Survival with cardiac-resynchronization therapy in mild heart failure.

BACKGROUND: The Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) showed that early intervention with cardiac-resynchronization therapy with a defibrillator (CRT-D) in patients with an electrocardiographic pattern showing left bundle-branch block was associated with a significant reduction in heart-failure events over a median follow-up of 2.4 years, as compared with defibrillator therapy alone. METHODS: We evaluated the effect of CRT-D on long-term survival in the MADIT-CRT population. Post-trial follow-up over a median period of 5.6 years was assessed among all 1691 surviving patients (phase 1) and subsequently among 854 patients who were enrolled in post-trial registries (phase 2). All reported analyses were performed on an intention-to-treat basis. RESULTS: At 7 years of follow-up after initial enrollment, the cumulative rate of death from any cause among patients with left bundle-branch block was 18% among patients randomly assigned to CRT-D, as compared with 29% among those randomly assigned to defibrillator therapy alone (adjusted hazard ratio in the CRT-D group, 0.59; 95% confidence interval [CI], 0.43 to 0.80; P<0.001). The long-term survival benefit of CRT-D in patients with left bundle-branch block did not differ significantly according to sex, cause of cardiomyopathy, or QRS duration. In contrast, CRT-D was not associated with any clinical benefit and possibly with harm in patients without left bundle-branch block (adjusted hazard ratio for death from any cause, 1.57; 95% CI, 1.03 to 2.39; P=0.04; P<0.001 for interaction of treatment with QRS morphologic findings). CONCLUSIONS: Our findings indicate that in patients with mild heart-failure symptoms, left ventricular dysfunction, and left bundle-branch block, early intervention with CRT-D was associated with a significant long-term survival benefit. (Funded by Boston Scientific; ClinicalTrials.gov numbers, NCT00180271, NCT01294449, and NCT02060110.).

Reduction in inappropriate therapy and mortality through ICD programming.

BACKGROUND: The implantable cardioverter-defibrillator (ICD) is highly effective in reducing mortality among patients at risk for fatal arrhythmias, but inappropriate ICD activations are frequent, with potential adverse effects. METHODS: We randomly assigned 1500 patients with a primary-prevention indication to receive an ICD with one of three programming configurations. The primary objective was to determine whether programmed high-rate therapy (with a 2.5-second delay before the initiation of therapy at a heart rate of ≥200 beats per minute) or delayed therapy (with a 60-second delay at 170 to 199 beats per minute, a 12-second delay at 200 to 249 beats per minute, and a 2.5-second delay at ≥250 beats per minute) was associated with a decrease in the number of patients with a first occurrence of inappropriate antitachycardia pacing or shocks, as compared with conventional programming (with a 2.5-second delay at 170 to 199 beats per minute and a 1.0-second delay at ≥200 beats per minute). RESULTS: During an average follow-up of 1.4 years, high-rate therapy and delayed ICD therapy, as compared with conventional device programming, were associated with reductions in a first occurrence of inappropriate therapy (hazard ratio with high-rate therapy vs. conventional therapy, 0.21; 95% confidence interval [CI], 0.13 to 0.34; P<0.001; hazard ratio with delayed therapy vs. conventional therapy, 0.24; 95% CI, 0.15 to 0.40; P<0.001) and reductions in all-cause mortality (hazard ratio with high-rate therapy vs. conventional therapy, 0.45; 95% CI, 0.24 to 0.85; P=0.01; hazard ratio with delayed therapy vs. conventional therapy, 0.56; 95% CI, 0.30 to 1.02; P=0.06). There were no significant differences in procedure-related adverse events among the three treatment groups. CONCLUSIONS: Programming of ICD therapies for tachyarrhythmias of 200 beats per minute or higher or with a prolonged delay in therapy at 170 beats per minute or higher, as compared with conventional programming, was associated with reductions in inappropriate therapy and all-cause mortality during long-term follow-up. (Funded by Boston Scientific; MADIT-RIT ClinicalTrials.gov number, NCT00947310.).

Amiodarone reduces the amount of ablation during catheter ablation for persistent atrial fibrillation.

AIMS: The step-wise approach to catheter ablation for persistent atrial fibrillation (AF) requires considerable substrate modification targeting at complex fractionated atrial electrograms (CFAEs) in addition to pulmonary vein (PV) isolation. An alternative strategy that minimizes the amount of ablation would be desirable. The aim of this study was to investigate whether the use of pre-procedural amiodarone affects: (i) the amount of ablation required to achieve procedural success, and (ii) long-term outcomes. METHODS AND RESULTS: We studied 121 consecutive patients with persistent AF who underwent catheter ablation. The patients were divided into two groups: Group 1, amiodarone (n = 31); Group 2, other antiarrhythmic drugs or rate control (n = 90). All the patients underwent a step-wise ablation procedure beginning with PV isolation, then proceeding with ablation of the CFAEs and linear lesions until sinus rhythm was achieved. Mean left atrial cycle length of AF (AFCL) was recorded at each step. The number of CFAE ablation sites was recorded. The number of CFAE sites in Group 1 was significantly less than that in Group 2 (P = 0.0121). The AFCLs after each step in Group 1 were significantly longer than those in Group 2. The procedure time and the radiofrequency time of CFAE ablation in Group 1 were significantly shorter than that in Group 2 (P = 0.0276 and P = 0.0458, respectively). There was no significant difference between the two groups in early and long-term outcomes. CONCLUSION: Use of pre-procedural amiodarone prolongs AFCL during catheter ablation and reduces the number of CFAE sites requiring ablation to achieve procedural success while maintaining equivalent long-term results.

Cardiac-resynchronization therapy for the prevention of heart-failure events.

BACKGROUND: This trial was designed to determine whether cardiac-resynchronization therapy (CRT) with biventricular pacing would reduce the risk of death or heart-failure events in patients with mild cardiac symptoms, a reduced ejection fraction, and a wide QRS complex. METHODS: During a 4.5-year period, we enrolled and followed 1820 patients with ischemic or nonischemic cardiomyopathy, an ejection fraction of 30% or less, a QRS duration of 130 msec or more, and New York Heart Association class I or II symptoms. Patients were randomly assigned in a 3:2 ratio to receive CRT plus an implantable cardioverter-defibrillator (ICD) (1089 patients) or an ICD alone (731 patients). The primary end point was death from any cause or a nonfatal heart-failure event (whichever came first). Heart-failure events were diagnosed by physicians who were aware of the treatment assignments, but they were adjudicated by a committee that was unaware of assignments. RESULTS: During an average follow-up of 2.4 years, the primary end point occurred in 187 of 1089 patients in the CRT-ICD group (17.2%) and 185 of 731 patients in the ICD-only group (25.3%) (hazard ratio in the CRT-ICD group, 0.66; 95% confidence interval [CI], 0.52 to 0.84; P=0.001). The benefit did not differ significantly between patients with ischemic cardiomyopathy and those with nonischemic cardiomyopathy. The superiority of CRT was driven by a 41% reduction in the risk of heart-failure events, a finding that was evident primarily in a prespecified subgroup of patients with a QRS duration of 150 msec or more. CRT was associated with a significant reduction in left ventricular volumes and improvement in the ejection fraction. There was no significant difference between the two groups in the overall risk of death, with a 3% annual mortality rate in each treatment group. Serious adverse events were infrequent in the two groups. CONCLUSIONS: CRT combined with ICD decreased the risk of heart-failure events in relatively asymptomatic patients with a low ejection fraction and wide QRS complex. (ClinicalTrials.gov number, NCT00180271.)

The use of balloon atrial septostomy to facilitate difficult transseptal access in patients undergoing catheter ablation for atrial fibrillation.

INTRODUCTION: With the increasing number of patients undergoing repeat catheter ablation procedures for atrial fibrillation, it is not uncommon to encounter a fibrotic interatrial septum that resists the conventional manual advancement of the transseptal sheath. Forceful advancement of the transseptal apparatus can reduce fine control and potentially lead to a higher rate of perforation. CASE: We report a case where adjunctive balloon atrial septostomy was used to facilitate transseptal access in a patient with fibrotic interatrial septum. Using a small-caliber angioplasty balloon and under direct fluoroscopic and transesophageal echocardiogram visualization, balloon septostomy was performed with hand inflation until a "waist" was seen. This technique provides a safe way to control the size of the transseptal access created, and allows the passage of a relatively soft-tipped transseptal sheath across a resistive septum. To our knowledge this is the first published use of balloon atrial septostomy during transseptal puncture for left atrium access in a catheter ablation procedure. CONCLUSION: Balloon atrial septostomy should be considered as an alternative technique for safe transseptal cannulation in select patients in the electrophysiology laboratory or other interventional procedures requiring left atrial access or delivery of large-caliber catheters or sheaths.

Improved outcome with preventive cardiac resynchronization therapy in the elderly: a MADIT-CRT substudy.

BACKGROUND: Elderly patients comprise a large portion of patients with heart failure (HF). Limited data exist on the effectiveness of cardiac resynchronization therapy with defibrillator (CRT-D) in patients with mild HF symptoms in this population. METHODS AND RESULTS: The benefit of CRT-D compared with ICD-only therapy in reducing HF or death was assessed by age categories (prespecified as <60 [n = 548], 60-74 [n = 941], and ≥75 [n = 331] years) among 1,820 patients in MADIT-CRT. In patients with ICD-only, there was a graded age-related increase in the Kaplan-Meier cumulative probability of HF or death at 3-year follow-up (19%, 33%, and 36%, in patients aged <60, 60-74, and ≥75 years, respectively, P = 0.003). Multivariate analysis demonstrated that CRT-D therapy was associated with a significant reduction in the risks of HF or death in patients aged 60-74, and ≥75 years (HR = 0.57, P = <0.001 and HR = 0.59, P = 0.017, respectively), and no significant benefit in patients aged <60 years (HR = 0.81, P = 0.3; P-value for all treatment-by-age interactions >0.10). There was no significant difference in the rate of device-related adverse events within 90 days following CRT-D implantation among age-subgroups (16.7%, 15.7%, and 11.7%, in patients <60, 60-74, and ≥75 years, respectively, P = 0.42). CONCLUSION: CRT-D was associated with a significant clinical benefit in older patients (≥60 years) during an average 2.4-year follow-up. These effects were preserved for the elderly patients ≥75 years of age but attenuated in patients <60 years. Elderly patients had no increase in device-related adverse events compared with younger patients.

Comparison of the point-by-point versus catheter dragging technique for curative radiofrequency ablation of atrial fibrillation.

BACKGROUND: The relationship between the applied techniques and clinical outcomes after radiofrequency (RF) ablation of atrial fibrillation (AF) remains unclear. We compared the results of ablation by RF delivered via a point-by-point versus catheter dragging technique for the treatment of AF. METHODS: This study included 66 patients with drug-refractory AF who underwent circumferential pulmonary vein (PV) ablation. A point-by-point technique was used in 35 (53%) patients (Group I), and catheter dragging technique in the remaining 31 (47%) patients (Group II). If AF persisted or remained inducible after the PV isolation, additional ablation of complex fractionated atrial electrograms and linear ablation were performed. RESULTS: Significantly, fewer RF applications were delivered in Group II than in Group I. The total RF energy duration delivered was comparable between the two groups (P = 0.55). However, the total energy of RF deliveries was significantly greater in Group II than in Group I (P = 0.02). Despite a longer fluoroscopic exposure time (P = 0.01), the total procedural duration was significantly shorter in Group II than in Group I (P = 0.005). Within 3 months after a single ablation procedure, 24 patients (69%) in Group I versus 13 patients (42%) in Group II had ≥1 recurrence(s) of atrial tachyarrhythmias (P = 0.03). A multivariate analysis showed that a point-by-point ablation was the only independent predictor of early atrial tachyarrhythmia recurrences. CONCLUSIONS: The catheter dragging technique for ablation of AF was associated with a lower early recurrence rate of atrial tachyarrhythmias than the point-by-point technique.

Mast Cell Activation Disorder and Postural Orthostatic Tachycardia Syndrome: A Clinical Association.

Background Recently there has been increased interest in a possible association between mast cell activation (MCA) disorder and postural orthostatic tachycardia syndrome (POTS). This study examined the frequency with which symptoms and laboratory findings suggesting MCA disorder occurred in patients diagnosed with POTS. Methods and Results Data were obtained from patients in whom symptoms and orthostatic testing were consistent with a POTS diagnosis. Individuals with <4 months symptom duration, evident ongoing inflammatory disease, suspected volume depletion, or declined consent were excluded. All patients had typical POTS symptoms; some, however, had additional nonorthostatic complaints not usually associated with POTS. The latter patients underwent additional testing for known MCA biochemical mediators including prostaglandins, histamine, methylhistamine, and plasma tryptase. The study comprised 69 patients who met POTS diagnostic criteria. In 44 patients (44/69, 64%) additional nonorthostatic symptoms included migraine, allergic complaints, skin rash, or gastrointestinal symptoms. Of these 44 patients, 29 (66%) exhibited at least 1 laboratory abnormality suggesting MCA disorder, and 11/29 patients had 2 or more such abnormalities. Elevated prostaglandins (n=16) or plasma histamine markers (n=23) were the most frequent findings. Thus, 42% (29/69) of patients initially diagnosed with POTS exhibited both additional symptoms and at least 1 elevated biochemical marker suggesting MCA disorder. Conclusions Laboratory findings suggesting MCA disorder were relatively common in patients diagnosed with POTS and who present with additional nonorthostatic gastrointestinal, cutaneous, and allergic symptoms. While solitary abnormal laboratory findings are not definitive, they favor MCA disorder being considered in such cases.

Sports and arrhythmias: a report of the International Workshop Venice Arrhythmias 2009.

This article is a report of an international symposium, endorsed by the Section on Sports Cardiology of the European Association for Cardiovascular Prevention and Rehabilitation, the Italian Society of Sports Cardiology, and the Italian Federation of Sports Medicine, which was held within the 11th International Workshop on Cardiac Arrhythmias (Venice Arrhythmias 2009, Venice, Italy, October 2009). The following main topics were discussed during the symposium: the role of novel diagnostic examinations to assess the risk of sudden death in athletes, controversies on arrhythmic risk evaluation in athletes, controversies on the relationship between sports and arrhythmias, and controversies on antiarrhythmic treatment in athletes.

Safety of Sports for Young Patients With Implantable Cardioverter-Defibrillators: Long-Term Results of the Multinational ICD Sports Registry.

BACKGROUND: Despite safety concerns, many young patients with implantable cardioverter-defibrillators (ICDs) participate in sports. We undertook a prospective, multinational registry to determine the incidence of serious adverse events because of sports participation. The primary end points were death or resuscitated arrest during sports or injury during sports because of arrhythmia or shock. Secondary end points included system malfunction and incidence of ventricular arrhythmias requiring multiple shocks for termination. METHODS: Athletes with ICDs aged ≤21 years were included in this post hoc subanalysis of the ICD Sports Registry. Data on sports and clinical outcomes were obtained by phone interview and medical records review. ICD shocks and clinical details of lead malfunction were classified by 2 electrophysiologists. RESULTS: A total of 129 young athletes participating in competitive (n=117) or dangerous (n=12) sports were enrolled. The mean age was 16 years (range, 10-21; 40% female; 92% white). The most common diagnoses were long QT syndrome (n=49), hypertrophic cardiomyopathy (n=30), and congenital heart disease (n=16). The most common sports were basketball and soccer, including 79 varsity/junior varsity high school and college athletes. During a median follow-up of 42 months, 35 athletes (27%) received 38 shocks. There were no occurrences of death, arrest, or injury related to arrhythmia, during sports. There was 1 ventricular tachycardia/ventricular fibrillation storm during competition. Freedom from lead malfunction was 92.3% at 5 years and 79.6% at 10 years. CONCLUSIONS: Although shocks related to competition/practice are not uncommon, there were no serious adverse sequelae. Lead malfunction rates were similar to previously reported in unselected pediatric ICD populations. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00637754.

Causes and consequences of heart failure after prophylactic implantation of a defibrillator in the multicenter automatic defibrillator implantation trial II.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy may be associated with an increased risk for heart failure (HF). The present study evaluated the frequency, causes, and consequences of HF after ICD implantation. METHODS AND RESULTS: We performed a retrospective analysis of the clinical factors and outcomes associated with postenrollment HF events in 1218 patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial II. The adjusted hazard ratios (HRs) of ICD:conventional therapy for first and recurrent HF events were 1.39 (P=0.02) and 1.58 (P<0.001), respectively. The risk was increased among patients who received single-chamber or dual-chamber ICDs. Development of HF was associated with an increased mortality risk (HR, 3.80; P<0.001). Among patients who received a single-chamber ICD, there was a similar survival benefit before and after the development of HF (HR, 0.59 and 0.61, respectively; P=0.92 for difference), whereas among patients with dual-chamber devices, there was a significant reduction in survival benefit after HF (HR, 0.26 and 0.83, respectively; P=0.01 for difference). Within the defibrillator arm of the trial, patients who received life-prolonging therapy from the ICD had an increased risk for first and recurrent HF events (HR, 1.90; P=0.01 and 1.74; P<0.001, respectively). CONCLUSIONS: Patients with chronic ischemic heart disease who are treated with either single-chamber or dual-chamber ICDs have improved survival but an increased risk of HF. The present data suggest that ICD therapy transforms sudden death risk to a subsequent HF risk. These findings should direct more attention to the prevention of HF in patients who receive an ICD.

Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction.

BACKGROUND: Patients with reduced left ventricular function after myocardial infarction are at risk for life-threatening ventricular arrhythmias. This randomized trial was designed to evaluate the effect of an implantable defibrillator on survival in such patients. METHODS: Over the course of four years, we enrolled 1232 patients with a prior myocardial infarction and a left ventricular ejection fraction of 0.30 or less. Patients were randomly assigned in a 3:2 ratio to receive an implantable defibrillator (742 patients) or conventional medical therapy (490 patients). Invasive electrophysiological testing for risk stratification was not required. Death from any cause was the end point. RESULTS: The clinical characteristics at base line and the prevalence of medication use at the time of the last follow-up visit were similar in the two treatment groups. During an average follow-up of 20 months, the mortality rates were 19.8 percent in the conventional-therapy group and 14.2 percent in the defibrillator group. The hazard ratio for the risk of death from any cause in the defibrillator group as compared with the conventional-therapy group was 0.69 (95 percent confidence interval, 0.51 to 0.93; P=0.016). The effect of defibrillator therapy on survival was similar in subgroup analyses stratified according to age, sex, ejection fraction, New York Heart Association class, and the QRS interval. CONCLUSIONS: In patients with a prior myocardial infarction and advanced left ventricular dysfunction, prophylactic implantation of a defibrillator improves survival and should be considered as a recommended therapy.

Validation and clinical application of time-frequency analysis of atrial fibrillation electrocardiograms.

INTRODUCTION: Fibrillatory rates can reliably be obtained from surface ECGs during atrial fibrillation (AF) and correspond with right atrial (RA) and coronary sinus (CS) rates, while both the relation with pulmonary venous (PV) rates and determinants of fibrillatory waveform are unknown. Class III antiarrhythmic drugs prolong atrial refractoriness and decrease its dispersion, effects that may be reflected in ECG parameters. Consequently, this study sought (1) to investigate the relation between ECG fibrillatory rate and waveform characteristics with intraatrial/PV fibrillatory activity and (2) to noninvasively monitor class III antiarrhythmic drug effects in patients with AF. METHODS AND RESULTS: Thirty-six patients with drug-refractory AF who underwent catheter-based pulmonary vein isolation and had AF at the beginning of the procedure were studied. A positive correlation between V1 rates obtained by time-frequency analysis and RA (R = 0.97, P < 0.001), CS (R = .71, P < 0.001), and PV rates (R = 0.65, P = 0.001) was found. Exponential decay defined as decay of the curve that connects power maxima of dominant and harmonic frequency components correlated with RA rate dispersion (R = 0.53, P = 0.004). In amiodarone-treated patients (n = 7), V1 rate (286 +/- 64 vs. 371 +/- 40 fpm, P < 0.001) and exponential decay (1.06 +/- 0.29 vs. 1.38 +/- 0.38, P = 0.034) were lower than in patients without amiodarone (n = 29). In 19 additional patients with persistent AF, oral dofetilide treatment decreased mean fibrillatory rate from 377 +/- 57 to 294 +/- 50 fpm (P < 0.001) and exponential decay from 1.24 +/- 0.43 to 0.85 +/- 0.22 (P = 0.002). CONCLUSIONS: Fibrillatory waves of surface ECG lead V1 closely reflect right atrial, and, to a lesser degree, left atrial activity. Time-frequency analysis allows noninvasive monitoring of antiarrhythmic drug effects on fibrillatory rate and waveform.

Clinical experience with pacemaker pulse generators and transvenous leads: an 8-year prospective multicenter study.

BACKGROUND: Pacemakers have improved the lives of patients worldwide. Unfortunately, the medical community has had little independent information regarding the performance of these vital medical devices. OBJECTIVES: The purpose of this study was to examine the reasons pacemaker pulse generators and transvenous leads were removed from service. We evaluated the causes and major adverse clinical events associated with device end-of-service life behavior and how they were detected and managed. METHODS: Pulse generator and lead data were entered prospectively using a web-based format. Normal battery depletion was signified by the elective replacement indicator appearing >3 years after implant. Lead failure was a device defect causing pacing, sensing, or fixation malfunction, high threshold, or abnormal impedance. Major adverse clinical events were death, angina, heart failure, syncope, and perioperative surgical complications. RESULTS: From 1998 to 2006, 2,652 pulse generator and 615 leads were removed from service. The average pulse generator was implanted for 7.3 +/- 3.1 years (range <1 day to 26 years). The majority of pulse generators (n = 2,317 [87%]) were replaced for normal battery depletion. Severe and accelerated battery depletion, manufacturers' advisories, and electronic or connector defects accounted for 13% of pulse generator removals. The proportion of pulse generators removed from service as a result of manufacturers' advisories, electronic failure, and housing defects were 4%, 2%, and 1%, respectively. Models with rate response capability had shorter battery longevities than those without rate response capability. Major adverse clinical events due to pulse generator end-of-service life behavior were related to electronic and connector defects, and both normal and severe battery depletion. Median time to lead failure was 7.2 +/- 5.2 years. Insulation defects caused the majority of lead failures, and most of these leads used polyurethane materials. Lead failure was associated with a 16% incidence of major adverse clinical events. No major adverse clinical events occurred when impending lead failure was detected at routine follow-up. Lead extraction was associated with a 5.6% complication rate, including one death. CONCLUSION: Overall pulse generator performance was satisfactory. Differences in battery longevity were observed among models. In some patients, elective replacement indicators signifying normal battery depletion resulted in major adverse clinical events. Pacemaker follow-up effectively identified pulse generator end-of-service life and often detected impending lead failure, thus avoiding major adverse clinical events. Long-term studies are needed to assess chronic lead performance so that appropriate clinical management strategies, including recommendations for lead extraction, can be developed.