Left bundle branch pacing versus left ventricular septal pacing as a primary procedural endpoint during left bundle branch area pacing: Evaluation of two different implant strategies.

INTRODUCTION: Implant procedure features and clinical implications of left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP) have not been yet fully described. We sought to compare two different left bundle branch area pacing (LBBAP) implant strategies: the first one accepting LVSP as a procedural endpoint and the second one aiming at achieving LBBP in every patient in spite of evidence of previous LVSP criteria. METHODS: LVSP was accepted as a procedural endpoint in 162 consecutive patients (LVSP strategy group). In a second phase, LBBP was attempted in every patient in spite of achieving previous LVSP criteria (n = 161, LBBP strategy group). Baseline patient characteristics, implant procedure, and follow-up data were compared. RESULTS: The final capture pattern was LBBP in 71.4% and LVSP in 24.2% in the LBBP strategy group compared to 42.7% and 50%, respectively, in the LVSP strategy group. One hundred and eighty-four patients (57%) had proven LBB capture criteria with a significantly shorter paced QRS duration than the 120 patients (37%) with LVSP criteria (115 ± 9 vs. 121 ± 13 ms, p < .001). Implant parameters were comparable between the two strategies but the LBBP strategy resulted in a higher rate of acute septal perforation (11.8% vs. 4.9%, p = .026) without any clinical sequelae. Patients with CRT indications significantly improved left ventricular ejection fraction (LVEF) during follow-up irrespective of the capture pattern (from 35 ± 11% to 45 ± 14% in proven LBBP, p = .024; and from 39 ± 13% to 47 ± 12% for LVSP, p = .003). The presence of structural heart disease and baseline LBBB independently predicted unsuccessful LBB capture. CONCLUSION: The LBBP strategy was associated with comparable implant parameters than the LVSP strategy but resulted in higher rates of septal perforation. Proven LBB capture and LVSP showed comparable effects on LVEF during follow-up.

Response rate in cardiac resynchronization therapy patients implanted with a left ventricular quadripolar lead and the MultiPoint™ pacing feature early activated. QUARTO III.

BACKGROUND: Although cardiac resynchronization therapy (CRT) is beneficial in most heart failure patients, up to 40% do not respond to CRT. It has been suggested that multipoint left ventricle pacing (MPP) would increase the response rate. AIM: To assess the CRT response rate at 6 months in patients implanted with a CRT device with the MPP feature activated early after the implant. METHODS: This was a multicentre, prospective, open-label and non-randomized study. The primary endpoint was response to biventricular pacing defined as >15% relative reduction in left ventricular end-systolic volume (LVESV) comparing echocardiography measurements performed at baseline and 6 months by a core laboratory. Among secondary endpoints the combined endpoint of mortality or all-cause hospitalizations was evaluated. Primary study endpoint and clinical outcomes were compared to a Quarto II control cohort. RESULTS: Totally, 105 patients were included. The response rate was 64.6% (97.5% lower confidence bound 53%). Mean relative reduction in LVESV was 25.3%, and mean absolute increase in LVEF was 9.4%. The subjects with device programmed using anatomical approach showed a trend towards higher responder rate than those using the electrical approach (72% vs. 61.1%, p = 0.32). Finally, the combined incidence of mortality and or all-cause hospitalizations at 6 month was 12.4%. CONCLUSIONS: Early activation of MPP was not associated to an advantage increasing echocardiography responders to CRT at 6 months of follow-up. Nevertheless, patients programmed using widest pacing cathodes had a numerically higher responder rate. Finally, early activation of MPP was associated to a low incidence of clinical endpoints at 6 months of follow-up.

Influence of baseline inducibility and activation mapping on ablation outcomes in patients with structural heart disease and ventricular tachycardia.

INTRODUCTION: Stand-alone substrate ablation has become a standard ventricular tachycardia (VT) ablation strategy. We sought to evaluate the influence of baseline VT inducibility and activation mapping on ablation outcomes in patients with structural heart disease (SHD) undergoing VT ablation. METHODS: Single center, observational and retrospective study including consecutive patients with SHD and documented VT undergoing ablation. Baseline VT induction was attempted before ablation in all patients and VT activation mapping performed when possible. Ablation was guided by activation mapping for mappable VTs plus substrate ablation for all patients. Ablation outcomes and complications were evaluated. RESULTS: One hundred and sixty patients were included and were classified in three groups according to baseline VT inducibility:group 1 (non inducible, n = 18), group 2 (1 VT morphology induced, n = 53), and group 3 (>1 VT morphology induced, n = 89). VT activation mapping was possible in 35%. After a median follow-up of 38.5 months, baseline inducibility of greater than 1 VT morphology was associated with a significant incidence of VT recurrence (42% for group 3 vs. 15.1% for group 2% and 5.6% for group 1, Log-rank p < .0001) and activation mapping with a lower rate of VT recurrence (24% vs. 36.3%, Log-rank p = .035). Baseline inducibility of greater than 1 VT morphology (hazards ratio [HR]: 12.05, 95% confidence interval [CI]: 1.60-90.79, p = .016) was an independent predictor of VT recurrence while left ventricular ejection fraction less than 30% (HR: 1.93, 95% CI: 1.13-3.25, p = .014) and advanced heart failure (HR: 4.69, 95% CI: 2.75-8.01, p < .0001) were predictors of mortality or heart transplantation. Complications occurred in 11.2% (5.6% hemodynamic decompensation). CONCLUSION: Baseline VT inducibility and activation mapping may add significant prognostic information during VT ablation procedures.

Safety and feasibility of conduction system pacing in patients with congenital heart disease.

INTRODUCTION: Conduction system pacing (CSP) has emerged as an ideal physiologic pacing strategy for patients with permanent pacing indications. We sought to evaluate the safety and feasibility of CSP in a consecutive series of unselected patients with congenital heart disease (CHD). METHODS: Consecutive patients with CHD in which CSP was attempted were included. Safety and feasibility, implant tools and electrical parameters at implant and at follow-up were evaluated. RESULTS: A total of 20 patients were included (10 with a previous device). A total of 10 patients had complex forms of CHD, 9 moderate defects and 1 a simple defect. CSP was achieved in 75% of cases (10 His bundle pacing, 5 left bundle branch pacing) with left ventricular septal pacing in the remaining 5 patients. Procedure times and fluoroscopy times were prolongued (126 ± 82 min and 27 ± 30 min, respectively). Ventricular lead implant times widely varied ranging from 4 to 115 min, (mean 31 ± 28 min) and the use of multiple delivery sheaths was frequent (50%). The QRS width was reduced from 145 ± 36 ms at baseline to 116 ± 18 ms with CSP. Implant electrical parameters included: CSP pacing threshold 0.95 ± 0.65 V; R wave amplitude 9.2 ± 8.8 mV and pacing impedance 632 ± 183 Ohms, and remained stable at a median follow-up of 478 days (interquartile range: 225-567). Systemic ventricle systolic function and NYHA class (1.50 ± 0.51 vs. 1.10 ± 0.31; p = .008) significantly improved at follow-up. Lead revision was required in one patient at Day 4. CONCLUSIONS: Permanent CSP is safe and feasible in patients with CHD although implant technique is complex.

Short-Time Estimation of Fractionation in Atrial Fibrillation with Coarse-Grained Correlation Dimension for Mapping the Atrial Substrate.

Atrial fibrillation (AF) is currently the most common cardiac arrhythmia, with catheter ablation (CA) of the pulmonary veins (PV) being its first line therapy. Ablation of complex fractionated atrial electrograms (CFAEs) outside the PVs has demonstrated improved long-term results, but their identification requires a reliable electrogram (EGM) fractionation estimator. This study proposes a technique aimed to assist CA procedures under real-time settings. The method has been tested on three groups of recordings: Group 1 consisted of 24 highly representative EGMs, eight of each belonging to a different AF Type. Group 2 contained the entire dataset of 119 EGMs, whereas Group 3 contained 20 pseudo-real EGMs of the special Type IV AF. Coarse-grained correlation dimension (CGCD) was computed at epochs of 1 s duration, obtaining a classification accuracy of 100% in Group 1 and 84.0-85.7% in Group 2, using 10-fold cross-validation. The receiver operating characteristics (ROC) analysis for highly fractionated EGMs, showed 100% specificity and sensitivity in Group 1 and 87.5% specificity and 93.6% sensitivity in Group 2. In addition, 100% of the pseudo-real EGMs were correctly identified as Type IV AF. This method can consistently express the fractionation level of AF EGMs and provides better performance than previous works. Its ability to compute fractionation in short-time can agilely detect sudden changes of AF Types and could be used for mapping the atrial substrate, thus assisting CA procedures under real-time settings for atrial substrate modification.

Management of patients with ventricular arrhythmias and prevention of sudden cardiac death-translating guidelines into practice: results of the European Heart Rhythm Association survey.

Prevention of sudden cardiac death (SCD) remains a partly unsolved task in cardiology. The European Society of Cardiology (ESC) guidelines on management of patients with ventricular arrhythmias and prevention of SCD published in 2015 considered the new insights of the natural history of diseases predisposing to SCD. The guidelines improved strategies for management of patients at risk of SCD and included both drug and device therapies. The intention of this survey was to evaluate the extent of the disparities between daily clinical practice and the 2015 SCD ESC guidelines among electrophysiology centres in Europe. The results suggest that the adherence to guidelines is reasonably high and strategies for the management of ischaemic disease are well-established. Implantable cardioverter-defibrillator indications for primary prevention are a difficult topic, particularly in non-ischaemic dilated cardiomyopathy. Disparities in the use of genetic testing are probably due to differences in local availability.

Utility of high density multielectrode mapping during ablation of scar-related ventricular tachycardia.

INTRODUCTION: Multielectrode mapping catheters (MEMC) allow the performance of high resolution and density maps but the utility of these catheters in ventricular tachycardia (VT) ablation procedures has not been yet widely described. We sought to evaluate the utility of a MEMC during scar-related VT ablation procedures. METHODS: Eighty-five consecutive scar-related VT ablation procedures were performed in 81 patients. In the first 26 procedures, a standard 3.5-mm tip linear catheter was employed for endocardial/epicardial mapping (control group). In the following 59 procedures mapping was performed with a MEMC (study group). Procedural time, LV endocardial and epicardial mapping time, complications and ablation outcomes were compared. RESULTS: The use of the MEMC resulted in a significant shortening of the endocardial and epicardial mapping times (38 ± 15 minutes vs. 56 ± 24 minutes for endocardial LV mapping in the study and control group, respectively, P = 0.001; and 28 ± 9 minutes vs 41 ± 16 minutes, for epicardial mapping, P = 0.011) as well as the total procedural time (177 ± 53 minutes vs. 206 ± 50 minutes, respectively, P = 0.02). The mapping density was also significantly increased in the study group (mean endocardial LV points: 2,143 ± 1,419 vs. 485 ± 174, for the study and control group, respectively, P < 0.0001), specially within the scar area (49.6 ± 34 points/cm2 vs. 8.4 ± 4.6 points/cm2 , P < 0.001). No differences in acute and long-term follow-up outcomes were observed. CONCLUSIONS: High-density multielectrode mapping is associated with a significant reduction of procedural and mapping times and a significant increase of mapping density without affecting outcomes in patients with scar-related VT.

Incidence and predictors of clinically relevant cardiac perforation associated with systematic implantation of active-fixation pacing and defibrillation leads: a single-centre experience with over 3800 implanted leads.

AIMS: Active-fixation leads have been associated with higher incidence of cardiac perforation. Large series specifically evaluating this complication are lacking. We sought to evaluate the incidence and predictors of clinically relevant cardiac perforation in a consecutive series of patients implanted with active-fixation pacing and defibrillation leads. METHODS AND RESULTS: We conducted a retrospective observational study including all consecutive patients implanted with an active-fixation pacing/defibrillation lead at our institution from July 2008 to July 2015. The incidence of clinically relevant cardiac perforation and cardiac tamponade was evaluated. Univariate and multivariate analyses were used to identify predictors of cardiac perforation. Acute and long-term management of these patients was also investigated. A total of 3822 active-fixation pacing (n = 3035) and defibrillation (n = 787) leads were implanted in 2200 patients. Seventeen patients (0.8%) had clinically relevant cardiac perforation (13 acute and 4 subacute perforations), and 13 (0.5%) had cardiac tamponade resolved with pericardiocentesis. None of the patients with cardiac perforation required surgical treatment. In multivariate analysis, an age >80 years (OR 3.84, 95% CI 1.14-12.87, P = 0.029), female sex (OR 3.14, 95% CI 1.07-9.22, P = 0.037), and an apical position of the right ventricular lead (OR 3.37, 95% CI 1.17-9.67, P = 0.024) were independent predictors of cardiac perforation. CONCLUSIONS: Implantation of active-fixation leads is associated with a low incidence of clinically relevant cardiac perforation. Older and female patients have a higher risk of perforation as well as those patients receiving the ventricular lead in an apical position.

The Role of Conventional and Right-Sided ECG Screening for Subcutaneous ICD in a Tetralogy of Fallot Population.

BACKGROUND: Information regarding suitability for subcutaneous implantable cardioverter-defibrillator (S-ICD) implant in tetralogy of Fallot (ToF) population is scarce and needs to be further explored. THE AIMS OF OUR STUDY WERE: (1) to determine the proportion of patients with ToF eligible for S-ICD, (2) to identify the optimal sensing vector in ToF patients, (3) to test specifically the eligibility for S-ICD with right-sided screening, and (4) to compare with the proportion of eligible patients in a nonselected ICD population. METHODS: We recruited 60 consecutive patients with ToF and 40 consecutive nonselected patients. Conventional electrocardiographic screening was performed as usual. Right-sided alternative screening was studied by positioning the left arm and right arm electrodes 1 cm right lateral to the xiphoid midline. The Boston Scientific electrocardiogram (ECG) screening tool was utilized. RESULTS: We found a higher proportion of patients with right-sided positive screening in comparison with standard screening (77 ± 0.4% vs. 67 ± 0.4%; P < 0.0001) and a trend to higher number of appropriate leads in right-sided screening (1.3 ± 1 vs. 1.1 ± 1 ms; P = 0.07). Patients who failed the screening had a longer QRS duration and longer QT interval. Standard and right-sided screening showed a higher percent of positive patients in the control group compared to ToF patients (P < 0.001). CONCLUSION: Right-sided screening was associated with a significant 10% increase in S-ICD eligibility in ToF patients. When comparing with an acquired cardiomyopathies group, ToF showed a lower eligibility for S-ICD. The most appropriate ECG vector was the alternate vector in contrast to what is observed in the general population.

Conventional and right-sided screening for subcutaneous ICD in a population with congenital heart disease at high risk of sudden cardiac death.

BACKGROUND: Information regarding suitability for subcutaneous defibrillator (sICD) implantation in tetralogy of Fallot (ToF) and systemic right ventricle is scarce and needs to be further explored. The main objective of our study was to determine the proportion of patients with ToF and systemic right ventricle eligible for sICD with both, standard and right-sided screening methods. Secondary objectives were: (i) to study sICD eligibility specifically in patients at high risk of sudden cardiac death, (ii) to identify independent predictors for sICD eligibility, and (iii) to compare the proportion of eligible patients in a nonselected ICD population. METHODS: We recruited 102 patients with ToF, 33 with systemic right ventricle, and 40 consecutive nonselected patients. Conventional electrocardiographic screening was performed as usual. Right-sided alternative screening was studied by positioning the left-arm and right-arm electrodes 1 cm right lateral of the xiphoid midline. The Boston Scientific ECG screening tool was utilized. RESULTS: In high-risk patients with ToF, eligibility was higher with right-sided screening in comparison with standard screening (61% vs. 44%; p = .018). Eligibility in high-risk right ventricle population was identical with both screening methods (77%, p = ns). The only independent predictor for sICD eligibility was QRS duration. CONCLUSION: In high-risk patients with ToF, right-sided implantation of the sICD could be an alternative to a conventional ICD. In patients with a systemic right ventricle, implantation of a sICD is an alternative to a conventional sICD.

Essential ECG clues in patients with congenital heart disease and arrhythmias.

The prevalence of adults with congenital heart disease has dramatically increased during the last decades due to significant advances in the surgical correction of these conditions. As a result, patient's survival has been prolonged and arrhythmias have become one of the principal causes of morbidity and mortality for these patients. The surface 12-lead ECG may play a critical role in the identification of the underlying heart disease of the patient, the recognition of the arrhythmia mechanism and may also help in the planification of the ablation procedure in this setting. Finally, important prognostic information can be also obtained from the ECG in these patients. The present review will offer an overview of the principal utilities of the surface ECG in the diagnosis and management of patients with CHD and arrhythmias.

The use of multisite left ventricular pacing via quadripolar lead improves acute haemodynamics and mechanical dyssynchrony assessed by radial strain speckle tracking: initial results.

AIMS: The objective of the present study was to evaluate the effect of multipoint pacing (MPP) on acute haemodynamics, cardiac contractility, and left ventricle (LV) dyssynchrony, in comparison with conventional cardiac resynchronization therapy (CRT). METHODS AND RESULTS: An open-label, non-randomized, single-centre, prospective study was designed. Twenty-seven consecutive patients were included. Evaluation of pacing configurations was performed in a random order. Transthoracic echocardiography was used to obtain haemodynamic and dyssynchrony parameters. Left ventricular ejection fraction (LVEF) was significantly superior in MPP compared with baseline (38.4 ± 1.8% vs. 26.1 ± 2.2%; P < 0.001), and in conventional pacing configuration compared with baseline (33.2 ± 1.8% vs. 26.1 ± 2.2%; P = 0.007). Cardiac index (CI) was increased by 21.8 ± 5.4% and 34.7 ± 5.1% in conventional and MPP configurations, respectively (P = 0.19). Percentage of acute responders (CI increase ≥10%) was 62.9 and 85.2% in conventional and MPP, respectively (P < 0.001). LV dyssynchrony was defined by radial strain rate parameters. Baseline anteroseptal-to-posterior wall time delay was 168 ± 21 ms. It was reduced until 70.4 ± 29 ms in conventional and -6.6 ± 11 ms in MPP (conventional vs. baseline P = 0.04; MPP vs. conventional P = 0.05). Standard deviation of the time-to-peak radial strain of the 6 LV basal segments was 101 ± 9.7, 80.3 ± 9.2, and 66 ± 8.03 ms in baseline, conventional, and MPP configurations, respectively (MPP vs. basal P = 0.012). Finally, we observed a positive correlation (r = 0.69) between reduction in dyssynchrony and CI increase (P < 0.0001). CONCLUSION: MPP showed a further reduction in LV dyssynchrony compared with conventional biventricular pacing. Moreover, MPP resulted in an additional improvement in LVEF and in CI, and this was translated into a higher number of acute responders to CRT.

Initial Experience with a New Image Integration Module Designed for Reducing Radiation Exposure During Electrophysiological Ablation Procedures.

INTRODUCTION: Reduction of radiation exposure during cardiac arrhythmia ablation procedures is desirable. We sought to evaluate the utility of a new image integration module (CARTOUNIVU(TM) ) in reducing fluoroscopy times and dosages during left atrial arrhythmia (LAA) and ventricular tachycardia (VT) ablation procedures. METHODS AND RESULTS: Consecutive patients undergoing LAA (n = 28)/VT (n = 13) ablation using the CARTOUNIVU(TM) module were included. Total fluoroscopy time, radiation dose (total dose area product [tDAP], effective dose [ED]), and procedure duration were evaluated. A retrospective cohort of patients who underwent LAA (n = 16)/VT(n = 8) ablation without the new image integration module served as a control group. The use of the new image integration module significantly reduced mean fluoroscopy time (5.2 minutes [IQR 1.9;6.8] in the LAA ablation UNIVU group vs. 28.2 minutes [IQR 15.3;37.8] in the control group, P<0.001; 9.8 minutes [IQR 4.5;13.1] vs. 25.5 minutes [IQR 14.1;30.9] for VT ablation, P = 0.013), tDAP (2,088 cGy*cm(2) [IQR 664;2911] vs. 5,893 cGy*cm(2) [IQR 3088;8483], P< 0.001 for LAA ablation; 3,917 cGy*cm(2) [IQR 948;4217] vs. 12,377 cGy*cm(2) (IQR 3385;23157) for VT ablation patients, P = 0.025) and ED (4.1 mSv [IQR 1;5.8] vs. 11.8 mSv [IQR 6.2;16.9] for LAA ablation patients, P< 0.001; 7.8 mSv [IQR 1.9;8.4] vs. 24.7 mSv [IQR 6.8;46.3] for VT ablation patients, P = 0.025). Procedure duration did not significantly change (174 ± 45 minutes vs. 197 ± 36 minutes for LAA ablation, P = 0.083; 201 ± 51 minutes vs. 201 ± 63 minutes for VT ablation, P = 0.860). No serious adverse events related to the use of the CARTOUNIVU(TM) module occurred. CONCLUSIONS: The new image integration module significantly reduced total fluoroscopy time and mean radiation dose without influence in procedure duration during ablation of complex atrial and ventricular arrhythmias.

The use of quadripolar left ventricular leads improves the hemodynamic response to cardiac resynchronization therapy.

BACKGROUND: The objective of the present study was to evaluate the usefulness of a left ventricle (LV) quadripolar lead in improving the hemodynamic response to cardiac resynchronization therapy (CRT). METHODS AND RESULTS: We included 27 consecutive patients implanted with a CRT device with an LV quadripolar lead. Hemodynamic parameters were evaluated at 3-month follow-up by using impedance cardiography. We assessed the highest cardiac output and the highest stroke volume (SV) obtained after atrioventricular and interventricular optimization with pacing from each of the four electrodes of the LV lead. Each patient was evaluated according to three different pacing configurations: unipolar-simulated, bipolar, and quadripolar. Biventricular pacing improved hemodynamics in comparison to the nonpaced measurements: cardiac index (CI): 2.69 L/min/m(2) versus 2.17 L/min/m(2) (P = 0.001). The hemodynamic response was highest in the quadripolar in comparison to unipolar-simulated and bipolar configurations, with an increase of 29%, 23%, and 27%, respectively, in relation to the reference CI and with an increase of 22%, 11%, and 18%, respectively, in relation to the reference indexed SV (P < 0.05, for the comparison between unipolar-simulated and quadripolar configurations). Twelve patients (44%) showed the best hemodynamic response by pacing from any of the two distal electrodes and 15 patients (56%) by pacing from the two proximal electrodes. Finally, CRT responder rates were higher in quadripolar versus bipolar and unipolar-simulated configurations: 90%, 85%, and 75%, respectively. CONCLUSIONS: The quadripolar LV lead was associated with a better hemodynamic response and higher CRT responder rates when compared with unipolar-simulated and bipolar LV leads.

Systematic Implantation of Pacemaker/ICDs under Active Oral Anticoagulation Irrespective of Patient's Individual Preoperative Thromboembolic Risk.

BACKGROUND: A wide variability in the perioperative management of oral anticoagulation (OAC) has been documented in patients receiving cardiac rhythm management devices (CRMDs). We sought to evaluate the safety and feasibility of a new perioperative strategy consisting in systematically continuing OAC in all patients irrespective of their individual thromboembolic (TE) risk. METHODS: A total of 278 consecutive patients on chronic OAC receiving CRMDs were prospectively included. Patients were classified in high and low TE risk according to current guidelines for the perioperative management of antithrombotic therapy, but underwent implantation under active OAC (international normalized ratio 2-4) irrespective of their preoperative TE risk. Bleeding and TE complications were evaluated as well as other procedure-related complications, hospital stays, and the feasibility of outpatient implantations. RESULTS: A total of 117 patients were considered at high TE risk and 161 at low TE risk. Overall, the incidence of pocket hematoma was 2.9% with only three patients requiring pocket revision. Low TE risk patients had a very low incidence of pocket hematoma (1.9%) without needing pocket revision. The mean hospital stay was 1.17 ± 1.8 days and 169 patients (61%) received their CRMD in an outpatient basis, including 77 patients who were implanted with an implantable cardioverter defibrillator. No TE events were detected during the 30-day postimplant observation period in any patient. No other significant complications related with the implant (pneumothorax, hemothorax, cardiac tamponade) were registered. CONCLUSIONS: Systematic continuation of OAC in all patients undergoing implantation of CRMDs is safe and feasible, thus simplifying and standardizing the perioperative management in this setting.

Influence of genetic mutations to atria vulnerability to atrial fibrillation: An in-silico 3D human atria study.

BACKGROUND AND OBJECTIVE: Personalized 3D computer models of atria have been extensively implemented in the last yearsas a tool to facilitate the understanding of the mechanisms underlying different forms of arrhythmia, such as atrial fibrillation (AF). Meanwhile, genetic mutations acting on potassium channel dynamics were demonstrated to induce fibrillatory episodes in asymptomatic patients. This research study aims at assessing the effects and the atrial susceptibility to AF of three gain-of-function mutations - namely, KCNH2 T895M, KCNH2 T436M, and KCNE3-V17M - associated with AF outbreaks, using highly detailed 3D atrial models with realistic wall thickness and heterogenous histological properties. METHODS: The 3D atrial model was generated by reconstructing segmented anatomical structures from CT scans of an AF patient. Modified versions of the Courtemanche human atrial myocyte model were used to reproduce the electrophysiological activity of the WT and of the three mutant cells. Ectopic foci (EF) were simulated in sixteen locations across the atrial mesh using an S1-S2 protocol with two S2 basic cycle lengths (BCL) and eleven coupling intervals in order to induce arrhythmias. RESULTS: The three genetic mutations at 3D level reduced the APD90. The KCNE3-V17M mutation provoked the highest shortening (55 % in RA and LA with respect to WT), followed by KCNH2 T895M (14 % in RA and 18 % LA with respect to WT)and KCNH2 T436M (7 % in RA and 9 % LA with respect to WT). The KCNE3-V17M mutation led to arrhythmia in 67 % of the cases simulated and in 94 % of ectopic foci considered, at S2 BCL equal to 100 ms. The KCNH2 T436M and KCNH2 T895M mutations increased the vulnerability to AF in a similar way, leading to arrhythmic episodes in 7 % of the simulated conditions, at S2 BCL set to 160 ms. Overall, 60 % of the arrhythmic events generated arise in the left atrium. Spiral waves, multiple rotors and disordered electrical pattern were elicited in the presence of the KCNE3-V17M mutation, exhibiting an instantaneous mean frequency of 7.6 Hz with a mean standard deviation of 1.12 Hz. The scroll waves induced in the presence of the KCNH2 T436M and KCNH2 T895M mutations showed steadiness and regularity with an instantaneous mean frequencies in the range of 4.9 - 5.1 Hz and a mean standard deviation within 0.19 - 0.53 Hz. CONCLUSIONS: The pro-arrhythmogenicity of the KCNE3-V17M, KCNH2 T895M and KCNH2 T436M mutations was studied and proved on personalized 3D cardiac models. The three genetic mutations were demonstrated to increase the predisposition of atrial tissue to the formation of AF-susceptible substrate in different ways based on their effects on electrophysiological properties of the atria.

Safety of pulsed field ablation in more than 17,000 patients with atrial fibrillation in the MANIFEST-17K study.

Pulsed field ablation (PFA) is an emerging technology for the treatment of atrial fibrillation (AF), for which pre-clinical and early-stage clinical data are suggestive of some degree of preferentiality to myocardial tissue ablation without damage to adjacent structures. Here in the MANIFEST-17K study we assessed the safety of PFA by studying the post-approval use of this treatment modality. Of the 116 centers performing post-approval PFA with a pentaspline catheter, data were received from 106 centers (91.4% participation) regarding 17,642 patients undergoing PFA (mean age 64, 34.7% female, 57.8% paroxysmal AF and 35.2% persistent AF). No esophageal complications, pulmonary vein stenosis or persistent phrenic palsy was reported (transient palsy was reported in 0.06% of patients; 11 of 17,642). Major complications, reported for ~1% of patients (173 of 17,642), were pericardial tamponade (0.36%; 63 of 17,642) and vascular events (0.30%; 53 of 17,642). Stroke was rare (0.12%; 22 of 17,642) and death was even rarer (0.03%; 5 of 17,642). Unexpected complications of PFA were coronary arterial spasm in 0.14% of patients (25 of 17,642) and hemolysis-related acute renal failure necessitating hemodialysis in 0.03% of patients (5 of 17,642). Taken together, these data indicate that PFA demonstrates a favorable safety profile by avoiding much of the collateral damage seen with conventional thermal ablation. PFA has the potential to be transformative for the management of patients with AF.

Conduction System Pacing for Cardiac Resynchronization Therapy.

Cardiac resynchronization therapy (CRT) via biventricular pacing (BiVP-CRT) is considered a mainstay treatment for symptomatic heart failure patients with reduced ejection fraction and wide QRS. However, up to one-third of patients receiving BiVP-CRT are considered non-responders to the therapy. Multiple strategies have been proposed to maximize the percentage of CRT responders including two new physiological pacing modalities that have emerged in recent years: His bundle pacing (HBP) and left bundle branch area pacing (LBBAP). Both pacing techniques aim at restoring the normal electrical activation of the ventricles through the native conduction system in opposition to the cell-to-cell activation of conventional right ventricular myocardial pacing. Conduction system pacing (CSP), including both HBP and LBBAP, appears to be a promising pacing modality for delivering CRT and has proven to be safe and feasible in this particular setting. This article will review the current state of the art of CSP-based CRT, its limitations, and future directions.

Acute performance of stylet driven leads for left bundle branch area pacing: A comparison with lumenless leads.

Background: Lumenless leads (LLLs) are widely used for left bundle branch area pacing (LBBAP). Recently, stylet-driven leads (SDLs) have also been used for LBBAP. Objective: The purpose of this study was to evaluate the acute performance of SDLs during LBBAP in comparison with LLLs. Methods: Consecutive patients undergoing LBBAP for bradycardia or cardiac resynchronization therapy indications at 2 high-volume, early conduction system pacing adopters, tertiary centers were included from January 2019 to July 2023. Patients received either SDLs or LLLs at the discretion of the implanting physician. Acute performance and follow-up data of both lead types were evaluated. Results: A total of 925 LBBAP implants were included, 655 using LLLs and 270 using SDLs. Overall, LBBAP acute success was significantly higher with LLLs than SDLs (95.3% vs 85.1%, respectively; P <.001) even after the learning curve (97% vs 86%; P = .013). LLLs were implanted in more mid-basal septal positions in comparison with SDLs, which tended to be implanted in more inferior and mid-apical septal positions. Acute lead-related complications were higher with SDLs than LLLs (15.9% vs 6.1%, respectively; P <.001) with 15 cases of lead damage during implant (4.4% vs 0.5%; P <.001) but decreased with acquired experience and were comparable in the last 100 patients included in each group. Lead implant and fluoroscopy times were shorter for SDLs, with lead dislodgment occurring in 0.9% with LLLs and 1.5% with SDLs (P = .489). Conclusion: Acute lead performance proved to be different between LLLs and SDLs. A specific learning curve should be considered for SDLs even for implanters with extensive previous experience with LLLs.

Atrial low voltage areas: A comparison between atrial fibrillation and sinus rhythm.

BACKGROUND: Atrial fibrosis can promote atrial fibrillation (AF). Electroanatomic mapping (EAM) can provide information regarding local voltage abnormalities that may be used as a surrogate marker for fibrosis. Specific voltage cut-off values have been reproduced accurately to identify fibrosis in the ventricles, but these values are not well defined in atrial tissue. METHODS: This study is a prospective single-center study. Patients with persistent AF referred for ablation were included. EAM was performed before ablation. We recorded bipolar signals, first in AF and later in sinus rhythm (SR). Two thresholds delimited low-voltage areas (LVA), 0.5 and 0.3 mV. We compared LVA extension between maps in SR and AF in each patient. RESULTS: A total of 23 patients were included in the study. The percentage of points with voltage lower than 0.5 mV and 0.3 mV was significantly higher in maps in AF compared with maps in SR: 38.2% of points < 0.5 mV in AF vs. 22.9% in SR (p < 0.001); 22.3% of points < 0.3 mV in AF vs. 14% in SR (p < 0.001). Areas with reduced voltage were significantly larger in maps in AF (0.5 mV threshold, mean area in AF 41.3 ± 42.5 cm2 vs. 11.7 ± 17.9 cm2 in SR, p < 0.001; 0.3 mV threshold, mean area in AF 15.6 ± 22.1 cm2 vs. 6.2 ± 11.5 cm2 in SR, p < 0.001). CONCLUSIONS: Using the same voltage thresholds, LVA extension in AF is greater than in SR in patients with persistent AF. These findings provide arguments for defining a different atrial fibrosis threshold based on EAM rhythm.