Bernd Lemke

Investigation of a novel algorithm for synchronized left-ventricular pacing and ambulatory optimization of cardiac resynchronization therapy: Results of the adaptive CRT trial

BACKGROUND In patients with sinus rhythm and normal atrioventricular conduction, pacing only the left ventricle with appropriate atrioventricular delays can result in superior left ventricular and right ventricular function compared with standard biventricular (BiV) pacing. OBJECTIVE To evaluate a novel adaptive cardiac resynchronization therapy ((aCRT) algorithm for CRT pacing that provides automatic ambulatory selection between synchronized left ventricular or BiV pacing with dynamic optimization of atrioventricular and interventricular delays. METHODS Patients (n = 522) indicated for a CRT-defibrillator were randomized to aCRT vs echo-optimized BiV pacing (Echo) in a 2:1 ratio and followed at 1-, 3-, and 6-month postrandomization. RESULTS The study met all 3 noninferiority primary objectives: (1) the percentage of aCRT patients who improved in their clinical composite score at 6 months was at least as high in the aCRT arm as in the Echo arm (73.6% vs 72.5%, with a noninferiority margin of 12%; P = .0007); (2) aCRT and echo-optimized settings resulted in similar cardiac performance, as demonstrated by a high concordance correlation coefficient between aortic velocity time integrals at aCRT and Echo settings at randomization (concordance correlation coefficient = 0.93; 95% confidence interval 0.91-0.94) and at 6-month postrandomization (concordance correlation coefficient = 0.90; 95% confidence interval 0.87-0.92); and (3) aCRT did not result in inappropriate device settings. There were no significant differences between the arms with respect to heart failure events or ventricular arrhythmia episodes. Secondary end points showed similar benefit, and right-ventricular pacing was reduced by 44% in the aCRT arm. CONCLUSIONS The aCRT algorithm is safe and at least as effective as BiV pacing with comprehensive echocardiographic optimization.

Saline-irrigated, cooled-tip radiofrequency ablation is an effective technique to perform the maze procedure.

BACKGROUND We evaluated the effectiveness of the saline-irrigated-cooled-tip-radiofrequency ablation (SICTRA) to produce linear intraatrial lesions. METHODS Thirty patients with chronic atrial fibrillation and mitral valve disease were consecutively randomized to have mitral valve operation either with a Maze procedure (group A) or without (group B). Intraatrial linear lesions were made with an SICTRA catheter (20 to 32 W; 200 to 320 mL/h saline). An echocardiography and 24-hour electrocardiogram were obtained 12 months postoperatively. RESULTS The cumulative frequencies of sinus rhythm in group A and B were 0.80 and 0.27 (p < 0.01). Restored biatrial contraction was present in 66.7% (6 of 9) of the group A patients in sinus rhythm. One patient from each group received a permanent pacemaker because of bradycardia. A fatal renal bleeding and mediastinitis occurred in 2 group A patients, 6 weeks postoperatively. One group A patient had sudden cardiac death at home, 4 months after operation. One patient from each group had lethal respiratory failure, 7 and 10 months after operation. Survival after 12 months for group A and B was 73% and 93% (p = 0.131). CONCLUSIONS The SICTRA appeared to be an effective technique to perform the Maze procedure.

Left atrial versus bi-atrial maze operation using intraoperatively cooled-tip radiofrequency ablation in patients undergoing open-heart surgery: Safety and efficacy

OBJECTIVES We sought to determine whether limited left atrial Maze surgery encircling each of the pulmonary veins, using cooled-tip radiofrequency (RF) ablation, is as effective as the bi-atrial approach? BACKGROUND The original Cox/Maze operation effectively restores sinus rhythm (SR) in patients with atrial fibrillation (AF). Ablation procedures aimed at eliminating pulmonary vein foci have produced promising short-term success. METHODS This was a prospective analysis of patients with chronic AF undergoing open-heart surgery in addition to the Maze operation, using intraoperatively cooled-tip RF ablation either in the left atrium alone (group A) or in both atria (group B). RESULTS Patients in group A (n = 21) and group B (n = 49) did not differ in terms of their baseline characteristics. Concomitant open-heart surgical procedures included mitral valve replacement (3 vs. 25), mitral valve plasty (0 vs. 2), mitral and aortic valve replacement (1 vs. 1), aortic valve replacement (4 vs. 6) and coronary artery bypass grafting (13 vs. 15) in groups A and B, respectively. Follow-up ranged from 1 to 50 months. The overall cumulative rates of SR were 82% in group A and 75% in group B, without a statistically significant difference (p = 0.571). Bi-atrial contraction was revealed in 92.3% of patients in SR in group A and in 79.2% in group B. The cumulative survival rates were 90.5% in group A and 77.9% in group B (p = 0.880). CONCLUSIONS A left or bi-atrial Maze operation using intraoperatively cooled-tip RF ablation can safely be combined with open-heart surgery. A left atrial Maze procedure seems to be as effective as the bi-atrial procedure and restores SR in 82% of patients.

Prevalence, Characteristics and Clinical Implications of Regular Atrial Tachyarrhythmias in Patients With Atrial Fibrillation: Insights From a Study Using a New Implantable Device

OBJECTIVES This study prospectively analyzed atrial tachyarrhythmia (AT) organization and antitachycardia pacing (ATP) success in patients with an implanted device for AT therapy. BACKGROUND In patients with atrial fibrillation (AF), the incidence of regular, slow ATs amendable by ATP is unknown. METHODS Forty patients with previously documented AT (70% with AF) received a new pacemaker with atrial electrogram (AEG) storage and atrial ATP capabilities for standard pacing indications. The AEGs acquired during the first month (study phase 1) were classified into high (type I), intermediate (type II) and low (type III) degrees of organization. Atrial ATP was then activated, and treated AT episodes were retrieved three and six months after implantation (study phase 2). RESULTS Of 824 AEGs retrieved before ATP activation (study phase 1), 351 (43%) were classified as type 1, 47% as type II and 10% as type III. Episodes of AT starting as type I (35%) and type II or III (65%) maintained their type over 1 min in 73%. All patients with an exclusive history of AF also showed type I AEGs. In 361 subsequently treated AT episodes (study phase 2), ATP was successful in 62% of type I and 34% of type II episodes, but not in type III (p < 0.0001). CONCLUSIONS The majority of patients with a history of AF show not only disorganized but also highly organized AT episodes, which can be successfully terminated by ATP.

Clinical outcomes with synchronized left ventricular pacing: analysis of the adaptive CRT trial.

BACKGROUND Acute studies have suggested that left ventricular pacing (LVP) may have benefits over biventricular pacing (BVP). The adaptive cardiac resynchronization therapy (aCRT) algorithm provides LVP synchronized to produce fusion with the intrinsic activation when the intrinsic atrioventricular (AV) interval is normal. The randomized double-blind adaptive cardiac resynchronization therapy trial demonstrated noninferiority of the aCRT algorithm compared to echocardiography-optimized BVP (control). OBJECTIVE To examine whether synchronized LVP (sLVP) resulted in better clinical outcomes. METHODS First, stratification by percent sLVP (%sLVP) and multivariate Cox proportional hazards model was used to assess the relationship between %sLVP and clinical outcomes. Second, outcomes were compared between patients in the aCRT arm (n = 318) and control patients (n = 160) stratified by intrinsic AV interval at randomization. RESULTS In the aCRT arm, %sLVP ≥50% (n = 142) was independently associated with a decreased risk of death or heart failure hospitalization (hazard ratio 0.49; 95% confidence interval 0.28-0.85; P = .012) compared with %sLVP <50% (n = 172). A greater proportion of patients with %sLVP ≥50% improved in Packers clinical composite score at 6-month (82% vs. 68%; P = .002) and 12-month (80% vs. 62%; P = .0006) follow-ups compared to controls. In the subgroup with normal AV (n = 241), there was a lower risk of death or heart failure hospitalization (hazard ratio 0.52; 95% confidence interval 0.27-0.98; P = .044) with the aCRT algorithm. A greater proportion of patients in the aCRT arm improved in the clinical composite score at 6-month (81% vs. 69%; P = .041) and 12-month (77% vs. 66%; P = .076) follow-ups compared to controls. CONCLUSIONS Higher %sLVP was independently associated with superior clinical outcomes. In patients with normal AV conduction, the aCRT algorithm provided mostly sLVP and demonstrated better clinical outcomes compared to echocardiography-optimized BVP.

The Influence of Left Ventricular Ejection Fraction on the Effectiveness of Cardiac Resynchronization Therapy MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy)

OBJECTIVES The aim of this study was to evaluate the relationship between left ventricular (LV) ejection fraction and clinical outcome to cardiac resynchronization therapy (CRT) in mild heart failure patients enrolled in MADIT-CRT [corrected]. BACKGROUND Left ventricular ejection fraction (LVEF) is a surrogate marker of heart failure (HF) status and associated risk. Data on the effectiveness of cardiac resynchronization therapy with defibrillator (CRT-D) in patients with mild HF and better LVEF are limited. METHODS In the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) study, the echocardiography core laboratory assessed baseline LVEF independent of the enrolling centers and identified a range of LVEFs, including those >30% (i.e., beyond the eligibility criteria). Echocardiographic response with CRT, defined as percent change in left ventricular end-diastolic volume (LVEDV), was analyzed in 3 prespecified LVEF groups: >30%, 26% to 30%, and ≤25%. The primary endpoint was HF or death. Secondary endpoint included all-cause mortality. RESULTS LVEF was evaluated in 1,809 study patients. There were 696 (38%) patients with LVEF >30% (in the range of 30.1% to 45.3%); 914 patients (50.5%) with LVEF 26% to 30%; and 199 patients with LVEF ≤25% (11%). The mean reduction in LVEDV with CRT-D therapy at the 1-year follow-up was directly related to increasing LVEF (LVEF >30%: 22.3%; LVEF 26% to 30%: 20.1%; and LVEF ≤25%: 18.7% reduction, respectively [p = 0.001]). CRT-D treatment similarly reduced the risk of HF/death in patients with LVEF >30% (hazard ratio [HR]: = 0.56 [95% confidence interval (CI): 0.39 to 0.82], p = 0.003), LVEF 26% to 30% (HR: 0.67: [95% CI: 0.50 to 0.90], p = 0.007), and LVEF ≤25% (HR: 0.57 [95% CI: 0.35 to 0.95], p = 0.03; all p values for LVEF-by-treatment interactions >0.1). CONCLUSIONS In MADIT-CRT, the clinical benefit of CRT was evident regardless of baseline LVEF, including those with LVEF >30%, whereas the echocardiographic response was increased with increasing LVEF, indicating that CRT might benefit patients with better LVEF. (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy [MADIT-CRT]; NCT00180271).

Atrial Pacing in the Prevention of Paroxysmal Atrial Fibrillation: First Results of a New Combined Algorithm

Pacing algorithms for prevention of atrial tachyarrhythmia (AT) are under clinical evaluation. The present study prospectively evaluated the efficacy of three simultaneously active algorithms for AT prevention and aimed at identifying patients in whom atrial preventive pacing (APP) may be particularly successful. Methods: In 31 patients with conventional pacing indications and paroxysmal AT, a DDDRP pacing system was implanted, which stores 35 AT episodes with atrial electrograms and marker annotations. Counters and stored AT episodes were retrieved 30 days after implant. APP algorithms (atrial preference pacing, atrial rate stabilization, postmode switching overdrive) were activated. Counters and stored AT episodes were again retrieved 60 days later. The number and duration of AT episodes was measured. Several clinical variables were examined with respect to their ability to identify candidates for APP. Results: During APP, the mean number of AT episodes/patient/day decreased from 7.67 to 1.68 (P = 0.04). However, time in AT was not significantly reduced (9.45% versus 10.41%). APP decreased the number of episodes/day in 11 patients and increased it in 9 patients. No clinical parameters predicting APP success was identified. Conclusions: APP using three algorithms significantly reduced the mean number of AT episodes/patient/day. However, the time during which patients were in AT was not reduced. No clinical variable predicted the success or failure of APP.

Catheter Ablation of Electrical Storm in a Collaborative Hospital Network

An electrical storm (ES) is defined as multiple ventricular arrhythmia episodes leading to implantable cardioverter defibrillator interventions. Although conventional rhythm stabilization might be of help acutely, ES involves high mortality and morbidity. We evaluated the effect of catheter ablation strategies in the setting of an interhospital collaborative network on the recurrence of ventricular arrhythmia episodes and mortality in patients with ES. Consecutive patients presenting for invasive treatment of ES from December 2007 to December 2009 were included. All patients underwent catheter ablation of ventricular arrhythmia. The strategies were adapted to the individual cardiac pathologic features. The follow-up examination constituted periodic implantable cardioverter defibrillator interrogation. A total of 32 patients were included. Of the 32 patients, 29 (91%) had monomorphic ventricular tachycardia and 3 ventricular fibrillation. The mean number of implantable cardioverter defibrillator-treated episodes within 7 days before ablation was 16 ± 11. Of the 32 patients, 27 underwent ablation within 24 hours after admission, and 5 underwent acute ablation within 8 hours. In 3 patients, epicardial ablation was performed. In all but 2 patients (6%), the clinical arrhythmia was successfully ablated. During a median follow-up of 15 months, 10 patients (31%) had recurrences of sustained ventricular arrhythmia, including 2 patients (6%) with recurrent ES. Three patients (9%) died during the follow-up period. In conclusion, catheter ablation effectively suppressed ventricular arrhythmia midterm recurrences in patients presenting with ES. Catheter ablation is complex in these severely sick patients. The recurrence rate of ventricular arrhythmia appears to be 31% and the mortality rate to be 9%. Collaborative hospital networks to increase the prompt availability of ES ablation might help to optimize the ES outcome.

A novel algorithm for individualized cardiac resynchronization therapy: Rationale and design of the adaptive cardiac resynchronization therapy trial

BACKGROUND The magnitude of benefit of cardiac resynchronization therapy (CRT) varies significantly among its recipients; approximately 30% of CRT patients do not report clinical improvement. Optimization of CRT pacing parameters can further improve cardiac function, both acutely and chronically. Echocardiographic optimization is used in clinical practice, but it is time and resource consuming. In addition, optimal settings at rest may change later with activity or cardiac remodeling. The adaptive CRT (aCRT) algorithm was designed to provide automatic ambulatory adjustment of CRT pacing configuration (left ventricular or biventricular pacing) and device delays based on periodic measurement of electrical conduction intervals. METHODS The aCRT algorithm is currently undergoing evaluation in a prospective, randomized, double-blinded, worldwide clinical trial. The trial enrolled 522 patients, who satisfied standard clinical indications for a CRT device. Within 2 weeks after the implant, the patients were randomized to aCRT versus echo-optimized biventricular pacing (Echo) settings in 2:1 ratio and followed up at 1-, 3-, 6-, and 12-month postrandomization. The noninferiority primary trial objectives at 6-month postrandomization are to demonstrate that (a) the percentage of aCRT patients who improved in their clinical composite score is at least as high as the percentage of Echo patients; (b) cardiac performance as assessed by echocardiography is similar when using aCRT settings versus echo-optimized settings; and (c) aCRT does not result in inappropriate device settings. First and last patient enrollments occurred in November 2009 and December 2010, respectively. CONCLUSIONS The safety and efficacy of the aCRT algorithm will be evaluated in this ongoing clinical trial.

Substrate-modification using electroanatomical mapping in sinus rhythm to treat ventricular tachycardia in patients with ischemic cardiomyopathy.

Ventrikuläre Tachykardien (VT) bei Patienten mit ischämischer Kardiomyopathie (KHK) sind mittels konventioneller Katheterablation häufig nur schwer behandelbar. Bei 25 konsekutiven Patienten mit häufigen symptomatischen medikamenten-refraktären VTs (rezidivierende Schockabgaben des ICD) auf dem Boden einer KHK (EF 37±12%) wurde ein linksventrikuläres (LV) elektroanatomisches Narbenmapping (Biosense Webster CARTO™) durchgeführt. Narbengewebe wurde als bipolare Voltage <0.5mV definiert. Vor Ablation wurde mittels Ventrikelstimulation die Anzahl der induzierbaren monomorphen VTs dokumentiert. Die grobe Lokalisation der Zielregion erfolgte mittels „pace-mapping“ und lineare Katheterablationen (8 mm Katheterspitze, 70 Watt, 70 °C) wurden basierend auf den zugrundeliegenden Narbenarealen in einer vermuteten Isthmus-Region durchgeführt. Der Follow-Up erfolgte klinisch sowie mittels ICD-Holter-Aufzeichnungen und EKG- und Langzeit-EKG-Untersuchungen. Im Mittel ließen sich pro Patient 2,4±0,8 unterschiedliche VT-Morphologien induzieren. Die klinische VT konnte in 23/25 (92%) durch lineare Ablation eliminiert werden. Bei 16/23 Patienten (70%) konnten durch Ablation (1,7(±1,0) Ablationslinien pro Patient) alle vorher auslösbaren VTs eliminiert werden (Kompletterfolg). Bei den restlichen 7 Patienten (30%) ließen sich nach erfolgreicher Ablation der klinischen VT weitere VTs auslösen, welche nicht abladiert werden konnten (Teilerfolg). Es traten keine Prozedur-bezogenen Komplikationen auf. Während des Follow-up (10±4 Monate; 3 bis 18) traten bei 4 Patienten (16%) (3 Patienten mit initialem Teilerfolg und 1 Patient mit komplettem Ablationserfolg) neue VTs auf (Zykluslänge kürzer als die klinisch, abladierte VT). Während es keinen Unterschied in Basis-Parametern der Patienten mit Kompletterfolg verglichen mit Patienten mit Teilerfolg gab zeigte sich ein statistisch signifikanter Unterschied bezogen auf die mittelfristige Ryhthmuserfolgsrate (93 vs. 48% Arrhythmiefreiheit, p=0.03). Ischämische VTs können sicher und mit einer Effektivität von über 90% basierend auf elektroanatomischem Narbenmapping während Sinusrhythmus linear abladiert werden. Bei 70% der Patienten können so durch lineare Ablation zwischen elektrisch stummen Hindernissen alle induzierbaren VTs mit hohem mittelfristigem Erfolg abladiert werden. Bei Patienten mit nur Teil-Ablationserfolg (nach Ablation weiterhin VTs auslösbar) traten in über 50% neue VTs während der mittelfristigen Nachsorge (2 bis 6 Monate) auf. The treatment especially of frequent ischemic VT remains a challenge for medical and catheter ablation procedures. We evaluated the efficacy of a substrate-based procedure to eliminate clinical VTs in this patient collective. In 25 consecutive patients (ejection fraction 37±12%) with frequent symptomatic medically refractory ischemic VT (with recurrent ICD-shocks), left ventricular anatomic scar mapping (Biosense Webster CARTO™) was performed in order to modify the underlying myocardial substrate. Scar tissue was identified as having bipolar voltages <0.5 mV. Prior to the procedure an electrophysiological study (EPS) to determine number and morphology of inducible VTs was performed. Linear ablation procedures (8 mm tip, 70 Watts, 70 °C) were based on the findings of scar areas and proximity to anatomic obstacles. Correct location of ablation was documented by similarity of the morphology during pace-mapping. Follow-up included clinical evaluation, ICD holter interrogation plus holter ECG recording. The clinical VT was eliminated by linear catheter ablation in 23/25 patients (92%) (failure due to unstable catheter position during transaortic approach in 1 and epicardial origin of VT in 1). In 16/23 patients (70%) complete success could be produced with no VT inducible after substrate modification (1.7±1.0 lines per patient). In 7 patients (30%) only partial success was documented with further VTs inducible after ablation. No procedure-related complications occurred. During follow- up (10±4 months) 4 patients (16%) had occurrences of new VTs documented on ICD holter (3 patients with initially partial success and 1 with initial complete success) differing in cycle length and morphology from the clinical VT. Comparing patients with complete to those with partial success, there was a statistically significant difference of 93 vs. 48% freedom of arrhythmia (p=0.03). No difference in regard to baseline characteristics existed in these two patient subgroups. Ablation of frequent VTs in patients with ischemic cardiomyopathy can be safely performed using electro-anatomic scar mapping with a high procedural success of 90%. Based on the morphological findings, linear ablation can suppress inducibility of all VTs in 70% of patients with high mid-term efficacy. In patients with only partial ablation success, non-clinical VTs often occur early during follow-up (50%).