A frozen decade: Ten years outcome of atrial fibrillation ablation using a single shot device for pulmonary vein isolation.

AIMS: Cryoballoon-guided pulmonary vein isolation (CB-PVI) for symptomatic atrial fibrillation (AF) has become an established treatment option with encouraging results in terms of safety and efficacy. Data reporting on long-term data beyond a follow-up (FU) period of 5 years is scarce. This prospective study aimed to evaluate very long-term outcome after CB-PVI for AF. METHODS: Data from consecutive patients treated with CB-PVI for symptomatic and drug refractory AF between 2005 and 2012 were analyzed. Patients with a FU of ≥9 years after index CB-PVI were included. All patients were continuously followed-up in our outpatient clinic. Arrhythmia recurrence was defined as AF or atrial tachycardia (AT) lasting >30 s beyond a 3-month blanking period. RESULTS: A total of 385 patients (71% male) were included. Mean age was 58 ± 10 years and paroxysmal AF was present in 93% of patients. Mean FU duration was 124 ± 24 months. At the end of the observational period, 73% of all patients were in stable sinus rhythm after a mean of 2 ± 0.8 ablation procedures. Patients with AF/AT recurrence were older (60 ± 8 vs. 57 ± 10 years; p = .019), had a higher CHA2 DS2 -Vasc Score (2.47 ± 1.46 vs. 1.98 ± 1.50; p = .01) and presented with a larger left atrium (LA)-diameter (43 ± 5.6 vs. 40 ± 5.1 mm; p = .002). The LA-diameter was also a significant predictor for AF/AT recurrence after CB-PVI (odds ratio: 0.939, 95% confidence interval: [0.886, 0.992], p = .03). CONCLUSIONS: CB-PVI as index procedure for AF ablation resulted in favorable long-term outcome in symptomatic AF. CB-PVI might be recommended as interventional therapy in patients with lower LA remodeling.

Catheter Ablation for Atrial Fibrillation with Heart Failure.

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 failure. RESULTS: After a median follow-up of 37.8 months, the primary composite end point occurred in significantly fewer patients in the ablation group than in the medical-therapy group (51 patients [28.5%] vs. 82 patients [44.6%]; hazard ratio, 0.62; 95% confidence interval [CI], 0.43 to 0.87; P=0.007). Significantly fewer patients in the ablation group died from any cause (24 [13.4%] vs. 46 [25.0%]; hazard ratio, 0.53; 95% CI, 0.32 to 0.86; P=0.01), were hospitalized for worsening heart failure (37 [20.7%] vs. 66 [35.9%]; hazard ratio, 0.56; 95% CI, 0.37 to 0.83; P=0.004), or died from cardiovascular causes (20 [11.2%] vs. 41 [22.3%]; hazard ratio, 0.49; 95% CI, 0.29 to 0.84; P=0.009). CONCLUSIONS: Catheter ablation for atrial fibrillation in patients with heart failure was associated with a significantly lower rate of a composite end point of death from any cause or hospitalization for worsening heart failure than was medical therapy. (Funded by Biotronik; CASTLE-AF ClinicalTrials.gov number, NCT00643188 .).

Reduction of radiation exposure in cryoballoon ablation procedures: a single-centre study applying intracardiac echocardiography and other radioprotective measures.

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.

The equilibrium molecular structures of 2-deoxyribose and fructose by the semiexperimental mixed estimation method and coupled-cluster computations.

Fructose and deoxyribose (24 and 19 atoms, respectively) are too large for determining accurate equilibrium structures, either by high-level ab initio methods or by experiments alone. We show in this work that the semiexperimental (SE) mixed estimation (ME) method offers a valuable alternative for equilibrium structure determinations in moderate-sized molecules such as these monosaccharides or other biochemical building blocks. The SE/ME method proceeds by fitting experimental rotational data for a number of isotopologues, which have been corrected with theoretical vibration-rotation interaction parameters (αi), and predicate observations for the structure. The derived SE constants are later supplemented by carefully chosen structural parameters from medium level ab initio calculations, including those for hydrogen atoms. The combined data are then used in a weighted least-squares fit to determine an equilibrium structure (r). We applied the ME method here to fructose and 2-deoxyribose and checked the accuracy of the calculations for 2-deoxyribose against the high level ab initio r structure fully optimized at the CCSD(T) level. We show that the ME method allows determining a complete and reliable equilibrium structure for relatively large molecules, even when experimental rotational information includes a limited number of isotopologues. With a moderate computational cost the ME method could be applied to larger molecules, thereby improving the structural evidence for subtle orbital interactions such as the anomeric effect.

Why it is sometimes difficult to determine the accurate position of a hydrogen atom by the semiexperimental method: structure of molecules containing the OH or the CH3 group.

The semiexperimental (SE) technique, whereby equilibrium rotational constants are derived from experimental ground-state rotational constants and corrections based on an ab initio cubic force field, has the reputation to be one of the most accurate methods to determine an equilibrium structure ( reSE). However, in some cases, it cannot determine accurately the position of the hydrogen. To investigate the origins of this difficulty, the SE structures of several molecules containing either the OH or the CH3 group are determined and compared to their best ab initio counterparts. It appears that an important factor is the accuracy of the geometry used to calculate the force field, in particular when the least-squares system is not well conditioned. In this case, the mixed regression method is often an easy way to circumvent this difficulty.

van der Waals radii of noble gases.

Consistent van der Waals radii are deduced for Ne-Xe, based on the noble gas···oxygen intermolecular distances found in gas phase structures. The set of radii proposed is shown to provide van der Waals distances for a wide variety of noble gas···element atom pairs that represent properly the distribution of distances both in the gas phase and in the solid state. Moreover, these radii show a smooth periodic trend down the group which is parallel to that shown by the halogens.

Treatment of Cheyne-Stokes respiration reduces arrhythmic events in chronic heart failure.

OBJECTIVE: This 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). METHODS: A cohort of 403 registry patients with CHF (LVEF≤45%, NYHA-class≥2) 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), and 182 having moderate to severe CSR (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. RESULTS: Event-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. CONCLUSION: This 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.

Left ventricular dyssynchrony predicts clinical response to CRT - a long-term follow-up single-center prospective observational cohort study.

BACKGROUND: 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. METHODS: 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 workload >10% as compared to baseline. RESULTS: 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 (ß-coefficient in the final model 0.1, P = 0.04) and LVD at baseline (ß-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 fraction >10% (P = 0.02) and a reduction of left ventricular end-diastolic diameter (LVEDD) >10% (P < 0.01) than patients without LVD at baseline. CONCLUSIONS: 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.

Predictors of recurrence in patients undergoing cryoballoon ablation for treatment of atrial fibrillation: the independent role of sleep-disordered breathing.

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.

Novel robotic catheter manipulation system integrated with remote magnetic navigation for fully remote ablation of atrial tachyarrhythmias: a two-centre evaluation.

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.

Cheyne-Stokes respiration and obstructive sleep apnoea are independent risk factors for malignant ventricular arrhythmias requiring appropriate cardioverter-defibrillator therapies in patients with congestive heart failure.

AIMS: The aim of this first large-scale long-term study was to investigate whether obstructive sleep apnoea (OSA) and/or central sleep apnoea (CSA) are associated with an increased risk of malignant cardiac arrhythmias in patients with congestive heart failure (CHF). METHODS AND RESULTS: Of 472 CHF patients who were screened for sleep disordered breathing (SDB) 6 months after implantation of a cardiac resynchronization device with cardioverter-defibrillator, 283 remained untreated [170 with mild or no sleep disordered breathing (mnSDB) and 113 patients declined ventilation therapy] and were included into this study. During follow-up (48 months), data on appropriately monitored ventricular arrhythmias as well as appropriate cardioverter-defibrillator therapies were obtained from 255 of these patients (90.1%). Time period to first monitored ventricular arrhythmias and to first appropriate cardioverter-defibrillator therapy were significantly shorter in patients with either CSA or OSA. Forward stepwise Cox models revealed an independent correlation for CSA and OSA regarding monitored ventricular arrhythmias [apnoea-hypopnoea index (AHI) ≥5 h(-1): CSA HR 2.15, 95% CI 1.40-3.30, P < 0.001; OSA HR 1.69, 95% CI 1.64-1.75, P = 0.001; AHI ≥15 h(-1): CSA HR 2.06, 95% CI 1.40-3.05, P < 0.001; OSA HR 1.69, 95% CI 1.14-2.51, P = 0.02] and appropriate cardioverter-defibrillator therapies (AHI ≥5 h(-1): CSA HR 3.24, 95% CI 1.86-5.64, P < 0.001; OSA HR 2.07, 95% CI 1.14-3.77, P = 0.02; AHI ≥15 h(-1): CSA HR 3.41, 95% CI 2.10-5.54, P < 0.001; OSA HR 2.10, 95% CI 1.17-3.78, P = 0.01). CONCLUSION: In patients with CHF, CSA and OSA are independently associated with an increased risk for ventricular arrhythmias and appropriate cardioverter-defibrillator therapies.

Intracardiac echocardiography for registration of rotational angiography-based left atrial reconstructions: a novel approach integrating two intraprocedural three-dimensional imaging techniques in atrial fibrillation ablation.

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.

Position-resolved determination of trace elements in mandibular gnathobases of the Antarctic copepod Calanoides acutus using a multimethod approach.

Previous studies have revealed silica formation in the teeth of mandibular gnathobases of copepods while significant amounts of zinc and copper are present, which might improve mechanical stability of the teeth and represent an adaptation to compact food particles. The present study aimed at analysing the distribution and concentration of trace elements in the mandibular gnathobases of females of the Antarctic copepod species Calanoides acutus. Because of the low overall masses of few micrograms per specimen the application of a combination of position-resolved micro-beam techniques was necessary and micro-particle-induced X-ray emission spectrometry and laser ablation inductively coupled plasma mass spectrometry were used to determine Ba, Br, Ca, Cl, Cu, Fe, K, Mg, Na, Ni, P, S, Si and Zn in the samples with µm to sub-µm resolution. Calibration strategies were optimised to fit for the carbonate matrix. The analyses revealed a distinct enrichment of Br, Ca, Fe, K, S, Si and Zn in the teeth of the gnathobases.

Cryoballoon pulmonary vein isolation supported by intracardiac echocardiography: integration of a nonfluoroscopic imaging technique in atrial fibrillation 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.

Incidence of adequate ICD interventions in patients with hypertrophic cardiomyopathy supposed to be at high risk for sudden cardiac death.

INTRODUCTION: Although the incidence of sudden cardiac death (SCD) is as low as 1%/year in un-selected patients (pts) with hypertrophic cardiomyopathy (HCM), higher-risk populations may benefit from prophylactic implantation of an ICD. Risk assessment in HCM is thus important and currently based on the presence or absence of different risk markers (RM). STUDY AIM: The objective of this study is to correlate the incidence of adequate ICD interventions in HCM with the presence of different RM. METHODS: Fifty pts with HCM had ICD implantation, either for secondary (n = 2/4%), or primary prophylaxis of SCD (n = 48/96%). ICD for primary prophylaxis pts had more than 1 (2-4) RM. Outflow obstruction was present in 25 pts, the other 25, including I patient each after septal ablation and myectomy, were non-obstructive. ICD memories were read out and interpreted in accordance with established guidelines. RESULTS: The number of RM per patient was 1.7 +/- 0.8. During follow-up of 2.0 +/- 0.5 [0.2-6.3] years, adequate ICD interventions (11 episodes) were documented in 5, inadequate ICD interventions in 3 pts.Thirteen pts had at least I episode of atrial fibrillation. Pts with versus without events had a longer follow-up (3.2 +/- 4.3 vs. 1.8 +/- 2.6 years, P < 0.05), and were more frequently nonobstructive (all 5; P = 0.05).Within the time period observed no single RM was predictive for arrhythmic events. CONCLUSIONS: Incidence of appropriate ICD discharges was 4-5%/patient-year, supporting the proposed risk stratification. No single RM was predictive for future arrhythmic events.

Flexibility of the saturated five-membered ring in 2,5-pyrrolidinedione (succinimide): electron diffraction and quantum-chemical studies with use of vibrational spectroscopy data.

The flexibility of succinimide molecule has been studied for the first time by quantum-chemical (at the MP2 level with up to the 6-311G(3df,2p) basis sets) and gas-phase electron diffraction (GED) methods using vibrational spectroscopy data from literature. The analysis of vibrational spectra, performed for the molecular model of C(2v) symmetry (predicted by high-level ab initio calculations) using the scaling procedure, has shown that the two out-of-plane ring motions, that is, ring-bending and ring-twisting, are practically pure modes of different symmetry types and can be considered separately. The one-dimensional potential curves for the ring-bending and ring-twisting vibrations calculated at the MP2(full)/6-311G(3df,2p) level could be approximated by harmonic and anharmonic functions, respectively. The diverged energy levels for the ring-twisting vibration and the constant transition frequencies for the bending motion, obtained by the solution of the direct one-dimensional problem for the nonrigid model, demonstrate this statement. In the GED analysis, the succinimide molecule with a large-amplitude ring-twisting motion was described by a dynamic model with the distribution of pseudoconformers according to the calculated potential function taking into account structural relaxation effects from the MP2(full)/6-311G(3df,2p) calculations. This model greatly improved the fit of the GED intensities (R factor decreased from 4.6% for static model to 2.8%). The equilibrium molecular parameters r(e) determined in the dynamic approximation are very close to the corresponding values from the ab initio calculations. At the same time, the parameters of the -CH(2)-CH(2)- fragment involved in the ring-twisting motion deviate considerably from those obtained for the static model (C-C bond length by 0.027 A, =C-C-H, C-C-H, and H-C-C-N angles by up to 7 degrees). The flexibility influence on the C-C bond length is several times larger than the calculated vibrational correction (r(e) - r(a)) as well as the experimental uncertainty.

A prospective randomized evaluation of VV delay optimization in CRT-D recipients: echocardiographic observations from the RHYTHM II ICD study.

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 (> or =10% decrease in LV end-systolic volume or > 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.

A new global database of meteorological drought events from 1951 to 2016.

STUDY REGION: This study has three spatial scales: global (0.5°), macro-regional, and country scale. The database of drought events has specific entries for each macro-region and country. STUDY FOCUS: We constructed a database of meteorological drought events from 1951 to 2016, now hosted by the Global Drought Observatory of the European Commission's Joint Research Centre. Events were detected at macro-regional and country scale based on the separate analysis of the Standardized Precipitation-Evapotranspiration Index (SPEI) and the Standardized Precipitation Index (SPI) at different accumulation scales (from 3 to 72 months), using as input the Global Precipitation Climatology Centre (GPCC) and Climatic Research Unit (CRU) Time Series datasets. The database includes approximately 4800 events based on SPEI-3 and 4500 based on SPI-3. Each event is described by its start and end date, duration, intensity, severity, peak, average and maximum area in drought, and a special score to classify 52 mega-droughts. NEW HYDROLOGICAL INSIGHTS FOR THE REGION UNDER STUDY: We derived trends in drought frequency and severity, separately for SPI and SPEI at a 12-month accumulation scale, which is usually related to hydrological droughts. Results show several drought hotspots in the last decades: Amazonia, southern South America, the Mediterranean region, most of Africa, north-eastern China and, to a lesser extent, central Asia and southern Australia. Over North America, central Europe, central Asia, and Australia, the recent progressive temperature increase outbalanced the increase in precipitation causing more frequent and severe droughts.

Study of the thymine molecule: equilibrium structure from joint analysis of gas-phase electron diffraction and microwave data and assignment of vibrational spectra using results of ab initio calculations.

Thymine is one of the nucleobases which forms the nucleic acid (NA) base pair with adenine in DNA. The study of molecular structure and dynamics of nucleobases can help to understand and explain some processes in biological systems and therefore it is of interest. Because the scattered intensities on the C, N, and O atoms as well as some bond lengths in thymine are close to each other the structural problem cannot been solved by the gas phase electron diffraction (GED) method alone. Therefore the rotational constants from microvawe (MW) studies and differences in the groups of N-C, C=O, N-H, and C-H bond lengths from MP2 (full)/cc-pVQZ calculations were used as supplementary data. The analysis of GED data was based on the C(s) molecular symmetry according to results of the structure optimizations at the MP2 (full) level using 6-311G (d,p), cc-pVTZ, and cc-pVQZ basis sets confirmed by vibrational frequency calculations with 6-311G (d,p) and cc-pVTZ basis sets. Mean-square amplitudes as well as harmonic and anharmonic vibrational corrections to the internuclear distances (r(e)-r(a)) and to the rotational constants (B(e)(k)-B(0)(k), where k = A, B, C) were calculated from the quadratic (MP2 (full)/cc-pVTZ) and cubic (MP2 (full)/6-311G (d,p)) force constants (the latter were used only for anharmonic corrections). The harmonic force field was scaled using published IR and Raman spectra of the parent and N1,N3-dideuterated species, which were for the first time completely assigned in the present work. The main equilibrium structural parameters of the thymine molecule determined from GED data supplemented by MW rotational constants and results of MP2 calculations are the following (bond lengths in Angstroms and bond angles in degrees with 3sigma in parentheses): r(e) (C5=C6) = 1.344 (16), r(e) (C5-C9) = 1.487 (8), r(e) (N1-C6) = 1.372 (3), r(e) (N1-C2) = 1.377 (3), r(e) (C2-N3) = 1.378 (3), r(e) (N3-C4) = 1.395 (3), r(e) (C2=O7) = 1.210 (1), r(e) (C4=O8) = 1.215 (1), angle e (N1-C6=C5) = 123.1 (5), angle e (C2-N1-C6) = 123.7 (5), angle e (N1-C2-N3) = 112.8 (5), angle e (C2-N3-C4) = 128.0 (5), angle e (N3-C4-C5) = 114.8 (5), angle e (C6=C5-C9) = 124.4 (9). The experimental structural parameters are in good agreement with those from MP2 (full) calculations with use of cc-pVTZ and cc-pVQZ basis sets.

Molecular structure of 1,5-diazabicyclo[3.1.0]hexane as determined by gas electron diffraction and quantum-chemical calculations.

The equilibrium molecular structure and conformation of 1,5-diazabicyclo[3.1.0]hexane (DABH) has been studied by the gas-phase electron-diffraction method at 20 degrees C and quantum-chemical calculations. Three possible conformations of DABH were considered: boat, chair, and twist. According to the experimental and theoretical results, DABH exists exclusively as a boat conformation of C s symmetry at the temperature of the experiment. The MP2 calculations predict the stable chair and twist conformations to be 3.8 and 49.5 kcal mol(-1) above the boat form, respectively. The most important semi-experimental geometrical parameters of DABH (r(e), A and angle)e), deg) are (N1-N5) = 1.506(13), (N1-C6) = 1.442(2), (N1-C2) = 1.469(4), (C2-C3) = 1.524(7), (C6-N1-C2) = 114.8(8), (N5-N1-C2) = 107.7(4), (N1-C2-C3) = 106.5(9), and (C2-C3-C4) = 104.0(10). The natural bond orbital (NBO) analysis has shown that the most important stabilization factor in the boat conformation is the n(N) --> sigma*(C-C) anomeric effect. The geometry calculations and NBO analysis have been performed also for the bicyclohexane molecule.