Heart Rate Variability Density Analysis (Dyx) and Prediction of Long-Term Mortality after Acute Myocardial Infarction.

AIMS: The density HRV parameter Dyx is a new heart rate variability (HRV) measure based on multipole analysis of the Poincaré plot obtained from RR interval time series, deriving information from both the time and frequency domain. Preliminary results have suggested that the parameter may provide new predictive information on mortality in survivors of acute myocardial infarction (MI). This study compares the prognostic significance of Dyx to that of traditional linear and nonlinear measures of HRV. METHODS AND RESULTS: In the Nordic ICD pilot study, patients with an acute MI were screened with 2D echocardiography and 24-hour Holter recordings. The study was designed to assess the power of several HRV measures to predict mortality. Dyx was tested in a subset of 206 consecutive Danish patients with analysable Holter recordings. After a median follow-up of 8.5 years 70 patients had died. Of all traditional and multipole HRV parameters, reduced Dyx was the most powerful predictor of all-cause mortality (HR 2.4; CI 1.5 to 3.8; P < 0.001). After adjustment for known risk markers, such as age, diabetes, ejection fraction, previous MI and hypertension, Dyx remained an independent predictor of mortality (P = 0.02). Reduced Dyx also predicted cardiovascular death (P < 0.01) and sudden cardiovascular death (P = 0.05). In Kaplan-Meier analysis, Dyx significantly predicted mortality in patients both with and without impaired left ventricular systolic function (P < 0.0001). CONCLUSION: The new nonlinear HRV measure Dyx is a promising independent predictor of mortality in a long-term follow-up study of patients surviving a MI, irrespectively of left ventricular systolic function.

Heart rate variability density analysis (Dyx) for identification of appropriate implantable cardioverter defibrillator recipients among elderly patients with acute myocardial infarction and left ventricular systolic dysfunction.

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.

The predictive value of CHADS2 risk score in post myocardial infarction arrhythmias - a Cardiac Arrhythmias and RIsk Stratification after Myocardial infArction (CARISMA) substudy.

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.

New-onset atrial fibrillation predicts malignant arrhythmias in post-myocardial infarction patients--a Cardiac Arrhythmias and RIsk Stratification after acute Myocardial infarction (CARISMA) substudy.

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.

Clinical significance of late high-degree atrioventricular block in patients with left ventricular dysfunction after an acute myocardial infarction--a Cardiac Arrhythmias and Risk Stratification After Acute Myocardial Infarction (CARISMA) substudy.

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.

Risk markers of late high-degree atrioventricular block in patients with left ventricular dysfunction after an acute myocardial infarction: a CARISMA substudy.

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.

Heart rhythm at the time of death documented by an implantable loop recorder.

AIMS: The aims of this study were to describe arrhythmias documented with an implantable loop recorder (ILR) in post-acute myocardial infarction (AMI) patients with left ventricular dysfunction at the time of death and to establish the correlation to mode of death. METHODS AND RESULTS: Post-mortem ILR device interrogations were analysed from patients dying in the CARISMA study. Mode of death was classified by a modified CAST classification. Twenty-six patients died with an implanted ILR. Of these, 16 had an electrocardiogram recorded at the time of death. Ventricular tachycardia (VT)/ventricular fibrillation (VF) was terminal rhythm in eight patients and bradyarrhythmias were observed in another eight patients. Of the deaths with peri-mortem recordings, seven were classified as sudden cardiac death (SCD). In six of these, VF was documented at the time of death. Six monitored deaths were classified as non-SCD (NSCD) of which only two had recordings of VT/VF, whereas four had bradyarrhythmias. All peri-mortem recordings in non-cardiac death (NCD) were bradyarrhythmia. CONCLUSION: Long-term monitoring in a population of post-AMI patients with left ventricular ejection fraction < or =40% showed that VT/VF and bradyarrhythmia each accounted for half of the recorded events at the time of death. The ILR confirmed that ventricular tachyarrhythmias are associated primarily with SCD, whereas bradyarrhythmias and electromechanical dissociation seems dominant in NSCD and NCD. The study was registered at ClinicalTrials.gov: NCT00145119.