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AimsThis study aimed to examine the clinical benefits of targeted ablation of all Premature ventricular complex (PVC) morphologies vs. predominant PVC only.Methods and resultsA total of 171 consecutive patients with reduced left ventricular ejection fraction (LVEF) and ≥2 PVC morphology with high burden (>10%/day) undergoing their first ablation procedure were included in the analysis. At the initial procedure, prevalent PVC alone was ablated in the majority. However, at the redo, all PVC morphologies were targeted for ablation. : At the first procedure, 152 (89%) patients received ablation of the dominant PVC only. In the remaining 19 (11%) patients, all PVC morphologies were ablated. At two years, high PVC burden was detected in 89 (52%) patients. Repeat procedure was performed in 78 of 89, where all PVC morphologies were ablated. At 5 years after the repeat procedure, 71 (91%) had PVC burden of ConclusionIn this observational series, ablation of all PVC morphologies was associated with significantly lower PVC burden and improvement of LVEF at long-term follow-up, compared with ablation of the dominant morphology only.

AIMS: Mitral valve prolapse (MVP) is a common valvular heart disease with a prevalence of >2% in the general adult population. Despite this high incidence, there is a limited understanding of the molecular mechanism of this disease, and no medical therapy is available for this disease. We aimed to elucidate the genetic basis of MVP in order to better understand this complex disorder.METHODS AND RESULTS: We performed a meta-analysis of six genome-wide association studies that included 4884 cases and 434 649 controls. We identified 14 loci associated with MVP in our primary analysis and 2 additional loci associated with a subset of the samples that additionally underwent mitral valve surgery. Integration of epigenetic, transcriptional, and proteomic data identified candidate MVP genes including LMCD1, SPTBN1, LTBP2, TGFB2, NMB, and ALPK3. We created a polygenic risk score (PRS) for MVP and showed an improved MVP risk prediction beyond age, sex, and clinical risk factors.CONCLUSION: We identified 14 genetic loci that are associated with MVP. Multiple analyses identified candidate genes including two transforming growth factor-β signalling molecules and spectrin β. We present the first PRS for MVP that could eventually aid risk stratification of patients for MVP screening in a clinical setting. These findings advance our understanding of this common valvular heart disease and may reveal novel therapeutic targets for intervention.KEY QUESTION: Expand our understanding of the genetic basis for mitral valve prolapse (MVP). Uncover relevant pathways and target genes for MVP pathophysiology. Leverage genetic data for MVP risk prediction.KEY FINDING: Sixteen genetic loci were significantly associated with MVP, including 13 novel loci. Interesting target genes at these loci included LTBP2, TGFB2, ALKP3, BAG3, RBM20, and SPTBN1. A risk score including clinical factors and a polygenic risk score, performed best at predicting MVP, with an area under the receiver operating characteristics curve of 0.677.TAKE-HOME MESSAGE: Mitral valve prolapse has a polygenic basis: many genetic variants cumulatively influence pre-disposition for disease. Disease risk may be modulated via changes to transforming growth factor-β signalling, the cytoskeleton, as well as cardiomyopathy pathways. Polygenic risk scores could enhance the MVP risk prediction.

In this study, the authors investigated the ablation success of scar homogenization with combined (epicardial + endocardial) vs endocardial-only approach for ventricular tachycardia (VT) in patients with ischemic cardiomyopathy (ICM) at 5 years of follow-up.Best ablation approach to achieve long-term success rate in VT patients with ICM is not known yet.Consecutive ICM patients undergoing VT ablation at our center were classified into group 1: endocardial + epicardial scar homogenization and group 2: endocardial scar homogenization. Patients with previous open heart surgery were excluded. Epicardial ablation was performed despite being noninducible after endocardial ablation in all group 1 patients. All patients underwent bipolar substrate mapping with standard scar settings defined as normal tissue1.5 mV and severe scar 0.5 mV. Noninducibility of monomorphic VT was the procedural endpoint in both groups. Patients were followed up every 4 months for 5 years with implantable device interrogations.A total of 361 patients (group 1: n = 70 and group 2: n = 291) were included in the study. At 5 years, 81.4% (n = 57/70) patients from group 1 and 66.3% (n = 193/291) from group 2 were arrhythmia-free (P = 0.01) Of those patients, 26 of 57 (45.6%) and 172 of 193 (89.1%) from group 1 and group 2 respectively were on anti-arrhythmic drugs (AAD) (log-rank P0.001). After adjusting for age, sex, and obstructive sleep apnea, endo-epicardial scar homogenization was associated with a significant reduction in arrhythmia-recurrence (HR: 0.48; 95% CI: 0.27-0.86; P = 0.02).In this series of patients with ICM and VT, epicardial substrate was detected in all group 1 patients despite being noninducible after endocardial ablation. Moreover, combined endo-epicardial scar homogenization was associated with a significantly higher success rate at 5 years of follow-up and a substantially lower need for antiarrhythmic drugs after the procedure compared with the endocardial ablation alone.

Objectives The aim of this study was to evaluate the efficacy of radiofrequency (RF) energy applications targeting the atrial side of a significant residual leak in patients with acute and chronic evidence of incomplete percutaneous left atrial appendage (LAA) occlusion. Background RF applications have been proved to prevent recanalization of intracranial aneurysms after coil embolization, thereby favoring complete sealing. From a mechanistic standpoint, in vitro and in vivo experiments have demonstrated that RF promotes collagen deposition and tissue retraction. Methods Forty-three patients (mean age 75 ± 7 years mean CHA2DS2-VASc score 4.6 ± 1.4, mean HAS-BLED score 4.0 ± 1.1) with residual leaks ≥4 mm after Watchman implantation were enrolled. Procedural success was defined as complete LAA occlusion or presence of a mild or minimal (1- to 2-mm) peridevice leak on follow-up transesophageal echocardiography (TEE), which was performed approximately 45 days after the procedure. Results RF-based leak closure was performed acutely after Watchman implantation in 19 patients (44.2%) or scheduled after evidence of significant leaks on follow-up TEE in 24 others (55.8%). The median leak size was 5 mm (range: 4-7 mm). On average, 18 ± 7 RF applications per patient (mean maximum contact force 16 ± 3 g, mean power 44 ± 2 W, mean RF time 5.1 ± 2.5 minutes) were performed targeting the atrial edge of the leak. Post-RF median leak size was 0 mm (range: 0-1 mm). A very low rate (2.3% [n = 1]) of major periprocedural complications was observed. Follow-up TEE revealed complete LAA sealing in 23 patients (53.5%) and negligible residual leaks in 15 (34.9%). Conclusions RF applications targeting the atrial edge of a significant peri-Watchman leak may promote LAA sealing via tissue remodeling, without increasing complications. (RF Applications for Residual LAA Leaks [REACT]; NCT04726943 )

Introduction Atrial fibrillation (AF) is the most common sustained arrhythmia and an important risk factor for stroke and heart. Recent technology advances have allowed for heart rhythm monitoring using smart gadgets/wearable devices which can be used for early AF diagnosis. Hypothesis We performed a systemic review and meta-analysis to assess the accuracy of AF diagnosis by smart gadgets/wearable devices. Methods We systematically searched Medline, Embase and Cochrane electronic databases up to April 15th, 2022 for observational studies of the diagnostic accuracy of smartphone application, wrist-worn wearables and external devices in detecting AF. We calculated the area under the curve (AUC) of the summary receiver operating characteristic curves (SROC) and pooled sensitivities and specificities. Results A total of 79 studies were included enrolling 36903 patients, 66.3% male with average age of 68.3±8 years. In the overall analysis of all devices, the AUC was 0.99 (95% CI: 0.98-1.00), the sensitivity 95%(95% CI: 94–96%), the specificity 96%(95% CI: 96–97%). Wrist-worn wearables had AUC of 0.99 (95% CI: 0.98-1.00), the sensitivity 95%(9% CI: 92–97%), the specificity 97%(95% CI: 96–98%)(Figure 1A). Smartphone applications had AUC of 0.98 (95% CI: 0.96-0.99), the sensitivity 96%(9% CI: 94–97%), the specificity 96%(95% CI: 93–98%)(Figure 1B). External devices had AUC of 0.99 (95% CI: 0.98-1.00), the sensitivity 95%(9% CI: 93–97%), the specificity 96%(95% CI: 95–97%)(Figure 1C). Single-lead ECG had AUC of 0.99 (95% CI: 0.98- 1.00), the sensitivity 95%(9% CI: 92–96%), the specificity 96%(95% CI: 95–97%). PPG had AUC of 0.99 (95% CI: 0.98-1.00), the sensitivity 96%(9% CI: 95–97%), the specificity 97%(95% CI: 95–98%). Conclusions Smartphone application, wrist-worn devices and external devices with PPG and single-lead ECG have excellent diagnostic accuracy in atrial fibrillation diagnosis. Figure 1. Summary Receiver Operating Characteristic curves and Areas Under The Curve of Wrist-worn wearables (A), Smartphone applications (B) and External devices (C).

Background Atrial fibrillation (AF) and heart failure (HF) often coexist and syner-gistically contribute to an increased risk of hospitalization, stroke, and mortality. Objective: To compare the efficacy of catheter ablation (CA) versus medical therapy (MT) in HF patients with AF. Methods Electronic databases were queried for randomized controlled trials (RCTs) of CA versus MT of AF in patients with HF. Risk ratios (RRs), mean differences (MDs), and 95% confidence in-tervals (CIs) were measured using the Mantel–Haenszel method. Results A total of nine RCTs enrolling 2155 patients met the inclusion criteria. Compared to MT, CA led to a significant reduction in the composite of all-cause mortality and HF hospitalization (24.6% vs. 37.1%; RR: 0.65 (95% CI: 0.53–0.80); p < 0.0001) (Figure 1), all-cause mortality (8.8% vs. 13.6%; RR: 0.65 (95% CI: 0.51–0.82); p = 0.0005), HF hospitalization (15.4% vs. 22.4%; (RR: 0.67 (95% CI: 0.54–0.82); p = 0.0001), AF re-currence (31.8% vs. 77.0%; RR: 0.36 (95% CI: 0.24–0.54); p < 0.0001), and cardiovascular (CV) death (4.9% vs. 8.4%; RR: 0.58 (95% CI: 0.39–0.86); p = 0.007). CA improved the left ventricular ejection fraction (MD:4.76% (95% CI: 2.35–7.18); p = 0.0001), 6 min walk test (MD: 20.48 m (95% CI: 10.83–30.14); p < 0.0001), peak oxygen consumption (MD: 3.1 2mL/kg/min (95% CI: 1.01–5.22); p = 0.004), Minnesota Living with Heart Failure Questionnaire score (MD: −6.98 (95% CI: −12–03, −1.93); p = 0.007), and brain natriuretic peptide levels (MD:−133.94 pg/mL (95% CI: −197.33, −70.55); p < 0.0001). Conclusions In HF patients, AF catheter ablation was superior to MT in re-ducing CV and all-cause mortality. Further significant benefits occurred within the ablation group in terms of HF hospitalizations, AF recurrences, the systolic function, exercise capacity, and quality of life. Figure 1: Forest plot displaying a decrease in the composite endpoint in patients with AF and HF undergoing CA versus MT.

Objectives This study evaluated the long-term efficacy of a standard antithrombotic strategy versus half-dose direct oral anticoagulation (DOAC) after Watchman implantation. Background No consensus currently exists on the selection of the most effective antithrombotic strategy to prevent device-related thrombosis (DRT) in patients undergoing endocardial left atrial appendage closure. Methods After successful left atrial appendage closure, consecutive patients were prescribed a standard antithrombotic strategy (SAT) or long-term half-dose DOAC (hdDOAC). The primary composite endpoint was DRT and thromboembolic (TE) and bleeding events. Results Overall, 555 patients (mean age 75 ± 8 years, 63% male; median CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65-74 years, sex category] score 4 [interquartile range (IQR): 3-6]; median HAS-BLED [hypertension, abnormal renal or liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol] score 3 [IQR: 2-4]) were included. Patients were categorized into 2 groups (SAT: n = 357 vs hdDOAC: n = 198). Baseline clinical characteristics were similar between groups. The median follow-up duration was 13 months (IQR: 12-15 months). DRT occurred in 12 (2.1%) patients, all in the SAT group (3.4% vs 0.0%; log-rank P = 0.009). The risk of nonprocedural major bleeding was significantly more favorable in the hdDOAC group (0.5% vs. 3.9%; log-rank P = 0.018). The rate of the primary composite endpoint of DRT and TE and major bleeding events was 9.5% in SAT patients and 1.0% in hdDOAC patients (HR: 9.8; 95% CI: 2.3-40.7; P = 0.002). Conclusions After successful Watchman implantation, long-term half-dose DOAC significantly reduced the risk of the composite endpoint of DRT and TE and major bleeding events compared with a standard, antiplatelet-based, antithrombotic therapy.

Aims: To develop Spoken Dialogue System in Indian language with Voice response and voice based biometric feature. Backgrounds: Most of research works in spoken dialogue system are carried out in U.S. and Europe and currently, few government funding projects on spoken dialogue system (SDS) are carried out in Indian academic institutes. Objective: We have tried to use our developed spoken language system to eliminate the desktop clutter. It is very normal tendency of computer users to place the most frequently used files, folders, applications shortcuts on their computer’s desktop. Cluttering of desktop not only slows down the productivity of computer but also looks very messy and very difficult to find files as well. Therefore, we tried to use the spoken dialogue system to eliminate the desktop clutters in painless manner and the services are provided to the computer users by opening the files, folders and frequently used application of users in spoken command mode with voice response. Methods: In this research article, we have attempted to utilize an Indian spoken language for communication with spoken dialogue system. We have adopted a statistical machine learning algorithm called Hidden Markov Model for development of speech recognition engine. The speaker verification module is developed using fuzzy c-means algorithm. Speech synthesis is carried out using diphone corpus. Results: The speaker verification module has yielded satisfactory results with average accuracy of 66.2% using FCM algorithm. It is also seen that fundamental frequency and formant frequency carry the distinctive characteristics of speaker verification over Indian spoken language. The vital module of SDS i.e. speech recognition engine is developed by using HMM, a statistical algorithm. It is observed that word accuracy of ASR engine is 78.22 % and 62.31 % for seen and unseen users respectively. The voice response is given to the user in terms of synthesized speech. The audio quality of synthesized speech is measured using the MOS test. The MOS test value is found as 3.8 and 3.6 over two distinct groups of listeners. Conclusion: In this research paper, we have developed a spoken dialogue system based on Odia language phone set. We have integrated speaker verification module in order to provide additional biometric based security.

Introduction Watchman FLX has been recently approved for left atrial appendage occlusion (LAAO) in the US. Intracardiac echocardiography (ICE) - which is already commonly used to guide trans-septal access - can serve as an alternative to TEE, simplifying the procedure and reducing associated costs. Herein, we report our experience with ICE-guided LAAO with Watchman FLX. Methods and results This cohort study included the first 190 consecutive patients who underwent LAAO with Watchman FLX in our center. LAAO was successful in all patients without significant peri-procedural, device-related complications in either group. Compared to TEE, we observed a significant reduction in procedural times when using ICE. In addition, there was a potentially clinically relevant reduction in fluoroscopy dose, mainly secondary to fewer cine acquisition runs. At follow-up, no cases of device embolism were noted, whereas the rate of device-related thrombosis and peri-device leaks were comparable between groups. Conclusion ICE-guided LAAO with Watchman FLX is safe and feasible, with a significant reduction in procedural time and potential reduction in fluoroscopy dose when compared to TEE.

Atrial fibrillation (AF) and premature ventricular complexes (PVC) are common arrhythmias. We aimed to investigate AF prevalence in patients with PVC and its impact on PVC ablation outcomes.Consecutive patients undergoing PVC ablation at a single institution between 2016 and 2019 were included and prospectively followed for 2 years. Patients with severe valvular heart disease, hyperthyroidism, malignancy, alcohol use disorder and advanced renal/hepatic diseases were excluded. Twelve-lead electrocardiograms were used to diagnose AF and assess PVC morphology. All PVCs were targeted for ablation using 4-mm irrigated-tip catheters at standardized radiofrequency power guided by 3-D mapping and intracardiac echocardiography. Patients were followed with remote monitoring, device interrogations and office visits every 6 months for 2 years. Detection of any PVCs in follow-up was considered as recurrence.A total of 394 patients underwent PVC ablation and 96 (24%) had concurrent AF. Patients with PVC and AF were significantly older (68.2 ± 10.8 vs. 58.3 ± 15.8 years, p .001), had lower LV ejection fraction (43.3 ± 13.3% vs. 49.6 ± 12.4%, p .001), higher CHAAF was documented in 1/4 of patients undergoing PVC ablation and was associated with lower procedural success at long-term follow-up. This was likely attributed to older age, worse LV function and higher prevalence of multiple PVC morphologies in patients with concurrent AF.

Background: Atrial fibrillation (AF) and heart failure (HF) often coexist and synergistically contribute to an increased risk of hospitalization, stroke, and mortality. Objective: To compare the efficacy of catheter ablation (CA) versus medical therapy (MT) in HF patients with AF. Methods: Electronic databases were queried for randomized controlled trials (RCTs) of CA versus MT of AF in patients with HF. Risk ratios (RRs), mean differences (MDs), and 95% confidence intervals (CIs) were measured using the Mantel–Haenszel method. Results: A total of nine RCTs enrolling 2155 patients met the inclusion criteria. Compared to MT, CA led to a significant reduction in the composite of all-cause mortality and HF hospitalization (24.6% vs. 37.1%; RR: 0.65 (95% CI: 0.53–0.80); p < 0.0001), all-cause mortality (8.8% vs. 13.6%; RR: 0.65 (95% CI: 0.51–0.82); p = 0.0005), HF hospitalization (15.4% vs. 22.4%; (RR: 0.67 (95% CI: 0.54–0.82); p = 0.0001), AF recurrence (31.8% vs. 77.0%; RR: 0.36 (95% CI: 0.24–0.54); p < 0.0001), and cardiovascular (CV) death (4.9% vs. 8.4%; RR: 0.58 (95% CI: 0.39–0.86); p = 0.007). CA improved the left ventricular ejection fraction (MD:4.76% (95% CI: 2.35–7.18); p = 0.0001), 6 min walk test (MD: 20.48 m (95% CI: 10.83–30.14); p < 0.0001), peak oxygen consumption (MD: 3.1 2mL/kg/min (95% CI: 1.01–5.22); p = 0.004), Minnesota Living with Heart Failure Questionnaire score (MD: −6.98 (95% CI: −12–03, −1.93); p = 0.007), and brain natriuretic peptide levels (MD:−133.94 pg/mL (95% CI: −197.33, −70.55); p < 0.0001). Conclusions: In HF patients, AF catheter ablation was superior to MT in reducing CV and all-cause mortality. Further significant benefits occurred within the ablation group in terms of HF hospitalizations, AF recurrences, the systolic function, exercise capacity, and quality of life.

Background: Data on atrial fibrillation (AF) ablation and outcomes are limited in patients with congenital heart disease (CHD). We aimed to investigate the characteristics of patients with CHD presenting for AF ablation and their outcomes. Methods: A multicenter, retrospective analysis was performed of patients with CHD undergoing AF ablation between 2004 and 2020 at 13 participating centers. The severity of CHD was classified using 2014 Pediatric and Congenital Electrophysiology Society/Heart Rhythm Society guidelines. Clinical data were collected. One-year complete procedural success was defined as freedom from atrial tachycardia or AF in the absence of antiarrhythmic drugs or including previously failed antiarrhythmic drugs (partial success). Results: Of 240 patients, 127 (53.4%) had persistent AF, 62.5% were male, and mean age was 55.2±13.3 years. CHD complexity categories included 147 (61.3%) simple, 68 (28.3%) intermediate, and 25 (10.4%) severe. The most common CHD type was atrial septal defect (n=78). More complex CHD conditions included transposition of the great arteries (n=14), anomalous pulmonary veins (n=13), tetralogy of Fallot (n=8), cor triatriatum (n=7), single ventricle physiology (n=2), among others. The majority (71.3%) of patients had trialed at least one antiarrhythmic drug. Forty-six patients (22.1%) had reduced systemic ventricular ejection fraction Conclusions: AF ablation in CHD was safe and resulted in AF control in a majority of patients, regardless of complexity. Future work should address the most appropriate ablation targets in this challenging population.

Increasing evidence has suggested improved outcomes in atrial fibrillation (AF) patients with heart failure (HF) undergoing catheter ablation (CA) as compared to medical therapy. We sought to investigate the benefit of CA on outcomes of patients with AF and HF as compared to medical therapy.A systematic review of PubMed, Embase, and Cochrane Central Register of Clinical Trials was performed for clinical studies evaluating the benefit of CA for patients with AF and HF. Primary endpoint was all-cause mortality. Secondary endpoints included atrial-arrhythmia recurrence and improvement in left ventricular ejection fraction (LVEF). Eight randomized controlled trials were included with a total of 2121 patients (mean age: 65 ± 5 years; 72% male). Mean follow-up duration was 32.9 ± 14.5 months. All-cause mortality in patients who underwent CA was significantly lower than in the medical treatment group (8.8% vs. 13.5%, RR 0.65, 95% confidence interval [CI] 0.51-0.83, p = .0005). A 35% relative risk reduction and 4.7% absolute risk reduction in all-cause mortality was observed with CA. Rates of all-atrial arrhythmia recurrence were significantly lower in the CA group (39.9% vs. 69.6%, RR: 0.55, 95% CI: 0.40-0.76, p = .0003). Improvement in LVEF was significantly higher in patients undergoing CA (+9.4 ± 7.6%) as compared to conventional treatment (+3.3 ± 8%) (mean difference 6.2, 95% CI: 3.6-8.8, p .00001).CA for AF in patients with HF decreases all-cause mortality, improves all-atrial arrhythmia recurrence rate and LVEF when compared to medical management. CA should be considered the treatment of choice to improve survival in this select group of patients. Nonetheless, the benefit of CA in patients with severely reduced ejection fraction and New York Heart Association class IV HF has not been clearly elucidated.

A significant issue in the domain of optical character recognition is handwritten text recognition. Here, two novel feature extraction techniques are proposed using a fixed-size sliding window, and also an edit distance-based architecture is suggested to recognize the off-line characters. These feature extraction techniques are designed for text recognition from the text images. It’s an off-line approach, that is why data from scanned documents or natural scenes are taken as input. In this paper, the freely available datasets, known as Chars74k and MNIST for English alphabets and digits are used. The proposed feature extraction technique for the off-line text images of characters as well as numbers generates the features successfully. The impact of the proposed method on text recognition accuracy is computed using several state-of-the-art machine learning algorithms. After that, these are again compared with the proposed Edit distance based text recognition system with the help of different conducted experiments. The proposed model has reached an accuracy of more than 96% for the MNIST dataset.

Objective To assess the safety and efficacy of a novel immunosuppressive regimen-combination Methotrexate/Prednisone (cMtx/P)-in the management of severe refractory rPPP. Methods In this multicenter, nonrandomized, retrospective, observational study, 408 consecutive patients diagnosed with persistent rPPP between 2017 and 19 were included. Patients with refractory symptoms despite 3 months of conventional therapy were initiated on a 4-week regimen of oral steroids. Persistence of symptoms at this point, that is, rPPP (n = 25; catheter based = 18, open surgical = 7) prompted therapy with Methotrexate (7.5-15 mg weekly) with folate supplementation along with low dose prednisone (5 mg PO) for a further 3 months. Patients were followed for a total of 11.3 ± 1.8 months. Results Treatment refractory rPPP occurred in 6.1% of the study population prompting immunosuppressive therapy with cMtx/P. All patients demonstrated complete symptom resolution following 3 months of treatment with an 85% decline in clinically significant pericardial effusions. One patient developed recurrent pericarditis during the 11-month follow-up. Therapy was well tolerated with no significant drug related adverse effects. Conclusion cMtx/P therapy is a safe and effective adjunct in the management of rPPP refractory to standard therapy.

Atrial fibrillation (AF) is a complex and multi-factorial rhythm disorder. Catheter ablation is widely used for the management of AF. However, it is limited by relapse of the arrhythmia necessitating repeat procedures.This review aims to discuss the predictors of post-ablation recurrent AF including age, gender, genetic predisposition, AF type and duration, comorbidities, lifestyle factors, echocardiographic parameters of heart chambers, left atrial fibrosis and ablation strategies and targets. An extensive literature search was undertaken on PubMed and Google Scholar to obtain full texts of relevant AF-related articles.Maintenance of stable sinus rhythm is the main intended outcome of AF ablation. Therefore, it is very crucial to identify the risk factors that may influence the ablation success. Most of these predictors such as comorbidities, ablation strategy and targets and lifestyle factors are either reversible or modifiable. Thus, not only the awareness of these known risk factors by both patients and their physicians but also future research to identify the unknown predictors are critical to optimize care in this multi-faceted morbidity.