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Background Mortality and morbidity are higher among patients with atrial fibrillation and heart failure than among those with heart failure alone. Catheter ablation for atrial fibrillation has been proposed as a means of improving outcomes among patients with heart failure who are otherwise receiving appropriate treatment. Methods We randomly assigned patients with symptomatic paroxysmal or persistent atrial fibrillation who did not have a response to antiarrhythmic drugs, had unacceptable side effects, or were unwilling to take these drugs to undergo either catheter ablation (179 patients) or medical therapy (rate or rhythm control) (184 patients) for atrial fibrillation in addition to guidelines-based therapy for heart failure. All the patients had New York Heart Association class II, III, or IV heart failure, a left ventricular ejection fraction of 35% or less, and an implanted defibrillator. The primary end point was a composite of death from any cause or hospitalization for worsening heart f...

Agricultural drought events can affect large regions across the world, implying the need for a suitable global tool for an accurate monitoring of this phenomenon. Soil moisture anomalies are considered a good metric to capture the occurrence of agricultural drought events, and they have become an important component of several operational drought monitoring systems. In the framework of the JRC Global Drought Observatory (GDO, http://edo.jrc.ec.europa.eu/gdo/), the suitability of three datasets as possible representations of root zone soil moisture anomalies has been evaluated: (1) the soil moisture from the Lisflood distributed hydrological model (namely LIS), (2) the remotely sensed Land Surface Temperature data from the MODIS satellite (namely LST), and (3) the ESA Climate Change Initiative combined passive/active microwave skin soil moisture dataset (namely CCI). Due to the independency of these three datasets, the triple collocation (TC) technique has been applied, aiming at quantifying the likely error associated with each dataset in comparison to the unknown true status of the system. TC analysis was performed on five macro-regions (namely North America, Europe, India, southern Africa and Australia) detected as suitable for the experiment, providing insight into the mutual relationship between these datasets as well as an assessment of the accuracy of each method. Even if no definitive statement on the spatial distribution of errors can be provided, a clear outcome of the TC analysis is the good performance of the remote sensing datasets, especially CCI, over dry regions such as Australia and southern Africa, whereas the outputs of LIS seem to be more reliable over areas that are well monitored through meteorological ground station networks, such as North America and Europe. In a global drought monitoring system, the results of the error analysis are used to design a weighted-average ensemble system that exploits the advantages of each dataset.

In the last decades drought has become one of the natural disasters with most relevant impacts in Europe and this not only in water scarce areas such as the Mediterranean that are inclined to such events. As a complex natural phenomenon, drought is characterized by many hydro-meteorological aspects, a large variety of possible impacts and definitions. This study focuses on meteorological drought, investigated by using indicators that include precipitation and potential evapotranspiration (PET), i.e. the Standardized Precipitation Index (SPI) and the Standardized Precipitation-Evapotranspiration Index (SPEI). These indicators account for the lack of precipitation and the drying effects of hot temperatures and in this study have been computed for short-accumulation periods (3-month) to capture the seasonality of droughts. The input variables, monthly precipitation and temperature for 1950–2015, stem from daily gridded E-OBS data and indicators were computed on regular grids spanning over the whole of Europe. PET was calculated from minimum and maximum temperatures using the Hargreaves-Samani formulation. Monthly precipitation and PET have then been used to compute the SPI-3 and the SPEI-3 time series. From these series drought events were defined at seasonal scale and trends of frequency and severity of droughts and extreme droughts were analyzed for the periods 1950–2015 and 1981–2015. According to the SPI (driven by precipitation), results show a statistically significant tendency towards less frequent and severe drought events over North-Eastern Europe, especially in winter and spring, and a moderate opposite tendency over Southern Europe, especially in spring and summer. According to the SPEI (driven by precipitation and temperature), Northern Europe shows similar wetting patterns, while Southern and Eastern Europe show a more remarkable drying tendency, especially in summer and autumn. Both for frequency and severity, the evolution towards drier conditions is more relevant in the last three decades over Central Europe in spring, the Mediterranean area in summer, and Eastern Europe in autumn. Fil: Spinoni, Jonathan. GFT Italy; Italia Fil: Naumann, Gustavo. European Commission. Joint Research Centre; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Vogt, Jürgen V.. European Commission. Joint Research Centre; Italia

Aims: The FREEZE-cohort study (NCT 01360008) is a prospective observational, multicenter and multinational study to evaluate safety and effectiveness of cryoballoon ablation for pulmonary vein isolation as compared to radiofrequency ablation in patients with paroxysmal or persistent atrial fibrillation (lasting < one year) under the conditions of clinical routine. Methods and Results: The study started in 2011 and anticipates inclusion up to 2000 patients in each of the two treatment groups. A total of 37 centers from 8 countries worldwide, all experienced in at least one of the two ablation techniques, participate in the study. The primary outcome parameter of the study is defined as atrial fibrillation recurrence rate during twelve months of follow-up. Secondary outcome parameters include primary success rates, complication rates in general, specific complications with respect to phrenic nerve palsy and pulmonary vein stenosis, radiation exposure, clinical course including death and repeat ablation. Finally specific procedural aspects will be evaluated in a descriptive manner. Preliminary data of the first 1882 patients show that in clinical practice cryoablation is preferentially performed in patients with paroxysmal atrial fibrillation, whereas application of radiofrequency ablation is equally distributed between patients with persistent and paroxysmal atrial fibrillation. Conclusion: Based on multi-center and multi-national data the FREEZE-cohort study will provide important information on long-term efficacy, clinical effectiveness, complication rates and procedural differences between atrial fibrillation patients treated with either cryoablation or radiofrequency ablation.

To analyze whether left ventricular dyssynchrony (LVD) at baseline is predictive for long-term outcome in heart failure (CHF) patients with left ventricular (LV) dysfunction and conduction disturbances treated with cardiac resynchronization therapy (CRT).In 535 consecutive individuals with CHF scheduled for implantation of a CRT device, LVD was assessed by tissue Doppler imaging (TDI), defined as an electromechanical delay (EMD) difference of ≥40 ms in 2 opposed left ventricular wall regions (septal vs. lateral, anterior vs. inferior). All-cause mortality, heart transplantation, or assist device implantation was defined as combined primary end point. Secondary end points were measures of reverse LV remodeling and of symptomatic improvement.Mean follow-up was 68 ± 36 [range: 4-150] months. LVD at baseline was present in 308 patients (61%). Of these, 24% reached the combined primary endpoint in contrast to 58% of patients without LVD (p0.001). Furthermore, patients with LVD showed pronounced improvement of all secondary end point parameters. In our cohort LVD was an independent predictor for outcome (hazard ratio [95% CI]: 0.30 [0.21-0.42], p0.001).LVD at baseline as assessed by TDI is associated with a more pronounced clinical improvement and is a predictor for transplant-free long-term survival in CRT recipients.

Cheyne-Stokes Respiration and Arrhythmias ObjectiveThis study aimed to investigate whether adequate treatment of Cheyne-Stokes respiration (CSR) reduces the risk of arrhythmic events in patients with chronic heart failure (CHF). MethodsA cohort of 403 registry patients with CHF (LVEF45%, NYHA-class2) and implanted cardioverter-defibrillator devices (ICD) was studied. They underwent overnight polygraphy, with 221 having mild or no CSR (apnea-hypopnea index [AHI] 15/h). Latter ones were offered therapy with adaptive servoventilation (ASV), which 96 patients accepted and 86 rejected. During follow-up (21 15 months) defibrillator therapies were recorded in addition to clinical and physiologic measures of heart failure severity. ResultsEvent-free survival from (a) appropriate cardioverter-defibrillator therapies and (b) appropriately monitored ventricular arrhythmias was shorter in the untreated CSR group compared to the treated CSR and the no CSR group. Stepwise Cox proportional hazard regression analysis showed untreated CSR (a: hazard ratio [HR] 1.99, 95% confidence interval [CI] 1.46-2.72, P < 0.001; b: HR 2.19, 95%CI 1.42-3.37, P < 0.001), but not treated CSR (a: HR 1.06, 95%CI 0.74-1.50; P = 0.77; b: HR 1.21, 95%CI 0.75-1.93, P = 0.43) was an independent risk factor. The treated CSR group showed improvements in cardiac function and respiratory stability compared to the untreated CSR group. ConclusionThis study demonstrates a decrease of appropriate defibrillator therapies by ASV treated CSR in patients with CHF and ICD. A reduced exposure to hyperventilation, hypoxia, and improvement in indices of CHF severity and neurohumoral disarrangements are potential causative mechanisms.

Objectives The purpose of this study was to investigate long-term outcomes of freedom from atrial fibrillation (AF) after pulmonary vein (PV) isolation using cryoballoon ablation with balloon-size selection based on individual PV diameters. Background Data are lacking on long-term outcomes from cryoablation and on the most effective balloon size. Methods This was a prospective observational study involving 605 consecutively enrolled patients with symptomatic paroxysmal AF (n = 579) or persistent AF. Cryoballoon size was based on magnetic resonance imaging and/or conventional angiograms. Patients were followed up every 3 months during the first year after discharge and every 6 months in the second year. After 24 months, follow-up was on an outpatient basis with documented AF episodes recorded. Results The PV isolation was achieved without touch-up in 91.1% of patients, using the smaller balloon in 26.7%, the larger balloon in 25.6%, and both balloons in 47.7% of patients. Follow-up data for >12 months (median 30 months; interquartile range 18 to 48 months) were available for 451 patients, 278 (61.6%) of whom were free of AF recurrence with no need for repeat procedures after the 3-month blanking period. Rates of freedom from AF after 1, 2, and 3 repeat procedures (using cryoballoon or radiofrequency ablation with similar success rates) were 74.9%, 76.2%, and 76.9%, respectively. Use of the smaller balloons or both balloons produced the highest rates of long-term freedom from AF. Phrenic nerve palsy occurred in 12 patients (2%), resolving within 3 to 9 months. Conclusions Rates of long-term freedom from AF after cryoballoon ablation are similar to those reported for radiofrequency ablation. A choice between balloons may improve outcomes.

Until now, there is no consensus regarding the definition of a clinical response to cardiac resynchronization therapy (CRT) in patients with chronic heart failure (CHF) and systolic left ventricular (LV) dysfunction. The aim of this study was to evaluate if echocardiography is predictive for an objective improvement in exercise capacity during long-term follow-up of CRT.Each patient underwent echocardiography and spiroergometry both at baseline and at last follow-up. Left ventricular dyssynchrony (LVD) before CRT was defined by tissue Doppler imaging (TDI) as intra-LV delay ≥40 msec (septal-lateral or anterior-posterior). Clinical response to CRT was defined as increase of peakVO2 or as increase of maximal workload10% as compared to baseline.Mean follow-up was 69 ± 37 months. From the 238 consecutive patients included in the study, 141 (59%) were classified as clinical responders and 97 (41%) as nonresponders. Baseline data of responders and nonresponders were comparable. However, clinical responders showed more often LVD (64%) than nonresponders (42%, P = 0.004). On multivariate regression analysis, nonischemic origin of CHF (β-coefficient in the final model 0.1, P = 0.04) and LVD at baseline (β-coefficient in the final model 0.2, P 0.001) were independently associated with clinical response during long-term follow-up. Patients with LVD at baseline had significant more often an improvement of left ventricular ejection fraction10% (P = 0.02) and a reduction of left ventricular end-diastolic diameter (LVEDD)10% (P 0.01) than patients without LVD at baseline.LVD at baseline as assessed by a straightforward echocardiographic approach predicts the long-term clinical response to CRT and is associated with a more pronounced reverse LV remodeling.

Background The purpose of our study was to correlate the incidence of adequate implantable cardioverter-defibrillator (ICD) interventions in hypertrophic cardiomyopathy (HCM) patients with risk markers (RMs) for sudden cardiac death (SCD) plus myocardial fibrosis as detected by late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) imaging. Methods In all, 87 patients with HCM underwent LGE-CMR imaging prior to ICD implantation, performed for secondary (n = 2; 2%) or primary SCD prophylaxis (n = 85; 98%). Fibrosis was graded with a 17-segment left ventricular model (0 = absent, 1=point-shaped, 2=limited to 1 left ventricular segment, 3=involving ≥ 2 segments). During follow-up, ICD memories were read out by a physician blinded to the individual patient data. Results The number of RMs per patient was 1.9 ± 0.8. Myocardial fibrosis was present in 78 patients (90%); 26 (30%) had a fibrosis score of 3. During follow-up (3.5 ± 2.6 [range, 0.2-11.4 years]), 15 patients had 50 appropriate ICD interventions. Episodes of atrial fibrillation were found in 28 patients. Fibrosis severity correlated with occurrence of ventricular tachycardia (Cramer's V, or φc = 0.4, P 0.001) and atrial fibrillation (φc = 0.6, P 0.001). On multivariate regression analysis, an independent association between myocardial fibrosis (s = 0.6, P 0.01) and sustained ventricular tachycardia was found. Conclusions In HCM patients treated with ICD implantation because of a high SCD risk by traditional RM assessment, a high rate of arrhythmic events was observed during long-term follow-up. In a cohort of patients with clinical markers for high risk of SCD, severity of myocardial fibrosis as detected by an easy LGE-CMR scoring system was associated with future arrhythmic events and appropriate ICD therapies.

Magnetically guided irrigated ablation has been introduced for atrial fibrillation (AF) ablation. However, data on ablation of persistent AF is scarce, and first-generation platinum–iridium catheters were burdened by char formation at the catheter tip. Furthermore, energy transmission of these catheters may be suboptimal. Irrigated gold-tip catheters have been introduced to overcome these problems. Antral pulmonary vein (PV) isolation (PVAI) was performed using a 5-mm irrigated gold-tip magnetic catheter (power setting, 48 °C maximum, 50 W, 15 s lesion duration; flow-rate, 30 mL/min). The catheter tip was guided by a uniform magnetic field and a motor drive. Left atrial maps were created using an impedance-based left atrial reconstruction and fused with a preprocedural CT or an intraprocedural rotational angiography-based scan. Fifty-seven patients (42 male, 61.9 ± 8.8 years) underwent PVAI for symptomatic, drug-refractory persistent AF. PVAI was performed successfully in all patients confirmed by entrance block. Procedure time (skin-to-skin) was 214 ± 47 min (104–354 min). Fluoroscopy time was 31 ± 21 min. Ablation time was 4,153 ± 1,350 s. No char or thrombus formation was found at the catheter tip. One pericardial tamponade was observed. Freedom from atrial tachyarrhythmias could be achieved in 57.9 % of the patients included in a follow-up of 11.6 ± 4.2 month. There was a trend to a better outcome in patients without previous attempts of AF ablation (n = 48; 60.4 % vs. 44.4 %, p = 0.47). Remote magnetic navigation for PVAI seems to be safe and feasible using an irrigated gold-tip catheter. Effectiveness of this novel technique can be confirmed by mid-term outcome.

Predictors of AF Recurrence After Cryoballoon PVI. Introduction: In patients with atrial fibrillation (AF) undergoing pulmonary vein isolation, cryoballoon technique (cryoPVI) has been adopted in many centers. This study aimed to evaluate predictors of AF recurrence including impact of sleep-disordered breathing (SDB). Methods and Results: In 82 patients consecutively assigned to cryoPVI cardiorespiratory screening for SDB, assessment of medical history, ECG, echocardiography, standard laboratory measurement, and blood gas analysis were performed prior to intervention. After a 3-month blanking period, a 7-day Holter ECG was performed at 3, 6 and then every 6 months to determine AF recurrence. Seventy-five patients (69 paroxysmal AF, 6 persistent AF, 22 female, age 60 ± 9 years) completed at least 6-month follow-up. Median follow-up of 12 months (interquartile range 6–18 months) confirmed maintenance of sinus rhythm in 69.4% of these patients. Stepwise forward regression model revealed moderate to severe SDB (cut-off apnea-hypopnea-index (AHI) ≥ 15 per hour; Hazard Ratio (HR) 2.95, P = 0.04), early recurrence of AF (HR 8.74, P < 0.001), persistent AF (HR 7.16, P < 0.001), preprocedural class III-antiarrhythmic drug treatment (HR 3.63, P = 0.02), but not SDB per se (AHI ≥ 5 per hour) as independent predictors for AF recurrence. Conclusion: Moderate to severe SDB is a treatable condition that independently predicts AF recurrence in patients undergoing cryoPVI. Screening for SDB and adequate treatment may improve long-term success of cryoPVI. (J Cardiovasc Electrophysiol, Vol. 23, pp. 18-25, January 2012)

Aims Image integration of three-dimensional (3D) reconstructions of left atrial (LA) and pulmonary vein (PV) anatomy into electroanatomical mapping (EAM) plays a major role in atrial fibrillation (AF) ablation. Point-by-point EAM is commonly used for registration of imported LA and PV anatomy. We aimed to assess the accuracy of intraprocedural rotational angiography-based LA imaging registered by spatial reconstruction of intracardiac echocardiography (ICE) in patients undergoing AF ablation. Methods and results Twenty-two patients (11 males, 66 ± 12 years) were studied. Reconstructions of LA and PVs based on rotational angiography were registered by a second 3D reconstruction based on ICE. In a second step, EAM points were added to ICE 3D reconstructions. A 3D image of the LA and PVs was reconstructed in all patients by both imaging modalities. Rotational angiography and ICE-based LA 3D reconstructions took 11.5 ± 5.2 and 20.4 ± 11.2 min, respectively. A total of 17 ± 6 two-dimensional ICE fans were used for spatial reconstruction of ICE. The deviation between the two 3D shells was 2.6 ± 0.5 mm. Integration of 78 ± 58 EAM points into ICE 3D reconstruction did not significantly reduce the deviation to rotational angiography-based reconstructions (2.7 ± 0.6 mm). All PVs were isolated successfully. Conclusions Intraprocedural 3D reconstruction of LA and PVs for ablation of AF is feasible based on both rotational angiography and ICE. LA reconstructions based on rotational angiography can accurately be registered using 3D ICE shells. Additional EAM does not enhance accuracy. Therefore, registration of rotational angiography-based 3D reconstructions by 3D reconstructions from ICE seems to be an alternative technique to support AF ablation.

Intracardiac Echo Supported Cryoballoon Ablation. Introduction: Cryoballoon ablation has been adopted for pulmonary vein (PV) isolation (PVI) in many centers. Complete occlusion of PV by an adequately sized balloon is crucial for effectiveness of cryoenergy delivery. The aim of this study was to evaluate intracardiac echocardiography (ICE) as an alternative imaging technique compared to angiographic imaging in cryoballoon PVI. Methods and Results: A total of 75 PVs were treated in 22 patients (61 ± 13 years, 17 male) undergoing PV cryoballoon ablation for drug refractory paroxysmal atrial fibrillation. Decision for an adequate balloon size was based on diameters of the PV antra assessed by ICE and PV angiography. Per PV 2.4 ± 0.4 cryoenergy pulses were applied. Decision for the balloon size was similar either based upon angiography or on ICE. A single 23 or 28 mm balloon was chosen in 10 and 3 patients, respectively. Two different sized balloons were used in 9 patients. PVI was evaluated after 2 cryoenergy applications. Total occlusion of the PV confirmed by ICE color flow Doppler (CFD) during ablation predicted successful PVI in 70 of 75 (93%) and unsuccessful PVI in 8 of 8 (100%). PV flow registered by pulsed wave Doppler at the PV ostium pre- and postablation was 0.48 ± 0.10 and 0.51 ± 0.12 m/s, respectively (n.s.). PVI was finally confirmed by entrance block in all PVs. No procedural complications occurred. Conclusions: ICE is a feasible novel imaging technique in cryoballoon ablation procedures. It allows decision for adequate balloon size, exact balloon placement, prediction of acute ablation success, and excludes acute narrowing of PV ostia. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1325-1330, December 2010)

We report on the efficacy and follow-up data of pulmonary vein Isolation using the 23 / 28 mm Arctic Front Cryoballoon (Cryocath Canada), which isolates parts of the venous antrum and venous ostium in patients with atrial fibrillation. The technique is safe and highly effective in treating paroxysmal atrial fibrillation. Acutely we could isolate 100 % of the targeted veins comparable to radiofrequency energy. During a mean follow-up period of 8,5 ± 6 months 57 % of the patients had no recurrence of atrial fibrillation at all. 15 % showed a recurrence only during the first three months. Right phrenic nerve damage is the most common complication, but it recovers within months. Avoidance of phrenic nerve palsy is possible with refined use of different balloon diameters and pacing maneuvers.

Background: All current cardiac resynchronization therapy (CRT) devices allow the programming of the atrioventricular (AV/PV) delays and the sequential stimulation of the ventricles via the inter ventricular (VV) delay. Aim: This post hoc analysis of the RHYTHM II study was conducted to compare the reverse remodeling associated with VV delay optimization in patients randomly assigned to simultaneous (SIM) biventricular stimulation versus patients assigned to optimized VV delay programming (OPT) (1:3 randomization scheme). Methods: The analysis included 14 patients assigned to the SIM group and 34 patients to the OPT group who completed the 6-month follow-up period with paired echocardiographic recordings. Results: In both study groups, changes consistent with left ventricular (LV) remodeling were observed between baseline and 6 months, with significant improvements in LV function and decrease in LV dimensions. In the OPT group, there was also a decrease in left atrial diameter and mitral valve closure to opening time. At 6 months, the overall proportion of echocardiographic responders (≥10% decrease in LV end-systolic volume or ≥5% absolute increase in LV ejection fraction) was similar in both groups. The optimal AV/VV delays, evaluated by maximization of LV outflow tract velocity time integral, changed over time. Conclusions: Ventriculo-ventricular delay optimization was associated with better immediate hemodynamic function than simultaneous biventricular stimulation, though did not promote additional reverse remodeling at 6 months and did not increase the proportion of echocardiographic responders to CRT. Optimization of both the AV and VV intervals was patient-specific and optimal values changed over time.

Objectives The purpose of this study was to investigate the efficacy safety of the novel cryoballoon device (Arctic Front, Cryocath, Quebec, Canada). Background Antral pulmonary vein (PV) ablation with radiofrequency energy is widely used as a strategy for catheter ablation of paroxysmal atrial fibrillation (PAF). A novel double lumen cryoballoon catheter was designed for circumferential pulmonary vein isolation (PVI) with the cryoablation technique. Methods We consecutively enrolled 346 patients with symptomatic, drug refractory paroxysmal (n = 293) or persistent (n = 53) atrial fibrillation (AF). In all patients, PVI of all targeted PVs was the therapeutic aim. The primary end points of this nonrandomized study were: 1) acute isolation rate of targeted PV; and 2) first electrocardiogram-documented recurrence of AF. The secondary end point was occurrence of PV stenosis or atrio-esophageal fistula. Results The 1,360 of 1,403 PVs (97%) were targeted with balloons or balloons in combination with the use of Freezor Max (Cryocath). We found that ablation with the cryoballoon resulted in maintenance of sinus rhythm in 74% of patients with PAF and 42% of patients with persistent AF. No PV narrowing occurred. The most frequent complication was right phrenic nerve palsy observed during cryoballoon ablation at the right superior PV. Conclusions Pulmonary vein isolation with a new cryoballoon technique is feasible. Sinus rhythm can be maintained in the majority of patients with PAF by circumferential PVI using a cryoballoon ablation system. Cryoablation was less effective in patients with persistent AF than in patients with PAF.

A correct identification of drought events over vegetated lands can be achieved by detecting those soil moisture conditions that are both unusually dry compared with the ‘normal’ state and causing severe water stress to the vegetation. In this paper, we propose a novel drought index that accounts for the mutual occurrence of these two conditions by means of a multiplicative approach of a water deficit factor and a dryness probability factor. The former quantifies the actual level of plant water stress, whereas the latter verifies that the current water deficit condition is unusual for the specific site and period. The methodology was tested over Europe between 1995 and 2012 using soil moisture maps simulated by Lisflood, a distributed hydrological precipitation–runoff model. The proposed drought severity index (DSI) demonstrates to be able to detect the main drought events observed over Europe in the last two decades, as well as to provide a reasonable estimation of both extension and magnitude of these events. It also displays an improved adaptability to the range of possible conditions encountered in the experiment as compared with currently available indices based on the sole magnitude or frequency. The results show that, for the analyzed period, the most extended drought events observed over Europe were the ones in Central Europe in 2003 and in southern Europe in 2011/2012, while the events affecting the Iberian Peninsula in 1995 and 2005 and Eastern Europe in 2000 were among the most severe ones. © 2015 European Commission - Joint Research Centre. Hydrological Processes published by John Wiley & Sons Ltd.

Aims Earlier ICD therapy included an electrophysiological study (EPS), an extensive defibrillation threshold test (DFT), and a pre-discharge test. Now that ICD-therapy is widely accepted, an EPS is no longer performed in most patients, extensive DFT-tests have been reduced to a minimum of two effective shocks and discharge tests have been discarded in most centres. However, it has never been demonstrated prospectively that this simplification is safe. Methods and results The Quick-Implantable-Defibrillator (Quick-ICD) Trial was a prospective multi-centre trial, which randomized patients, who had survived a cardiac arrest (SCD) or an unstable ventricular tachycardia (VT), to two different clinical strategies:(a) The extensive strategy included an EPS, an extensive DFT-test, and a pre-discharge test; (b) In the simplified approach ( quick strategy ) the ICD was implanted without an EPS and a pre-discharge test. Two effective shocks during implantation at 21 J were sufficient. The primary endpoint of this trial was a cluster of adverse events related to the diagnostic approach and to ICD-therapy. One hundred and ninety patients were included, 97 randomized to the extensive-, 93 to the quick strategy. Mean follow-up was 12 ± 7 months. Twenty-seven patients reached the endpoint in the quick group and 32 in the extensive group. During follow-up, the event-free survival was equal in the two study arms (test for equivalence, P = 0.0044). The initial hospital stay was significantly shorter in the quick population (8.4 ± 4.7 vs. 11.2 ± 7.4 days, P = 0.004) Conclusion It is safe and cost-effective to implant an ICD without an EPS, an extensive DFT-, and a pre-discharge test in carefully selected patients after survived SCD or unstable VTs.

Aims This study investigates the influence of cardiac resynchronisation therapy (CRT) on sleep disordered breathing (SDB) in patients with severe heart failure (HF). Methods and results Seventy-seven patients with HF (19 females; 62.6±10 years) eligible for CRT were screened for presence, type, and severity of SDB before and after CRT initiation (5.3±3 months) using cardiorespiratory polygraphy. NYHA class, frequency of nycturia, cardiopulmonary exercise, 6-minute walking test results, and echocardiography parameters were obtained at baseline and follow-up. Central sleep apnoea (CSA) was documented in 36 (47%), obstructive sleep apnoea (OSA) in 26 (34%), and no SDB in 15 (19%) patients. CRT improved clinical and haemodynamic parameters. SDB parameters improved in CSA patients only (apnoea hypopnoea index: 31.2±15.5 to 17.3±13.7/h, p

Failure to enter the coronary sinus (CS) with a guiding catheter and entering its tributaries remains challenging in left ventricle (LV) pacing lead implants for cardiac resynchronization therapy (CRT). A dual telescoping catheter system (8F outer/6F inner) is designed to provide the ability to adjust the catheter curve size, shape and/or reach to the patients' anatomy avoiding the need for catheter change.Five different designs for CS cannulation were randomly tested in 64 patients scheduled for CRT device implant.In 33 consecutive patients three adaptable telescoping guiding catheter systems were tested per patient, the adaptable catheters had higher overall cannulation success rates (68, 63 and 62%) compared to the fixed shape catheter (46%) and an greater cannulation success rate when the CS location was not known (70, 53 and 72% vs 33% for the fixed shape). In a second group of 31 CRT patients the two telescoping catheters had similar high levels of success (71-80%), with or without using the inner catheter.The telescopic system is adaptable to a wide range of anatomical variations in patients and can result in a higher CS cannulation success rate due to its adjustability in the RA in search for the CS ostium. On top of this the inner catheter allows for sub-selecting the CS tributaries.

Sirs: A 68-year-old man with mitral valve replacement but former mitral regurgitation II (left atrial size 39 mm) and coronary artery sclerosis suffered syncope due to a sustained ventricular tachycardia. Before this event, the patient had neither palpitations nor was arrhythmia documented by Holter ECGs. A single chamber cardioverter/defibrillator (SJM, Atlas VR) was implanted. Routine abdominal ultrasound did not reveal pathologic findings at that

Objective: Mutations in the cardiac ryanodine receptor ( RYR2 ) gene have been reported to cause arrhythmogenic right ventricular cardiomyopathy (ARVC). The molecular mechanisms by which genetic modifications lead to ARVC are still not well understood. Methods ARVC patients were screened for mutations in the RYR2 gene by denaturing HPLC and DNA sequencing. Single channel measurements were carried out with RyR2 channels purified from explanted hearts of ARVC patients. Results: None of the published RYR2 mutations were found in our ARVC-cohort. However, we identified two single nucleotide polymorphisms (SNPs) in exon 37 of the human RYR2 gene which lead to the amino acid exchanges G1885E and G1886S, respectively. Both SNPs together were found exclusively in 3 out of 85 ARVC patients in a composite heterozygous fashion (genotype T4). This genotype was associated with ARVC ( p

Background The clinical value of interventricular (V-V) delay optimization in patients with chronic congestive heart failure (CHF) undergoing implantation of a device for cardiac resynchronization therapy (CRT) has not been clearly demonstrated. Methods RHYTHM II was a single-blind randomized trial including 121 recipients of a device for CRT with cardioverter/defibrillator capabilities (CRT-D) randomly assigned in a 1:3 ratio to simultaneous (n = 30) versus optimized (OPT) (n = 91) biventricular pacing. V-V delay was optimized by echocardiography. The study end points were (1) freedom from CRT-D system–related complications and (2) changes between preimplant and 6 months of follow-up in ( a ) New York Heart Association CHF functional class, ( b ) distance covered during a 6-minute hall walk, and ( c ) quality of life (QOL). Results In the OPT group, the V-V delay ranged from 0 to 80 milliseconds, with 28.4% of patients stimulated at an OPT V-V delay of 0 milliseconds. The overall 6-month survival free of adverse events requiring invasive interventions was 81.8%. In the whole cohort, 6 months of CRT-D was associated with a significant decrease in New York Heart Association class, increase in the distance covered during the 6-minute hall walk, and improvement in QOL (each P Conclusions Cardioverter-defibrillator capabilities was associated with a significant alleviation of CHF symptoms, increase in functional capacity, and improvement in QOL. The optimization of the V-V delay conferred no additional benefit compared with simultaneous biventricular stimulation.

Since the development of the first epicardial left ventricular pacemaker leads, the design of transvenous coronary leads has progressed tremendously. Due to the safe access to the target region independent of previous surgical interventions and a low morbidity, the transvenous placement has become the method of choice. Catheterization of the coronary sinus is required to place the coronary venous lead. The most difficult anatomical situation is the pipe-shaped coronary sinus. A systolic compression of the proximal coronary sinus may be associated with a risk of dissection particularly in elderly patients. Access to the coronary sinus is best made by two combinationsystemswithasteerableelectrophysiology catheter oratelescoping inner catheter. Furthermore, special guiding catheters for the access from the right subclavian vein particularly to upgrade right-sided pacemakers and ICD systems have been developed. Complex, i.e. sharp-angled and corkscrew veins may only serve as target veins, if sharp-angled angiography catheters and over the wire technique are used. The pseudobipolar stimulation against the ring of the right ventricular lead has been developed for the safe function of a CRT defibrillator. This design is associated with an anodal stimulation of the right ventricle, which might result in clinical nonresponders especially in patients with optimal left ventricular pacing mode (30%). For this reason, coronary sinus leads should basically be designed as bipolar leads.

Introduction Patients with advanced heart failure received cardiac resynchronisation therapy at our centre, if the following selection criteria were fulfilled: NYH/ class ≥3, left bundle branch block with QRS width ≥150 ms, left ventricular ejection fraction 60 mm, VO 2 peak

Inter- and intraventricular conduction defects may result in unfavourable haemodynamic consequences which may significantly deteriorate preexisting heart failure. Cardiac resynchronization therapy (CRT) has been shown to improve the outcome in patients with severely symptomatic systolic heart failure and wide QRS complex. Still unanswered questions are: (a) optimal patient selection and prediction of response, (b) optimal definition of "asynchrony" (QRS duration, echo parameters), (c) optimal tailoring of CRT (AV-delay, VV-delay, pacing site), (d) extended indications. This review will discuss "extended" indications for CRT not yet proven effective but worth being studied in controlled trials in the near future.

Pressure–volume measurements by conductance catheter enable assessment of systolic and diastolic left ventricular function and quantification of mechanical dyssynchrony in a continuous and on-line fashion. The present review gives an overview of the (potential) applications of this methodology in relation to cardiac resynchronization therapy.

Aims Several studies on the acute effect of cardiac resynchronization in patients with advanced heart failure (HF) and left bundle branch block (LBBB) have shown that left and biventricular stimulation increase pulse pressure and contractility, while patients with a QRS complex \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \({\) \end{document}150 ms underwent right, left and biventricular stimulation at different AV delays. Acute response was defined as 10% pulse pressure increase. 165 of 188 patients (88%) in sinus rhythm (47 women, mean age 62.5±10 years, ejection fraction 23±8%, NYHA class 3.1±0.3) were regarded acute responders. 10% of 103 patients with dilated cardiomyopathy and 16.5% of 79 patients with coronary artery disease were considered non-responders. 29 patients (81%) with two posterolateral veins were acute responders with 10 of them (33%) being responders in only one vein. 54 patients had an atrio-left ventricular pulse pressure increase of 10.7±10.6%, 9.8±6.4% in 48 patients with atrio-biventricular stimulation. At one-year follow-up, heart failure had significantly improved from NYHA class 3.1±0.4 to 2.1±0.7 (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(P{

In patients with systolic heart failure the assessment of peak oxygen consumption during cardiopulmonary exercise (CPX) testing provides an objective measure of functional capacity and important prognostic information. Several studies in pacemaker therapy and in cardiac resynchronization therapy (CRT) have used peak oxygen uptake as an endpoint. This article reviews the impact of CPX testing on patient selection for CRT.

Based on the recent experience of 464 patients with left ventricular pacing, we report on specific characteristics of various leads and lead types for left ventricular stimulation. In addition to describing the technique and indications for epicardial lead usage, commercially available coronary vein leads are introduced and discussed. Since there is no universally applicable coronary vein lead, the individually optimal lead choice and the sequelae of an erroneous lead selection are described in typical clinical examples.

The implantable defibrillator (ICD) is an established therapy in the prevention of sudden cardiac death by defibrillation of ventricular fibrillation. Another specific feature of the ICDs is antitachycardia pacing (ATP) of ventricular tachycardia. Several studies report success rates of ATP in 83 to 98% of cases. In clinical practice the success of terminating ventricular tachycardia is estimated only by automatic device analysis. Therefore the objective of this study was to confirm the efficacy of ATP based on the evaluation of stored electrograms. From the German Ventritex MD-register stored electrograms of 613 monomorphic ventricular tachycardias in 44 patients were analyzed retrospectively. The cycle length of the ventricular tachycardias was between 265 and 560 ms. The success rate of ATP-induced termination of the episodes reached 89.3%; another 2.3% of the ventricular tachycardias were accelerated by antitachycardia pacing into ventricular fibrillation. Left ventricular function did not influence the success rate, but the success rate was lower for fast ventricular tachycardias >200/min (63.9%). For ventricular tachycardias 90% was recorded for 80% of them. The very high success rate of the first ATP attempt in ICD therapy can be achieved with uniform programming, and is confirmed for ventricular tachycardias analyzed on the basis of stored electrograms.

Supraventricular tachyarrhythmias are a major cause of inappropriate defibrillator shocks. Sleep-disordered breathing (SDB) is a known risk factor for atrial fibrillation (AF). We hypothesized that Cheyne–Stokes respiration (CSA) and obstructive sleep apnea (OSA) have an impact on inappropriate defibrillator discharges in patients witch chronic heart failure (CHF) and cardiac resynchronization therapy with defibrillator (CRT-D). In this study, 172 patients with CHF (LVEF ≤ 45 %, NYHA-class ≥ 2) and CRT-D underwent overnight polygraphy; 54 had no SDB (apnea–hypopnea index

GRONEFELD, G.C., et al.: Morphology Discrimination: A Beat-to-Beat Algorithm for the Discrimination of Ventricular From Supraventricular Tachycardia by Implantable Cardioverter Defibrillators. Inappropriate therapy of SVTs by ICDs remains a major clinical problem despite enhanced detection criteria like “sudden onset” and “rate stability” in third-generation devices. Electrogram morphology discrimination offers an additional approach to improve discrimination of supraventricular tachycardia (SVT) from ventricular tachycardia (VT). In a prospective, multicenter study, patients received an ICD with a beat-to-beat algorithm for morphological analysis of the intracardiac electrogram (Morphology Discrimination, MD). A nominal programming for standard enhancement criteria and morphology discrimination was required at implant. Electrogram storage of tachycardia episodes irrespective of delivery of therapy was used to assess sensitivity and specificity of the morphology algorithm alone and in combination with established detection criteria. During a 12 6 6-month follow-up, 886 episodes of device stored electrograms from 82 of 256 patients were evaluated. At nominal settings, the MD algorithm correctly identified 423 of 551 episodes as VT resulting in sensitivity of 77%. The classification of SVT was met in 239 of 335 episodes resulting in specificity of 71%. In combination with sudden onset, sensitivity increased to 99.5% at the expense of specificity (48%). In conclusion, SVT-VT discrimination based on morphological analysis alone results in limited sensitivity and specificity. Programming the monitor mode allows individual assessment of the performance of this detection enhancement feature during clinical followup without compromising device safety. Only in patients with documented efficacy of morphology discrimination should this feature be subsequently activated.

Background —Previous studies of pacing therapy for dilated congestive heart failure (CHF) have not established the relative importance of pacing site, AV delay, and patient heterogeneity on outcome. These variables were compared by a novel technique that evaluated immediate changes in hemodynamic function during brief periods of atrial-synchronous ventricular pacing. Methods and Results —Twenty-seven CHF patients with severe left ventricular (LV) systolic dysfunction and LV conduction disorder were implanted with endocardial pacing leads in the right atrium and right ventricle (RV) and an epicardial lead on the LV and instrumented with micromanometer catheters in the LV, aorta, and RV. Patients in normal sinus rhythm were stimulated in the RV, LV, or both ventricles simultaneously (BV) at preselected AV delays in a repeating 5-paced/15-nonpaced beat sequence. Maximum LV pressure derivative (LV+dP/dt) and aortic pulse pressure (PP) changed immediately at pacing onset, increasing at a patient-specific optimal AV delay in 20 patients with wide surface QRS (180±22 ms) and decreasing at short AV delays in 5 patients with narrower QRS (128±12 ms) ( P P P Conclusions —In this population, CHF patients with sufficiently wide surface QRS benefit from atrial-synchronous ventricular pacing, LV stimulation is required for maximum acute benefit, and the maximum benefit at any site occurs with a patient-specific AV delay.

In conjunction with pharmacologic therapy, pacing has been proposed as a potential treatment to decrease symptoms in patients with moderate-to-severe congestive heart failure (CHF). Uncontrolled studies of pacing therapy for CHF dealing with different pacing sites, modes of pacing, and atrioventricular delays have reported mixed outcomes. The Pacing Therapies in Congestive Heart Failure (PATH-CHF) study is a single-blind, randomized, crossover, controlled trial designed to evaluate the effects of pacing on acute hemodynamic function and to assess chronic clinical benefit in patients with moderate-to-severe CHF. The effect of pacing on oxygen consumption at peak exercise and at anaerobic threshold during cardiopulmonary exercise tests, and on 6-minute walk distance, have been selected as primary endpoints of the study. Secondary endpoints of the trial were changes in New York Heart Association (NYHA) functional class, quality-of-life as assessed by the Minnesota Living with Heart Failure questionnaire, and hospitalization frequency. Finally, changes in ejection fraction, cardiac output, and filling pattern were assessed by echocardiography. The trial was planned to include 53 patients from 7 centers in Europe over a period of 3 years. The study was divided into 2 parts: acute testing and chronic follow-up. The acute study, performed during the pacemaker implantation, involved extensive testing using a custom-designed computer (FLEXSTIM) and a unique burst pacing protocol (FLEXSTIM protocol) to determine the best ventricular pacing sites and the most appropriate atrioventricular delays. The chronic phase consisted of a crossover study designed to test in each patient the best univentricular pacing site and biventricular pacing as assessed by the acute hemodynamic study. The study started with the first implant in 1995 and has, to date, included 42 patients. The study is expected to be completed by the end of 1998. The results of a first interim analysis showed trends toward improvement in all primary and secondary endpoints during the pacing periods compared with no pacing.

Aims The population treated with cryoballoon (CB) ablation is relatively young, and radiation protection is of major importance. We aimed to demonstrate that radiation exposure can be markedly reduced by intracardiac echocardiography (ICE) and optimized settings of the X-ray system. Methods and results We analysed 100 patients undergoing CB pulmonary vein isolation (PVI) for treatment of paroxysmal atrial fibrillation. In 50 consecutive patients (25 male, 59 ± 13 years; Group 1), we used ICE, skipped PV angiography prior to CB inflation, and avoided fluoroscopy whenever possible. Furthermore, we reduced the frame rate, minimized distance between patient and detector, and consequently applied collimation. These patients were compared with 50 similar preceding patients in Group 2 (29 male, 61 ± 12 years). Total fluoroscopy time was reduced from 18 ± 6 min in Group 2 to 12 ± 5 min in Group 1 ( P < 0.001). Moreover, the dose area product was significantly lower (1555 ± 1219 vs. 4935 ± 2094 cGycm2, P < 0.001), total freezing time was significantly shortened (1855 ± 399 vs. 2121 ± 756 s, P = 0.031), and contrast media use was significantly reduced (66 ± 25 vs. 109 ± 27 mL, P < 0.001). At the same time, total procedure duration and complication rates did not differ significantly between both groups. After a 12 months follow-up, a similar percentage of patients was free from recurrences (74% in Group 1 vs. 78% in Group 2, P = 0.640). Conclusion Radiation exposure in CB PVI can be markedly reduced without prolonging procedure times, affecting the outcome or complication rates. Moreover, ICE seems to shorten total freezing time.

Aims Studies have shown that remote magnetic navigation is safe and effective for ablation of atrial arrhythmias, although optimal outcomes often require frequent manual manipulation of a circular mapping catheter. The Vdrive robotic system ('Vdrive') was designed for remote navigation of circular mapping catheters to enable a fully remote procedure. This study details the first human clinical experience with remote circular catheter manipulation in the left atrium. Methods and results This was a prospective, multi-centre, non-randomized consecutive case series that included patients presenting for catheter ablation of left atrial arrhythmias. Remote systems were used exclusively to manipulate both the circular mapping catheter and the ablation catheter. Patients were followed through hospital discharge. Ninety-four patients were included in the study, including 23 with paroxysmal atrial fibrillation (AF), 48 with persistent AF, and 15 suffering from atrial tachycardias. The population was predominately male (77%) with a mean age of 60.5 ± 11.7 years. The Vdrive was used for remote navigation between veins, creation of chamber maps, and gap identification with segmental isolation. The intended acute clinical endpoints were achieved in 100% of patients. Mean case time was 225.9 ± 70.5 min. Three patients (3.2%) crossed over to manual circular mapping catheter navigation. There were no adverse events related to the use of the remote manipulation system. Conclusions The results of this study demonstrate that remote manipulation of a circular mapping catheter in the ablation of atrial arrhythmias is feasible and safe. Prospective randomized studies are needed to prove efficiency improvements over manual techniques.

Our goal was to evaluate acute effects of left atrial lesion formation and volume overload on hemodynamics during pulmonary vein antrum isolation (PVAI) as it might be a potential cause of acute pulmonary edema. In consecutive patients presenting for PVAI, open irrigation ablation was performed (50 W, 48°C, 15 s lesion duration, saline flow rate 30 mL/min). Blood samples were drawn from the left atrium and the pulmonary artery immediately before and 30 min after PVAI. The cardiac output (CO) and stroke volume (SV) were calculated by the method of Fick. We included 61 (27 female, 61 ± 11 years) patients suffering from paroxysmal (px; 33) or persistent (per; 28) atrial fibrillation (AF) in this study. A total of 2,917 ± 242 mL of volume was infused (2,651 ± 223 mL pxAF vs. 3,184 ± 255 mL perAF, (p

Background Recent studies have shown that cryoablation and radiofrequency (RF) ablation are comparable with regard to success rates and safety in the treatment of common atrial flutter (AFL). Long-term success requires persistence of bidirectional conduction block (BCB) in the inferior cavotricuspid isthmus (CTI). Objective The purpose of this study was to determine the persistence of BCB in a prospective randomized multicenter trial of the two ablation techniques. Methods A total of 191 patients were randomized to RF ablation or cryoablation of the CTI using an 8-mm-tip catheter. In all patients, BCB was defined as the ablation end-point. Primary end-point of the study was nonpersistence of achieved BCB and/or ECG-documented relapse of common AFL within 3-month follow-up. Results Acute success rates were 91% (83/91) in the RF group and 89% (80/90) in the cryoablation group (P = NS). Invasive follow-up after 3 months with repeated electrophysiologic study was available for 60 patients in the RF group and 64 patients in the cryoablation group. Persistent BCB could be confirmed in 85% of the RF group versus 65.6% of the cryoablation group. The primary end-point was achieved in 15% of the RF group and 34.4% of the cryoablation group (P = .014). As a secondary end-point, pain perception during ablation was significant lower in the cryoablation group (P Conclusion Persistence of BCB in patients treated with cryoablation reinvestigated after 3 months is inferior to that patients treated with RF ablation, as evidenced by the higher recurrence rate of common AFL seen in this study.

SUMMARY Background: Obstructive sleep apnea (OSA) is more common in patients with atrial fibrillation (AFib). Recently, an additional association between central sleep apnea/CheyneStokes respiration (CSA/CSR) and AFib has been described. The aim of this study was to investigate the prevalence and type of sleep-disordered breathing in patients with AFib and normal systolic left ventricular function. Methods: 150 patients (110 men and 40 women, aged 66.1 ± 1.7 years) underwent cardiorespiratory polygraphy, capillary blood gas analysis, measurement of NT-proBNP, and echocardiography to determine the diameter of the left atrium (LAD) and the peak systolic pulmonary artery pressure (PAP). Results: Sleep-disordered breathing was documented in 74% of all patients with AFib (43% had OSA and 31% had CSA/CSR). Patients with CSA/CSR had a higher PAP, a higher apnea-hypopnea index, a greater LAD, and a lower capillary blood pCO2 than patients with OSA. Conclusions: Patients with AFib were found to have not only a high prevalence of obstructive sleep apnea, as has been described previously, but also a high prevalence of CSA/CSR. It remains unknown whether CSA/CSR is more common in AFib because of diastolic dysfunction or whether phenomena associated with CSA/CSR predispose to AFib. Further research on this question is needed.

Background Cardiac transplantation remains the gold standard for treating end-stage heart failure. However, because of donor shortage and posttransplant complications alternative options are needed. Methods We investigated the impact of cardiac resynchronization therapy on clinical outcome in 545 patients with left bundle-branch block and interventricular asynchrony, who fulfilled the cardiac criteria for cardiac transplantation listing. Primary end point was heart failure death. Secondary end points were New York Heart Association class, functional (cardiopulmonary exercise tolerance, 6-minute hall walk distance), and morphologic (left ventricular end-diastolic diameter) factors. Results The average follow-up period was 39.6 months (standard deviation, 26.1 months). In total, 1,784 years of observation were accrued. The percentage of nonresponders (no functional and morphologic improvement during follow-up) was 21.2%. One-year and 3-year freedom from heart failure death was 92.3% and 77.3%, respectively. Functional variables improved, but the left ventricular end-diastolic diameter decreased during the first 6 months of cardiac resynchronization therapy only in patients who survived during follow-up. Under cardiac resynchronization therapy, 42.5% (n = 34) of the cardiac transplantation candidates with atrial fibrillation at baseline returned to sinus rhythm. Conclusions Our data suggest that cardiac resynchronization therapy is a reliable long-term therapeutic option for the treatment of end-stage heart failure and intraventricular asynchrony.

Aims We studied the effects of cardiac resynchronization therapy (CRT) on global and regional myocardial oxygen consumption (MVO2) and myocardial blood flow (MBF) in non-ischaemic (NICM) and ischaemic dilated cardiomyopathy (ICM). Methods and results Thirty-one NICM and 11 ICM patients, all of them acute responders, were investigated. MVO2 and MBF were obtained by 11C-acetate PET before and after 4 months of CRT. In NICM global MVO2 and MBF did not change during CRT, while the rate pressure product (RPP) normalized MVO2 increased ( P =0.03). Before CRT regional MVO2 and MBF were highest in the lateral wall and lowest in the septum. Under therapy, MVO2 and MBF decreased in the lateral wall ( P =0.045) and increased in the septum ( P =0.045) resulting in a more uniform distribution. In ICM, global MVO2, MBF, and RPP did not change under CRT. Regional MVO2 and MBF showed no significant changes but a similar tendency in the lateral and septal wall to that in NICM. Conclusion CRT induces changes of MVO2 and MBF on a regional level with a more uniform distribution between the myocardial walls and improved ventricular efficiency in NICM. Based on the investigated parameters, CRT appears to be more effective in NICM than in ICM.

Objective: In patients with dilated cardiomyopathy (DCM), left bundle branch block (LBBB) is a common finding. The characteristic feature is an asynchronous septal wall motion and most frequently a delay of the lateral and/or posterior wall segments. With the onset of cardiac resynchronization therapy, there is a focus on the specific pathophysiology of a LBBB. However, quantitative data on regional myocardial oxygen consumption (MVO2) and blood flow (MBF) are missing. Methods: We studied 31 patients with severe DCM and LBBB (ejection fraction 22.1±7.1%) and 14 patients with mild to moderate DCM without LBBB (ejection fraction 46.7±7.9%). Global and regional MVO2 as well as MBF were determined from a dynamic 11C-acetate positron emission tomography (PET) study. Results: Global MVO2 and MBF were lower in the DCM group with LBBB than in the control group (P

Bystander effects have been proposed as a third action pathway of ionising radiation besides direct and indirect effects. The purpose of the study was to investigate whether expression of interleukin-1alpha (IL-1alpha) and beta1-integrin is elevated in bystander cells as a marker for bystander effects in comparison with classical markers such as the clonogenic assay, apoptosis and the presence of micronuclei. The hybrid cell line E.A. hy.926 obtained by fusion of HUVEC cells with the epithelial cell line A 459 was irradiated with 0-5 Gy. Bystander effects were established via medium transfer at 45 min and 4 h after irradiation from irradiated to nonirradiated cell populations. In order to exclude effects of the irradiated medium itself, irradiated medium only was also used for transfer to nonirradiated cells. Then, cells were fixed at 1, 2, 6, and 24 h after irradiation or medium transport and IL-1alpha and beta1-integrin were detected and evaluated. A higher number of beta1-integrin-positive cells was observed in both irradiated and bystander cell populations than in the control group at 1 and 24 h after irradiation with 1 Gy or medium transfer. Significantly higher numbers of IL-1alpha-positive cells were found at 1, 2, and 6 h after irradiation with 1 Gy or medium transfer as well as at 2 and 6 h after irradiation with 5 Gy or medium transfer. Clonogenic survival decreased dependently on the dose in irradiated cells but did not show any significant difference between the bystander cell populations and sham-irradiated cells. The irradiated medium itself did not have any effect. It is concluded that beta1-integrin and IL-1alpha expression may serve as more sensitive markers of post-irradiation responses in bystander cell populations than the classical radiobiological markers. Moreover, overexpression of beta1-integrin and IL-1alpha may induce increased susceptibility to inflammation of bystander cells.

The bystander effect is a relatively new area of radiobiological research, which is aimed at studying post-radiation changes in neighboring non-hit cells or tissues. The bystander effect of ionizing irradiation is important after low-dose irradiation in the range of up to 0.2 Gy, where a higher incidence of stochastic damage was observed than was expected from a linear-quadratic model. It is also important when the irradiation of a cell population is highly non-uniform. Objective: This review summarizes most of the important results and proposed bystander effect mechanisms as well as their impact on theory and clinical practice. The literature, in parts contradictory, is collected, the main topics are outlined, and some basic papers are described in more detail. In order to illustrate the microbeam technique, which is considered relevant for the bystander effect research, the state of the Leipzig LIPSION nanoprobe facility is described. Results: The resistence of a radiation-induced bystander effect is now generally accepted. The current state of knowledge on it is summarized here. Several groups worldwide are working on understanding its different aspects and its impact on radiobiology and radiation protection. Conclusion: The observation of a bystander effect has posed many questions, and answering them is a challenging topic for radiobiology in the future.

NIEHAUS, M., et al.: Adjustment of Maximum Automatic Sensitivity (Automatic Gain Control) Reduces Inappropriate Therapies in Patients with Implantable Cardioverter Defibrillators. Patients with ICDs might experience oversensing associated with inappropriate shock therapy when paced at low bradycardia rates or if they have a low intrinsic rhythm. The amplifier gain of automatic gain control is maximal at long RR intervals and might lead to oversensing of myopotentials. The hypothesis was that an individual adjustment of the sensitivity floor could reduce inappropriate ICD therapies. Fourteen patients implanted with the VENTAK MINI I/II and III in whom oversensing and/or inappropriate shocks had been documented were included in this evaluation based on stored episodes. Sensitivity was modified in all ICDs by means of noninvasive software downloading that allowed reprogramming of the maximum sensitivity from 0.14 mV in two steps to 0.27 mV (“Normal,”“Less,”“Least”). Provocation testing (deep inspiration, sit-ups, and abdominal pressing) was conducted at “Nominal” settings (0.14 mV) while the intracardiac electrogram with annotated event marker was running continuously and was repeated at 0.22 mV (Less) and 0.27 mV (Least). All patients evaluated had documented spontaneous episodes due to oversensing before the sensitivity floor was reprogrammed. During provocation testing at Nominal settings, oversensing could be documented in 9 of (64.3%) 14 patients. Provocation testing was repeated after the sensitivity selection was reprogrammed and oversensing could not be provoked in any of the 14 implanted devices. Sensitivity was reprogrammed in all 14 patients to a higher value (5 patients Less, 9 patients Least). After sensitivity adjustment, VF was induced in all patients to verify appropriate arrhythmia detection and termination. Sensitivity reprogramming in patients with documented oversensing eliminates the incidence of inappropriate shock therapy without compromising the ability to detect VF appropriately.

Ventricular resynchronization therapy (VRT) by left or biventricular stimulation is gaining increasing acceptance as a new therapy in addition to drugs in patients with advanced heart failure and intraventricular conduction disturbances. Several studies have demonstrated acute hemodynamic benefit of VRT in these patients, although there are only limited long-term data in small patient cohorts. Many open questions remain: whether to pace both ventricles or the left ventricle alone, the optimal left ventricular pacing site, the criteria used to identify the optimal candidate for VRT (e.g., QRS width), and the importance of an integrated defibrillator function in a VRT device. The Pacing Therapy in Congestive Heart Failure (PATH-CHF) II study is a prospective, randomized, cross-over study currently investigating the potential benefit of VRT in a population with advanced heart failure, with or without an accepted indication for an implantable defibrillator. It focuses on the effects of optimized univentricular pacing in these patients, and both acute hemodynamic and chronic functional effects are assessed. Acute hemodynamic testing mainly investigates the impact of different left ventricular pacing sites, alone or combined with right ventricular sites, on hemodynamic performance. Primary endpoint of the study is an improvement in functional capacity as assessed by cardiopulmonary exercise testing and 6-minute walk distance; secondary endpoints include improvement in quality of life (assessed by Minnesota quality of life score, New York Heart Association (NYHA) functional class, and hospitalization frequency), and improvements in prognostic and hemodynamic parameters. The trial aims to enroll 64 patients with full datum sets (separately in 2 groups with a QRS ofor = 150 or150 msec, respectively) in 9 European centers. The enrollment began September 1998, and is expected to conclude in summer 2000 to reach the number of necessary datum sets.