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.

Influence of time between last myocardial infarction and prophylactic implantable defibrillator implant on device detections and therapies. "Routine Practice" data from the SEARCH MI registry.

BACKGROUND: A multicenter European Registry, SEARCH-MI, was instituted in the year 2002 in order to assess patients' outcomes and ICD interventions in patients with a previous MI and depressed LV function, treated with an ICD according to MADIT II results. In this analysis, we evaluate the influence of the time elapsed between last myocardial infarction (MI) and prophylactic cardioverter defibrillator (ICD) implant on device activations. METHODS: 643 patients with left ventricular dysfunction (mean LVEF 26 ± 5%) and NYHA class I-III were prospectively followed for 1.8 ± 1.2 years in a multicenter registry. The population was divided into 3 groups according to the time between last MI and ICD implant: [1] from 40 days to less than 1.5 years; [2] from 1.5 to less than 7 years and [3] at least 7 years. RESULTS: The cumulative incidence of ventricular tachyarrhymias and appropriate device therapy (ATP or shock) were higher in patients implanted longer time from last MI (Gray's Test p=0.002 and p=0.013 respectively). No significant differences were seen in all cause mortality (Gray's Test p=0.618) or sudden cardiac death across the MI stratification groups (Gray's Test p=0.663). CONCLUSIONS: Patients implanted with an ICD longer after the MI have a higher chance of presenting ventricular tachyarrhythmias and appropriate ICD therapy, while no differences were seen in overall mortality. These observations may be important for improving patient targeting in sudden death prevention.

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.

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 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.

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.

Anti-HBs antibody persistence following primary vaccination with an investigational AS02(v)-adjuvanted hepatitis B vaccine in patients with renal insufficiency.

BACKGROUND: Three doses of the investigational AS02(v)-adjuvanted hepatitis B virus (HBV) vaccine HB-AS02 have been shown to induce more rapid seroprotection and higher anti-HBs antibody concentrations in patients with renal insufficiency than four doses of FENDrix™ (HB-AS04), an adjuvanted HBV vaccine licensed in Europe for use in this population. This study evaluated persistence of immune response up to 36 months after primary vaccination. METHODS: In this open, international, Phase III follow-up study, 151 pre-dialysis, peritoneal dialysis and hemodialysis patients ≥15 years of age received HB-AS02 at 0, 1, 6 months and 149 received HB-AS04 at 0, 1, 2, 6 months. Of these, 99 and 80 returned at Month 36, 76 and 62 of whom were eligible for inclusion in the Long-Term According-To-Protocol (LT-ATP) cohort for descriptive analysis of antibody persistence (mean age: 65.6 years). RESULTS: At Month 36, 89.5% of subjects in the HB-AS02 group and 72.6% of those in the HB-AS04 group had anti-HBs antibody concentrations ≥10 mIU/ml. Anti-HBs antibody concentrations were ≥100 mIU/ml in 82.9% and 35.5% of subjects, respectively. Anti-HBs geometric mean antibody concentrations were higher in the HB-AS02 group over the 36 months of follow-up. An exploratory "time to boost" analysis confirmed that subjects who received HB-AS02 were 2.54 times more likely than those who received HB-AS04 to have anti-HBs antibody concentrations ≥10 mIU/ml at Month 36 (p=0.013 [95% CI: 1.22, 5.31]). CONCLUSION: HB-AS02 candidate vaccine induces high and persistent anti-HBs antibody levels in pre-dialysis, peritoneal dialysis and hemodialysis patients, potentially reducing the need for booster doses in this population.

Prevalence and risk factors related to infections of cardiac resynchronization therapy devices.

AIMS: Device-related infections (DRI) are not well understood in patients implanted with a cardiac resynchronization therapy (CRT) device. The aims of this study were: (i) to evaluate the prevalence of CRT DRI; (ii) to establish the factors predictive of CRT DRI. METHODS AND RESULTS: Between January 2001 and May 2007, CRT implantation was performed in 303 patients (247 men, 82%). The mean follow-up was 31 +/- 19 months. Population characteristics were a mean age of 70 +/- 10 years old; 56 female; aetiology includes (202 dilated and 101 ischaemic cardiomyopathy); NYHA class 3.2 +/- 0.3; LVEF (26 +/- 6%), and a QRS width of 171 +/- 31 ms. Thirteen patients developed a DRI: endocarditis in four, pocket erosion in three, pocket abscess in five, and septicaemia in one. The prevalence of DRI was 4.3%. By univariate analysis, predictive factors of DRI were: procedure time (skin to skin: median of 85 vs. 57.5 min; P = 0.03), re-intervention (54 vs. 6.5%; P < 0.0001), haematoma (31 vs. 8.6% P = 0.01), lead dislodgement (23 vs. 6.2%; P = 0.03), dialysis (23.1 vs. 1.72%; P = 0.003), and procedure type [CRT-ICD (8.6%) vs. CRT PM (1.6%) or system up-grade (1.5%); P = 0.03]. Significant correlations were found between re-intervention and lead dislodgement (r = 0.8; P < 0.001), haematoma (r = 0.2; P < 0.001). Four independent predictive factors of DRI were identified as procedure time (P = 0.002); dialysis (P = 0.0001); re-intervention (P = 0.006), and procedure type (CRT-ICD vs. other procedures; P = 0.01). CONCLUSION: This study found that the prevalence of CRT DRI is close to 4.3% at 2.6 years (1.7% per year incidence). Four independent predictive factors of infections were identified including re-intervention, procedure time, dialysis, and primo CRT-ICD implantation. These parameters should be part of the risk-benefit evaluation in patients selected for CRT implantation.

Autonomic dysfunction and new-onset atrial fibrillation in patients with left ventricular systolic dysfunction after acute myocardial infarction: a CARISMA substudy.

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.

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.

Diastolic dysfunction predicts new-onset atrial fibrillation and cardiovascular events in patients with acute myocardial infarction and depressed left ventricular systolic function: a CARISMA substudy.

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

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.

Clinical and arrhythmic outcomes after implantation of a defibrillator for primary prevention of sudden death in patients with post-myocardial infarction cardiomyopathy: The Survey to Evaluate Arrhythmia Rate in High-risk MI patients (SEARCH-MI).

AIMS: To evaluate clinical and arrhythmic outcomes in post-infarction cardiomyopathy patients implanted with a defibrillator (ICD) for primary prevention of sudden death. METHODS AND RESULTS: The SEARCH-MI registry is a European multi-centre, prospective, observational study enrolling patients after myocardial infarction, chronic left ventricular dysfunction and an ICD implanted for primary prevention of sudden death. Data on 556 patients with at least one recorded follow-up are presented. Survey to Evaluate Arrhythmia Rate in High-risk MI (SEARCH-MI) patients were sicker than those enrolled in MADIT-II with higher New York Heart Association class and left bundle branch block. Total mortality was 10.4%. Close to one-third (30%) of patients experienced episodes of sustained ventricular arrhythmia. One-quarter (23%) received at least one appropriate therapy and 10% inappropriate therapy. Gender (25% males vs. 5% females, P = 0.0009) and history of non-sustained ventricular tachycardia (24% with vs. 18% without P = 0.037) were predictive of appropriate ventricular therapy. CONCLUSION: SEARCH-MI represents the current clinical management of post-MI patients with left ventricular dysfunction indicated to defibrillator implant for primary prevention. European routine clinical practice was influenced by landmark trials and guidelines which impacted on the implantation of cardiac resynchronization therapy in over 25% of such patients. Non-sustained ventricular tachycardia identifies subjects with a higher incidence of appropriate ICD therapy.

Improved arrhythmia detection in implantable loop recorders.

INTRODUCTION: Implantable loop recorders (ILR) have an automatic arrhythmia detection feature that can be compromised by inappropriately detected episodes. This study evaluated a new ILR sensing and detection scheme for automatically detecting asystole, bradyarrhythmia, and tachyarrhythmia events, which is implemented in the next generation device (Reveal DX/XT). METHODS AND RESULTS: The new scheme employs an automatically adjusting R-wave sensing threshold, enhanced noise rejection, and algorithms to detect asystole, bradyarrhythmia, and tachyarrhythmia. Performance of the new algorithms was evaluated using 2,613 previously recorded, automatically detected Reveal Plus episodes from 533 patients. A total of 71.9% of episodes were inappropriately detected by the original ILR, and at least 88.6% of patients had one or more inappropriate episodes, with most inappropriate detections due to R-wave amplitude reductions, amplifier saturation, and T-wave oversensing. With the new scheme, inappropriate detections were reduced by 85.2% (P < 0.001), with a small reduction in the detection of appropriate episodes (1.7%, P < 0.001). The new scheme avoided inappropriate detections in 67.4% of patients that had them with the original scheme. CONCLUSIONS: The new sensing and detection scheme is expected to substantially reduce the occurrence of inappropriately detected episodes, relative to that of the original ILR.

Results from the Loire-Ardèche-Drôme-Isère-Puy-de-Dôme (LADIP) trial on atrial flutter, a multicentric prospective randomized study comparing amiodarone and radiofrequency ablation after the first episode of symptomatic atrial flutter.

BACKGROUND: There is no published randomized study comparing amiodarone therapy and radiofrequency catheter ablation (RFA) after only 1 episode of symptomatic atrial flutter (AFL). The aim of the Loire-Ardèche-Drôme-Isère-Puy-de-Dôme (LADIP) Trial of Atrial Flutter was 2-fold: (1) to prospectively compare first-line RFA (group I) versus cardioversion and amiodarone therapy (group II) after only 1 AFL episode; and (2) to determine the impact of both treatments on the long-term risk of subsequent atrial fibrillation (AF). METHODS AND RESULTS: From October 2002 to February 2006, 104 patients (aged 78+/-5 years; 20 women) with AFL were included, with 52 patients in group I and 52 patients in group II. The cumulative risk of AFL or AF was interpreted with the use of Kaplan-Meier curves and compared by the log-rank test. Clinical presentation, echocardiographic data, and follow-up were as follows: age (78.5+/-5 versus 78+/-5 years), history of AF (27% versus 21.6%); structural heart disease (58% versus 65%), left ventricular ejection fraction (56+/-14% versus 54.5+/-14%), left atrial size (43+/-7 versus 43+/-6 mm), mean follow-up (13+/-6 versus 13+/-6 months; P=NS), recurrence of AFL (3.8% versus 29.5%; P<0.0001), and occurrence of significant AF beyond 10 minutes (25% versus 18%; P=0.3). Five complications (10%) were noted in group II (sick sinus syndrome in 2, hyperthyroidism in 1, and hypothyroidism in 2) and none in group I (0%) (P=0.03). CONCLUSIONS: RFA should be considered a first-line therapy even after the first episode of symptomatic AFL. There is a better long-term success rate, the same risk of subsequent AF, and fewer secondary effects.

Prospective validation of stress echocardiography as an identifier of cardiac resynchronization therapy responders.

BACKGROUND: Cardiac resynchronization therapy (CRT) provides benefit for congestive heart failure (CHF), but predictors of the clinical response are debated. OBJECTIVE: The aim of this prospective study was to assess the predictive role of dobutamine stress echocardiography (DSE) in identifying a suitable candidate for CRT. METHODS: From March 2001 to December 2003, 71 CHF patients were prospectively enrolled on the basis of four criteria: New York Heart Association (NYHA) class III and IV; QRS > or =150 ms with a left bundle branch block pattern, and left ventricular ejection fraction (LVEF) < or =35% under optimal medical treatment. The combined endpoints were hospital readmission for class IV CHF, heart transplant (HT), and CHF-related death. RESULTS: The 67 patients completing the study presented with the following characteristics: age (70 +/- 10 years; 11 women); etiology (idiopathic in 44, ischemic in 23); NYHA class (40 in class III and 27 in class IV); LVEF 26% (+/-5%); QRS duration (190 +/- 28 ms); 6-minute walk test 330 m (+/-108); peak oxygen uptake 10.7 (+/-3.3 mL/kg/min); mitral insufficiency in 42 (> or =III grade); interventricular (IV) delay (62 +/- 21 ms); and intraventricular dyssynchrony in 30 patients. Over the follow-up period of 12.1 +/- 8.7 months, 20 (29.9%) of 67 patients presented with at least one hemodynamic event: hospitalization for CHF in 19 (28%) of 67, HT in 2 (3%) of 67, and CHF death in 7 (10%) 67. Univariate analysis identified NYHA class (P = .03), LVEF (P = .015), IV dyssynchrony before (P = .038) and after CRT (P = .0035), IV delay after CRT (P = .002), 6-minute walk distance (P = .01), and DSE Res+ (P = .008) as significant predictors of clinical events. A receiver operating curve established a cut-off value of 1.25 for the DSE responders (Res+: 34 patients at 10 microg/kg/min infusion rates), and the improvement at the 10 microg/kg/min level was 41% +/- 7% in Res+ and 29% +/- 8% in nonresponders (P<.0001). With a cut-off value of 1.25-fold the LVEF increase, the DSE test exhibits 70% sensitivity, 61.7% specificity, 43.8% positive predictive value, and 82.9% negative predictive value. Cox analysis identified IV dyssynchrony before CRT (P = .01) and DSE Res+ (P = .003) as independent predictive factors. CONCLUSIONS: Independent predictive factors of severe hemodynamic clinical outcome in patients with CRT are IV dyssynchrony and DSE.

Clinical predictors of cardiac events in patients with isolated syncope and negative electrophysiologic study.

BACKGROUND: Patients with syncope or near syncope of unknown etiology represent a great challenge to cardiologists. An initial symptomatic episode triggers a series of diagnostic analysis which remain unsatisfactory when negative. More invasive tools such as electrophysiologic testing yield only partial answers to risk stratification while the complementary implantable holter diagnostics are not usually considered until a recurrent episode is documented. OBJECTIVE: This study targets predictors of significant cardiac rhythmic events in patients with a reported episode of syncope or near syncope presenting with negative diagnostics and electrophysiologic study results (EPS). A significant cardiac rhythmic event was defined as a combined end-point of (1) symptomatic AV block; (2) symptomatic conduction abnormalities requiring pacemaker therapy; (3) symptomatic sustained ventricular arrhythmia; and (4) sudden death. METHODS: All patients undergoing EPS after a first episode of syncope or presyncope between January 1997 and December 2001 were included for analysis. The study population consisted of 329 pts (42.6% women), 21 to 96 years old (mean 70+/-15 years) referred for an EP study for syncope or near syncope. RESULTS: Of the 329 patients who underwent EPS, 305 (92.7%) had follow-up data. The population, mean age 70 (+/- 15 years) and composed of 42% women, presented with hypertension (51.5%), diabetes mellitus (14.4%), hypercholesterolemia (30%), tobacco use (35%), a familial history of coronary heart disease (22%), history of stroke (4%), history of MI (12%), history of atrial fibrillation (10%), structural heart disease (17.4%), left ventricular ejection fraction 61 (+/- 11%) and ECG abnormalities (37%). These anomalies included right (RBBB) or left (LBBB) bundle branch blocks, left anterior fascicular block (LAFB), left posterior fascicular block (LPFB), bifascicular block (RBBB+LAFB) and traces of myocardial infarction. The mean follow-up was 31+/-20 months with 5% of patients recording significant cardiac rhythmic events (15/305): AV block requiring pacemaker therapy in 7 patients, sinus dysfunction in 4, sudden death in 3 and ventricular tachycardia in 1. Univariate analysis reveals structural heart disease, ECG abnormalities and LVEF associated with the risk of significant cardiac rhythmic events defined by the combined end-point. Multivariate analysis using a Cox model found that the only independent predictor of events was an ECG abnormality. The long-term risk of significant event in the subset with ECG abnormalities is of 10.6% (12/113). If unexplained syncope recurrence was included in the combined end-point, ECG abnormality and LVEF were both determinants with a 13.3% (15/113) risk of a arrhythmic events analysis in the subset of patients presenting with ECG abnormalities and Cox model found ECG abnormality as the only independent predictor of event. CONCLUSIONS: This study demonstrated that an ECG abnormality is the only predictive variable associated with a significant arrhythmic event in patients with a lone episode of syncope or near syncope and a negative EPS.

Catheter selection for ablation of the cavotricuspid isthmus for treatment of typical atrial flutter.

Radiofrequency catheter ablation (RFA) represents the first line therapy of the cavotricuspid isthmus-dependent atrial flutter (CTI-AFL) with a high efficacy and low secondary effects. RFA of CTI-dependent AFL can be performed by using various types of ablation catheters. Recent evaluations comparing externally cooled tip RFA (ecRFA) catheters and large-tip (8 mm) catheters have revealed that these catheters have a higher efficacy for CTI-AFL ablation compared to 4-mm catheters. The reliability of RFA catheters for AFL is variable and an optimal catheter selection may enhance the RFA effectiveness. The main goal of this article is to review the elements that improve the management of CTI RFA. Preliminary examinations of histopathologic and anatomical elements that may interfere with conventional CTI RFA are presented. Experimental studies concerning the electrobiology of large-tip and cooled-tip catheters are compared. The different catheter designs between cooled-tip and 8-mm-tip catheters are examined (size of the deflectable curve, rotation stability, and size of the distal nonsteerable catheter part) because of their critical role in CTI RFA results. A thorough review of clinical trials of each catheter is presented, and comparison of both catheters in this clinical setting is analyzed. In addition, the role of CTI morphology on AFL RF duration is underlined such as the value of right atrial angiography as an adjunct tool for CTI RFA catheter selection. Based on randomized studies, 8-mm-tip catheters seem to be more effective for ablation in case of straight angiographic isthmus morphology. On the other hand, ecRFA catheters appear to be more effective in cases of complex CTI anatomy or difficult CTI RFA. To reduce X-ray exposition and RFA application time, few studies report that CTI angiographic evaluation before RFA allows a catheter selection based on both CTI morphology and length. Moreover, preliminary data of randomized studies showed that an angiographic isthmus evaluation may predict both the effectiveness of a RFA catheter and the risk of an expensive catheter crossover.

Isthmus characteristics of reentrant ventricular tachycardia after myocardial infarction.

BACKGROUND: The reentrant mechanism of postinfarct ventricular tachycardia (VT) has been documented by surgical mapping analysis, but little is known about postinfarct VT circuits and the characteristics of their related protected isthmus with the use of 3D catheter mapping systems. METHODS AND RESULTS: A 3D electroanatomic mapping was performed in 21 patients with well-tolerated, postinfarct, sustained VT. In total, 33 episodes of tachycardia (mean cycle length 432+/-74 ms) were induced and mapped. Complete maps demonstrated macroreentrant circuits with 1 loop (n=8) or 2 loops (n=25) rotating around a protected isthmus bounded by 2 approximately parallel conduction barriers that consisted of a line of double potentials, a scar area, or the mitral annulus. A total of 26 critical isthmi were identified for the 33 VTs mapped, with the same isthmus being shared by 2 to 4 different tachycardic morphologies in 5 patients. On average, isthmi were 31+/-7 mm long (ranging from 18 to 41 mm) and 16+/-8 mm wide (ranging from 6 to 36 mm) and harbored diastolic electrograms. The isthmus axis was oriented parallel to the mitral annulus plane in perimitral circuits and perpendicular to the mitral annulus plane in all other circuits. Linear radiofrequency ablation performed across the most accessible part of the isthmus prevented the recurrence of tachycardia in 19 patients (90%) with a follow-up at 16+/-8 months. CONCLUSIONS: Detailed 3D electroanatomic mapping is helpful in reconstructing postinfarct VT circuits and in defining the characteristics of their related protected isthmi. The wide range of isthmus width values supports the need of linear radiofrequency lesions to eliminate the reentrant substrate of postinfarct VTs.

Effect of isthmus anatomy and ablation catheter on radiofrequency catheter ablation of the cavotricuspid isthmus.

BACKGROUND: Cavotricuspid isthmus (CTI) characteristics are rarely documented when comparing catheters in radiofrequency ablation (RFA) of atrial flutter (AFL). Our objectives were (1) to evaluate the impact of CTI morphology and length on ablation procedures and (2) to compare the efficacy of an 8-mm-tip catheter with an irrigated cooled-tip RFA in the subgroup presumed to be more difficult to treat (with a long CTI, >35 mm). METHODS AND RESULTS: Over a period of 17 months, 185 patients accepted the protocol and underwent an isthmogram in preparation for RFA. Groups were classified according to CTI length and CTI morphology. RFA was performed with an 8-mm-tip catheter for patients with a short CTI, < or =35 mm (n=123), whereas randomization between an 8-mm-tip and a cooled-tip catheter applied to patients with a longer CTI, >35 mm (n=62). For long CTI, 32 patients were assigned to an 8-mm catheter and 30 patients to the cooled-tip RFA ablation group. In this subset, RF application (18.2+/-17 versus 19+/-13 minutes) and x-ray exposure (20.8+/-18 versus 18+/-13 minutes) did not differ between the 8-mm-tip and the cooled-tip procedures. Number of applications (9.9+/-11 versus 18.6+/-15 minutes; P<0.0001) and x-ray exposure (11.7+/-11 versus 19.5+/-16 minutes, P=0.0001) differed significantly between patients with short and long CTIs. Patients with short and straight CTIs required 3 times fewer RFA applications and shorter x-ray exposure compared with other CTI morphologies (pouch-like recesses and concave characteristics). CONCLUSIONS: The number of RF applications required for a complete isthmus block in long CTIs is not influenced by the choice between an 8-mm or cooled-tip catheter. Procedure parameters, however, are significantly influenced by CTI length and morphology. Pouch-like recesses and concave characteristics account for much longer ablation times at all CTI lengths.