Genetic characterization of KCNQ1 variants improves risk stratification in type 1 long QT syndrome patients.

BACKGROUND: KCNQ1 mutations cause QTc prolongation increasing life-threatening arrhythmias risks. Heterozygous mutations (type-1 LQTS) are common. Homozygous KCNQ1 mutations cause type-1 Jervell and Lange-Nielsen syndrome (JLNS) with deafness and higher sudden cardiac death risk. KCNQ1 variants causing JLNS or type-1 LQTS might have distinct phenotypic expressions in heterozygous patients. The aim of this study is to evaluate QTc duration and incidence of LQTS-related cardiac events according to genetic presentation. METHODS: We enrolled LQT1 or JLNS patients with class IV/V KCNQ1 variants from our inherited arrhythmia clinic (September 1993 to January 2023). Medical history, ECG, follow-up were collected. Additionally, we conducted a thorough literature review for JLNS variants. Survival curves were compared between groups, and multivariate Cox regression models identified genetic and clinical risk factors. RESULTS: Among 789 KCNQ1 variants carriers, 3 groups were identified; 30 JLNS (JLNS), 161 heterozygous carriers of JLNS variants (HTZ-JLNS), 550 LQT1 heterozygous carriers of non-JLNS variants (HTZ-Non-JLNS).At diagnosis, mean age was, 3.4±4.7 years (JLNS), 26.7±21 years (HTZ-JLNS), and 26±21 years (HTZ-non-JLNS), 55.3% were female, and the mean QTc was 551±54ms (JLNS), 441±32ms (HTZ-JLNS), 467±36ms (HTZ-Non-JLNS).Patients with heterozygous JLNS mutations (HTZ-JLNS) represented 22% of heterozygous KCNQ1 variants carriers and had a lower risk of cardiac events than heterozygous non-JLNS variants carriers (HTZ-Non-JLNS) (HR 0.34 [0.22-0.54]; p<0.01).After multivariate analysis, 4 genetic parameters were independently associated with events: haploinsufficiency (HR=0.60 [0.37-0.97]; p=0.04), pore localization (HR=1.61 [1.14-1.2.26]; p<0.01), C-terminal localization (HR=0.67 [0.46-0.98]; p=0.04), and group (HR=0.43 [0.27-0.69]; p<0.01). CONCLUSION: Heterozygous carriers of JLNS variants have a lower risk of cardiac arrhythmic events than other type 1 LQTS patients.

Left atrial cardiomyopathy: Pathophysiological insights, assessment methods and clinical implications.

Atrial cardiomyopathy is defined as any complex of structural, architectural, contractile or electrophysiological changes affecting atria, with the potential to produce clinically relevant manifestations. Most of our knowledge about the mechanistic aspects of atrial cardiomyopathy is derived from studies investigating animal models of atrial fibrillation and atrial tissue samples obtained from individuals who have a history of atrial fibrillation. Several noninvasive tools have been reported to characterize atrial cardiomyopathy in patients, which may be relevant for predicting the risk of incident atrial fibrillation and its related outcomes, such as stroke. Here, we provide an overview of the pathophysiological mechanisms involved in atrial cardiomyopathy, and discuss the complex interplay of these mechanisms, including aging, left atrial pressure overload, metabolic disorders and genetic factors. We discuss clinical tools currently available to characterize atrial cardiomyopathy, including electrocardiograms, cardiac imaging and serum biomarkers. Finally, we discuss the clinical impact of atrial cardiomyopathy, and its potential role for predicting atrial fibrillation, stroke, heart failure and dementia. Overall, this review aims to highlight the critical need for a clinically relevant definition of atrial cardiomyopathy to improve treatment strategies.

Intracardiac electrophysiology to characterize susceptibility to ventricular arrhythmias in murine models.

Introduction: Sudden cardiac death (SCD) and ventricular fibrillation are rare but severe complications of many cardiovascular diseases and represent a major health issue worldwide. Although the primary causes are often acute or chronic coronary diseases, genetic conditions, such as inherited channelopathies or non-ischemic cardiomyopathies are leading causes of SCD among the young. However, relevant experimental models to study the underlying mechanisms of arrhythmias and develop new therapies are still needed. The number of genetically engineered mouse models with cardiac phenotype is growing, making electrophysiological studies in mice essential tools to study arrhythmogenicity and arrhythmia mechanisms and to test novel treatments. Recently, intracardiac catheterization via the jugular vein was described to induce and record ventricular arrhythmias in living anesthetized mice. Several strategies have been reported, developed in healthy wild-type animals and based on aggressive right ventricular stimulation. Methods: Here, we report a protocol based on programmed electrical stimulation (PES) performed in clinical practice in patients with cardiac rhythm disorders, adapted to two transgenic mice models of arrhythmia - Brugada syndrome and cardiolaminopathy. Results: We show that this progressive protocol, based on a limited number of right ventricular extrastimuli, enables to reveal different rhythmic phenotypes between control and diseased mice. In this study, we provide detailed information on PES in mice, including catheter positioning, stimulation protocols, intracardiac and surface ECG interpretation and we reveal a higher susceptibility of two mouse lines to experience triggered ventricular arrhythmias, when compared to control mice. Discussion: Overall, this technique allows to characterize arrhythmias and provides results in phenotyping 2 arrhythmogenic-disease murine models.

Incidence and survival of transthyretin amyloid cardiomyopathy from a French nationwide study of in- and out-patient databases.

BACKGROUND: Precise data about ATTR-CM incidence rates at national level are scarce. Consequently, this study aimed to estimate the annual incidence and survival of transthyretin amyloid cardiomyopathy (ATTR-CM) in France between 2011 and 2019 using real world data. We used the French nationwide exhaustive data (SNDS database) gathering in- and out-patient claims. As there is no specific ICD-10 marker code for ATTR-CM, diagnosis required both amyloidosis (identified by E85. ICD-10 code or a tafamidis meglumine delivery) and a cardiovascular condition (identified by ICD-10 or medical procedure codes related to either heart failure, arrhythmias, conduction disorders or cardiomyopathies), not necessarily reported at the same visit. Patients with probable AL-form of amyloidosis or probable AA-form of amyloidosis were excluded. RESULTS: Between 2011 and 2019, 8,950 patients with incident ATTR-CM were identified. Incidence rates increased from 0.6 / 100,000 person-years in 2011 to 3.6 / 100,000 person-years in 2019 (p < 0.001), reaching 2377 new cases in 2019. Sex ratios (M/F) increased from 1.52 in 2011 to 2.23 in 2019. In 2019, median age at diagnosis was 84.0 years (85.5 for women and 83.5 for men). Median survival after diagnosis was 41.9 months (95% CI [39.6, 44.1]). CONCLUSIONS: This is the first estimate of nationwide ATTR-CM incidence in France using comprehensive real-world databases. We observed an increased incidence over the study period, consistent with an improvement in ATTR-CM diagnosis in recent years.

Prophylactic epicardial pacemaker implantation in tricuspid valve replacement.

OBJECTIVES: Patients undergoing surgical tricuspid valve replacement (TVR) are at high risk of atrioventricular conduction disorders. Because implanting a lead through the tricuspid bioprosthesis is discouraged, the patients who undergo TVR in our centre are usually given a prophylactic epicardial pacemaker. Our aim was to assess the benefits and risks of this strategy. METHODS: Among the patients who underwent TVR with prophylactic epicardial pacemaker implantation, clinical evaluations and pacemaker reports were analysed retrospectively after surgery. The need for cardiac pacing were assessed by characterizing the atrioventricular conduction, while the risks were evaluated by listing and adjudicating post-operative events. RESULTS: A total of 80 patients were analysed (mean age was 57 ± 16 years old, 30% males). TVR was isolated in 28 (35%) patients, but most often associated with another valve surgery. In the postoperative period, heart rhythm was analysed in 59/80 patients during a median follow-up of 35 months. Cardiac pacing was needed in 46% patients: 14% had complete pacing dependency, 17% had high degree AV block, while 15% had a high ventricular pacing rate (>80%). No pre- or per-operative variables could predict cardiac pacing requirement. Post-operatively, a spontaneous heart rate >70 bpm (P = 0.02) and the presence of narrow QRS (P = 0.03) were significantly associated with a lower risk of cardiac pacing requirement. Complications related to epicardial pacemaker were documented in 2 (2.5%) patients. CONCLUSIONS: After TVR, cardiac pacing was needed in 46% of patients for post-operative atrioventricular conduction disorders. This high incidence associated with an acceptable safety profile supports a prophylactic epicardial pacing strategy for the patients undergoing TVR.

Detailed clinical, physiological and pathological phenotyping can impact access to disease-modifying treatments in ATTR carriers.

BACKGROUND: Hereditary transthyretin amyloidosis is a life-threatening autosomal dominant systemic disease due to pathogenic TTR variants (ATTRv), mostly affecting the peripheral nerves and heart. The disease is characterised by a combination of symptoms, organ involvement and histological amyloid deposition. The available disease-modifying ATTRv treatments (DMTs) are more effective if initiated early. Pathological nerve conduction studies (NCS) results are the cornerstone of large-fibre polyneuropathy diagnosis, but this anomaly occurs late in the disease. We investigated the utility of a multimodal neurological and cardiac evaluation for detecting early disease onset in ATTRv carriers. METHODS: We retrospectively analysed a cohort of ATTRv carriers with normal NCS results regardless of symptoms. Multimodal denervation and infiltration evaluations included a clinical questionnaire (Lauria and New York Heart Association (NYHA)) and examination, intra-epidermal nerve fibre density assessment, autonomic assessment based on heart rate variability, Sudoscan, meta-iodo-benzyl-guanidine scintigraphy, cardiac biomarkers, echocardiography, MRI and searches for amyloidosis on skin biopsy and bone scintigraphy. RESULTS: We included 130 ATTRv carriers (40.8% men, age: 43.6±13.5 years), with 18 amyloidogenic TTR gene mutations, the majority of which was the late-onset Val30Met variant (42.3%). Amyloidosis was detected in 16.9% of mutation carriers, including 9 (6.9%) with overt disease (Lauria>2 or NYHA>1) and 13 asymptomatic carriers (10%) with organ involvement (small-fibre neuropathy or cardiomyopathy). Most of these patients received DMT. Abnormal test results of unknown significance were obtained for 105 carriers (80.8%). Investigations were normal in only three carriers (2.3%). CONCLUSIONS: Multimodal neurological and cardiac investigation of TTRv carriers is crucial for the early detection of ATTRv amyloidosis and initiation of DMT.

Hereditary transthyretin amyloidosis in the era of RNA interference, antisense oligonucleotide, and CRISPR-Cas9 treatments.

Hereditary transthyretin amyloidosis (ATTRv) is a rare autosomal dominant adult-onset disorder caused by point mutations in the transthyretin (TTR) gene encoding TTR, also known as prealbumin. ATTRv survival ranges from 3 to 10 years, and peripheral nervous system and heart are usually the 2 main tissues affected, although central nervous system and eye may also be involved. Because the liver is the main TTR protein secretor organ, it has been the main target of treatments developed these last years, including liver transplantation, which has been shown to significantly increase survival in a subset of patients carrying the so-called "early-onset Val30Met" TTR gene mutation. More recently, treatments targeting hepatic TTR RNA have been developed. Hepatic TTR RNA targeting is performed using RNA interference (RNAi) and antisense oligonucleotide (ASO) technologies involving lipid nanoparticle carriers or N-acetylgalactosamine fragments. RNAi and ASO treatments induce an 80% decrease in TTR liver production for a period of 1 to 12 weeks. ASO and RNAi phase 3 trials in patients with TTR-related polyneuropathy have shown a positive impact on neuropathy clinical scores and quality of life end points, and delayed RNAi treatment negatively affects survival. Clinical trials specifically investigating RNAi therapy in TTR cardiomyopathy are underway. Hepatic RNA targeting has revolutionized ATTRv treatment and may allow for the transforming a fatal disease into a treatable disorder. Because retina and choroid plexus secrete limited quantities of TTR protein, both tissues are now seen as the next targets for fully controlling the disease.

Permanent Pacemaker Implantation After Tricuspid Valve Surgery.

Tricuspid valve (TV) surgery carries a high risk of atrioventricular block. In this report, we illustrate several options for managing conduction disorders after TV surgery. The choice of cardiac implantable devices must take account of several parameters such as surgical procedure, patient's rhythm and history, and etiology of TV disease. (Level of Difficulty: Intermediate.).

Impact of peri-procedural management of direct oral anticoagulants on pocket haematoma after cardiac electronic device implantation: the StimAOD multicentre prospective study.

AIMS: The study aims to investigate the impact of direct oral anticoagulant (DOAC) management on the incidence of pocket haematoma in patients undergoing pacemaker or implantable cardioverter-defibrillator implantation. METHODS AND RESULTS: All consecutive patients receiving DOAC and undergoing cardiac electronic device implantation were included in a large multicentre prospective observational study (NCT03879473). The primary endpoint was clinically relevant haematoma within 30 days after implantation. Overall, 789 patients were enrolled [median age 80 (IQR 72-85) years old, 36.4% women, median CHA2DS2-VASc score 4 (IQR 0-8)], of which 632 (80.1%) received a pacemaker implantation. Antiplatelet therapy was combined with DOAC in 146 patients (18.5%). Direct oral anticoagulants (DOACs) were interrupted 52 (IQR 37-62) h before the procedure and resumed 31 (IQR 21-47) h later. Ninety-six percent of the patients had at least 12 h DOAC interruption before the procedure, and 78% had at least 12 h DOAC interruption after the procedure. Overall, anticoagulation was interrupted for 72 (IQR 48-96) h. Pre- or post-procedural heparin bridging was used in 8.2% and 3.9%, respectively. Timing of DOAC interruption of resumption was not associated with clinically relevant haematoma. Clinically relevant haematoma occurred in 26 patients (3.3%), and thromboembolic events occurred in 5 patients (0.6%). CONCLUSION: In this large real-life registry where most patients had DOAC interruption, clinically relevant haematoma was rare. Despite DOAC interruption and high CHA2DS2-VASc score, thromboembolic events occurred seldomly, highlighting that bleeding exceeds thromboembolic risk in this peri-procedural period. Future research is needed to identify risk factors for clinically relevant haematoma and meaningfully guide clinicians in optimizing DOAC management.

Comparison between tafamidis and liver transplantation as first-line therapy for hereditary transthyretin amyloidosis.

BACKGROUND: By stabilizing transthyretin, tafamidis delays progression of amyloidosis due to transthyretin variant (ATTRv) and replaced liver transplantation (LT) as the first-line therapy. No study compared these two therapeutic strategies. METHODS: In a monocentric retrospective cohort analysis, patients with ATTRv amyloidosis treated with either tafamidis or LT were compared using a propensity score and a competing risk analysis for three endpoints: all-cause mortality, cardiac worsening (heart failure or cardiovascular death) and neurological worsening (worsening in PolyNeuropathy Disability score). RESULTS: 345 patients treated with tafamidis (n = 129) or LT (n = 216) were analyzed, and 144 patients were matched (72 patients in each group, median age 54 years, 60% carrying the V30M mutation, 81% of stage I, 69% with cardiac involvement, median follow-up: 68 months). Patients treated with tafamidis had longer survival than LT patients (HR: 0.35; p = .032). Conversely, they also presented a 3.0-fold higher risk of cardiac worsening and a 7.1-fold higher risk of neurological worsening (p = .0071 and p < .0001 respectively). CONCLUSIONS: ATTRv amyloidosis patients treated with tafamidis would present a better survival but also a faster deterioration of their cardiac and neurological statuses as compared with LT. Further studies are needed to clarify the therapeutic strategy in ATTRv amyloidosis.

Recurrences of Atrial Fibrillation Despite Durable Pulmonary Vein Isolation: The PARTY-PVI Study.

BACKGROUND: Recurrences of atrial fibrillation (AF) after pulmonary vein isolation (PVI) are mainly due to pulmonary vein reconnection. However, a growing number of patients have AF recurrences despite durable PVI. The optimal ablative strategy for these patients is unknown. We analyzed the impact of current ablation strategies in a large multicenter study. METHODS: Patients undergoing a redo ablation for AF and presenting durable PVI were included. The freedom from atrial arrhythmia after pulmonary vein-based, linear-based, electrogram-based, and trigger-based ablation strategies were compared. RESULTS: Between 2010 and 2020, 367 patients (67% men, 63±10 years, 44% paroxysmal) underwent a redo ablation for AF recurrences despite durable PVI at 39 centers. After durable PVI was confirmed, linear-based ablation was performed in 219 (60%) patients, electrogram-based ablation in 168 (45%) patients, trigger-based ablation in 101 (27%) patients, and pulmonary vein-based ablation in 56 (15%) patients. Seven patients (2%) did not undergo any additional ablation during the redo procedure. After 22±19 months of follow-up, 122 (33%) and 159 (43%) patients had a recurrence of atrial arrhythmia at 12 and 24 months, respectively. No significant difference in arrhythmia-free survival was observed between the different ablation strategies. Left atrial dilatation was the only independent factor associated with arrhythmia-free survival (HR, 1.59 [95% CI, 1.13-2.23]; P=0.006). CONCLUSIONS: In patients with recurrent AF despite durable PVI, no ablation strategy used alone or in combination during the redo procedure appears to be superior in improving arrhythmia-free survival. Left atrial size is a significant predictor of ablation outcome in this population.

Lack of early etiologic investigations in young sudden cardiac death.

BACKGROUND: Since majority of sudden cardiac arrest (SCA) victims die in the intensive care unit (ICU), early etiologic investigations may improve understanding of SCA and targeted prevention. METHODS: In this prospective, population-based registry all SCA admitted alive across the 48 hospitals of the Paris area were enrolled. We investigated the extent of early etiologic work-up among young SCD cases (<45 years) eventually dying within the ICU. RESULTS: From May 2011 to May 2018, 4,314 SCA patients were admitted alive. Among them, 3,044 died in ICU, including 484 (15.9%) young patients. SCA etiology was established in 233 (48.1%) and remained unexplained in 251 (51.9%). Among unexplained (compared to explained) cases, coronary angiography (17.9 vs. 49.4%, P < 0.001), computed tomography scan (24.7 vs. 46.8%, P < 0.001) and trans-thoracic echocardiography (31.1 vs. 56.7%, P < 0.001) were less frequently performed. Only 22 (8.8%) patients with unexplained SCD underwent all three investigations. SCDs with unexplained status decreased significantly over the 7 years of the study period (from 62.9 to 35.2%, P = 0.005). While specialized TTE and CT scan performances have increased significantly, performance of early coronary angiography did not change. Autopsy, genetic analysis and family screening were performed in only 48 (9.9%), 5 (1.0%) and 14 cases (2.9%) respectively. CONCLUSIONS: More than half of young SCD dying in ICU remained etiologically unexplained; this was associated with a lack of early investigations. Improving early diagnosis may enhance both SCA understanding and prevention, including for relatives. Failure to identify familial conditions may result in other preventable deaths within these families.

Electrical cardioversion of atrial arrhythmias with cardiac amyloidosis in the era of direct oral anticogulants.

AIMS: Atrial fibrillation (AF)/atrial flutter is common during cardiac amyloidosis (CA). Electrical cardioversion (EC) is a strategy to restore sinus rhythm (SR). However, left atrial thrombus (LAT) represents a contraindication for EC. CA patients with AF/atrial flutter have a high prevalence of LAT. We aimed to evaluate EC characteristics, LAT prevalence and risk factors, and AF/atrial flutter outcome in CA patients undergoing EC, predominantly treated with direct oral anticoagulants (DOACs). METHODS AND RESULTS: All patients with CA and AF/atrial flutter referred for the first time to our national referral centre of amyloidosis for EC from June 2017 to February 2021 were included in this study. In total, 66 patients (median age 74.5 [70;80.75] years, 67% male) were included with anticoagulation consisted of DOAC in 74% of cases. All patients underwent cardiac imaging before EC to rule out LAT. EC was cancelled due to LAT in 14% of cases. Complete thrombus resolution was observed in only 17% of cases. The two independent parameters associated with LAT were creatinine [hazard ratio (HR) = 1.01; confidence interval (CI) = 1.00-1.03, P = 0.036] and the use of antiplatelet agents (HR = 13.47; CI = 1.85-98.02). EC acute success rate was 88%, and we observed no complication after EC. With 64% of patients under amiodarone, AF/atrial flutter recurrence rate following EC was 51% after a mean follow-up of 30 ± 27 months. CONCLUSIONS: Left atrial thrombus was observed in 14% of CA patients listed for EC and mainly treated with DOAC. The acute EC success rate was high with no complication. The long-term EC success rate was acceptable (49%).

Characteristics and factors associated to patients discharging from hospital without an implantable cardioverter defibrillator after out-of-hospital cardiac arrest.

AIMS: Guidelines recommend that in the absence of reversible cause for sudden cardiac arrest (SCA), implantable cardioverter defibrillator (ICD) should be performed to prevent further fatal event. We sought to describe the frequency and characteristics of patients discharged from the hospital without ICD after the SCA in the daily practice. METHODS AND RESULTS: From 2011 to 2018, all SCAs related to a cardiac cause admitted alive across the 48 hospitals of Great Paris Area were prospectively enrolled. Two investigators thoroughly reviewed each medical report to ensure accuracy of the assigned diagnosis towards identifying the cause of SCA and ICD implantation. Out of the 4314 SCA admitted alive at hospital admission, 1064 cardiac-related SCA survivors were discharged alive from hospital, including 356 patients (33.5%) with an ICD and 708 (66.5%) without. The principal underlying cause of SCA among those discharged without an ICD was acute coronary syndrome (ACS; 602, 85%), chronic coronary artery disease (41, 5.8%), structural non-ischaemic heart disease (48, 6.8%), and non-structural heart disease (17, 2.4%). Among ACS-related SCA, 93.8% (602/642) discharged without an ICD. The unique factor associated with non-ICD implantation in the setting of ACS was immediate coronary angioplasty (odds ratio 4.22, 95% confidence interval 1.86-9.30, P < 0.001). CONCLUSION: Two-thirds of SCA survivors were discharged without an ICD, mainly in the setting of ACS. The unique factor associated with non-ICD implantation among ACS was immediate coronary angioplasty emphasizing the fact that ACS definition must be precise since associated with ICD implantation or not.

Expert opinion on monitoring symptomatic hereditary transthyretin-mediated amyloidosis and assessment of disease progression.

BACKGROUND: Hereditary transthyretin-mediated amyloidosis, also known as ATTRv amyloidosis (v for variant), is a rare, autosomal dominant, fatal disease, in which systemic amyloid progressively impairs multiple organs, leading to disability and death. The recent approval of disease-modifying therapies offers the hope of stabilization or eventual reversal of disease progression, and yet highlights a lack of disease-management guidance. A multidisciplinary panel of expert clinicians from France and the US came to consensus on monitoring the disease and identifying progression through a clinical opinion questionnaire, a roundtable meeting, and multiple rounds of feedback. MONITORING DISEASE AND PROGRESSION: A multidisciplinary team should monitor ATTRv amyloidosis disease course by assessing potential target organs at baseline and during follow-up for signs and symptoms of somatic and autonomic neuropathy, cardiac dysfunction and restrictive cardiomyopathy, and other manifestations. Variability in penetrance, symptoms, and course of ATTRv amyloidosis requires that all patients, regardless of variant status, undergo regular and standardized assessment in all these categories. Progression in ATTRv amyloidosis may be indicated by: worsening of several existing quantifiable symptoms or signs; the appearance of a new symptom; or the worsening of a single symptom that results in a meaningful functional impairment. CONCLUSIONS: We suggest that a multisystem approach to monitoring the signs and symptoms of ATTRv amyloidosis best captures the course of the disease. We hope this work will help form the basis of further, consensus-based guidance for the treatment of ATTRv amyloidosis.

Predictive value of premature atrial complex characteristics in pulmonary vein isolation for patients with paroxysmal atrial fibrillation.

BACKGROUND: Premature atrial complexes from pulmonary veins are the main triggers for atrial fibrillation in the early stages. Thus, pulmonary vein isolation is the cornerstone of catheter ablation for paroxysmal atrial fibrillation. However, the success rate remains perfectible. AIM: To assess whether premature atrial complex characteristics before catheter ablation can predict pulmonary vein isolation success in paroxysmal atrial fibrillation. METHODS: We investigated consecutive patients who underwent catheter ablation for paroxysmal atrial fibrillation from January 2013 to April 2017 in two French centres. Patients were included if they were treated with pulmonary vein isolation alone, and had 24-hour Holter electrocardiogram data before catheter ablation available and a follow-up of≥6 months. Catheter ablation success was defined as freedom from any sustained atrial arrhythmia recurrence after a 3-month blanking period following catheter ablation. RESULTS: One hundred and three patients were included; all had an acute successful pulmonary vein isolation procedure, and 34 (33%) had atrial arrhythmia recurrences during a mean follow-up of 30±15 months (group 1). Patients in group 1 presented a longer history of atrial fibrillation (71.9±65.8 vs. 42.9±48.4 months; P=0.008) compared with those who were "free from arrhythmia" (group 2). Importantly, the daily number of premature atrial complexes before catheter ablation was significantly lower in group 1 (498±1413 vs. 1493±3366 in group 2; P=0.028). A daily premature atrial complex cut-off number of<670 predicted recurrences after pulmonary vein isolation (41.1% vs. 13.3%; sensitivity 88.2%; specificity 37.7%; area under the curve 0.635; P=0.017), and was the only independent predictive criterion in the multivariable analysis (4-fold increased risk). CONCLUSION: Preprocedural premature atrial complex analysis on 24-hour Holter electrocardiogram in paroxysmal atrial fibrillation may improve patient selection for pulmonary vein isolation.