Outcome Studies with Device Therapy in Patients with Heart Failure

Device Therapy for Heart Failure. Heart failure is a common debilitating condition for which pharmacologic therapy thus far has provided only partial relief. Despite, and sometimes because of, medical therapy, the overall prognosis remains poor, with high rates of sudden death and death from progressive heart failure. Device‐based therapies offer considerable promise for relief of symptoms and for improving prognosis. It is clear that implantable defibrillators should be considered for patients with heart failure who have been resuscitated from ventricular fibrillation or sustained ventricular tachycardia. Several large studies currently are investigating the effects of implantable defibrillators on total mortality in patients with major left ventricular systolic dysfunction but without other risk factors for sudden death. Cardiac resynchronization is a promising new therapy that may relieve the symptoms of heart failure in appropriately selected patients resistant to optimal pharmacologic therapy. Two large trials (CARE‐HF and COMPANION) currently are investigating the effects of cardiac resynchronization therapy (CRT) on morbidity and mortality. It is important that those involved in these trials enroll patients quickly and minimize device implantation into patients who have not been assigned this therapy (cross‐overs). Overenthusiasm for the benefits that doctors believe devices might bring could destroy the future basis for our clinical practice, denying future generations of patients and the doctors themselves access to what they believe to be effective treatments.     

Implantation Feasibility,Procedure‐Related Adverse Events and Lead Performance During 1‐Year Follow‐Up in Patients Undergoing Triple‐Site Cardiac Resynchronization Therapy: A Substudy of TRUST CRT Randomized Trial

Feasibility and Safety of Triple‐Site CRT . Introduction: This substudy was to assess implantation feasibility and long‐term safety of triple‐site resynchronization therapy (CRT) in a series of consecutive patients included in a randomized trial. Methods and results: One hundred consecutive patients enrolled into Triple‐Site Versus Standard Cardiac Resynchronization Therapy Randomized Trial were analyzed. Eligibility criteria included NYHA class III‐IV, sinus rhythm, QRS ≥ 120 milliseconds, left ventricular ejection fraction ≤35%, and significant mechanical dyssynchrony. Patients were randomized in a 1:1 ratio to conventional or triple‐site CRT with defibrillator–cardioverter. After 12 months of resynchronization 30% of patients with conventional resynchronization and 12.5% with triple‐site CRT were in NYHA functional class III or IV (P < 0.05). Implantation of triple‐site systems was significantly longer (median 125 minutes vs 96 minutes; P < 0.001), with higher fluoroscopic exposure, especially in patients with very enlarged left ventricle or pulmonary hypertension. Implantation success‐rate was similar in the triple‐site and conventional group (94% vs 98%; P = NS); however, additional techniques had to be used in a greater proportion of the triple‐site patients (33.3% vs 16%; P < 0.05). Long‐term lead performance tests revealed significantly higher pacing threshold and lower impedance in the triple‐site group. The 1‐year incidence of serious, CRT‐related adverse events was similar in triple‐site and conventional group (20.8% vs 30%; P = NS). Conclusions: Triple‐site CRT is associated with more pronounced functional improvement than standard resynchronization. This form of pacing is equally safe and feasible as the conventional CRT. However, triple‐site procedure is more time‐consuming, associated with higher radiation exposure and the need to use additional techniques. Triple‐site resynchronization is associated with less favorable electrical lead characteristics. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1228–1236, November 2012)     

QRS Axis and the Benefit of Cardiac Resynchronization Therapy in Patients with Mildly Symptomatic Heart Failure Enrolled in MADIT‐CRT

Cardiac Resynchronization Therapy and QRS Axis . Background: Mildly symptomatic heart failure (HF) patients derive substantial clinical benefit from cardiac resynchronization therapy with defibrillator (CRT‐D) as shown in MADIT‐CRT. The presence of QRS axis deviation may influence response to CRT‐D. The objective of this study was to determine whether QRS axis deviation will be associated with differential benefit from CRT‐D. Methods : Baseline electrocardiograms of 1,820 patients from MADIT‐CRT were evaluated for left axis deviation (LAD: quantitative QRS axis ‐30 to ‐90) or right axis deviation (RAD: QRS axis 90–180) in left bundle branch block (LBBB), right bundle branch block (RBBB), and nonspecific interventricular conduction delay QRS morphologies. The primary endpoints were the first occurrence of a HF event or death and the separate occurrence of all‐cause mortality as in MADIT‐CRT. Results: Among LBBB patients, those with LAD had a higher risk of primary events at 2 years than non‐LAD patients (20% vs 16%; P = 0.024). The same was observed among RBBB patients (20% vs 10%; P = 0.05) but not in IVCD patients (22% vs 23%; P = NS). RAD did not convey any increased risk of the primary combined endpoint in any QRS morphology subgroup. When analyzing the benefit of CRT‐D in the non‐LBBB subgroups, there was no significant difference in hazard ratios for CRT‐D versus ICD for either LAD or RAD. However, LBBB patients without LAD showed a trend toward greater benefit from CRT therapy than LBBB patients with LAD (HR for no LAD: 0.37, 95% CI: 0.26–0.53 and with LAD: 0.54, 95% CI: 0.36–0.79; P value for interaction = 0.18). Conclusions: LAD in non‐LBBB patients (RBBB or IVCD) is not associated with an increased benefit from CRT. In LBBB patients, those without LAD seem to benefit more from CRT‐D than those with LAD. (J Cardiovasc Electrophysiol, Vol. 24, pp. 442‐448, April 2013)     

Real‐World Data on the Lifespan of Implantable Cardioverter‐Defibrillators Depending on Manufacturers and the Amount of Ventricular Pacing

Real‐World Data on the Lifespan of ICDs Introduction: Implantable cardioverter‐defibrillator (ICD) longevity is crucial for both patients and public health systems because it determines the number of surgical ICD replacements, which can generally be considered an additional risk factor for complications, and the cost‐effectiveness of ICD therapy. Our objective was to obtain insight into the “real‐world” longevities of implantable cardioverter‐defibrillators, which quite often differ from those stated in the manufacturers’ declarations. Methods and Results: On the basis of a prospective database, we analyzed all ICD implantations performed in our hospital from June 1988 to June 2009. We studied 980 patients (follow‐up 58 ± 51 months) with 1,502 ICDs and all respective data until August 2010. We compared the percentage of still operating ICDs at different points in time in relation to manufacturers, types of device (single chamber 623, dual chamber 588, cardiac resynchronization therapy ICDs [CRT‐D] 291), and amount of right ventricular pacing (VP). We found distinct differences between the mean lifespans of ICDs of different manufacturers (Biotronik 4.3 years, Sorin 4.5 years, Guidant/Boston Scientific 4.7 years, St. Jude Medical 5 years, Medtronic 5.8 years). CRT‐D devices (hazard ratio [HR] 1.778, P = 0.0005) were associated with an elevated annual relative risk for device replacement while a decrease in the proportion of VP (HR 0.934 for each 10% decrease in VP, P < 0.0001) and Medtronic ICDs were associated with a reduced risk of device replacement (HR 0.544, P < 0.0001). Conclusion: CRT‐Ds and an elevated percentage of VP are associated with a significantly elevated risk for device replacement, while Medtronic ICDs showed the longest lifespans. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1336‐1342, December 2012)     

The right ventricular septum presents the optimum site for maximal electrical separation during left ventricular pacing

Septum Presents the Optimum Site for Maximal Electrical Separation. Cardiac resynchronization therapy (CRT) benefits selected heart failure (HF) patients. The optimal placement of the right ventricle (RV) lead during biventricular pacing has not been assessed. Greater electrical separation (ES) between left ventricle (LV) and RV leads has been associated with better clinical outcomes. The site of maximal electrical separation(MES) in the RV is unknown. Methods: Prospective study of 50 CRT patients. The LV lead was placed in a postero‐lateral branch of the coronary sinus. ES was recorded at 6 sites within the RV during LV pacing at 600 milliseconds cycle length (CL). The median ES was recorded with a roving deflectable catheter at the RV outflow tract (RVOT), high septum, inflow septum, mid‐septum, apical septum and apex. Results: Mean age was 67 ± 7 years, 39 were male (78%). Thirty had ischemic etiology (60%). Mean left ventricular ejection fraction (LVEF) was 25 ± 7%, QRS duration pre and post was 165 ± 26 milliseconds and 138.5 ± 15.6 milliseconds (P < 0.001). Mapping ES showed a difference between 20 and 50 milliseconds distributed across the RV in the majority of patients (40/49). However, 7 subjects demonstrated delay distribution of between 50 and 82 milliseconds. ES was significant greater in the RV mid‐septum (161.2 ± 23.7 milliseconds) compared with RVOT (154.1 ± 20.8 milliseconds) and apex (148.0 ± 25.5 milliseconds; P < 0.001). The site of Maximal ES was most commonly found at the mid‐septum (40 patients, 80%) and only rarely at the RVOT (5, 10%) and apex (5, 10%; P < 0.01). Conclusion: MES was observed most commonly at the RV septum and rarely at the RV apex. Better correction of electrical and mechanical dyssynchrony by CRT may be achieved by placing the RV lead in a site outside of the apex in the majority of patients. Clinical studies exploring RV septal pacing in CRT seem warranted.     

A Randomized‐Controlled Pilot Study Comparing ICD Implantation with and Without Intraoperative Defibrillation Testing in Patients with Heart Failure and Severe Left Ventricular Dysfunction: A Substudy of the RAFT Trial

Comparing ICD Implantation with and Without Intraoperative Defibrillation Testing. Introduction: The need to perform defibrillation testing (DT) at the time of implantable cardioverter defibrillator (ICD) insertion is controversial. In the absence of randomized trials, some regions now perform more than half of ICD implants without DT. Methods: During the last year of enrolment in the Resynchronization for Ambulatory Heart Failure Trial, a substudy randomized patients to ICD implantation with versus without DT. Results: Among 252 patients screened, 145 were enrolled; 75 randomized to DT and 70 to no DT. Patients were similar in terms of age (65.9 ± 9.3 years vs 67.9 ± 8.9 years); LVEF (24.7 ± 4.6% vs 23.6 ± 4.6%), QRS width (154.8 ± 23.5 vs 155.8 ± 23.6 ms), and history of atrial fibrillation (5% vs 6%). All 68 patients in the DT arm tested according to the protocol achieved a successful DT (≤25 J); 96% without requiring any system modification. No patient experienced perioperative stroke, myocardial infarction, heart failure (HF), intubation or unplanned ICU stay. The length of hospital stay was not prolonged in the DT group: 20.2 ± 26.3 hours versus 21.3 ± 23.0 hours, P = 0.79. One patient in the DT arm had a failed appropriate shock and no patient suffered an arrhythmic death. The composite of HF hospitalization or all‐cause mortality occurred in 10% of patients in the no‐DT arm and 19% of patients in the DT arm (HR = 0.53, 95% CI: 0.21–1.31, P = 0.14). Conclusions: In this randomized trial, perioperative complications, failed appropriate shocks, and arrhythmic death were all uncommon regardless of DT. There was a nonsignificant increase in the risk of death or HF hospitalization with DT. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1313‐1316, December 2012)     

Atrial Pacing Therapies for Prevention of Atrial Fibrillation in Patients with Implantable Defibrillators

Atrial fibrillation (AF), atrial flutter and atrial tachycardia (AT) occur frequently in patients following implantation of an implantable cardioverter defibrillator (ICD) for the treatment of ventricular tachyarrhythmias. Some new generation ICDs have incorporated atrial antitachycardia pacing therapy (ATP) and atrial pacing algorithms designed specifically for the prevention of AF. In the GEM III AT clinical evaluation, atrial ATP efficacy for termination of AF and AT was assessed. Overall ATP efficacy for AF/AT, based on device classification, was 40% when adjusted using the Generalized Estimating Equations to account for correlated data that arises from utilizing multiple episodes in some patients. However, many episodes of AF/AT were noted to terminate within 10 minutes of onset. Applying a more conservative definition of efficacy, termination within 20 sec of delivery of the last atrial ATP, efficacy for termination of AF/AT was 26%. 50 Hz burst pacing was shown to have minimal efficacy for termination of AF and modest incremental benefit following ramp or burst pacing therapies for AT. These observations provide a more realistic expectation of the value of atrial ATP in the ICD population with AF. Atrial ATP terminates some episodes of AT but previously reported efficacy rates of 40-50% are exaggerated and in part reflect spontaneous terminations of some AF/AT episodes.     

心脏同步化治疗慢性心力衰竭疗效及临床经验总结

目的总结心脏同步化起搏治疗慢性心力衰竭的疗效及临床经验。方法回顾性分析接受再同步化治疗的26例慢性心力衰竭伴心室内传导延迟患者的临床资料,着重分析再同步化治疗的方法和疗效。结果患者均接受心脏再同步化治疗,年龄（57.0±11.6）岁,男22例（84.6%,22/26）,其中再同步化转复除颤器16例（62%,16/26）,非缺血性心肌病22例（85%,22/26）,9例（35%,9/26）有慢性房性心律失常,2例需外科植入左心室心外膜电极。心脏再同步化治疗后QRS波时限由（161±29）ms缩短为（137±15）ms,差异有统计学意义（P≤0.01）;患者心功能均有明显改善,心功能分级比治疗前降低,差异有统计学意义[（1.9±0.9）级vs.（3.2±0.6）级,P≤0.01];射血分数比治疗前提高,差异有统计学意义（34.0%±13.3%vs.24.9%±6.8%,P≤0.01）。6分钟步行距离、血清脑钠肽浓度以及左心室舒张或收缩末内径均有显著改善（P≤0.05）。术后随访（2.5±1.7）年,7例（27%,7/26）死亡,其中2例心源性猝死。结论心脏同步化起搏治疗显著改善慢性心力衰竭患者心功能,逆转心肌重构,减低病死率。     

Postoperative Performance of the Quartet® Left Ventricular Heart Lead

Promote^® Q CRT‐D and Quartet^® LV Lead Study . Introduction: The Quartet^® left ventricular (LV) lead is the first with 4 pacing electrodes (tip and 3 rings) that enables pacing from 10 different pacing vectors. Postoperative performance of this lead was evaluated in a prospective, nonrandomized, multicenter IDE study. Methods: Patients with standard indications for CRT‐D were enrolled. Electrical performance and presence of phrenic nerve stimulation (PNS) were assessed during pacing from each of 10 vectors at predischarge (within 7 days), 1 month, and 3 months postimplant. Results: The Quartet LV lead was implanted successfully in 170 patients (95.5% implant success rate, 68 ± 11 years, 68.5% male, LVEF: 25 ± 7%, NYHA class III: 98.3% and class IV: 1.7%). Mean follow‐up was 4.7 ± 1.9 months. Capture threshold and impedance for each of the 10 LV lead pacing vectors remained stable during follow‐up. LV lead dislodgement occurred in 6 (3.5%) patients and PNS was observed in 23 (13.5%) patients. PNS was resolved noninvasively in all 23 (100%) patients, either by reprogramming to pace from the additional LV lead pacing vectors alone (13 pts, 56.5%), reprogramming to pace from the additional LV lead pacing vectors and reprogramming pacing output (4 pts, 17.4%), or by reprogramming pacing output alone (6 pts, 26.1%). Conclusions: The Quartet LV lead electrical performance was stable and was associated with a high implant success and low dislodgement rate during 3‐month follow‐up. In all patients with PNS, the 10 pacing vectors combined with reduced output programming enabled the elimination of PNS noninvasively. (J Cardiovasc Electrophysiol, Vol. 24, pp. 449‐456, April 2013)     

Optimizing Resynchronization Therapy: Can We Increase the Number of True Responders?

Cardiac resynchronization therapy is now considered a standard therapy for patients with cardiomyopathy, heart failure, and interventricular conduction delay. Despite the demonstrated benefits in multiple large-scale trials, there is a clear nonresponder rate. This brief review will address some of the issues associated with maximizing the benefit of biventricular pacing, and whether or not advances in programming of such devices will increase the number of true responders.     

Outcome of Right Ventricular Bifocal Pacing in Patients with Permanent Atrial Fibrillation and Severe Dilated Cardiomiopathy Due to Chagas Disease: Three Years of Follow-up

OBJECTIVES OF STUDY: Several studies have shown that heart failure may benefit from cardiac resynchronization therapy (CRT). Studies have demonstrated a beneficial effect of right ventricular (RV) bifocal pacing, using two leads at different positions, in similar patient populations. The aim was to evaluate this approach in Chagas disease patients who developed both severe dilated cardiomiopathy and chronic atrial fibrillation. METHODS: The study included 30 patients with a mean age of 52 +/- 6 years (16 male), who had atrioventricular block at functional class II or IV (NYHA). Patients underwent endocardial dual-chamber pacemaker implantation with two RV leads-one placed near the RV outflow tract and the other in the apex. Patients were examined by echocardiography, 24-hour Holter, and New York Heart Association (NYHA) class determination before and 3, 6, 12, 18, 24, and 36 months after CRT. RESULTS: Compared to the baseline, the left ventricular ejection fraction increased in the first month of CRT, the left ventricular end diastolic diameter decreased, all patients were downgraded to NYHA class I or II, and the incidence of ventricular arrhythmias decreased. However, these could not be maintained and worsened after 6 months CRT. There was a mortality rate of 43.3% during the first year, and only 23.3% of patients remained alive after 3 years. They underwent an electrophysiological study, which revealed complex arrhythmias justifying implantable cardioverter defibrillator (ICD) in six out of seven patients. CONCLUSION: The favorable effects of RV bifocal pacing could not be maintained beyond the first 6 months, likely due to the ventricular arrhythmias. Therefore, CRT combined with ICD from the outset may be recommended for this patient group.