Dual energy for pulmonary vein isolation using dual-energy focal ablation technology integrated with a three-dimensional mapping system: SmartfIRE 3-month results.

AIMS: Contact force (CF)-sensing radiofrequency (RF) catheters with an ablation index have shown reproducible outcomes for the treatment of atrial fibrillation (AF) in large multicentre studies. A dual-energy (DE) focal CF catheter to deliver RF and unipolar/biphasic pulsed field ablation (PFA), integrated with a three-dimensional (3D) mapping system, can provide operators with additional flexibility. The SmartfIRE study assessed the safety and efficacy of this novel technology for the treatment of drug-refractory, symptomatic paroxysmal AF. Results at 3 months post-ablation are presented here. METHODS AND RESULTS: Pulmonary vein isolation (PVI) was performed using a DE focal, irrigated CF-sensing catheter with the recommendation of PFA at posterior/inferior and RF ablation at the anterior/ridge/carina segments. Irrespective of energy, a tag size of 3 mm; an inter-tag distance ≤6 mm; a target index of 550 for anterior, roof, ridge, and carina; and a target index of 400 for posterior and inferior were recommended. Cavotricuspid isthmus ablation was permitted in patients with documented typical atrial flutter. The primary effectiveness endpoint was acute procedural success. The primary safety endpoint was the rate of primary adverse events (PAEs) within 7 days of the procedure. A prespecified patient subset underwent oesophageal endoscopy (EE; 72 h post-procedure), neurological assessment (NA; pre-procedure and discharge), and cardiac computed tomography (CT)/magnetic resonance angiogram (MRA) imaging (pre-procedure and 3 months post-procedure) for additional safety evaluation, and a mandatory remapping procedure (Day 75 ± 15) for PVI durability assessment. Of 149 patients enrolled between February and June 2023, 140 had the study catheter inserted (safety analysis set) and 137 had ablation energy delivered (per-protocol analysis set). The median (Q1/Q3) total procedure and fluoroscopy times were 108.0 (91.0/126.0) and 4.2 (2.3/7.7) min (n = 137). The acute procedural success rate was 100%. First-pass isolation was achieved in 89.1% of patients and 96.8% of veins. Cavotricuspid isthmus ablations were successfully performed in 12 patients [pulsed field (PF) only: 6, RF only: 5, and RF/PF: 1]. The PAE rate was 4.4% [6/137 patients; 2 pulmonary vein (PV) stenoses, 2 cardiac tamponades/perforations, 1 stroke, and 1 pericarditis]. No coronary artery spasm was reported. No oesophageal lesion was seen in the EE subset (0/31, 0%). In the NA subset (n = 30), microemboli lesions were identified in 2 patients (2/30, 6.7%), both of which were resolved at follow-up; only 1 was symptomatic (silent cerebral lesion, 3.3%). In the CT/MRA subset (n = 30), severe PV narrowing (of >70%) was detected in 2 patients (2/30, 6.7%; vein level 2/128, 1.6%), of whom 1 underwent dilatation and stenting and 1 was asymptomatic; both were associated with high index values and a small inter-tag distance. In the PV durability subset (n = 30), 100/115 treated PVs (87%) were durably isolated and 18/30 patients (60.0%) had all PVs durably isolated. CONCLUSION: A DE focal CF catheter with 3D mapping integration showed a 100% acute success rate with an acceptable safety profile in the treatment of paroxysmal AF. Prespecified 3-month remapping showed notable PVI durability. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05752487.

The impact of steerable sheath visualization during catheter ablation for atrial fibrillation.

AIMS: Incorporating a steerable sheath that can be visualized using an electroanatomical mapping (EAM) system may allow for more efficient mapping and catheter placement, while reducing radiation exposure, during ablation procedures for atrial fibrillation (AF). This study evaluated fluoroscopy usage and procedure times when a visualizable steerable sheath was used compared with a non-visualizable steerable sheath for catheter ablation for AF. METHODS AND RESULTS: In this retrospective, observational, single-centre study, patients underwent catheter ablation for AF using a steerable sheath that is visualizable using the CARTO EAM (VIZIGO; n = 57) or a non-visualizable steerable sheath (n = 34). The acute procedural success rate was 100%, with no acute complications in either group. Use of the visualizable sheath vs. the non-visualizable sheath was associated with a significantly shorter fluoroscopy time [median (first quartile, third quartile), 3.4 (2.1, 5.4) vs. 5.8 (3.8, 8.6) min; P = 0.003], significantly lower fluoroscopy dose [10.0 (5.0, 20.0) vs. 18.5 (12.3, 34.0) mGy; P = 0.015], and significantly lower dose area product [93.0 (48.0, 197.9) vs. 182.2 (124.5, 355.0) µGy·m2; P = 0.017] but with a significantly longer mapping time [12.0 (9.0, 15.0) vs. 9.0 (7.0, 11.0) min; P = 0.004]. There was no significant difference between the visualizable and non-visualizable sheaths in skin-to-skin time [72.0 (60.0, 82.0) vs. 72.0 (55.5, 80.8) min; P = 0.623]. CONCLUSION: In this retrospective study, use of a visualizable steerable sheath for catheter ablation of AF significantly reduced radiation exposure vs. a non-visualizable steerable sheath. Although mapping time was longer with the visualizable sheath, the overall procedure time was not increased.

Selection of an impedance- or magnetic field-based electro-anatomical mapping platform does not affect outcomes of outflow tract premature ventricular complex manual ablation.

Comparative data are virtually missing about the performance of different electro-anatomical mapping (EAM) system platforms on outflow tract (OT) premature ventricular complex (PVC) ablation outcomes with manual ablation catheters. We aimed to compare the acute success-, complication-, and long-term recurrence rates of impedance-based (IMP) and magnetic field-based (MAG) EAM platforms in manual OT PVC ablation. Single-centre, propensity score matched data of 39-39 patients ablated for OT PVCs in 2015-17 with IMP or MAG platforms were analysed. Acute success rate, peri-procedural complications, post-ablation daily PVC burden, and long-term recurrence rates were compared on intention-to-treat basis. Acute success rate was similar in the IMP and MAG group (77 vs. 82%, p = 0.78). There was a single case of femoral pseudo-aneurysm and no cardiac tamponade occurred. PVC burden fell significantly from baseline 24.0% [15.0-30.0%] to 3.3% [0.25-10.5%] (p < 0.001) post-ablation, with no difference between EAM platforms (IMP: 2.6% [0.5-12.0%] vs. MAG: 4.0% [2.0-6.5%]; p = 0.60). There was no significant difference in recurrence-free survival of the intention-to-treat cohort of the IMP and MAG groups (54 vs. 60%, p = 0.82, respectively) during 12 months of follow-up. Ablation with the aid of both impedance- and magnetic field-based EAM platforms can considerably reduce OT PVC burden and give similar acute- and long-term freedom from arrhythmia.

Similar outcomes with manual contact force ablation catheters and traditional catheters in the treatment of outflow tract premature ventricular complexes.

AIMS: Unlike in atrial fibrillation ablation, there is a lack of appropriately sized and properly designed studies regarding outflow tract (OT) premature ventricular complex (PVC) ablation outcomes with contact force sensing (CFS) catheters. We aimed to compare the acute success-, complication-, and long-term recurrence rates of manual CFS catheters with traditional irrigated catheters (T) in OT PVC ablation. METHODS AND RESULTS: Single-centre, propensity-matched data of 75-75 patients ablated for right-sided OT (RVOT) or left-sided OT (LVOT) PVCs in 2015-17 with CFS or T catheters were compared. Acute success rate, peri-procedural complications, post-procedural daily PVC burden, and long-term recurrence rates were compared on intention-to-treat basis. Acute success rate equalled 80% in both groups, with no difference in force values in the CFS group comparing successful or failed cases [12.0 (8.75-17.0) vs. 16.0 (10.25-22.25) g, P = 0.21]. There were three cases of pseudo-aneurysm and one cardiac tamponade. PVC burden fell significantly from baseline 22 (15-30)% to 2 (0-10)% (P < 0.0001), with no difference between catheter types [CFS: 1 (0-7)% vs. T: 4 (1-12) %; P = 0.21]. There was no significant difference in recurrence-free survival of CFS and T catheters (58 vs. 59%, P = 0.29) during 12 months of follow-up, respectively. Recurrence in the CFS group did not differ either by the force exerted below or above the median value of 12 g (P = 0.66). CONCLUSION: Both types of catheters can effectively reduce OT PVC burden with minimal serious complication rates. Ablation with CFS or T catheters gives similar acute- and long-term results.

Implementation of a zero fluoroscopic workflow using a simplified intracardiac echocardiography guided method for catheter ablation of atrial fibrillation, including repeat procedures.

OBJECTIVE: Pulmonary vein isolation (PVI) is the cornerstone of the interventional treatment of atrial fibrillation (AF). Traditionally, during these procedures the catheters are guided by fluoroscopy, which poses a risk to the patient and staff by ionizing radiation. Our aim was to describe our experience in the implementation of an intracardiac echocardiography (ICE) guided zero fluoroscopic (ZF) ablation approach to our routine clinical practice. METHODS: We developed a simplified ICE guided technique to perform ablation procedures for AF, with the aid of a 3D electroanatomical mapping system. The workflow was implemented in two phases: (1) the Introductory phase, where the first 16 ZF PVIs were compared with 16 cases performed with fluoroscopy and (2) the Extension phase, where 71 consecutive patients (including repeat procedures) with ZF approach were included. Standard PVI (and redoPVI) procedures were performed, data on feasibility of the ZF approach, complications, acute and 1-year success rates were collected. RESULTS: In the Introductory phase, 94% of the procedures could be performed with complete ZF with a median procedure time of 77.5 (73.5-83) minutes. In one case fluoroscopy was used to guide the ICE catheter to the atrium. There was no difference in the complication, acute and 1-year success rates, compared with fluoroscopy guided procedures. In the Extension phase, 97% of the procedures could be completed with complete ZF. In one case fluoroscopy was used to guide the transseptal puncture and in another to position the ICE catheter. Acute success of PVI was achieved in all cases, 64.4% patients were arrhythmia free at 1-year. Acute major complications were observed in 4 cases, all of these occurred in the redo PVI group and consisted of 2 tamponades, 1 transient ischemic attack and 1 pseudoaneurysm at the puncture site. The procedures were carried out by all members of the electrophysiology unit in the Extension phase, including less experienced operators and electrophysiology fellows (3 physicians) under the supervision of the senior electrophysiologist. Consequently, procedure times became longer [90 (75-105) vs 77.5 (73.5-85) min, p = 0.014]. CONCLUSIONS: According to our results, a ZF workflow of AF ablations can be successfully implemented into the routine practice of an electrophysiology laboratory, without compromising safety and effectivity.

Machine learning-based mortality prediction of patients undergoing cardiac resynchronization therapy: the SEMMELWEIS-CRT score.

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 < 0.001), 0.793 (95% CI: 0.718-0.867; P < 0.001), 0.785 (95% CI: 0.711-0.859; P < 0.001), 0.776 (95% CI: 0.703-0.849; P < 0.001), and 0.803 (95% CI: 0.733-0.872; P < 0.001), respectively. The discriminative ability of our model was superior to other evaluated scores. 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.

Standardized pulmonary vein isolation workflow to enclose veins with contiguous lesions: the multicentre VISTAX trial.

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.

Silent cerebral lesions and cognitive function after pulmonary vein isolation with an irrigated gold-tip catheter: REDUCE-TE Pilot study.

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 CHA2 DS 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.

Sex differences in rate and rhythm control for atrial fibrillation.

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.

Repeat procedure is a new independent predictor of complications of atrial fibrillation ablation.

AIMS: Atrial fibrillation (AF) ablation has made huge progress with respect to innovation, efficacy, and safety, however, complications are still present. Recent studies examined various predictors of complications. However, limited data exist regarding the role of a repeat procedure. Our aim was the prospective evaluation of the incidence and predictors of complications related to AF ablation procedures in consecutive patients, including repeat procedures. METHODS AND RESULTS: All ablation procedures for AF between January 2013 and December 2015 were analysed in our electrophysiology laboratory. During the study period 1243 procedures were analysed [394 female, median age 62 (55-69)]. Overall complication rate was 6.84%, major complication rate was 2.82%. Major complications were the following: 18 pericardial tamponades; 5 pseudoaneurysms; 1 arteriovenous fistula; 6 thromboembolic cerebrovascular events; 3 pulmonary vein stenosis; and 2 atrioventricular blocks. No atrio-oesophageal fistula or procedure related death occurred. Univariate analysis for overall complications showed that age ≥ 65 years (P = 0.0231), female gender (P = 0.0438), hypertension (P = 0.0488), CHA2DS2-VASc score ≥ 2 (P = 0.0156), and previous AF ablation procedure (P < 0.0001) is associated with higher risk for adverse events. Multivariate analysis showed that the only independent predictor of overall complications was previous AF ablation procedure (P < 0.0001). Similarly, the only predictor of major complications was previous AF ablation procedure (P < 0.0001). CONCLUSION: Incidence of complications associated with AF ablation in our high volume electrophysiology laboratory is similar to other cohorts. The only independent predictor of complications was previous AF ablation procedure in our series.

Quality of life measured with EuroQol-five dimensions questionnaire predicts long-term mortality, response, and reverse remodelling in cardiac resynchronization therapy patients.

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 < 0.001), self-care (HR 7.69, 95% CI 2.23-25.9; P = 0.001), or ≥ 10% visual analogue scale (VAS) (HR 2.24, 95% CI 1.27-3.94; P = 0.005) improvement anticipated better survival at 5 years. Conclusion: EuroQol-five dimension is a simple method assessing QoL in CRT population. Mobility issues at baseline are associated with lower clinical response, whereas self-care issues predict lack of reverse remodelling. Problems with mobility or anxiety before CRT and persistent issues with mobility, self-care, and VAS scale at 6 months predict adverse outcome.

Sex differences in outcomes of primary prevention implantable cardioverter-defibrillator therapy: combined registry data from eleven European countries.

Aims: Therapy with an implantable cardioverter defibrillator (ICD) is established for the prevention of sudden cardiac death (SCD) in high risk patients. We aimed to determine the effectiveness of primary prevention ICD therapy by analysing registry data from 14 centres in 11 European countries compiled between 2002 and 2014, with emphasis on outcomes in women who have been underrepresented in all trials. Methods and results: Retrospective data of 14 local registries of primary prevention ICD implantations between 2002 and 2014 were compiled in a central database. Predefined primary outcome measures were overall mortality and first appropriate and first inappropriate shocks. A multivariable model enforcing a common hazard ratio for sex category across the centres, but allowing for centre-specific baseline hazards and centre specific effects of other covariates, was adjusted for age, the presence of ischaemic cardiomyopathy or a CRT-D, and left ventricular ejection fraction ≤25%. Of the 5033 patients, 957 (19%) were women. During a median follow-up of 33 months (IQR 16-55 months) 129 women (13%) and 807 men (20%) died (HR 0.65; 95% CI: [0.53, 0.79], P-value < 0.0001). An appropriate ICD shock occurred in 66 women (8%) and 514 men (14%; HR 0.61; 95% CI: 0.47-0.79; P = 0.0002). Conclusion: Our retrospective analysis of 14 local registries in 11 European countries demonstrates that fewer women than men undergo ICD implantation for primary prevention. After multivariate adjustment, women have a significantly lower mortality and receive fewer appropriate ICD shocks.

Hyperuricemia predicts adverse clinical outcomes after cardiac resynchronization therapy.

OBJECTIVES: Changes in the levels of serum creatinine and N-terminal of prohormone brain natriuretic peptide (NT-proBNP) are useful risk markers after cardiac resynchronization therapy (CRT). The diagnostic value of changes in serum uric acid levels has been established in chronic heart failure, but no data are available on the prognostic value of hyperuricemia in a CRT population. DESIGN: We measured markers of renal function [creatinine, blood urea nitrogen (BUN) and uric acid] and NT-proBNP levels of 129 heart failure patients undergoing CRT in a prospective, observational study. The 5-year all-cause mortality and the 6-month clinical response (≥ 15% increase in the left ventricular ejection fraction) were considered as study end points. RESULTS: In multivariable analyses, the uric acid was found to be a statistically significant predictor of the outcome. Uric acid levels exceeding 386 mmol/L before CRT increased the chances of mortality [n = 55, hazard ratio = 2.39 (1.30-4.39), p < 0.01] and poor clinical response [n = 37, odds ratio = 2.89 (1.22-6.87), p = 0.01] independently of serum NT-proBNP and other factors. CONCLUSIONS: Elevated uric acid concentrations in patients with CRT are associated with an increased risk of mortality and poor clinical response independently of the NT-proBNP levels and other relevant clinical factors.

Impact of CT-apelin and NT-proBNP on identifying non-responders to cardiac resynchronization therapy.

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 (<4% increase in LVEF) after six months. RESULTS: From 81 patients, 15 proved to be non-responders. Six-month CT-apelin was superior compared to NT-proBNP in identifying non-responders by multivariate ROC (CT-apelin: p = 0.01, NT-proBNP: p = 0.13) and by logistic regression (CT-apelin: p = 0.01, NT-proBNP: p = 0.41) analyses. CONCLUSION: Six-month CT-apelin might be a valuable novel biomarker in identifying non-responders to CRT that was superior to NT-proBNP.

High rate of in-stent restenosis after coronary intervention in carriers of the mutant mannose-binding lectin allele.

BACKGROUND: In-stent restenosis occurs in 10-30% of patients following bare metal stent (BMS) implantation and has various risk factors. Mannose-binding lectin (MBL) is known to have effect on the progression of atherosclerosis. Single nucleotide polymorphisms (SNP) of the MBL2 gene intron 1 (codon 52, 54, 57) are known to modulate the bioavailability of the MBL protein. Our aim was to identify the association of these polymorphisms of the MBL gene in the occurrence of in-stent restenosis after coronary artery bare metal stent implantation. METHODS: In a non-randomized prospective study venous blood samples were collected after recoronarography from 225 patients with prior BMS implantation. Patients were assigned to diffuse restenosis group and control group based on the result of the coronarography. MBL genotypes were determined using quantitative real-time PCR. Proportion of different genotypes was compared and adjusted with traditional risk factors using multivariate logistic regression. RESULTS: Average follow-up time was 1.0 (+ - 1.4) year in the diffuse restenosis group (N = 117) and 2.7 (+ - 2.5) years in the control group (N = 108). The age, gender distribution and risk status was not different between study groups. Proportion of the MBL variant genotype was 26.8% (29 vs. 79 normal homozygous) in the control group and 39.3% (46 vs. 71 normal homozygous) in the restenosis group (p = 0.04). In multivariate analysis the mutant allele was an independent risk factor (OR = 1.96, p = 0.03) of in-stent restenosis. CONCLUSIONS: MBL polymorphisms are associated with higher incidence of development of coronary in-stent restenosis. The attenuated protein function in the mutant allelic genotype may represent the underlying mechanism.

Complement C3a predicts outcome in cardiac resynchronization therapy of heart failure.

BACKGROUND: The chronic inflammation plays an important role in heart failure and complement components might be useful markers of the prognosis. We set out to evaluate their predictive value in the clinical outcomes of patients with cardiac resynchronization therapy (CRT). METHODS: We determined the complement levels C3, C3a, sC5b-9 and also the N-terminus of the prohormone brain natriuretic peptide (NT-proBNP) of 126 heart failure patients in a prospective, single-center observational study before and 6 months after CRT implantation. RESULTS: CRT reduced the C3a [212.5 (148.2-283.6) vs. 153 (119.8-218.3) ng/mL, p < 0.0001] and the sC5b-9 levels [296.9 (234.2-358.8) vs. 255.1 (210.1-319.0) ng/mL, p = 0.0006], but not the total C3 levels [1.43 (1.26-1.61) vs. 1.38 (1.23-1.57) g/L, p = 0.57]. C3a predicted the 5-year mortality of the patients [C3a > 165 ng/mL hazard ratio = 4.21 (1.65-10.72), p = 0.003] independent of the NT-proBNP and other factors. After reclassification, we observed a significant net reclassification improvement [NRI = 0.71 (0.43-0.98), p < 0.0001] and integrated discrimination improvement [IDI = 0.08 (0.03-0.12), p = 0.0002]. CONCLUSIONS: In patients with CRT, elevated C3a levels increase the risk of mortality independent of the NT-proBNP levels or other factors. CRT exerts anti-inflammatory effect by reducing the complement activation.

The ratio of the neutrophil leucocytes to the lymphocytes predicts the outcome after cardiac resynchronization therapy.

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.

Longer right to left ventricular activation delay at cardiac resynchronization therapy implantation is associated with improved clinical outcome in left bundle branch block patients.

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<0.001), NT-proBNP (2771-1216 ng/mL; P < 0.001), and they had better HF-free survival (HR: 0.23, 95% CI: 0.11-0.49, P < 0.001) and overall survival (HR: 0.35, 95% CI: 0.16-0.75; P = 0.007). There was no difference in outcome by RV-LV AD in non-LBBB patients. CONCLUSION: Left bundle branch block patients with longer RV-LV activation delay at CRT implantation had greater improvement in NT-proBNP, EF, and significantly better clinical outcome.

[Successful direct thrombin inhibitor treatment of a left atrial appendage thrombus developed under rivaroxaban therapy]. / Rivaroxabankezelés mellett kialakult bal pitvari fülcsethrombus sikeres kezelése direkt trombininhibitorral.

The authors present the history of a 62-year-old man on continuous rivaroxaban therapy who was scheduled for pulmonary vein isolation due to persistent atrial fibrillation. Preoperative transesophageal echocardiography detected the presence of left atrial appendage thrombus. Thrombophilia tests showed that the patient was heterozygous carrier of the methylene-tetrahydrofolate reductase gene mutation. The authors hypothesized that a direct thrombin inhibitor might exert a more appropriate effect against thrombosis in this case and, therefore, a switch to dabigatran was performed. After two months of anticoagulation with the direct thrombin inhibitor and folic acid supplementation the thrombus resolved. The authors underline that thrombus formation may develop in atrial fibrillation even if the patient is adequately treated with rivaroxaban. This case suggests, that methylene-tetrahydrofolate reductase gene mutation may modulate the efficacy of direct Xa factor inhibitors. According to this case history, dabigatran may be an effective therapeutic option in resolving established thrombus.

Comparison of the Effects of Epicardial and Endocardial Cardiac Resynchronization Therapy on Transmural Dispersion of Repolarization.

BACKGROUND: Despite significant improvements in cardiac output and functional capacity with cardiac resynchronization therapy (CRT), incidence of sudden cardiac death still remains high. Reversal of physiological myocardial activation sequence during epicardial pacing increases the transmural dispersion of repolarization (TDR). The aim of this study was to compare the effects of endocardial and epicardial biventricular pacing on repolarization parameters in the same patient group. METHODS: Seven patients who had transseptal endocardial left ventricle (LV) lead placement, in whom epicardial CRT had failed due to coronary sinus (CS) lead dislodgement after successful implantation, were admitted to the study. LV endocardial leads were implanted through the interatrial septum in a lateral position. Electrocardiograms (ECGs) were scanned before and after successful epicardial and endocardial biventricular pacing and analyzed using digital calipers. ECG markers of TDR (TpTe and TpTe/QT ratio) were measured and compared. RESULTS: Baseline QRS durations (161.7 ± 15.9 ms vs 162.2 ± 17.8 ms, P = 0.95), TpTe values (107.1 ± 20.5 ms vs 108.5 ± 17.6 ms, P = 0.89), and TpTe/QT ratios (0.24 ± 0.05 vs 0.24 ± 0.03, P = 0.88) were similar before epicardial and endocardial CRT. QRS interval reduction was similar (-28.3 ± 11.6 ms vs -29.1 ± 11.4 ms, P = 0.89) in both groups. Compared to transseptal endocardial CRT, epicardial CRT was associated with a significant increase in TpTe (17.1 ± 19.5 ms vs -12.6 ± 18.9 ms, P = 0.01) and TpTe/QT ratio (0.03 ± 0.04 vs -0.02 ± 0.03, P = 0.04). CONCLUSION: Transseptal LV endocardial pacing is associated with significant reduction in TDR characteristics compared to epicardial pacing in CRT. Further studies are warranted to determine whether these effects may contribute to reduction of arrhythmias in patients with CRT.