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Aims Our aim was to develop a machine learning (ML)-based risk stratification system to predict 1-, 2-, 3-, 4-, and 5-year all-cause mortality from pre-implant parameters of patients undergoing cardiac resynchronization therapy (CRT). Methods and results Multiple ML models were trained on a retrospective database of 1510 patients undergoing CRT implantation to predict 1- to 5-year all-cause mortality. Thirty-three pre-implant clinical features were selected to train the models. The best performing model [SEMMELWEIS-CRT score (perSonalizEd assessMent of estiMatEd risk of mortaLity With machinE learnIng in patientS undergoing CRT implantation)], along with pre-existing scores (Seattle Heart Failure Model, VALID-CRT, EAARN, ScREEN, and CRT-score), was tested on an independent cohort of 158 patients. There were 805 (53%) deaths in the training cohort and 80 (51%) deaths in the test cohort during the 5-year follow-up period. Among the trained classifiers, random forest demonstrated the best performance. For the prediction of 1-, 2-, 3-, 4-, and 5-year mortality, the areas under the receiver operating characteristic curves of the SEMMELWEIS-CRT score were 0.768 (95% CI: 0.674–0.861; P Conclusion The SEMMELWEIS-CRT score (available at semmelweiscrtscore.com) exhibited good discriminative capabilities for the prediction of all-cause death in CRT patients and outperformed the already existing risk scores. By capturing the non-linear association of predictors, the utilization of ML approaches may facilitate optimal candidate selection and prognostication of patients undergoing CRT implantation.

Introduction Stroke is one of the most feared complications during catheter ablation of atrial fibrillation (AF). While symptomatic thromboembolic events are rare, magnetic resonance imaging (MRI) may identify asymptomatic (ie, silent) cerebral lesions (SCLs) following pulmonary vein isolation (PVI) procedures. Methods and Results The REDUCE‐TE Pilot was a prospective multicenter, single‐arm observational study investigating the incidence of SCL in patients with symptomatic paroxysmal AF undergoing PVI with a novel gold‐tip, externally irrigated ablation catheter. After ablation, cerebral diffusion‐weighted MRI and a postablation follow‐up were performed at 1 to 3 days after the ablation procedure. A neurocognitive test was done before and after ablation. The primary study endpoint was the occurrence of one or more new SCLs. Secondary study endpoints included neurocognitive status, procedural success rate, and periprocedural complications including symptomatic thromboembolic events. A total of 104 patients were enrolled (69% male, mean age: 61.5 ± 9.7 years, mean CHA2DS 2‐VASc score: 1.7 ± 1.2). Postprocedural MRI examination was performed in 97 patients, and in nine of them (9.3%; 95% CI: 4.3‐16.9%) a total of 11 SCLs were detected. Univariate analyses did not reveal any significant predictor for new SCLs. Nonsignificant trends were observed for low activated clotting time during ablation and for international normalized ratio value outside the range of 2 to 3 at ablation. There was no evidence of significant deterioration of neurocognitive function after PVI. In four patients, a pericardial tamponade was noted but all patients fully recovered during follow‐up. Conclusions Ablation of AF using a novel gold‐tip, externally irrigated ablation catheter, resulted in SCLs in approximately one out of 10 patients without a measurable effect on neurocognitive function.

Background. The burden and persistence of atrial fibrillation (AF) have been associated with the presence and extent of left atrial (LA) fibrosis. Recent reports have implicated an association between the extent of LA fibrosis and the outcome of pulmonary vein isolation (PVI). We aimed to analyse the value of an automated scar quantification method in the prediction of success following PVI. Methods. One hundred and nine consecutive patients undergoing PVI for paroxysmal or persistent AF were included in our observational study with a 2-year follow-up. Prior to PVI, patients underwent high-definition LA electroanatomical mapping, and scar burden was quantified by automated software (Voltage Histogram Analysis, CARTO 3, Biosense Webster), then classified into 4 subgroups (Dublin Classes I-IV). Recurrence rates were analysed on and off antiarrhythmic drug therapy (AAD), respectively. Results. The overall success rate was 74% and 67% off AAD at 1- and 2-year follow-up, respectively. Patients with Dublin Class IV had significantly lower success rates ( p = 0.008 , off AAD). Dublin Class IV ( OR = 2.27 , p = 0.022 , off AAD) and the presence of arrhythmia in the blanking period ( OR = 3.28 , p = 0.001 , off AAD) were the only significant predictors of recurrence. The use of AAD did not affect these results. Conclusions. We propose a classification of low voltage areas based on automated quantification by software during 3D mapping prior to PVI. Patients with high burden of low voltage areas (>31% of

Aims To evaluate the safety and effectiveness of pulmonary vein isolation in paroxysmal atrial fibrillation (PAF) using a standardized workflow aiming to enclose the veins with contiguous and optimized radiofrequency lesions. Methods and results This multicentre, prospective, non-randomized study was conducted at 17 European sites. Pulmonary vein isolation was guided by VISITAG SURPOINT (VS target ≥550 on the anterior wall; ≥400 on the posterior wall) and intertag distance (≤6 mm). Atrial arrhythmia recurrence was stringently monitored with weekly and symptom-driven transtelephonic monitoring on top of standard-of-care monitoring (24-h Holter and 12-lead electrocardiogram at 3, 6, and 12 months follow-up). Three hundred and forty participants with drug refractory PAF were enrolled. Acute effectiveness (first-pass isolation proof to a 30-min wait period and adenosine challenge) was 82.4% [95% confidence interval (CI) 77.4–86.7%]. At 12-month follow-up, the rate of freedom from any documented atrial arrhythmia was 78.3% (95% CI 73.8–82.8%), while freedom from atrial arrhythmia by standard-of-care monitoring was 89.4% (95% CI 78.8–87.0%). Freedom fromrepeat ablations by the Kaplan–Meier analysis was 90.4% during 12 months of follow-up. Of the 34 patients with repeat ablations, 14 (41.2%) demonstrated full isolation of all pulmonary vein circles. Primary adverse event (PAE) rate was 3.6% (95% CI 1.9–6.3%). Conclusions The VISTAX trial demonstrated that a standardized PAF ablation workflow aiming for contiguous lesions leads to low rates of PAEs, high acute first-pass isolation rates, and 12-month freedom from arrhythmias approaching 80%. Further research is needed to improve the reproducibility of the outcomes across a wider range of centres. Clinical trial registration: ClinicalTrials.gov, number NCT03062046, https://clinicaltrials.gov/ct2/show/NCT03062046.

Introduction. Growing evidence suggests that fibrotic changes can be observed in atrial fibrillation (AF) in both atria. Quantification of the scar burden during electroanatomical mapping might have important therapeutic and prognostic consequences. However, as the current invasive treatment of AF is focused on the left atrium (LA), the role of the right atrium (RA) is less well understood. We aimed to characterize the clinical determinates of the RA low-voltage burden and its relation to the LA scaring. Methods. We have included 36 patients who underwent catheter ablation for AF in a prospective observational study. In addition to LA mapping and ablation, high-density RA bipolar voltage maps (HD-EAM) were also reconstructed. The extent of the diseased RA tissue (≤0.5 mV) was quantified using the voltage histogram analysis tool (CARTO®3, Biosense Webster). Results. The percentage of RA diseased tissue burden was significantly higher in patients with a CHA2DS2-VASc score ≥ 2 p=0.0305, higher indexed LA volume on the CTA scan and on the HD‐EAM (p=0.0223 and p=0.0064, respectively), or higher indexed RA volume on the HD‐EAM p=0.0026. High RA diseased tissue burden predicted the presence of high LA diseased tissue burden (OR = 7.1, CI (95%): 1.3–38.9, p=0.0145), and there was a significant correlation of the same (r = 0.6461, p<0.0001). Conclusions. Determining the extent of the right atrial low-voltage burden might give useful clinical information. According to our results, the diseased tissue burden correlates well between the two atria: the right atrium mirrors the left atrium.

Aims There are previous studies on quality of life (QoL) in cardiac resynchronization therapy (CRT) patients; however, there are no data with the short EuroQol-five dimensions (EQ-5D) questionnaire predicting outcomes. We aimed to assess the predictive role of baseline QoL and QoL change at 6 months after CRT with EQ-5D on 5-year mortality and response. Methods and results In our prospective follow-up study, 130 heart failure (HF) patients undergoing CRT were enrolled. Clinical evaluation, echocardiography, and EQ-5D were performed at baseline and at 6 months of follow–up, continued to 5 years. Primary endpoint was all-cause mortality at 5 years. Secondary endpoints were (i) clinical response with at least one class improvement in New York Heart Association without HF hospitalization and (ii) reverse remodelling with 15% reduction in left ventricular end-systolic volume at 6 months. Fifty-four (41.5%) patients died during 5 years, 85 (65.3%) clinical responders were identified, and 63 patients (48.5%) had reverse remodelling. Baseline issues with mobility were associated with lower response [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.16–0.84; P = 0.018]. Lack of reverse remodelling correlated with self-care issues at baseline (OR 0.10, 95% CI 0.01–0.94; P = 0.04). Furthermore, self-care difficulties [hazard ratio (HR) 2.39, 95% CI 1.17–4.86; P = 0.01) or more anxiety (HR 1.51, 95% CI 1.00–2.26; P = 0.04) predicted worse long-term survival. At 6 months, mobility (HR 3.95, 95% CI 1.89–8.20; P

Atrial fibrillation (AF), is the most common sustained arrhythmia and is associated with a substantial increase in morbidity and mortality. Several studies have demonstrated sex-related differences in various aspects, including age at diagnosis, clinical manifestations, management and prognosis. These dissimilarities may dictate different approaches to management and could translate to differences in outcomes. However, similarly to other cardiovascular therapies, there may be a tendency to treat females more conservatively and less aggressively than male patients. The use of oral anticoagulants, for example, is lower in female patients with AF. Electrical cardioversion is less often used. Likewise, despite higher rates of adverse reactions to antiarrhythmic drugs in women, they are less likely to undergo catheter ablations, a well-established therapeutic approach to symptomatic patients with recurrences of AF. In this article, we review sex related dissimilarities in patients with AF. In addition, we discuss various treatment options, and specifically refer to differences in access of treatment, success rates, and potential treatment-related complications. ispartof: EUROPACE vol:21 issue:5 pages:690-697 ispartof: location:England status: published

Aims Data on longer right to left ventricular activation delay (RV-LV AD) predicting clinical outcome after cardiac resynchronization therapy (CRT) by left bundle branch block (LBBB) are limited. We aimed to evaluate the impact of RV-LV AD on N-terminal pro–B-type natriuretic peptide (NT-proBNP), ejection fraction (EF), and clinical outcome in patients implanted with CRT, stratified by LBBB at baseline. Methods and results Heart failure (HF) patients undergoing CRT implantation with EF ≤ 35% and QRS ≥ 120 ms were evaluated based on their RV-LV AD at implantation. Baseline and 6-month clinical parameters, EF, and NT-proBNP values were assessed. The primary endpoint was HF or death, the secondary endpoint was all-cause mortality. A total of 125 patients with CRT were studied, 62% had LBBB. During the median follow-up of 2.2 years, 44 (35%) patients had HF/death, 36 (29%) patients died. Patients with RV-LV AD ≥ 86 ms (lower quartile) had significantly lower risk of HF/death [hazard ratio (HR): 0.44; 95% confidence interval (95% CI): 0.23–0.82; P = 0.001] and all-cause mortality (HR: 0.48; 95% CI: 0.23–1.00; P = 0.05), compared with those with RV-LV AD < 86 ms. Patients with RV-LV AD ≥ 86 ms and LBBB showed the greatest improvement in EF (28–36%; P

Aims The low lymphocyte counts and high neutrophil leucocyte fractions have been associated with poor prognosis in chronic heart failure. We hypothesized that the baseline ratio of the neutrophil leucocytes to the lymphocytes (NL ratio) would predict the outcome of chronic heart failure patients undergoing cardiac resynchronization therapy (CRT). Methods and results The qualitative blood counts and the serum levels of N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) of 122 chronic heart failure patients and 122 healthy controls were analysed prospectively in this observational study. The 2-year mortality was considered as primary endpoint and the 6-month reverse remodelling (≥15% decrease in the end-systolic volume) as secondary endpoint. Multivariable regression analyses were applied and net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated. The NL ratio was elevated in chronic heart failure patients when compared with the healthy controls [2.93 (2.12–4.05) vs. 2.21 (1.64–2.81), P < 0.0001]. The baseline NL ratio exceeding 2.95 predicted the lack of the 6-month reverse remodelling [n = 63, odds ratio = 0.38 (0.17–0.85), P = 0.01; NRI = 0.49 (0.14–0.83), P = 0.005; IDI = 0.04 (0.00–0.07), P = 0.02] and the 2-year mortality [n = 29, hazard ratio = 2.44 (1.04–5.71), P = 0.03; NRI = 0.63 (0.24–1.01), P = 0.001; IDI = 0.04 (0.00–0.08), P = 0.02] independently of the NT-proBNP levels or other factors. Conclusion The NL ratio is elevated in chronic heart failure and predicts outcome after CRT. According to the reclassification analysis, 4% of the patients would have been better categorized in the prediction models by combining the NT-proBNP with the NL ratio. Thus, a single blood count measurement could facilitate the optimal patient selection for the CRT.

Lead dislocations of pacemaker systems are reported in all and even in high-volume centers. Repeated procedures necessitated by lead dislocations are associated with an increased risk of complications. We investigated a minimal invasive method for right atrial and ventricular lead repositioning. The minimal invasive method was applied only when passive fixation leads were implanted. During the minimal invasive procedure, a steerable catheter was advanced through the femoral vein to move the distal end of the lead to the appropriate position. Retrospective data collection was conducted in all patients with minimal invasive and with conventional method, at a single center between September 2006 and December 2012. Forty-five minimal invasive lead repositionings were performed, of which eight were acutely unsuccessful and nine electrodes re-dislocated after the procedure. One hundred two leads were repositioned with opening of the pocket during the same time, including the ones with unsuccessful minimal invasive repositionings. One procedure was acutely unsuccessful in this group and four re-dislocations happened. A significant difference of success rates was noted (66.6% vs. 95.1%, p = 0.001). One complication was observed during the minimal invasive lead repositionings (left ventricular lead microdislodgement). Open-pocket procedures showed different types of complications (pneumothorax, subclavian artery puncture, pericardial effusion, hematoma, fever, device-associated infection which necessitated explantation, atrial lead dislodgement while repositioning the ventricular one, deterioration of renal function). The minimal invasive method as a first alternative is safe and feasible. In those cases when it cannot be carried out successfully, the conventional method is applicable.

Context: Assessment of response to cardiac resynchronization therapy (CRT) is essential.Objective: To assess the predictive value of CT-apelin together with NT-proBNP in patients undergoing CRT.Methods: Serum CT-apelin and NT-proBNP were measured by ELISA before, and six months after CRT. Primary endpoint was non-response (

Objectives. Increases in red blood cell distribution width (RDW) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) predict the mortality of chronic heart failure patients undergoing cardiac resynchronization therapy (CRT). It was hypothesized that RDW is independent of and possibly even superior to NT-proBNP from the aspect of long-term mortality prediction.Design. The blood counts and serum NT-proBNP levels of 134 patients undergoing CRT were measured. Multivariable Cox regression models were applied and reclassification analyses were performed.Results. After separate adjustment to the basic model of left bundle branch block, beta blocker therapy, and serum creatinine, both the RDW > 13.35% and NT-proBNP > 1975 pg/mL predicted the 5-year mortality (n=57). In the final model including all variables, the RDW [HR = 2.49 (1.27–4.86);p=0.008] remained a significant predictor, whereas the NT-proBNP [HR = 1.18 (0.93–3.51);p=0.07] lost its predictive value. On addition of the RDW measurement, a 64% net reclassification improvement and a 3% integrated discrimination improvement were achieved over the NT-proBNP-adjusted basic model.Conclusions. Increased RDW levels accurately predict the long-term mortality of CRT patients independently of NT-proBNP. Reclassification analysis revealed that the RDW improves the risk stratification and could enhance the optimal patient selection for CRT.

Congenital anomalies of the venous system are a challenge for cardiac catheterization and radiofrequency ablation. This article describes ablation of atrioventricular nodal re-entrant tachycardia performed solely through the azygos continuation in a patient with inferior vena cava interruption.

Introduction: Transvenous left ventricular (LV) lead positioning via the coronary sinus (CS) sidebranches might be challenging or in some instances impossible, in these cases alternative methods would be preferable. The aim of this study was to investigate the effectiveness and safety of transseptal endocardial left ventricular lead implantation (TELVLI) in severe heart failure patients, and evaluate the long term follow ups of the patients. Objectives: TELVLI was performed in 28 patients (24 men, 61±7 years, NYHA III-IV stage). Methods: Transseptal (TS) puncture was performed via the femoral vein. Intracardiac ulrasound was used to guide the puncture in 21 pts. The site of the puncture was dilated with a 6mm (3 pts), later with an 8 mm balloon (25 pts). After the puncture of the left subclavian vein, an electrophysiological deflectable CS catheter was introduced into the CS sheath. The CS catheter was used to reach the left atrium and the left ventricle through the dilated transseptal puncture hole. In four cases CARTO system was used to find the site of the latest activation, in the other cases right and left ventricular (RV-LV) signals were evaluated and the latest RV-LV delay was determined as latest activation. At the latest LV activation site 65 cm active fixation bipolar lead was screwed into the LV wall. Results: The lead was fixed in the left ventricle in all cases with good pacing threshold values (0,82±0,4 V; 0,4 ms). Puncture complication, pericardial effusion was not observed. Because of intraoperatively started anticoagulation therapy, pocket haematoma was observed postoperatively in three (11%) and needed surgical evacuation in one case (4%). Follow-up is longer than one month in all patients (21±13 months). Significant improvement of the NYHA class was observed in all but one case (96%), on the first month control LV EF was 29±7% vs 36±7%. Early lead dislocation was noticed in three cases (10%), reposition was performed using the original puncture site in two patients, and transvenous implantation was succesfully carried out in the other case. Explantation of the system was necessary because of pocket infection in four cases (14%), in two of these cases TELVLI was carried out succesfully 3 months later. All patients were maintained on anticoagulation therapy either with warfarine or cumarine with INR between 2-3. No thromboembolic complication was noticed during the follow up. Conclusions: TELVLI approach might be an alternative of the surgical epicardial procedure, if transvenous implantation could not be applied, however more evidences and studies are needed to evaluate this method.

Dual ventricular response to a single supraventricular impulse through dual atrioventricular (AV) nodal pathways is an interesting and uncommon phenomenon. Rarely, some patients can exhibit sustained one-to-two conduction producing a non-reentrant AV nodal tachycardia during sinus rhythm [1–6]. We report the case of a patient whose arrhythmia was caused by this mechanism. A 44-years-old male patient who had frequent irregular palpitations was admitted to hospital. He was misdiagnosed with atrial fibrillation and referred to our institute for consideration of pulmonary vein isolation. He did not have any significant disease in his medical history. Echocardiography was normal. The electrocardiogram showed an irregular narrow QRS complex tachycardia. Careful evaluation of the electrocardiograms revealed the presence of two ventricular activations for each atrial beat (Fig. 1). On some occasions, the wide QRS complexes with right bundle branch block (RBBB) morphology not preceded by P waves simulating premature ventricular complexes (PVCs) were observed. Electrophysiological study revealed regular 1:2 AV relationship. Each ventricular signal was preceded by a His deflection with a constant HV interval (46 ms) (Fig. 2a). The AH1 interval between the atrial wave and the first His deflection was 159 ms. The AH2 interval between the atrial wave and the second His deflection was 528 ms. Both AH1 and AH2 intervals were slightly variable. When AH2 interval was shorter than 520 ms, second ventricular responses were conducted by RBBB morphology (Fig. 2a). Because of sustained double responses, we could not perform programmed atrial extra stimulation to identify a jump in AH interval. After detailed electrophysiological examination, radiofrequency (RF) energy was delivered (40 W, 55 C, 66 s) in the posterior aspect of Koch’s triangle, where the typical ‘‘slow pathway potentials’’ were observed. After first RF application, 1:2 response disappeared (Fig. 2b). During post-ablation tests, we did not observe dual AV nodal conduction properties, and we could not induce any arrhythmia. On the 6 month follow-up, the patient was asymptomatic. Non-reentrant AV nodal tachycardia (1:2 tachycardia) is a rare manifestation of dual AV nodal physiology. Persistent simultaneous conduction of P waves over a fast and a slow nodal pathways may lead irregular supraventricular tachycardia. The two major electrophysiological properties of simultaneous anterograde fast and slow conduction during sinus rhythm are: (1) Absence of retrograde ventriculoatrial conduction via fast and slow pathways and (2) Critical conduction delay in slow pathway to allow sequential conduction of impulse from both pathways [1, 2]. Delay has to be longer than the effective refractory period of infranodal conduction system. A recently published review reported just 49 cases between dates of 1950 and 2011 [3]. Nevertheless, the prevalence of AV nodal non-reentrant tachycardia is likely to be underestimated because of difficulties in differential diagnosis. Sustained cycle length alternans is the characteristic for this arrhythmia [4]. However, changes in autonomic tone affecting conduction properties may lead irregular cycle length alternans and rate-dependent aberrancy. For these reasons, it can be erroneously diagnosed as atrial fibrillation, atrial flutter or atrial tachycardia with Wenckebach periodicity [3, 5, 7, 8]. These arrhythmias, E. E. Ozcan G. Szeplaki B. Merkely L. Geller (&) Heart Center, Semmelweis University, Gaal Jozsef street 9, Budapest 1122, Hungary e-mail: laszlo.geller@gmail.com

Summary The possibility of simultaneous measurement of the classical pathway (CP), mannan-binding lectin (MBL)–lectin pathway (LP) and alternative pathway (AP) of complement activation by the recently developed Wielisa method allowed us to investigate the in vivo significance of the C1-inhibitor (C1INH) in three complement activation pathways. Functional activity of the CP, LP and AP were measured in the sera of 68 adult patients with hereditary angioedema (HAE) and 64 healthy controls. In addition, the level of C1q, MBL, MBL-associated serine protease-2 (MASP-2), C4-, C3- and C1INH was measured by standard laboratory methods. MBL-2 genotypes were determined by polymerase chain reaction. Besides the complement alterations (low CP and C1INH activity, low C4-, C1INH concentrations), which characterize HAE, the level of MASP-2 was also lower (P = 0·0001) in patients compared with controls. Depressed LP activity was found in patients compared with controls (P = 0·0008) in homozygous carriers of the normal MBL genotype (A/A), but not in carriers of variant genotypes (A/O, O/O). Activity of CP correlated with LP in patients (Spearman's r = 0·64; P

Background A number of data indicate that the lectin pathway of complement activation contributes to the pathophysiology of ischemic stroke. The lectin pathway may be triggered by the binding of mannose-binding lectin (MBL), ficolin-2 or ficolin-3 to different ligands. Although several papers demonstrated the significance of MBL in ischemic stroke, the role of ficolins has not been examined. Methods Sera were obtained within 12 hours after the onset of ischemic stroke (admission samples) and 3-4 days later (follow-up samples) from 65 patients. The control group comprised 100 healthy individuals and 135 patients with significant carotid stenosis (patient controls). The concentrations of ficolin-2 and ficolin-3, initiator molecules of the lectin complement pathway, were measured by ELISA methods. Concentration of C-reactive protein (CRP) was also determined by a particle-enhanced immunturbidimetric assay. Results Concentrations of both ficolin-2 and ficolin-3 were significantly (p < 0.001) decreased in both the admission and in the follow-up samples of patients with definite ischemic stroke as compared to healthy subjects. Concentrations of ficolin-2 and ficolin-3 were even higher in patient controls than in healthy subjects, indicating that the decreased levels in sera during the acute phase of stroke are related to the acute ischemic event. Ficolin-3 levels in the follow-up samples inversely correlated with the severity of stroke indicated by NIH scale on admission. In follow-up samples an inverse correlation was observed between ficolin-3 levels and concentration of S100β, an indicator of the size of cerebral infarct. Patients with low ficolin-3 levels and high CRP levels in the follow up samples had a significantly worse outcome (adjusted ORs 5.6 and 3.9, respectively) as measured by the modified Rankin scale compared to patients with higher ficolin-3 and lower CRP concentrations. High CRP concentrations were similarly predictive for worse outcome, and the effects of low ficolin-3 and high CRP were independent. Conclusions Our findings indicate that ficolin-mediated lectin pathways of complement activation contribute to the pathogenesis of ischemic stroke and may be additive to complement-independent inflammatory processes.