whether the natriuretic peptides predict cardiac death among patients using beta-blocking therapy after an acute myocardial infarction (AMI)., Background: Natriuretic peptides have provided prognostic information after AMI, but their predictive value has not been well established in the era of beta-blocker use., Methods: A series of 521 patients (mean age 61 +/- 10 years) with AMI was included in the study. The end points were total mortality and non-sudden and sudden cardiac death (SCD). Plasma concentrations of atrial natriuretic peptide (ANP), N-terminal atrial natriuretic propeptide (N-ANP), brain natriuretic peptide (BNP), and ejection fraction (EF) were analyzed before hospital discharge. The cardiac medication was optimized (e.g., adherence to beta-blocking therapy was 97% at discharge and 95% at one year after AMI)., Results: During a mean follow-up of 43 +/- 13 months, total mortality was 11.5% (60/521), cardiac mortality was 6.3% (33/521), and 3.1% (16/521) experienced SCD. On univariate analysis, high levels of all measured peptides and low EF predicted the occurrence of non-SCD (p < 0.001 for all). Peptides and EF also predicted the occurrence of SCD (p < 0.05), with elevated BNP (>23.0 pmol/l) being the most powerful predictor (hazard ratio [HR] 4.4, 95% confidence interval [CI] 1.4 to 13.8; p = 0.01). After adjusting for clinical variables, only elevated BNP (HR 3.9, 95% CI 1.2 to 12.3, p = 0.02) and low EF (<40%) (p = 0.03) remained as significant predictors of SCD., Conclusions: Natriuretic peptides retain their prognostic value in the beta-blocking era among survivors of AMI. Elevated BNP provides information on the risk of subsequent SCD, independent of clinical variables and left ventricular EF.

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.

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.