Transvenous lead extraction of implantable cardioverter-defibrillators: A comprehensive outcome-and risk factor analysis.

BACKGROUND: Device complications, such as infection or lead dysfunction necessitating transvenous lead extraction (TLE) are continuously rising amongst patients with transvenous implantable-cardioverter-defibrillator (ICD). OBJECTIVES: Aim of this study was to characterize the procedural outcome and risk-factors of patients with indwelling 1- and 2-chamber ICD undergoing TLE. METHODS: We conducted a subgroup analysis of all ICD patients in the GALLERY (GermAn Laser Lead Extraction RegistrY) database. Predictors for procedural failure and all-cause mortality were assessed. RESULTS: We identified 842 patients with an ICD undergoing TLE with the mean age of 62.8 ± 13.8 years. A total number of 1610 leads were treated with lead dysfunction (48.5%) as leading indication for extraction, followed by device-related infection (45.4%). Lead-per-patient ratio was 1.91 ± 0.88 and 60.0% of patients had dual-coil defibrillator leads. Additional extraction tools, such as mechanical rotating dilator sheaths and snares were utilized in 6.5% of cases. Overall procedural complications occurred in 4.3% with 2.0% major complications and a procedure-related mortality of 0.8%. Clinical success rate was 97.9%. All-cause in-hospital mortality was 3.4%, with sepsis being the leading cause for mortality. Multivariate analysis revealed lead-age ≥10 years (OR:5.82, 95%CI:2.1-16.6; p = .001) as independent predictor for procedural failure. Systemic infection (OR:9.57, 95%CI:2.2-42.4; p < .001) and procedural complications (OR:8.0, 95%CI:2.8-23.3; p < .001) were identified as risk factors for all-cause mortality. CONCLUSIONS: TLE is safe and efficacious in patients with 1- and 2-chamber ICD. Although lead dysfunction is the leading indication for extraction, systemic device-related infection is the main driver of all-cause mortality for ICD patients undergoing TLE.

Laser lead extraction in octo- and nonagenarians. A subgroup analysis from the GALLERY registry.

INTRODUCTION: In an aging population with cardiac implantable electronic devices, an increasing number of octo- and even nonagenarians present for lead extraction procedures. Those patients are considered at increased risk for surgical procedures including lead extraction. Here, we investigated safety and efficacy of transvenous lead extraction in a large patient cohort of octo- and nonagenarians. METHODS AND RESULTS: A subgroup analysis of all patients aged ≥80 years (n = 499) in the German Laser Lead Extraction Registry (GALLERY) was performed. Outcomes were compared to the nonoctogenarians from the registry. Primary extraction method was Laser lead extraction, with additional use of mechanical rotational sheaths or femoral snares, if necessary. An analysis of patient- and device characteristics, as well as an assessment of predictors for adverse events via multivariate analyses was conducted. Mean patients age was 84.3 ± 3.7 years in the octogenarians group and 64.1 ± 12.4 years in the nonoctogenarians group. The median lead dwell time was 118.0 months (78; 167) and 92.0 months [60; 133], p < .001 in the octogenarians and nonoctogenarians group, respectively. Clinical procedural success rate was achieved in 97.6% of the cases in octogenarians and 97.9% in nonoctogenarians (p = .70). Overall complication rate was 4.4% in octogenarians and 4.3% in nonoctogenarians (0.91). In octogenarians procedure-related mortality was 0.8% and all-cause in-hospital mortality was 5.4%, while in nonoctogenarians, procedure related and all-cause in-hospital mortality were 0.5% and 3.1%, respectively. A body mass index (BMI) <20 kg/m2 , was the only statistically significant predictor for procedure-related complications in octogenarians, while systemic infection, BMI ≤20 kg/m2 , procedural complications and chronic kidney disease were predictors for in-hospital mortality. CONCLUSIONS: Laser lead extraction in octo- and nonagenarians is safe and effective. BMI ≤20 kg/m2 was the only statistically significant predictor for procedural complications. According to our data, advanced age should not be considered as contraindication for laser lead extraction.

Safety and Efficacy of Excimer Laser Powered Lead Extractions in Obese Patients: A GALLERY Subgroup Analysis.

BACKGROUND: The incidence of cardiac implantable electronic device (CIED)-related complications, as well as the prevalence of obesity, is rising worldwide. Transvenous laser lead extraction (LLE) has grown into a crucial therapeutic option for patients with CIED-related complications but the impact of obesity on LLE is not well understood. METHODS AND RESULTS: All patients (n = 2524) from the GermAn Laser Lead Extraction RegistrY (GALLERY) were stratified into five groups according to their body mass index (BMI, <18.5; 18.5-24.9; 25-29.9; 30-34.9; ≥35 kg/m2). Patients with a BMI ≥ 35.0 kg/m2 had the highest prevalence of arterial hypertension (84.2%, p < 0.001), chronic kidney disease (36.8%, p = 0.020) and diabetes mellitus (51.1%, p < 0.001). The rates for procedural minor (p = 0.684) and major complications (p = 0.498), as well as procedural success (p = 0.437), procedure-related (p = 0.533) and all-cause mortality (p = 0.333) were not different between groups. In obese patients (BMI ≥ 30 kg/m2), lead age ≥10 years was identified as a predictor of procedural failure (OR: 2.99; 95% CI: 1.06-8.45; p = 0.038). Lead age ≥10 years (OR: 3.25; 95% CI: 1,31-8.10; p = 0.011) and abandoned leads (OR: 3.08; 95% CI: 1.03-9.22; p = 0.044) were predictors of procedural complications, while patient age ≥75 years seemed protective (OR: 0.27; 95% CI: 0.08-0.93; p = 0.039). Systemic infection was the only predictor for all-cause mortality (OR: 17.68; 95% CI: 4.03-77.49; p < 0.001). CONCLUSIONS: LLE in obese patients is as safe and effective as in other weight classes, if performed in experienced high-volume centers. Systemic infection remains the main cause of in-hospital mortality in obese patients.

Transvenous lead extraction in patients with systemic cardiac device-related infection-Procedural outcome and risk prediction: A GALLERY subgroup analysis.

BACKGROUND: Transvenous lead extraction (TLE) has evolved as one of the most crucial treatment options for patients with cardiac device-related systemic infection (CDRSI). OBJECTIVE: The aim of this study was to characterize the procedural outcome and risk factors of patients with CDRSI undergoing TLE. METHODS: A subgroup analysis of patients with CDRSI of the GALLERY (GermAn Laser Lead Extraction RegistrY) database was performed. Predictors for complications, procedural failure, and all-cause mortality were evaluated. RESULTS: A total of 722 patients (28.6%) in the GALLERY had "systemic infection" as extraction indication. Patients with CDRSI were older (70.1 ± 12.2 years vs 67.3 ± 14.3 years; P < .001) and had more comorbidities than patients with local infections or noninfectious extraction indications. There were no differences in complete procedural success (90.6% vs 91.7%; P = .328) or major complications (2.5% vs 1.9%; P = .416) but increased procedure-related (1.4% vs 0.3%; P = .003) and all-cause in-hospital mortality (11.1% vs 0.6%; P < .001) for patients with CDRSI. Multivariate analyses revealed lead age ≥10 years as a predictor for procedural complications (odds ratio [OR] 3.23; 95% confidence interval [CI] 1.58-6.60; P = .001). Lead age ≥10 years (OR 2.57; 95% CI 1.03-6.46; P = .04) was also a predictor for procedural failure. We identified left ventricular ejection fraction <30% (OR 1.70; 95% CI 1.00-2.99; P = .049), age ≥75 years (OR 2.1; 95% CI 1.27-3.48; P = .004), chronic kidney disease (OR 1.92; 95% CI 1.17-3.14; P = .01), and overall procedural complications (OR 5.15; 95% CI 2.44-10.84; P < .001) as predictors for all-cause mortality. CONCLUSION: Patients with CDRSI undergoing TLE demonstrate an increased rate of all-cause in-hospital, as well as procedure-related mortality, despite having comparable procedural success rates. Given these data, it seems paramount to develop preventive strategies to detect and treat CDRSI in its earliest stages.

[Surgical basics of cardiac implantable electronic device implantation from skin incision through closure]. / Chirurgische Basics der Device-Implantation vom Hautschnitt bis zur Naht.

Implantation of pacemakers is generally considered a "minor intervention". Younger colleagues obtain their skills from experienced ones; ideally not just over the course of one or two interventions under surveillance but until a certain level of confidence is achieved. In Germany, certification is still optional. The German Cardiology Society (DSC, "Deutsche Gesellschaft für Kardiologie") provides expertise courses to obtain basic knowledge of pacemaker therapy; the GCS/GSCVS has been offering certification modules since 2013 to acquire fundamental knowledge from experts and basic technical skills by simulator training. The present article illustrates the major aspects of pacemaker implantation procedures and some avoidable pitfalls.

The GermAn Laser Lead Extraction RegistrY: GALLERY.

AIMS: The GermAn Laser Lead Extraction RegistrY: GALLERY is a retrospective, national multicentre registry, investigating the safety and efficacy of laser lead extraction procedures in Germany. METHODS AND RESULTS: Twenty-four German centres that are performing laser lead extraction have participated in the registry. All patients, treated with a laser lead extraction procedure between January 2013 and March 2017, were consecutively enrolled. Safety and efficacy of laser lead extraction were investigated. A total number of 2524 consecutive patients with 6117 leads were included into the registry. 5499 leads with a median lead dwell time of 96 (62-141) months were treated. The mean number of treated leads per patient was 2.18 ± 1.02. The clinical procedural success rate was 97.86% and the complete lead removal was observed in 94.85%. Additional extraction tools were used in 6.65% of cases. The rate of procedural failure was 2.14% with lead age ≥10 years being its only predictor. The overall complication rate was 4.32%, including 2.06% major and 2.26% minor complications. Procedure-related mortality was 0.55%. Female sex and the presence of abandoned leads were predictors for procedure-related complications. The all-cause in-hospital mortality was 3.56% with systemic infection being the strongest predictor, followed by age ≥75 years and chronic kidney disease. CONCLUSION: In the GALLERY, a high success- and low procedure-related complication rates have been demonstrated. In multivariate analysis, female sex and the presence of abandoned leads were predictors for procedure-related complications, while the presence of systemic infection, age ≥75 years, and chronic kidney disease were independent predictors for all-cause mortality.

Complications and Risk Assessment of 25 Years in Pediatric Pacing.

BACKGROUND: Children who require cardiac pacemaker implantation have presented a small patient sub-population since the breakthrough of this technology in the 1950s and 1960s. Their small bodies result in a technical challenge for the operating surgeon and put the patient at risk for a series of specific complications. Our study aims to analyze complications and to identify risk factors of endocardial and epicardial pacemaker systems in children. METHODS: All pacemaker-related operations in pediatric patients up to the age of 18 years from 1985 through 2010 were retrospectively evaluated. Demographic data including age, height, and weight were recorded. Idiopathic and postoperative dysrhythmias were analyzed separately. RESULTS: A total of 149 pacemaker operations were performed in 73 patients. Thirty-two patients did not have a previous cardiac operation. Indications for revision included box exchange, lead-related problems, pacemaker pocket complications, impaired left ventricular function, and pectoral muscle stimulation. Increased pacing thresholds occurred in 17.2% of the patients with epicardial leads compared with 2.9% in the endocardial group. Aside from threshold-related revision, lead problems are more common in the endocardial group (30.4% vs 17.2%). Venous thrombosis occurred in 13.7% of the patients (only endocardial), preferentially (25%) in the weight group less than 15 kg and in idiopathic patients (15.6% vs 10.5% with prior cardiac surgery). CONCLUSIONS: Cardiac pacing is particularly challenging in the pediatric patient population facing a large number of reoperations during their lifetime. The lack of clear superiority of either epicardial or endocardial pacing systems requires an individual concept.

Use of donors who have suffered cardiopulmonary arrest and resuscitation in lung transplantation.

OBJECTIVES: Shortage of donors is one of the major limitations in lung transplantation (LuTX) and an aggressive expansion of criteria for donor selection has been proposed. This study evaluates the outcome of recipients of pulmonary grafts coming from resuscitated donors when compared with recipients of non-resuscitated donors. METHODS: We retrospectively analyzed the donor and recipient charts of all double LuTX performed at our institution between 2000 and 2008 with regard to the performance of donor-cardiopulmonary resuscitation (CPR). RESULTS: Out of 186 eligible transplants, 22 patients (11.8%) received lungs from donors who have suffered cardiac arrest (CA) and subsequent CPR. Mean duration of CPR was 15.2 ± 11.3 min. Terminal laboratory profiles of CPR donors and non-CPR donors were similar as were ventilation time and paO(2)/FiO(2) ratio before organ harvesting or chest X-ray. CPR-donor status did not affect the following indices of graft function: length of postoperative ventilation, paO(2)/FiO(2) ratio up to 48 h and lung function up to 60 months. Length of intensive care and hospital stay, need for inotropic support and 30-day mortality were not significantly different for the transplantation of CPR or no-CPR donor lungs. One- and 3-year survival rates were comparable as well with 84.4% and 66.3% for CPR donors versus 88.5% and 69.8% no-CPR donors. CONCLUSIONS: This study indicates that transplantation of lungs from resuscitated donors may not affect outcome after LuTX. Therefore, donor history of CA should not automatically preclude LuTX.

The EuroSCORE - still helpful in patients undergoing isolated aortic valve replacement?

BACKGROUND: The European System for Cardiac Operative Risk Evaluation (EuroSCORE) is one of the most prominent scores used for the evaluation of predicted mortality in cardiac surgery. The aim of our study was to analyze the logistic and additive EuroSCORE in view of its accuracy for patients undergoing isolated aortic valve replacement (AVR). METHODS: A total of 652 patients underwent isolated AVR from January 1999 to June 2007. Emergency and redo operations were included. Acute endocarditis was excluded. Out of logistic regression analyses, receiver operating characteristic (ROC) curve statistics were calculated both for the logistic and additive EuroSCORE. RESULTS: By using the identical variables used in the EuroSCORE, the area under curve was 70.7% for the logistic and 72.4% for the additive EuroSCORE, respectively. If age, which is by nature positively correlated with increasing cardiac and non-cardiac comorbidity, is calculated as a single parameter, the area under curve remains at 69.9% being very close to the result of the EuroSCORE. CONCLUSIONS: For the subgroup of patients undergoing isolated AVR, the use of the EuroSCORE provides a comparable precision concerning the estimation of early mortality compared with the simple factor 'age'. The extended use of the EuroSCORE in view of percutaneous AVR, the insufficient accuracy of the score bears the risk of incorrect decision-making.

Avoidance of proximal endoleak using a hybrid stent graft in arch replacement and descending aorta stenting.

BACKGROUND: In complex thoracic aortic procedures, proximal repair and antegrade stent grafting of the descending aorta is an emerging technique to achieve one-stage treatment of the thoracic aorta. To overcome problems of proximal endoleak, a hybrid stent graft was designed and used. This study assessed technical feasibility and early results. METHODS: From Jan 2005 to May 2008, 41 patients (age, 60 +/- 13 years) comprising 35 aortic dissections (AD) and 6 aortic aneurysms underwent arch replacement and antegrade stent grafting of the descending aorta using the hybrid stent graft. Endoleaks were evaluated by computed tomography (CT) scans. In AD cases, the false lumen (FL) was evaluated with CT volume measurements. RESULTS: Combined arch replacement and antegrade stent grafting was technically successful. One proximal endoleak was observed, which was not related to the hybrid prosthesis (40 of 41, 98%). Three patients died (7%). No paraplegia occurred. Incidence of immediate FL thrombosis was 97% at the proximal and 80% at the distal stent graft level. During follow-up (17 +/- 11 months), complete thrombosis of the perigraft space was 91%. FL volume shrinkage was documented (p < 0.01). No perfusion of the perigraft space was observed in aneurysm cases. Intermediate survival was 33 of 38 (87%). CONCLUSIONS: One-stage repair of complex thoracic aortic disease using a hybrid stent graft can be reliably performed with low hospital mortality. Proximal endoleak can be definitely avoided; in AD, exclusion and ongoing significant shrinkage of the FL can be achieved.

Society of Thoracic Surgeons score is superior to the EuroSCORE determining mortality in high risk patients undergoing isolated aortic valve replacement.

BACKGROUND: Major scores for the evaluation of procedural risk in cardiac surgery are the European system for cardiac operative risk evaluation score (EuroSCORE), the Society of Thoracic Surgeons (STS) score, and the Parsonnet score. The aim of our study was to analyze the predictive value of these scores in "high risk" patients undergoing isolated aortic valve replacement (AVR). METHODS: Six hundred and fifty-two patients underwent isolated AVR from January 1999 through June 2007. Emergency and redo operations were included; acute endocarditis was excluded. Evaluation was performed by logistic regression analysis. Data collection was prospective. RESULTS: The mean logistic EuroSCORE of all patients was 8.5 +/- 7.9%, the mean STS score was 4.4 +/- 3.9%, and the mean logistic Parsonnet score was 9.8 +/- 8.5%. In-hospital mortality was 2.5% (n = 16). Freedom from all-cause death was 93.4% at 1 year, 90.2% at 2 years, and 75.8% at 5 years, respectively. A total of 182 patients had a logistic EuroSCORE greater than 10. For the group of patients with a EuroSCORE between 10% and 20% (n = 130) the mean EuroSCORE was 13.9 +/- 2.8% and the STS score was 6.5 +/- 3.8%. Observed mortality was 4.6% in this group. For the 52 patients with a logistic EuroSCORE of at least 20 (mean 28.5 +/- 10.3%, STS score 10.1 +/- 7.3%) the observed mortality was 3.9% (n = 2). By stepwise logistic regression, none of the EuroSCORE variables could be identified as an independent predictor in the "high- risk" group. CONCLUSIONS: The logistic EuroSCORE was primarily created to allow patient grouping for the total spectrum of cardiac surgery. In patients undergoing isolated AVR, the EuroSCORE highly overestimates mortality, whereas the STS score seems to be actually more suitable in assessing perioperative mortality for these patients.

High defibrillation threshold in patients with implantable defibrillator: how effective is the subcutaneous finger lead?

OBJECTIVE: Even in the era of high output implantable cardioverter defibrillator (ICD) devices, a certain proportion of patients cannot be successfully defibrillated with 10 J safety margin. In practice, either the use of a single- or double-coil lead does not guarantee successful termination of induced ventricular fibrillation. Therefore, we investigated the effectiveness of the subcutaneous finger lead placed at the subcutaneous tissue dorsal to the left ventricle in terms of defibrillation threshold (DFT) lowering. METHODS: Two thousand, eight hundred and three consecutive, unselected patients underwent first-time ICD implantation or ICD device exchange from 6/1999 through 3/2007. The mean age of the patients was 65.4 years. A total of 79.3% of the patients were male. The only implanted subcutaneous lead was the 6996 model by Medtronic Inc. RESULTS: One hundred and seventy-seven patients (6.3%) received a subcutaneous finger lead implantation. According to the current institutional DFT testing protocol, any failure of the two standard DFT tests in first-time ICD implantation or a failure at the single test in ICD exchange operations was the trigger for subcutaneous finger lead implantation. The proportion of subcutaneous finger lead implantations increased parallel to a markedly larger amount of implantations. Since high output devices became standard, the implantation number of subcutaneous finger leads decreases. The mean of unsuccessful DFTs prior to subcutaneous finger lead implantation was 27.2+/-5.3 J. After subcutaneous finger lead implantation, the mean successful DFT was 17.9+/-3.3 J. No complication due to subcutaneous finger lead implantation occurred. CONCLUSION: The subcutaneous finger lead is a quick, safe and effective method for DFT lowering.

Massive alterations of the left internal thoracic artery late after repair for aortic coarctation.

Adhesions or unattended injury are known but are seldom reasons to prevent withdrawing the use of the left internal thoracic artery during coronary artery bypass grafting. The patient in this case report was a 68-year-old man, who had undergone repair for aortic coarctation 34 years prior to coronary artery bypass grafting. After left internal thoracic artery harvesting, a no-flow situation of the graft was present. Transection of the graft revealed massive atherosclerotic alterations. To avoid unnecessary left internal thoracic artery harvesting, preoperative imaging in terms of a left internal thoracic artery angiography during coronary angiography is mandatory. The fact of finding massive alterations decades after pressure reduction indicates that relief from shear stress is not necessarily combined with remodeling of vascular alterations.

Overestimation of aortic valve replacement risk by EuroSCORE: implications for percutaneous valve replacement.

AIMS: The EuroSCORE has been proposed to identify patients at high risk for surgical aortic valve replacement (AVR) and estimate for them the risk-benefit of percutaneous valve replacement. The aim of our study was to investigate the validity of this proposal. METHODS AND RESULTS: From 1994 to March 2006, 1545 consecutive patients with aortic stenosis underwent isolated surgical AVR at the Department of Cardiac Surgery of Heidelberg. Both additive and logistic EuroSCOREs were calculated for each patient and summed for expected 30-day mortality. Expected and observed mortalities were compared, particularly with respect to 'high-risk' status and era of operation. Overall, 30-day mortality was low (34/1545, 2.2%) and substantially overestimated by both additive (6.1%) and logistic (9.3%) EuroSCOREs. Although both EuroSCOREs stratified patients monotonically with respect to mortality risk, high-risk patients had a 3.6% mortality (29/833), whereas additive and logistic EuroSCOREs predicted 8.3 and 14.8%. Indeed, none of the 71 patients with a EuroSCORE of 11-20 (extremely high risk) died. The more recent the era of operation, the more pronounced was the discrepancy between expected and observed mortalities. CONCLUSION: Although the EuroSCORE still successfully stratifies patients undergoing surgical AVR relative to 30-day mortality, it has become increasingly uncalibrated with absolute risk, resulting in overestimation of 30-day mortality. Inaccurately predicted mortality, especially in 'high-risk' patients, renders it unsuitable for assessing risk reduction of percutaneous valve replacement.

Preventive ablation strategies in a biophysical model of atrial fibrillation based on realistic anatomical data.

Ablation strategies to prevent episodes of paroxysmal atrial fibrillation (AF) have been subject to many clinical studies. The issues mainly concern pattern and transmurality of the lesions. This paper investigates ten different ablation strategies on a multilayered 3-D anatomical model of the atria with respect to 23 different setups of AF initiation in a biophysical computer model. There were 495 simulations carried out showing that circumferential lesions around the pulmonary veins (PVs) yield the highest success rate if at least two additional linear lesions are carried out. The findings compare with clinical studies as well as with other computer simulations. The anatomy and the setup of ectopic beats play an important role in the initiation and maintenance of AF as well as the resulting therapy. The computer model presented in this paper is a suitable tool to investigate different ablation strategies. By including individual patient anatomy and electrophysiological measurement, the model could be parameterized to yield an effective tool for future investigation of tailored ablation strategies and their effects on atrial fibrillation.

Cardiac surgery in patients on dialysis: decreased 30-day mortality, unchanged overall survival.

BACKGROUND: The risk of cardiac surgery in dialysis-dependent patients is high, but little is known about the determinants of survival. We initiated a retrospective multicenter study to overcome this limitation. METHODS: Nine centers provided data on 522 patients (70% male, aged 61 +/- 11 years) who had chronic dialysis-dependent renal failure. A 14-year period was covered. Most patients had coronary artery bypass grafting, either with (n = 103) or without (n = 326) valve surgery. Multivariable analysis of survival was explored using Cox models. RESULTS: The proportion of patients with diabetes mellitus increased significantly (from 17%, 1989 to 1993, to 32%, 2000 to 2003; p = 0.021) and was independently associated with 30-day mortality (odds ratio = 3.30, p = 0.001) The mean 30-day mortality was 12% (n = 60), but declined significantly during the study period (from 28%, 1989 to 1993, to 7%, 2000 to 2003; p = 0.003). The 5-year survival probability was 42% (95% confidence interval: 36% to 47%). Patients who had renal transplantation during follow-up (n = 17) had the best survival probability (hazard ratio [HR] = 0.14, p = 0.007). Sinus rhythm (HR = 0.48, p < 0.001) and use of internal thoracic artery grafts (HR = 0.67, p = 0.006) proved beneficial for long-term survival. Predictors of death during long-term follow-up were emergency surgery (HR = 2.25, p = 0.001), diabetes mellitus (HR = 1.46, p = 0.020), number of allogenic transfusions (HR = 1.03/unit, p = 0.015), and age (HR = 1.04/year, p < 0.001). CONCLUSIONS: In dialysis-dependent patients, cardiac surgery has become significantly safer in recent years, but the overall prognosis of the patients remains poor. The observed improvements in the perioperative survival do not necessarily translate into an improved long-term prognosis. Diabetes mellitus is an important independent risk factor for perioperative mortality and death during follow-up.

Noninvasive, automatic optimization strategy in cardiac resynchronization therapy.

OBJECTIVE: Optimization of cardiac resynchronization therapy (CRT) is still unsolved. It has been shown that optimal electrode position,atrioventricular (AV) and interventricular (VV) delays improve the success of CRT and reduce the number of non-responders. However, no automatic, noninvasive optimization strategy exists to date. METHODS: Cardiac resynchronization therapy was simulated on the Visible Man and a patient data-set including fiber orientation and ventricular heterogeneity. A cellular automaton was used for fast computation of ventricular excitation. An AV block and a left bundle branch block were simulated with 100%, 80% and 60% interventricular conduction velocity. A right apical and 12 left ventricular lead positions were set. Sequential optimization and optimization with the downhill simplex algorithm (DSA) were carried out. The minimal error between isochrones of the physiologic excitation and the therapy was computed automatically and leads to an optimal lead position and timing. RESULTS: Up to 1512 simulations were carried out per pathology per patient. One simulation took 4 minutes on an Apple Macintosh 2 GHz PowerPC G5. For each electrode pair an optimal pacemaker delay was found. The DSA reduced the number of simulations by an order of magnitude and the AV-delay and VV - delay were determined with a much higher resolution. The findings are well comparable with clinical studies. CONCLUSION: The presented computer model of CRT automatically evaluates an optimal lead position and AV-delay and VV-delay, which can be used to noninvasively plan an optimal therapy for an individual patient. The application of the DSA reduces the simulation time so that the strategy is suitable for pre-operative planning in clinical routine. Future work will focus on clinical evaluation of the computer models and integration of patient data for individualized therapy planning and optimization.