Arrhythmia monitoring and outcome after myocardial infarction (BIO|GUARD-MI): a randomized trial.

Objectives: Cardiac arrhythmias predict poor outcome after myocardial infarction (MI). We studied if arrhythmia monitoring with an insertable cardiac monitor (ICM) can improve treatment and outcome. Design: BIO|GUARD-MI was a randomized, international open-label study with blinded outcome assessment. Setting: Tertiary care facilities monitored the arrhythmias, while the follow-up remained with primary care physicians. Participants: Patients after ST-elevation (STEMI) or non-ST-elevation MI with an ejection fraction >35% and a CHA2DS2-VASc score ≥4 (men) or ≥5 (women). Interventions: Patients were randomly assigned to receive or not receive an ICM in addition to standard post-MI treatment. Device-detected arrhythmias triggered immediate guideline recommended therapy changes via remote monitoring. Main outcome measures: MACE, defined as a composite of cardiovascular death or acute unscheduled hospitalization for cardiovascular causes. Results: 790 patients (mean age 71 years, 72% male, 51% non-STEMI) of planned 1,400 pts were enrolled and followed for a median of 31.6 months. At 2 years, 39.4% of the device group and 6.7% of the control group had their therapy adapted for an arrhythmia [hazard ratio (HR) = 5.9, P < 0.0001]. Most frequent arrhythmias were atrial fibrillation, pauses and bradycardia. The use of an ICM did not improve outcome in the entire cohort (HR = 0.84, 95%-CI: 0.65-1.10; P = 0.21). In secondary analysis, a statistically significant interaction of the type of infarction suggests a benefit in the pre-specified non-STEMI subgroup. Risk factor analysis indicates that this may be connected to the higher incidence of MACE in patients with non-STEMI. Conclusions: The burden of asymptomatic but actionable arrhythmias is large in post-infarction patients. However, arrhythmia monitoring with an ICM did not improve outcome in the entire cohort. Post-hoc analysis suggests that it may be beneficial in non-STEMI patients or other high-risk subgroups. Clinical Trial Registration: [https://www.clinicaltrials.gov/ct2/show/NCT02341534], NCT02341534.

Risk of arrhythmias after myocardial infarction in patients with left ventricular systolic dysfunction according to mode of revascularization: a Cardiac Arrhythmias and RIsk Stratification after Myocardial infArction (CARISMA) substudy.

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%.

The clinical effect of arrhythmia monitoring after myocardial infarction (BIO-GUARD|MI):study protocol for a randomized controlled trial.

BACKGROUND: The increasing use of implantable cardiac monitors (ICMs) allows early documentation of asymptomatic cardiac arrhythmias that would previously have gone unnoticed. The addition of remote monitoring to cardiac devices means that physicians receive an early warning in cases of new-onset arrhythmias. While remote monitoring has been suggested to increase survival in heart failure patients with implantable defibrillators, trials using ICMs for continuous electrocardiographic monitoring of cardiac arrhythmias in the postmyocardial infarction setting have shown that patients who experienced cardiac arrhythmias such as atrial fibrillation, bradycardia, and ventricular tachyarrhythmia have an increased risk of major adverse cardiac events. METHODS: The Biomonitoring in patients with preserved left ventricular function after diagnosed myocardial infarction (BIO-GUARD-MI) study is designed to investigate and clarify whether the incidence of major adverse cardiac events can be decreased by early detection and treatment of cardiac arrhythmias using an ICM in patients after myocardial infarction. In addition, the study will allow us to describe the interplay between baseline characteristics, arrhythmias, and clinical events to improve the treatment of this high-risk patient population. The study will enroll and randomize a cohort of high-risk postmyocardial infarction patients with CHA2DS2-VASc score ≥ 4 and left ventricular ejection fraction > 35% to an ICM or conventional treatment. Physicians are provided with suggestions on how to respond to ICM-documented arrhythmias. An estimated 1400 patients will be enrolled and followed until 372 primary endpoints have occurred. In this paper, we describe the literature and rationale behind the design and interventions towards new-onset arrhythmias, as well as future perspectives and limitations for the use of ICMs. DISCUSSION: Remote monitoring may improve clinical outcome if it uncovers conditions with low symptom burden which cause or indicate an increased risk. A simple and easily implementable response to the information is important. Cardiac arrhythmias frequently start as asymptomatic, shorter lasting, and nightly events. The BIO-GUARD-MI trial represents the first attempt to simplify the response to the rather complex nature of heart arrhythmias. TRIAL REGISTRATION: Clinical Trials, NCT02341534 . Registered on 19 January 2015.

Transmission and loss of ECG snapshots: Remote monitoring in implantable cardiac monitors.

INTRODUCTION: Remote monitoring including transmission of electrocardiogram (ECG) strips has been implemented in implantable cardiac monitors (ICM). We appraise whether the physician can rely on remote monitoring to be informed of all possibly significant arrhythmias. METHODS: We analyzed remote monitoring transmissions of patients in the ongoing BIO|GUARD-MI study, in which Biotronik devices are used. Once per day, the devices automatically transmit messages with up to six ECG snapshots to the Home Monitoring Service Center. If more than one type of arrhythmia is recorded during a day, at least one ECG of each arrhythmia type is transmitted. RESULTS: 212 study patients were registered at the service center. The mean age of the patients was 70 ±â€¯8 years, and 74% were male. Patients were followed for an average of 13 months. The median time from device implantation until the first message receipt in the service center was 2 days. The median patient-individual transmission success was 98.0% (IQR 93.6-99.8) and remained stable in the second and third year. The most frequent arrhythmias were atrial fibrillation, bradycardia and high ventricular rate. 17.3% of the messages with ECG snapshots contained more than one arrhythmia type. DISCUSSION: Our analysis confirms that the physician can rely on Home Monitoring to be informed of all possibly significant arrhythmias during long-term follow-up. We have found hints that the transmission of only one episode per day may lead to the loss of clinically relevant information if patients with ICMs are followed by remote monitoring only.

Change in Left Ventricular Ejection Fraction Following First Myocardial Infarction and Outcome.

OBJECTIVES: This study hypothesizes that a lack of left ventricular ejection fraction (LVEF) recovery after myocardial infarction (MI) would be associated with a poor outcome. BACKGROUND: A reduced LVEF early after MI identifies patients at risk of adverse outcomes. Whether the change in LVEF in the weeks to months following MI provides additional information on prognosis is less certain. METHODS: Change in LVEF between the early (2 to 7 days) and later (2 to 12 weeks) post-MI periods in patients with a first MI was assessed in 3 independent cohorts (REFINE [Risk Estimation Following Infarction Noninvasive Evaluation]; CARISMA [Cardiac Arrhythmia and Risk Stratification after Myocardial Infarction]; ISAR [Improved Stratification of Autonomy Regulation]). Patients were categorized as having no recovery (Δ ≤0%), a modest increase (Δ 1% to 9%), or a large increase (Δ ≥10%) in LVEF. The relationship between change in LVEF and risk of sudden cardiac arrest (SCA) and all-cause mortality were assessed in Cox multivariable models. RESULTS: In REFINE, patients with no LVEF recovery had a higher risk of sudden cardiac arrest (hazard ratio: 5.8; 95% confidence interval: 2.1 to 16.6; p = 0.001) and death (hazard ratio: 3.9; 95% confidence interval: 1.5 to 10.1; p < 0.001), independent of revascularization, baseline LVEF, and medical therapy compared with patients with recovery. Similar findings were observed in the other cohorts. LVEF reassessments beyond 6 weeks post-MI were more predictive of outcome than were earlier reassessments. CONCLUSIONS: The degree of LVEF recovery after a first MI provides important prognostic information. Patients with no recovery in LVEF after MI are at high risk of sudden cardiac arrest events and death.

New strict left bundle branch block criteria reflect left ventricular activation differences.

AIMS: Pacing lead electrical delays and strict left bundle branch block (LBBB) criteria were assessed against cardiac resynchronization therapy (CRT) outcome. METHODS: Forty-nine patients with LBBB and QRS duration >130 milliseconds underwent CRT-implantation. Sensed right ventricular to left ventricular electrical delay (RV-LV-IED) was measured. Response to CRT was defined as ≥15% decrease in left ventricular end-systolic volume. RESULTS: Eighteen of 20 (90%) patients with non-ischemic dilated cardiomyopathy (DCM) and 18 of 29 (62%) with ischemic heart disease (IHD) responded to CRT, p<0.01. When applying new strict ECG criteria subsequent rates of response in DCM were 18/19 (95%) and in IHD of 18/23 (78%) respectively, p<0.05 between IHD groups. Correspondingly, RV-LV-IED was longer in DCM compared to IHD patients and in responders compared to non-responders, p=0.017 and p<0.001, respectively. CONCLUSION: Interventricular electrical delay predicts left ventricular remodeling after CRT and new, strict ECG criteria of LBBB are superior in predicting remodeling.

Prognostic Significance of Heart Rate Variability Among Patients Treated With Cardiac Resynchronization Therapy: MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy).

OBJECTIVES: This study sought to evaluate the prognostic value of heart rate variability (HRV) for death or heart failure in patients with mildly symptomatic heart failure undergoing cardiac resynchronization therapy with a defibrillator (CRT-D). BACKGROUND: There are limited data regarding the prognostic value of HRV as a means of identifying high-risk patients treated with CRT-D. METHODS: We analyzed the relationship between pre-implant time-domain (SD of all normal-to-normal RR intervals [SDNN], SDs of averaged 5-min normal-to-normal RR intervals, root mean square of successive differences, and mean of the SDs of all normal-to-normal RR intervals for all 5-min segments of the entire recording), and frequency-domain (low-frequency power, very-low-frequency power [VLF], high-frequency power, low-frequency power/low-frequency power ratio) HRV parameters, and the end point of death or heart failure and death alone. Study subjects include 719 patients in normal sinus rhythm enrolled in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy); outcomes of CRT-D patients with low HRV (lower tertile) were compared with CRT-D patients with preserved HRV (2 upper tertiles) and with patients receiving implantable cardioverter-defibrillators only. RESULTS: During a mean 3.4 ± 0.9 years of follow-up, 124 patients reached the primary end point of death or heart failure, and 47 died. In multivariate analysis, low SDNN (≤93 ms) was associated with significantly higher risk of death or heart failure (hazard ratio [HR] 1.63 [95% confidence interval (CI): 1.12 to 2.36]; p = 0.010) and mortality (HR 2.10 [95% CI: 1.14 to 3.87]; p = 0.017) compared with higher SDNN (>93 ms). Similarly, low VLF (≤179 ms2) was associated with an increased risk of death or heart failure (HR 2.14 [95% CI: 1.46 to 3.13]; p < 0.001) and death alone (HR 2.49 [95% CI: 1.35 to 4.57]; p = 0.003). There was no significant difference in outcome between low HRV patients treated with CRT-D and patients receiving an implantable cardioverter-defibrillator only. CONCLUSIONS: Our findings indicate that autonomic dysfunction (quantified by low SDNN and low VLF) identified patients with no benefit or limited benefit from cardiac resynchronization therapy. Pre-implant HRV analysis might help in optimizing qualifications for this treatment.

Flecainide provocation reveals concealed brugada syndrome in a long QT syndrome family with a novel L1786Q mutation in SCN5A.

BACKGROUND: Mutations in SCN5A can result in both long QT type 3 (LQT3) and Brugada syndrome (BrS), and a few mutations have been found to have an overlapping phenotype. Long QT syndrome is characterized by prolonged QT interval, and a prerequisite for a BrS diagnosis is ST elevation in the right precordial leads of the electrocardiogram. METHODS AND RESULTS: In a Danish family suffering from long QT syndrome, a novel missense mutation in SCN5A, changing a leucine residue into a glutamine residue at position 1786 (L1786Q), was found to be present in heterozygous form co-segregating with prolonged QT interval. The proband presented with an aborted cardiac arrest, and his mother died suddenly and unexpectedly at the age of 65. Flecainide treatment revealed coved ST elevation in all mutation carriers. Electrophysiological investigations of the mutant in HEK293 cells indicated a reduced peak current, a negative shift in inactivation properties and a positive shift in activation properties, compatible with BrS. Furthermore, the sustained (I(Na,late)) tetrodotoxin-sensitive sodium current was found to be drastically increased, explaining the association between the mutation and LQT syndrome. CONCLUSIONS: The L1786Q mutation is associated with a combined LQT3 and concealed BrS phenotype explained by gating characteristics of the mutated ion channel protein. Hence, sodium channel blockade should be considered in clinical evaluation of apparent LQT3 patients.

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.

Impact of the right ventricular lead position on clinical outcome and on the incidence of ventricular tachyarrhythmias in patients with CRT-D.

BACKGROUND: Data on the impact of right ventricular (RV) lead location on clinical outcome and ventricular tachyarrhythmias in cardiac resynchronization therapy with defibrillator (CRT-D) patients are limited. OBJECTIVE: To evaluate the impact of different RV lead locations on clinical outcome in CRT-D patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy trial. METHODS: We investigated 742 of 1089 CRT-D patients (68%) with adjudicated RV lead location enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy trial to evaluate the impact of RV lead location on cardiac events. The primary end point was heart failure or death; secondary end points included ventricular tachycardia (VT), ventricular fibrillation (VF), or death and VT or VF alone. RESULTS: Eighty-six patients had the RV lead positioned at the RV septal or right ventricular outflow tract region, combined as nonapical RV group, and 656 patients had apical RV lead location. There was no difference in the primary end point in patients with nonapical RV lead location versus those with apical RV lead location (hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.54-1.80; P = .983). Echocardiographic response to CRT-D was comparable across RV lead location groups (P > .05 for left ventricular end-diastolic volume, left ventricular end-systolic volume, and left atrial volume percent change). However, nonapical RV lead location was associated with significantly higher risk of VT/VF/death (HR 2.45; 95% CI 1.36-4.41; P = .003) and VT/VF alone (HR 2.52; 95% CI 1.36-4.65; P = .002), predominantly in the first year after device implantation. Results were consistent in patients with left bundle branch block. CONCLUSIONS: In CRT-D patients, there is no benefit of nonapical RV lead location in clinical outcome or echocardiographic response. Moreover, nonapical RV lead location is associated with an increased risk of ventricular tachyarrhythmias, particularly in the first year after device implantation.

Clinical impact, safety, and efficacy of single- versus dual-coil ICD leads in MADIT-CRT.

BACKGROUND: Current data on efficacy, safety and impact on clinical outcome of single- versus dual-coil implantable cardioverter-defibrillator (ICD) leads are limited and contradictory. METHODS: Defibrillation threshold (DFT) at implantation and first shock efficacy were compared in patients implanted with single- versus dual-coil ICD leads in MADIT-CRT. The risk for atrial tachyarrhythmias and all-cause mortality were evaluated. Short- (< 30 days after the implantation) and long-term (throughout the entire study duration) complications were assessed. RESULTS: Patients with dual-coil ICD leads had significantly lower DFTs compared to patients with single-coil ICD leads (17.6 ± 5.8 J vs 19.4 ± 6.1 J, P < 0.001). First shock efficacy was similar among patients with dual and single-coil ICD leads (89.6% vs 92.3%, P = 1.00). When comparing patients with dual versus single-coil ICD leads, there was no difference in the risk of atrial tachyarrhythmias (HR = 1.57, 95% CI: 0.81-3.02, P = 0.18), or in the risk of all-cause mortality (HR = 1.10, 95% CI: 0.58-2.07, P = 0.77). Patients implanted with single- or dual-coil ICD lead had similar short and long-term complication rates (short-term HR = 0.96, 95% CI: 0.56-1.65, P = 0.88, long-term procedure-related HR = 0.99, 95% CI: 0.62-1.59, P = 1.00, long-term ICD lead related: HR = 1.2, 95% CI: 0.5-2.9, P = 0.68) during the mean follow-up of 3.3 years. CONCLUSIONS: Patients with single-coil ICD leads have slightly higher DFTs compared to those with dual-coil leads, but the efficacy, safety, and clinical impact on atrial tachyarrhythmias, and mortality is similar. Implantation of single-coil ICD leads may be favorable in most patients.

Influence of diabetes mellitus on inappropriate and appropriate implantable cardioverter-defibrillator therapy and mortality in the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) Trial.

BACKGROUND: The relationship between diabetes mellitus and risk of inappropriate or appropriate therapy in patients receiving an implantable cardioverter-defibrillator (ICD) and resynchronization therapy has not been investigated thoroughly. The effect of innovative ICD programming on therapy delivery in these patients is unknown. METHODS AND RESULTS: The Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) randomized patients with a primary prophylactic ICD indication to 3 different types of ICD programming: conventional programming with a ventricular tachycardia zone of 170 to 199 bpm (arm A), high-rate cutoff with a ventricular tachycardia zone ≥200 bpm (arm B), or 60-second-delayed therapy (arm C). The end points of inappropriate therapy, appropriate therapy, and death were assessed among 485 patients with and 998 without diabetes mellitus. Innovative ICD programming reduced the risk of inappropriate therapy regardless of diabetes mellitus, although a trend toward a more pronounced effect of high-rate cutoff programming was seen in patients without diabetes mellitus (P for interaction=0.06). Diabetes mellitus was associated with a decreased risk of inappropriate therapy (hazard ratio, 0.54; 95% confidence interval, 0.36-0.80; P=0.002) and increased risk of appropriate therapy (hazard ratio, 1.58; 95% confidence interval, 1.17-2.14; P=0.003). In diabetic patients, there was significantly increased risk of death in those who had inappropriate therapy (hazard ratio, 4.17; 95% confidence interval, 1.52-11.40; P=0.005) and appropriate therapy (hazard ratio, 2.49; 95% confidence interval, 1.06-5.87; P=0.037) compared with those who did not. CONCLUSIONS: Innovative high-rate cutoff or delayed ICD programming was associated with a reduction in inappropriate therapy in patients with and without diabetes mellitus. Diabetes mellitus was associated with lower risk of inappropriate therapy but higher risk of appropriate therapy. Appropriate and inappropriate ICD therapy was associated with increased mortality in diabetic patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00947310.

Risk factors of self-terminating and perpetuating ventricular tachyarrhythmias in post-infarction patients with moderately depressed left ventricular function, a CARISMA sub-analysis.

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.

Long-term recording of cardiac arrhythmias with an implantable cardiac monitor in patients with reduced ejection fraction after acute myocardial infarction: the Cardiac Arrhythmias and Risk Stratification After Acute Myocardial Infarction (CARISMA) study.

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.

Echocardiographic effects of changing atrioventricular delay in cardiac resynchronization therapy based on displacement.

BACKGROUND: In studies showing benefits of cardiac resynchronization therapy (CRT), individual atrioventricular (AV) delays have been optimized using echocardiography. However, the method for AV delay optimization remains controversial. METHODS: In 100 consecutive patients with CRT device implantation, AV delay was optimized using echocardiography. The optimal AV delay was determined by changing the interval in 20-ms increments while measuring displacement in 6 basal left ventricular segments (averaged and reported as left ventricular displacement [D(LV)]) and other echocardiographic measures. RESULTS: A single optimal AV delay existed for each patient, and the associated highest D(LV) corresponded with the maximal velocity-time integral (VTI) in the left ventricular outflow tract (VTI(LVOT)) and the E/e' ratio. Significant increases in D(LV) and the VTI(LVOT) from before to after implantation with standard settings and from standard to optimal AV delay by displacement were found. Diastolic filling time corresponded poorly with D(LV) and the VTI(LVOT). CONCLUSION: Individual optimal AV delay programming provides significant improvement in left ventricular performance and hemodynamics. Displacement analysis and the VTI(LVOT) are interchangeable, whereas diastolic filling time cannot be recommended.

The role of local voltage potentials in outflow tract ectopy.

AIMS: Discrete, fragmented, local voltage potentials (LVPs) have been observed in electrograms recorded at the ablation site in patients undergoing radiofrequency ablation for arrhythmias originating in both the right and left ventricular outflow tract; however, the incidence and the significance of the LVP with respect to arrhythmogenesis is uncertain. METHODS AND RESULTS: We studied 25 patients with outflow tract arrhythmias referred for radiofrequency catheter ablation and recorded high-amplified intracardiac electrograms close to the site of origin of the arrhythmia. Ten patients undergoing ablation for supraventricular arrhythmias served as controls. During sinus rhythm, LVPs were recorded in 24 of the 25 patients, 10-85 ms (41 +/- 19 ms) after the onset of the QRS complex, duration 33 +/- 11 ms, voltage 2.0 +/- 1.5 mV. The same potential was recorded 10-52 ms (mean 37 +/- 11 ms) prior to the V potential in the ventricular premature beats. In 10 patients, ventricular parasystole was suggested by varying coupling intervals >100 ms, and fusion beats allowing for the estimation of the least common denominator of R-R intervals. In 23 of the 25 patients, the 12-lead electrocardiogram (ECG) and intracardiac contact mapping located the arrhythmias to an area of 3-4 cm(2) in the septal region of the right ventricular outflow tract; in two patients, the site of origin was in the left coronary cusp. Radiofrequency ablation carried out in 24 of the 25 patients was successful in 21 patients, and after successful ablation, the LVP could still be recorded in all these 21 patients. The LVP was not present in 10 controls. CONCLUSION: Local potentials are recorded close to the site of origin of ventricular ectopy in >90% of patients with idiopathic outflow tract ectopy and imply successful ablation. The potentials may reflect an area of depressed conductivity known to be a prerequisite for experimental ventricular ectopy including parasystole.

Attenuated recovery of heart rate turbulence early after myocardial infarction identifies patients at high risk for fatal or near-fatal arrhythmic events.

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.

Prediction of fatal or near-fatal cardiac arrhythmia events in patients with depressed left ventricular function after an acute myocardial infarction.

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.

Long QT syndrome genotyping by electrocardiography: fact, fiction, or something in between?

Diagnosis of long QT syndrome (LQTS) is difficult. A prolonged QT interval is easily overlooked, and in 10% of all patients with LQTS, the QT interval is normal. Genotyping is unfortunately not able to detect all patients and healthy subjects correctly. Although QT prolongation is the most used risk parameter, there is no clear correlation between the prolonged QT interval and the risk of arrhythmias in drug-induced LQTS. Quantification of T-wave morphology is a promising method that is able to provide more information about repolarization than QT prolongation alone. It is a fact that ECG evaluation can serve as a guide for genotyping and can reduce the costs by suggesting which gene to start sequencing, but it is fiction that the ECG can replace genotyping.