Electrophysiology lab efficiency comparison between cryoballoon and point-by-point radiofrequency ablation: a German sub-analysis of the FREEZE Cohort study.

BACKGROUND: Pulmonary vein isolation (PVI) is recommended to treat paroxysmal and persistent atrial fibrillation (AF). This analysis aimed to assess the hospital efficiency of single-shot cryoballoon ablation (CBA) and point-by-point radiofrequency ablation (RFA). METHODS: The discrete event simulation used PVI procedure times from the FREEZE Cohort study to establish the electrophysiology (EP) lab occupancy time. 1000 EP lab days were simulated according to an illustrative German hospital, including 3 PVI cases per day using CBA at one site and RFA at the other. RESULTS: The analysis included 1560 CBA patients and 1344 RFA patients from the FREEZE Cohort. Some baseline patients' characteristics were different between groups (age, AF type, and some concomitant diseases), without being statistically associated to ablation procedure time. Mean procedure time was 122.2 ± 39.4 min for CBA and 160.3 ± 53.5 min for RFA (p < 0.0001). RFA was associated with a more than five-fold increase of cumulative overtime compared to CBA over the simulated period (1285 h with RFA and 253 h with CBA). 70.7% of RFA lab days included overtime versus 25.7% for CBA. CBA was associated with more days with an additional hour at the end of the EP lab shift compared to RFA (47.8% vs 11.5% days with one hour left, respectively). CONCLUSION: CBA is faster and more predictable than point-by-point RFA, and enables improvements in EP lab efficiency, including: fewer cumulative overtime hours, more days where overtime is avoided and more days with remaining time for the staff or for any EP lab usage. Clinical trial registration NCT01360008 (first registration 25/05/2011).

Impact of lifestyle modification on left ventricular function and cardiopulmonary exercise capacity in patients with heart failure with normal ejection fraction and cardiometabolic syndrome: a prospective interventional study.

BACKGROUND: Heart failure with normal left ventricular ejection fraction (HFNEF) accounts for about one third of all heart failure patients with considerable mortality. The metabolic syndrome (MS) is a risk factor for diastolic dysfunction and HFNEF. We hypothesized that modifying metabolic burden by exercise training and weight loss might improve left ventricular diastolic function, heart failure symptoms and rehospitalization rate. METHODS AND RESULTS: Forty patients with HFNEF, MS and prediabetes were enrolled in this prospective study. Echocardiography and cardiopulmonary exercise testing (CPET) were done at baseline and after 3 months lifestyle modification (LSM). NT-pro BNP and adiponectin were determined at baseline as both peptidehormones play a crucial role in MS and heart failure. After discharge a 3-month LSM program with the aim of weight reduction by diet and exercise was started. After the intervention period a weight reduction of ≥ 2% was defined as successful LSM (group A = 23 patients), while a weight reduction < 2% was classified as unsuccessful LSM (group B = 17 patients). At baseline NT-pro BNP (424 ± 381 versus 121 ± 99 pg/ml, P < 0.01) and adiponectin (10.1 ± 6.2 versus 4.6-2.0 µg/ml, P < 0.01) were higher in group A than in group B. After 3 months of LSM, CPET showed a significant improve- ment of VO2 peak (P < 0.01), EqCO2 (P < 0.001), O2-pulse (P = 0.02) and VE / VCO2 slope (P = 0.01) in group A. After one year of follow-up a modest but significant reduction of left atrial size and mitral flow to mitral annulus velocity ratio E/E' was seen in group A. LSM resulted in significant improvement of NYHA status (P = 0.03) and higher freedom of rehospitalization (P = 0.04) in group A. CONCLUSION: Successful lifestyle modification in obese, prediabetic patients with HFNEF improves diastolic left ventricular function and cardiopulmonary exercise capacity. As these measures result in improved NYHA status and less hospitalization, LSM might be a promising approach to prevent chronic diastolic heart failure.

Principles of artificial intelligence and its application in cardiovascular medicine.

Artificial intelligence (AI) represents a rapidly developing field. Its use can improve diagnosis and therapy in many areas of medicine. Despite this enormous progress, many physicians perceive it as a black box and are skeptical about it. This review will present the basics of machine learning. Different classifications of artificial intelligence, such as supervised versus unsupervised and discriminative versus generative AI, are given. Analogies to human intelligence are discussed as far as algorithms are oriented toward it. In the second step, the most common models like random forest, k-means clustering, convolutional neural network, and transformers will be presented in a way that the underlying idea can be understood. Corresponding medical applications in cardiovascular medicine will be named for all models, respectively. The overview is intended to show that the term artificial intelligence covers a wide range of different concepts. It should help physicians understand the principles of AI to make up one's minds about its application in cardiology. It should also enable them to evaluate results obtained with AI's help critically.

Cardiac arrest related lung edema: examining the role of downtimes in transpulmonary thermodilution analysis.

Pulmonary edema and its association with low flow times has been observed in postcardiac arrest patients. However, diagnosis of distinct types of lung pathology is difficult.The aim of this study was to investigate pulmonary edema by transpulmonary thermodilution (TPTD) after out-of-hospital cardiac arrest (OHCA), and the correlation to downtimes. In this retrospective single-center study consecutive patients with return of spontaneous circulation (ROSC) following OHCA, age ≥ 18, and applied TPTD were enrolled. According to downtimes, patients were divided into a short and a long no-flow-time group, and data of TPTD were analysed. We identified 45 patients (n = 25 short no-flow time; n = 20 long no-flow time) who met the inclusion criteria. 24 h after ROSC, the extra vascular lung water index (EVLWI) was found to be lower in the group with short no-flow time compared to the group with long no-flow time (10.7 ± 3.5 ml/kg vs. 12.8 ± 3.9 ml/kg; p = 0.08) and remained at a similar level 48 h (10.9 ± 4.3 ml/kg vs. 12.9 ± 4.9 ml/kg; p = 0.25) and 72 h (11.1 ± 5.0 ml/kg vs. 13.9 ± 7.7 ml/kg; p = 0.27) post-ROSC. We found a statistically significant and moderate correlation between no-flow duration and EVLWI 48 h (r = 0.51; p = 0.002) and 72 h (r = 0.54; p = 0.004) post-ROSC. Pulmonary vascular permeability index (PVPI) was not correlated with downtimes. Our observation underlines the presence of cardiac arrest-related lung edema by determination of EVLWI. The duration of no-flow times is a relevant factor for increased extravascular lung water index.

Leadless pacing using induction technology: impact of pulse shape and geometric factors on pacing efficiency.

AIMS: Leadless pacing can be done by transmitting energy by an alternating magnetic field from a subcutaneous transmitter unit (TU) to an endocardial receiver unit (RU). Safety and energy consumption are key issues that determine the clinical feasibility of this new technique. The aims of the study were (i) to evaluate the stimulation characteristics of the non-rectangular pacing pulses induced by the alternating magnetic field, (ii) to determine the extent and impact of RU movement caused by the beating heart, and (iii) to evaluate the influence of the relative position between TU and RU on pacing efficiency and energy consumption. METHODS AND RESULTS: In the first step pacing efficiency and energy consumption for predefined positions were determined by bench testing. Subsequently, in a goat at five different ventricular sites (three in the right ventricle, two in the left ventricle) pacing thresholds using non-rectangular induction pulses were compared with conventional pulses. Relative position, defined by parallel distance, radial distance, and angulation between TU and RU, were determined in vivo by X-ray and an inclination angle measurement system. Bench testing showed that by magnetic induction for every alignment between TU and RU appropriate pulses can be produced up to a distance of 100 mm. In the animal experiment pacing thresholds were similar for non-rectangular pulses as compared with conventional pulse shapes. In all five positions with distances between 62 and 102 mm effective pacing was obtained in vivo. Variations in distance, displacement and angle caused by the beating heart did not cause loss of capture. At pacing threshold energy consumptions between 0.28 and 5.36 mJ were measured. Major determinants of energy consumption were distance and pacing threshold. CONCLUSION: For any given RU position up to a distance of 100 mm reliable pacing using induction can be obtained. In anatomically crucial distances, up to 60 mm energy consumption is within a reasonable range.

A deep neural network using audio files for detection of aortic stenosis.

BACKGROUND: Although aortic stenosis (AS) is the most common valvular heart disease in the western world, many affected patients remain undiagnosed. Auscultation is a readily available screening tool for AS. However, it requires a high level of professional expertise. HYPOTHESIS: An AI algorithm can detect AS using audio files with the same accuracy as experienced cardiologists. METHODS: A deep neural network (DNN) was trained by preprocessed audio files of 100 patients with AS and 100 controls. The DNN's performance was evaluated with a test data set of 40 patients. The primary outcome measures were sensitivity, specificity, and F1-score. Results of the DNN were compared with the performance of cardiologists, residents, and medical students. RESULTS: Eighteen percent of patients without AS and 22% of patients with AS showed an additional moderate or severe mitral regurgitation. The DNN showed a sensitivity of 0.90 (0.81-0.99), a specificity of 1, and an F1-score of 0.95 (0.89-1.0) for the detection of AS. In comparison, we calculated an F1-score of 0.94 (0.86-1.0) for cardiologists, 0.88 (0.78-0.98) for residents, and 0.88 (0.78-0.98) for students. CONCLUSIONS: The present study shows that deep learning-guided auscultation predicts significant AS with similar accuracy as cardiologists. The results of this pilot study suggest that AI-assisted auscultation may help general practitioners without special cardiology training in daily practice.

A spear to the heart-the accidental discovery of a giant cement embolism in the right heart: a case report.

BACKGROUND: The incidence of recognized cardiopulmonary cement embolism in the context of percutaneous vertebroplasty varies between 0% and 23%. In most cases, only small fragments embolize in the pulmonary arteries or the right heart cavities. The latter can cause potential harm by right ventricular perforation. CASE SUMMARY: A 57-year-old patient was admitted to our department of cardiology due to exertional dyspnoea and chest pain. In the course of further diagnostic tests, a huge cement embolus was accidentally discovered in the right ventricle. The unusual size and length and the threat of ventricular perforation make this case so unique. DISCUSSION: Large cement embolisms in kyphoplasty settings are possible and associated with the risk of fulminant complications.

Stroke due to Left Atrial Appendage Thrombus after Pulmonary Vein Isolation despite Novel Oral Anticoagulant: A Case Report.

In patients with atrial fibrillation, catheter ablation is suggested to reduce the mortality rate and is thus frequently performed. However, peri- and postprocedural thromboembolic complications as well as high recurrence rates of atrial fibrillation limit its advantages and require concomitant anticoagulation. With the advent of novel oral anticoagulants (NOACs), fixed dosing without routine laboratory monitoring became feasible. Nevertheless, several factors are associated with either an overdose or an insufficient drug activity of NOACs. We report on a patient with atrial fibrillation undergoing catheter ablation and cardioversion suffering from ischemic stroke despite being under oral anticoagulation. It turned out that the drug activity of the NOACs used was repeatedly insufficient in spite of regular intake and adequate dosing. In sum, drug activity controls should be taken into consideration in patients with thrombotic events despite oral anticoagulation with NOACs.

Polymorphisms associated with ventricular tachyarrhythmias: rationale, design, and endpoints of the 'diagnostic data influence on disease management and relation of genomics to ventricular tachyarrhythmias in implantable cardioverter/defibrillator patients (DISCOVERY)' study.

Implantable cardioverter-defibrillator (ICD) therapy is effective in primary and secondary prevention for patients who are at high risk of sudden cardiac death. However, the current risk stratification of patients who may benefit from this therapy is unsatisfactory. Single nucleotide polymorphisms (SNPs) are DNA sequence variations occurring when a single nucleotide in the genome differs among members of a species. A novel concept has emerged being that these common genetic variations might modify the susceptibility of a certain population to specific diseases. Thus, genetic factors may also modulate the risk for arrhythmias and sudden cardiac death, and identification of common variants could help to better identify patients at risk. The DISCOVERY study is an interventional, longitudinal, prospective, multi-centre diagnostic study that will enrol 1287 patients in approximately 80 European centres. In the genetic part of the DISCOVERY study, candidate gene polymorphisms involved in coding of the G-protein subunits will be correlated with the occurrence of ventricular arrhythmias in patients receiving an ICD for primary prevention. Furthermore, in order to search for additional sequence variants contributing to ventricular arrhythmias, a genome-wide association study will be conducted if sufficient a priori evidence can be gathered. In the second part of the study, associations of SNPs with ventricular arrhythmias will be sought and a search for potential new biological arrhythmic pathways will be investigated. As it is a diagnostic study, DISCOVERY will also investigate the impact of long-term device diagnostic data on the management of patients suffering from chronic cardiac disease as well as medical decisions made regarding their treatment.

Iterative cardiac output measurement for optimizing cardiac resynchronization therapy: a randomized, blinded, crossover study.

BACKGROUND: Many invasive and noninvasive methods have been proposed for guiding optimal programming of cardiac resynchronization therapy (CRT) devices. However, results are not satisfying. Preliminary results suggest that cardiac output (CO) measurements using inert gas rebreathing (IGR) might be an eligible method to tailor atrioventricular (AV) and ventriculo-ventricular (VV) programming. The aims of the present study were: (1) to evaluate whether an optimization of CRT can be obtained by noninvasive CO measurements and (2) to evaluate whether acute hemodynamic improvements obtained by this approach relate into increase in cardiac exercise capacity. METHODS: In 24 patients on CRT, iterative VV- and AV-delay optimization was done using the IGR method. This blinded, randomized, crossover study compared the responses to optimization during two periods: a 4-week optimized and a 4-week standard programming. Exercise capacity after optimization was assessed after each period by New York Heart Association (NYHA) classification, a 6-minute walking test, and quality of life (QoL) questionnaire. RESULTS: CO could be determined by IGR in all patients. The NYHA class decreased by 17.8% (2.8 ± 0.3 vs 2.3 ± 0.4, P < 0.001), the mean (± standard deviation) distance walked in 6 minutes was 9.3% greater after optimization (456 ± 140 m vs 417 ± 134 m, P < 0.001), and the QoL improved by 14.5% (41.8 ± 10.4 vs 36.5 ± 9.5, P < 0.001). The portion of responders to CRT increased from 66.5% to 87.5%. CONCLUSION: CRT optimization by iterative CO measurements leads to an increase in CO and an improvement of exercise capacity. Our results suggest that this method might become an important additive tool to adjust CRT programming.

Attenuation of post-shock increases in brain natriuretic Peptide with post shock overdrive pacing.

BACKGROUND: Predischarge defibrillation threshold testing is often performed a few days after ICD implantation in order to validate defibrillation thresholds obtained at the time of implant. Ventricular fibrillation is induced with such testing and causes an increase in serum Brain Natriuretic Peptide (BNP) levels. BNP is an indicator for cardiac stress. We wanted to examine the feasibility to alter the trend of BNP after predischarge testing in VVI, DDD and CRT ICD's. METHODS: We measured BNP before predischarge testing and 5, 10, 20 and 40 minutes after predischarge testing in 13 groups with each 20 patients. We evaluated patients without post shock pacing and patients with a post shock pacing frequency of 60, 70, 80, 90 and 100 bpm and a duration of 30 and 60 sec as well as a post shock pacing frequency of 80 and 90 bpm and a duration of 120 sec post shock pacing. RESULTS: Patients without post shock pacing showed the highest BNP during the follow-up. The percentage values of BNP increased consistent significantly after 5 minutes compared with BNP before predischarge testing. The percentage values of BNP trend was significantly lower with a post shock pacing of 90 bpm and duration of 60 sec. In addition, we excluded a cardiac necrosis by predischarge testing because of similar values of myoglobin, cardiac troponin I and creatine kinase during the follow-up. CONCLUSIONS: Our results suggested that post shock pacing with 90 bpm and duration of 60 sec as the best optimized post shock pacing frequency and duration for VVI, DDD and CRT ICD's. A reduction of cardiac stress is going to be achieved with the optimization of the post shock pacing frequency and duration.

Leadless pacing of the heart using induction technology: a feasibility study.

OBJECTIVES: To develop a leadless pacemaker system based on induction technology and to investigate its feasibility and safety in the pig model. BACKGROUND: Despite tremendous technical advances during the last decades, cardiac pacing is still associated with a considerable rate of complications that can be primarily attributed to the leads. METHODS: The device consists of a transmitter unit implanted subcutaneously just above the heart and an endocardial receiver unit implanted in the apex of the right ventricle. The transmitter unit generates an alternating magnetic field that is converted into a voltage pulse by the receiver unit. In order to test feasibility, the receiver unit was attached to an electrophysiology catheter for signal recording and placed in the apex of the right ventricle of a pig. Subsequently, the receiver unit was implanted without external connection in the right ventricle. RESULTS: An alternating magnetic field of about 0.5 mT was generated by the transmitter unit in a distance of 3 cm. Voltage pulses with a duration of 0.4 ms and voltage amplitude of 0.6-1.0 V were generated. Using these pulse characteristics, a reliable stimulation of the heart could be achieved. A secure fixation of the receiver unit in the apex of the right ventricle could be obtained for the duration of this short-term study by using screw fixation. CONCLUSIONS: This study shows that induction technology is feasible for cardiac pacing. Typical voltage pulses could be generated by which an effectively stimulation in vivo could be achieved.

The prediction of ICD therapy in multicenter automatic defibrillator implantation trial (MADIT) II like patients: a retrospective analysis.

OBJECTIVES: MADIT II like patients have not been compared to patients without an electrophysiological study, patients in whom ventricular tachycardia or fibrillation were induced in an electrophysiological study (EPS) and patients without an inducibility in EPS in one study. BACKGROUND: The multicenter automatic defibrillator implantation trial (MADIT) II showed a benefit of ICD implantation in patients with ischemic heart disease. METHODS: We performed a retrospective analysis in 93 patients with an ischemic heart disease and an ejection fraction

Acute and long-term outcome of focal atrial tachycardia ablation in the real world: results of the german ablation registry.

INTRODUCTION: Catheter ablation of focal atrial tachycardia (FAT) can be a challenging procedure and results have been rarely described. The purpose of this study was to determine the characteristics and results of FAT ablation in the large cohort of the German Ablation Registry. METHODS: The German Ablation Registry is a nationwide prospective multicenter database including 12566 patients who underwent an ablation procedure between 2007 and 2010. Among them 431 (3.4%) underwent an FAT ablation and 413 patients with documented locations were analyzed. Patients were divided into three groups according to the FAT location: biatrial (BiA, n = 31, 7.5%), left atrial (LA, n = 110, 26.5%), and right atrial (RA, n = 272, 66%). RESULTS: Acute success rate was 84% (68 vs. 85 vs. 85% in biA, LA, and RA, respectively, p = 0.038). 4.8% of patients had an early recurrence during hospitalization, most in biatrial location (p < 0.001). No major acute complication occurred. At 12 months, 81% were asymptomatic or improved. The incidence of major adverse cardiovascular and cerebrovascular events (MACCE) was 3.7%. Arrhythmia freedom without antiarrhythmic drugs was 58% and was lower in biA (34 vs. 56% in LA vs. 62% in RA, p = 0.019). Early recurrence during hospitalization was an outstanding predictive factor for recurrence during follow-up. CONCLUSION: In this large patient population, FAT ablation had a relatively high acute success rate with a low complication rate. During follow-up, the recurrence rate was high, particularly in biatrial location. This was frequently predicted by an early recurrence during hospitalization.

Ablation Outcomes and Predictors of Mortality Following Catheter Ablation for Ventricular Tachycardia: Data From the German Multicenter Ablation Registry.

BACKGROUND: Ventricular tachycardia (VT) causes significant morbidity and mortality. Implantable cardioverter-defibrillator shocks terminate VT but confer a significant morbidity and mortality risk. Therefore, VT ablation is increasingly common. Patients with structural heart disease (SHD) and patients with structurally normal hearts as well as the subgroup with and without ischemic heart disease were assessed for predictors of mortality and nonfatal VT recurrence. We present the first multicenter, prospective German VT registry. METHODS AND RESULTS: In 334 patients, 118 structurally normal hearts and 216 SHD (74.5% ischemic heart disease), referred for VT ablation in 38 centers, long-term follow-up was assessed for a minimum of 12 months and analyzed for factors predicting VT recurrence rates and mortality. The VTs in SHD patients were more frequently hemodynamically unstable (34.7% versus 12.7%, P<0.0001) or incessant (9.7% versus 2.7%, P<0.05). More SHD patients underwent substrate modification than patients with structurally normal hearts who had more focal ablations. Ablation failure was 9% in both groups. Two-year mortality was higher in patients with SHD (18.7% versus 3.5%, P<0.001). Predictors of mortality include age >60 years, incessant VT, left ventricular ejection fraction ≤30%, procedural failure, and Class I and III anti-arrhythmic drug use at discharge. Only procedural failure is a predictor of nonfatal VT recurrence. CONCLUSIONS: Procedural failure was the sole independent predictor for nonfatal VT recurrence for our study cohort. This emphasizes the importance of a successful ablation procedure in experienced hands to reduce long-term mortality and nonfatal VT recurrence.

Effect of induced ventricular fibrillation and shock delivery on brain natriuretic peptide measured serially following a predischarge ICD test.

OBJECTIVES: Brain natriuretic peptide (BNP) was a marker for heart failure and cardiac wall tension. We analysed the trend of BNP after predischarge testing in order to get non-invasive details about the cardiac stress during predischarge testing. METHODS: 4-5 days after ICD implant we measured BNP, myoglobin, cardiac troponin I and creatine kinase in 20 patients before and 1, 5, 10, 20, 40, 60, 80, 100, 120 minutes and at the next day after predischarge testing. We evaluated actual values and percentage alterations of BNP. RESULTS: BNP significantly increased with a maximum after 5 minutes (804.0 +/- 803.4 vs. 475.7 +/- 629.5 pg/ml, P < 0.0001) and in terms of the percentage values (100 vs. 199.4 +/- 61.4 %, P < 0.0001) compared with baseline BNP. BNP decreased after that with the last significantly increased BNP value after 20 minutes (540.2 +/- 604.9 vs. 475.7 +/- 629.5 pg/ml, P = 0.017). We excluded a cardiac necrosis during predischarge testing because of similar values of myoglobin, cardiac troponin I and creatine kinase during the 2-hour follow-up. CONCLUSION: Our data showed a great increase with a doubling of BNP after 5 minutes as a result of induced ventricular fibrillation during predischarge test. This increase was not generated by myocardial necrosis but rather caused by an acute cardiac failure as a consequence of induced ventricular fibrillation in predischarge testing.

Relation between plaque progression and low-density lipoprotein cholesterol during aging as assessed with serial long-term (> or =12 months) follow-up intravascular ultrasound of the left main coronary artery.

Because of the clinical benefit of lipid lowering in older patients, we hypothesized that the relation between low-density lipoprotein (LDL) cholesterol serum levels and coronary plaque progression may persist throughout aging. We analyzed serial intravascular ultrasound (IVUS) data of 60 left main stems (18 +/- 9 months apart) and evaluated the relation between LDL cholesterol levels and coronary plaque progression at different ages. The population (n = 60) was divided into 3 groups according to age: tertile 1 (n = 20) was a mean age of 48 +/- 6 years (median 51, range 33 to 55), tertile 2 (n = 20) was a mean age of 58 +/- 2 years (median 59, range 55 to 61), and tertile 3 (n = 20) was a mean age of 66 +/- 6 years (median 65, range 61 to 83). Between groups, there was no significant difference in non-age-related demographics, clinical data, lipid profiles, or medications (e.g., statins). There was a positive linear relation between LDL cholesterol and annual changes in plaque plus media area in all age tertiles, which was statistically significant in tertiles 2 and 3 (r = 0.56, p <0.01; r = 0.50, p <0.02) and showed a strong trend in tertile 1 (r = 0.41, p = 0.07). The estimated LDL cholesterol thresholds, which, as determined by regression analysis, would correspond to no plaque progression, were 74, 60, and 78 mg/dl, respectively, in tertiles 1, 2, and 3. In conclusion, serial IVUS data in left main coronary arteries suggest that the relation between LDL cholesterol serum levels and plaque progression persists during aging.

Single-chamber versus dual-chamber implantable cardioverter defibrillators: do we need physiologic pacing in the course?

BACKGROUND: Many patients with ICD receive different antiarrhythmic drugs (e.g. sotalol, amiodarone, beta-blockers) because of ventricular or atrial tachycardias. These drugs can cause AV-block or chronotropic incompetence resulting in a higher percentage of ventricular pacing. METHODS: We analyzed in a retrospective study the impact of DDD(R) versus VVI(R) mode on subjective (NYHA classification) and objective parameters [brain natriuretic peptide (BNP), 6 minute walk test, echocardiography] in 12 of 120 patients (age 60.2 +/- 11.2 years; 10 males, 2 females) who needed an upgrading of a single to a dual chamber ICD. The ICD had to be upgraded because of chronotropic incompetence in all patients with signs of progressing heart failure. Data were collected in VVI(R)-pacing and after 6 and 12 months in DDD(R)-pacing with a long AV-interval and AV hysteresis to reduce ventricular pacing. RESULTS: The 6 minute walk test (392.4 +/- 91.4 vs. 324.6 +/- 93.3 m, P < 0.001), NYHA-classification (1.4 +/- 0.3 vs. 2.6 +/- 0.8, P < 0.0001), BNP (234.1 +/- 73.5 vs. 410.4 +/- 297.0 pg/ml, P < 0.001), left ventricular ejection fraction (49.8 +/- 9.6 vs. 36.5 +/- 10.9 %, P < 0.0001) and A-wave (73.6 +/- 13.7 vs. 41.0 +/- 14.0 cm/sec, P < 0.0001) improved with DDD(R)-pacing after 12 months. The ventricular pacing decreased (84.2 +/- 18.1 vs. 1.1 +/- 1.7 %, P < 0.0001) after 12 months by DDD(R)-pacing with long AV-interval (220.0 +/- 10.4 ms) and AV hysteresis. CONCLUSION: Our data show a superiority of DDD(R) mode versus VVI(R) mode regarding subjective and objective parameters as NYHA-classification, BNP, 6 minute walk test, left ventricular ejection fraction and left ventricular endsystolic volume after 12 months. The improvements seem to depend on the reduction of ventricular pacing with advanced atrial contraction. But only a small number of patients needed the upgradation.

Polymorphisms in the GNAS Gene as Predictors of Ventricular Tachyarrhythmias and Sudden Cardiac Death: Results From the DISCOVERY Trial and Oregon Sudden Unexpected Death Study.

BACKGROUND: Population-based studies suggest that genetic factors contribute to sudden cardiac death (SCD). METHODS AND RESULTS: In the first part of the present study (Diagnostic Data Influence on Disease Management and Relation of Genetic Polymorphisms to Ventricular Tachy-arrhythmia in ICD Patients [DISCOVERY] trial) Cox regression was done to determine if 7 single-nucleotide polymorphisms (SNPs) in 3 genes coding G-protein subunits (GNB3, GNAQ, GNAS) were associated with ventricular tachyarrhythmia (VT) in 1145 patients receiving an implantable cardioverter-defibrillator (ICD). In the second part of the study, SNPs significantly associated with VT were further investigated in 1335 subjects from the Oregon SUDS, a community-based study analyzing causes of SCD. In the DISCOVERY trial, genotypes of 2 SNPs in the GNAS gene were nominally significant in the prospective screening and significantly associated with VT when viewed as recessive traits in post hoc analyses (TT vs CC/CT in c.393C>T: HR 1.42 [CI 1.11-1.80], P=0.005; TT vs CC/CT in c.2273C>T: HR 1.57 [CI 1.18-2.09], P=0.002). TT genotype in either SNP was associated with a HR of 1.58 (CI 1.26-1.99) (P=0.0001). In the Oregon SUDS cohort significant evidence for association with SCD was observed for GNAS c.393C>T under the additive (P=0.039, OR=1.21 [CI 1.05-1.45]) and recessive (P=0.01, OR=1.52 [CI 1.10-2.13]) genetic models. CONCLUSIONS: GNAS harbors 2 SNPs that were associated with an increased risk for VT in ICD patients, of which 1 was successfully replicated in a community-based population of SCD cases. To the best of our knowledge, this is the first example of a gene variant identified by ICD VT monitoring as a surrogate parameter for SCD and also confirmed in the general population. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00478933.