International evaluation of an artificial intelligence-powered electrocardiogram model detecting acute coronary occlusion myocardial infarction.

Aims: A majority of acute coronary syndromes (ACS) present without typical ST elevation. One-third of non-ST-elevation myocardial infarction (NSTEMI) patients have an acutely occluded culprit coronary artery [occlusion myocardial infarction (OMI)], leading to poor outcomes due to delayed identification and invasive management. In this study, we sought to develop a versatile artificial intelligence (AI) model detecting acute OMI on single-standard 12-lead electrocardiograms (ECGs) and compare its performance with existing state-of-the-art diagnostic criteria. Methods and results: An AI model was developed using 18 616 ECGs from 10 543 patients with suspected ACS from an international database with clinically validated outcomes. The model was evaluated in an international cohort and compared with STEMI criteria and ECG experts in detecting OMI. The primary outcome of OMI was an acutely occluded or flow-limiting culprit artery requiring emergent revascularization. In the overall test set of 3254 ECGs from 2222 patients (age 62 ± 14 years, 67% males, 21.6% OMI), the AI model achieved an area under the curve of 0.938 [95% confidence interval (CI): 0.924-0.951] in identifying the primary OMI outcome, with superior performance [accuracy 90.9% (95% CI: 89.7-92.0), sensitivity 80.6% (95% CI: 76.8-84.0), and specificity 93.7 (95% CI: 92.6-94.8)] compared with STEMI criteria [accuracy 83.6% (95% CI: 82.1-85.1), sensitivity 32.5% (95% CI: 28.4-36.6), and specificity 97.7% (95% CI: 97.0-98.3)] and with similar performance compared with ECG experts [accuracy 90.8% (95% CI: 89.5-91.9), sensitivity 73.0% (95% CI: 68.7-77.0), and specificity 95.7% (95% CI: 94.7-96.6)]. Conclusion: The present novel ECG AI model demonstrates superior accuracy to detect acute OMI when compared with STEMI criteria. This suggests its potential to improve ACS triage, ensuring appropriate and timely referral for immediate revascularization.

Prediction of certainty in artificial intelligence-enabled electrocardiography.

BACKGROUND: The 12­lead ECG provides an excellent substrate for artificial intelligence (AI) enabled prediction of various cardiovascular diseases. However, a measure of prediction certainty is lacking. OBJECTIVES: To assess a novel approach for estimating certainty of AI-ECG predictions. METHODS: Two convolutional neural networks (CNN) were developed to predict patient age and sex. Model 1 applied a 5 s sliding time-window, allowing multiple CNN predictions. The consistency of the output values, expressed as interquartile range (IQR), was used to estimate prediction certainty. Model 2 was trained on the full 10s ECG signal, resulting in a single CNN point prediction value. Performance was evaluated on an internal test set and externally validated on the PTB-XL dataset. RESULTS: Both CNNs were trained on 269,979 standard 12­lead ECGs (82,477 patients). Model 1 showed higher accuracy for both age and sex prediction (mean absolute error, MAE 6.9 ± 6.3 years vs. 7.7 ± 6.3 years and AUC 0.946 vs. 0.916, respectively, P < 0.001 for both). The IQR of multiple CNN output values allowed to differentiate between high and low accuracy of ECG based predictions (P < 0.001 for both). Among 10% of patients with narrowest IQR, sex prediction accuracy increased from 65.4% to 99.2%, and MAE of age prediction decreased from 9.7 to 4.1 years compared to the 10% with widest IQR. Accuracy and estimation of prediction certainty of model 1 remained true in the external validation dataset. CONCLUSIONS: Sliding window-based approach improves ECG based prediction of age and sex and may aid in addressing the challenge of prediction certainty estimation.

Validation of an automated artificial intelligence system for 12­lead ECG interpretation.

BACKGROUND: The electrocardiogram (ECG) is one of the most accessible and comprehensive diagnostic tools used to assess cardiac patients at the first point of contact. Despite advances in computerized interpretation of the electrocardiogram (CIE), its accuracy remains inferior to physicians. This study evaluated the diagnostic performance of an artificial intelligence (AI)-powered ECG system and compared its performance to current state-of-the-art CIE. METHODS: An AI-powered system consisting of 6 deep neural networks (DNN) was trained on standard 12­lead ECGs to detect 20 essential diagnostic patterns (grouped into 6 categories: rhythm, acute coronary syndrome (ACS), conduction abnormalities, ectopy, chamber enlargement and axis). An independent test set of ECGs with diagnostic consensus of two expert cardiologists was used as a reference standard. AI system performance was compared to current state-of-the-art CIE. The key metrics used to compare performances were sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1 score. RESULTS: A total of 932,711 standard 12­lead ECGs from 173,949 patients were used for AI system development. The independent test set pooled 11,932 annotated ECG labels. In all 6 diagnostic categories, the DNNs achieved high F1 scores: Rhythm 0.957, ACS 0.925, Conduction abnormalities 0.893, Ectopy 0.966, Chamber enlargement 0.972, and Axis 0.897. The diagnostic performance of DNNs surpassed state-of-the-art CIE for the 13 out of 20 essential diagnostic patterns and was non-inferior for the remaining individual diagnoses. CONCLUSIONS: Our results demonstrate the AI-powered ECG model's ability to accurately identify electrocardiographic abnormalities from the 12­lead ECG, highlighting its potential as a clinical tool for healthcare professionals.

No Effect of Continued Antiarrhythmic Drug Treatment on Top of Optimized Pulmonary Vein Isolation in Patients With Persistent Atrial Fibrillation: Results From the POWDER-AF2 Trial.

BACKGROUND: In patients with persistent atrial fibrillation (PersAF), catheter ablation aiming for pulmonary vein isolation (PVI) is associated with moderate clinical effectiveness. We investigated the benefit of continuing previously ineffective class 1C or 3 antiarrhythmic drug therapy (ADT) in the setting of a standardized PVI-only ablation strategy. METHODS: In this multicenter, randomized controlled study, patients with PersAF (≥7 days and <12 months) despite ADT were prospectively randomized 1:1 to PVI with ADT continued versus discontinued beyond the blanking period (ADT ON versus ADT OFF). Standardized catheter ablation was performed aiming for durable isolation with stable, contiguous, and optimized radio frequency applications encircling the pulmonary veins (CLOSE protocol). Clinical visits and 1-to-7-day Holter were performed at 3, 6, and 12 months. The primary end point was any documented atrial tachyarrhythmia lasting >30 seconds beyond 3 months. Prospectively defined secondary end points included repeat ablations, unscheduled arrhythmia-related visits, and quality of life among groups. RESULTS: Of 200 PersAF patients, 98 were assigned to ADT OFF and 102 to ADT ON. The longest atrial fibrillation episode qualifying for PersAF was 28 (10-90) versus 30 (11-90) days. Clinical characteristics and procedural characteristics were similar. Recurrence of atrial tachyarrhythmia was comparable in both groups (20% OFF versus 21.2% ON). No differences were observed in repeat ablations and unscheduled arrhythmia-related visits. Marked improvement in quality of life was observed in both groups. CONCLUSIONS: In patients with PersAF, there is no benefit in continuing previously ineffective ADT beyond the blanking period after catheter ablation. The high success rate of PVI-only might be explained by the high rate of durable isolation after optimized PVI and the early stage of PersAF (POWDER-AF2). REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03437356.

Generation of human induced pluripotent stem cell line UGENTi001-A from a patient with Marfan syndrome carrying a heterozygous c.7754 T > C variant in FBN1 and the isogenic control UGENT001-A-1 using CRISPR/Cas9 editing.

Marfan syndrome is an autosomal dominant genetic disorder resulting from pathogenic variants in FBN1 gene. FBN1 encodes for fibrillin-1, an important extracellular matrix protein. Impaired fibrillin-1 affects multiple organ systems, including the cardiovascular system. We generated an iPSC line carrying a heterozygous variant c.7754 T > C (p.Ile2585Thr, missense) in FBN1 from a patient with Marfan syndrome. Also, an isogenic control is generated, where the pathogenic variant is repaired using CRISPR-Cas9. This isogenic pair provides a valuable resource for in vitro disease modelling.

Mitral Annular Disjunction: Associated Pathologies and Clinical Consequences.

PURPOSE OF REVIEW: To provide an overview of mitral annular disjunction (MAD) and to discuss important challenges in diagnosis and management of MAD. RECENT FINDINGS: MAD has regained interest in the context of sudden cardiac death (SCD) in patients with mitral valve prolapse (MVP), coined as the "arrhythmic" MVP syndrome. In addition, MAD in isolation was recently suggested to be associated with severe arrhythmia and SCD. There is a lack of consensus on the definition of MAD and the imaging modality to be used for diagnosing MAD, and the therapeutic implications of MAD remain uncertain. Furthermore, the exact mechanism underlying the association of MAD with SCD remains largely unexplored.

An Electrocardiographic Characterization of Left Bundle Branch Area Pacing-Induced Right Ventricular Activation Delay: A Comparison With Native Right Bundle Branch Block.

Background: Left bundle branch area pacing (LBBAP) induces delayed RV activation and is thought to be harmless, since the electrocardiographic signature is reminiscent to native RBBB. However, to what extent the delayed RV activation during LBBAP truly resembles that of native RBBB remains unexplored. Methods: This study included patients with incomplete RBBB (iRBBB), complete RBBB (cRBBB) and patients who underwent LBBAP. Global and right ventricular activation times were estimated by QRS duration and R wave peak time in lead V1 (V1RWPT) respectively. Delayed RV activation was further characterized by duration, amplitude and area of the terminal R wave in V1. Results: In patients with LBBAP (n = 86), QRS duration [120 ms (116, 132)] was longer compared to iRBBB patients (n = 422): 104 ms (98, 110), p < 0.001, but shorter compared to cRBBB (n = 223): 138 ms (130, 152), p < 0.001. V1RWPT during LBBAP [84 ms (72, 92)] was longer compared to iRBBB [74 ms (68, 80), p < 0.001], but shorter than cRBBB [96 ms (86, 108), p < 0.001]. LBBAP resulted in V1 R' durations [42 ms (28, 55)] comparable to iRBBB [42 ms (35, 49), p = 0.49] but shorter than in cRBBB [81 ms (68, 91), p < 0.001]. During LBBAP, the amplitude and area of the V1 R' wave were more comparable with iRBBB than cRBBB. V1RWPT during LBBAP was determined by baseline conduction disease, but not by LBBAP capture type. Conclusion: LBBAP-induced delayed RV activation electrocardiographically most closely mirrors the delayed RV activation as seen with incomplete rather than complete RBBB.

Arrhythmia and impaired myocardial function in heritable thoracic aortic disease: An international retrospective cohort study.

BACKGROUND: Heritable thoracic aortic diseases (HTAD), typically entailing aortic complications, can be caused by pathogenic variants or likely pathogenic variants (PV/LPVs) in several genes, including fibrillin1 (FBN1), Actin Alpha2 (ACTA2) and genes encoding components of the transforming growth factor (TGF)-ß signaling pathway. In addition to aortic complications, non-aortic cardiac disease such as impaired myocardial function and/or arrhythmia have been increasingly reported, mainly in Marfan syndrome with underlying FBN1 PV/LPVs and are acknowledged as additional causes of morbidity and mortality. The prevalence of these manifestations in the various HTAD entities is largely unknown. METHODS: This international multicentre retrospective study collected data on patients with HTAD presenting non-aortic cardiac disease. A total of 9 centers from 7 different countries participated. Patients 12 years or older carrying a PV/LPV in one of the following genes: FBN1, TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD3 and ACTA2 were screened. Non-aortic cardiac disease included impaired myocardial function and/or arrhythmia. Impaired myocardial function was defined as (a)symptomatic reduced ejection fraction (EF<50%). Arrhythmias included atrial fibrillation (AF), atrial flutter (AFL), ventricular tachycardia (VT), ventricular fibrillation (VF) and (aborted) sudden cardiac death (presumed arrhythmogenic) (SCD). RESULTS: Medical records of 3219 patients with HTAD were screened (2761, 385 and 73 carrying a PV/LPV in FBN1, in a TGF-ß signaling gene and in ACTA2 respectively). Non-aortic cardiac disease was reported 142 times in 101 patients (3.1%) (age 37 [range 12-77] years, 39% female): 88 patients carrying an FBN1 PV/LPV and 13 carrying a PV/LPV in one of the TGF-ß signaling genes. Neither impaired myocardial function nor arrhythmia was reported in screened patients carrying a PV/LPV in ACTA2. Among the 142 reported non-aortic cardiac diseases, 68 (48%) were impaired myocardial function, 47 (33%) were AF/AFL and 27 (19%) were VT/VF/SCD. Among the patients with non-aortic cardiac disease, prior cardiac surgery was noted in 80% and severe valvular disease (valvular surgery or severe valvular regurgitation) in 58%, while 18% of the patients developed non-aortic cardiac disease in the absence of any of the latter. CONCLUSIONS: In patients with HTAD, arrhythmia and impaired myocardial function was reported in patients with PV/LPVs in FBN1 and in the TGF-ß signaling genes and not in patients harboring PV/LPVs in ACTA2. Though infrequent, non-aortic cardiac disease should be acknowledged as potentially severe, also occurring in young patients with no underlying significant valvular or aortic disease.

Mortality in STEMI Patients With Cardiogenic Shock: Results From a Nationwide PCI Registry and Focus on Left Main PCI.

BACKGROUND: The study aims to assess real-life short- and long-term outcomes of patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) complicated with cardiogenic shock (CS). Outcome after left main (LM) PCI is of particular interest. METHODS: Procedural, 30-day, and >30-day mortality rates were assessed in 2744 CS-STEMI patients enrolled between 2012 and 2019 in a nationwide registry involving 49 centers. RESULTS: Procedural, 30-day, and >30-day mortality rates were 6.9%, 39.8%, and 12.6%, respectively. The mortality rates were significantly higher in the 348 patients (12.7%) who underwent LM-PCI (13.5%, 59.5%, and 18.4%, respectively). LM-PCI, a suboptimal PCI result, and transfemoral access were independent predictors of procedural and 30-day mortality. Operator experience was an independent predictor of procedural mortality, but not 30-day mortality. CONCLUSIONS: Mortality remains high in CS-STEMI patients, especially within the first month. Patients undergoing LM-PCI are particularly at risk. Operator experience is predictive of procedural mortality.

Clinical validation of a 13-lead electrocardiogram derived from a self-applicable 3-lead recording for diagnosis of myocardial supply ischaemia and common non-ischaemic electrocardiogram abnormalities at rest.

Aims: In this study, we compare the diagnostic accuracy of a standard 12-lead electrocardiogram (ECG) with a novel 13-lead ECG derived from a self-applicable 3-lead ECG recorded with the right exploratory left foot (RELF) device. The 13th lead is a novel age and sex orthonormalized computed ST (ASO-ST) lead to increase the sensitivity for detecting ischaemia during acute coronary artery occlusion. Methods and results: A database of simultaneously recorded 12-lead ECGs and RELF recordings from 110 patients undergoing coronary angioplasty and 30 healthy subjects was used. Five cardiologists scored the learning data set and five other cardiologists scored the validation data set. In addition, the presence of non-ischaemic ECG abnormalities was compared. The accuracy for detection of myocardial supply ischaemia with the derived 12 leads was comparable with that of the standard 12-lead ECG (P = 0.126). By adding the ASO-ST lead, the accuracy increased to 77.4% [95% confidence interval (CI): 72.4-82.3; P < 0.001], which was attributed to a higher sensitivity of 81.9% (95% CI: 74.8-89.1) for the RELF 13-lead ECG compared with a sensitivity of 76.8% (95% CI: 71.9-81.7; P < 0.001) for the 12-lead ECG. There was no significant difference in the diagnosis of non-ischaemic ECG abnormalities, except for Q-waves that were more frequently detected on the standard ECG compared with the derived ECG (25.9 vs. 13.8%; P < 0.001). Conclusion: A self-applicable and easy-to-use 3-lead RELF device can compute a 12-lead ECG plus an ischaemia-specific 13th lead that is, compared with the standard 12-lead ECG, more accurate for the visual diagnosis of myocardial supply ischaemia by cardiologists.

Association of Mitral Annular Disjunction With Cardiovascular Outcomes Among Patients With Marfan Syndrome.

Importance: Mitral annular disjunction (MAD) has received particular interest in patients with mitral valve prolapse, ventricular tachycardia, and sudden cardiac death. The clinical significance of MAD for patients with Marfan syndrome (MFS) remains largely unexplored. Objective: To define the prevalence of MAD and examine its association with cardiovascular outcomes and arrhythmia among patients with MFS. Design, Setting, and Participants: This retrospective, single-center cohort study included 142 patients with a diagnosis of MFS based on the revised Ghent criteria and a confirmed (likely) pathogenic variant in the FBN1 gene who underwent regular follow-up between January 1, 2004, and December 31, 2019. Main Outcomes and Measures: The presence of MAD was assessed by echocardiography, and the extent of MAD was categorized in tertiles. Patients also underwent resting electrocardiography and 24-hour Holter monitoring. Outcomes included aortic events (aortic dissection or prophylactic aortic surgery), arrhythmic events (defined as sustained ventricular tachycardia or sudden cardiac death), and mitral valve surgery. Results: A total of 142 patients (72 female patients [51%]; median age at first examination, 25 years [range, 2-64 years]) were evaluated. Forty-eight patients (34%) had MAD. Patients with MAD had larger aortic root z scores than patients without MAD (4.1 [interquartile range, 2.8-5.7] vs 3.0 [interquartile range, 1.8-4.0]; P < .001) and more often had mitral valve prolapse (34 of 48 [71%] vs 14 of 94 [15%]; P < .001), ventricular ectopy (14 of 33 [42%] vs 15 of 70 [21%]; P = .03), and nonsustained ventricular tachycardia (13 of 33 [39%] vs 12 of 70 [17%]; P = .01). During follow-up, aortic events occurred at similar rates among patients with vs without MAD (15 of 43 [35%] vs 21 of 84 [25%]; P = .24), but patients in the upper MAD tertile (>10 mm) showed a higher occurrence of aortic events compared with patients with MAD of 10 mm or smaller (9 of 15 [60%] vs 6 of 28 [21%]; P = .01). Patients with arrhythmic events (n = 5) and patients requiring mitral valve surgery (n = 7) were observed exclusively in the group displaying MAD. Conclusions and Relevance: This study suggests that MAD among patients with MFS is associated with the occurrence of arrhythmic events, a higher need for mitral valve intervention, and, among patients with extensive MAD, more aortic events. Cardiac imaging for patients with MFS should consider the assessment of MAD as a potential marker for adverse outcomes.

Myocardial disease and ventricular arrhythmia in Marfan syndrome: a prospective study.

BACKGROUND: Aortic root dilatation and-dissection and mitral valve prolapse are established cardiovascular manifestations in Marfan syndrome (MFS). Heart failure and arrhythmic sudden cardiac death have emerged as additional causes of morbidity and mortality. METHODS: To characterize myocardial dysfunction and arrhythmia in MFS we conducted a prospective longitudinal case-control study including 86 patients with MFS (55.8% women, mean age 36.3 yr-range 13-70 yr-) and 40 age-and sex-matched healthy controls. Cardiac ultrasound, resting and ambulatory ECG (AECG) and NT-proBNP measurements were performed in all subjects at baseline. Additionally, patients with MFS underwent 2 extra evaluations during 30 ± 7 months follow-up. To study primary versus secondary myocardial involvement, patients with MFS were divided in 2 groups: without previous surgery and normal/mild valvular function (MFS-1; N = 55) and with previous surgery or valvular dysfunction (MFS-2; N = 31). RESULTS: Compared to controls, patients in MFS-1 showed mild myocardial disease reflected in a larger left ventricular end-diastolic diameter (LVEDD), lower TAPSE and higher amount of (supra) ventricular extrasystoles [(S)VES]. Patients in MFS-2 were more severely affected. Seven patients (five in MFS-2) presented decreased LV ejection fraction. Twenty patients (twelve in MFS-2) had non-sustained ventricular tachycardia (NSVT) in at least one AECG. Larger LVEDD and higher amount of VES were independently associated with NSVT. CONCLUSION: Our study shows mild but significant myocardial involvement in patients with MFS. Patients with previous surgery or valvular dysfunction are more severely affected. Evaluation of myocardial function with echocardiography and AECG should be considered in all patients with MFS, especially in those with valvular disease and a history of cardiac surgery.

Myocardial Function, Heart Failure and Arrhythmia in Marfan Syndrome: A Systematic Literature Review.

Marfan syndrome (MFS) is a heritable systemic connective tissue disease with important cardiovascular involvement, including aortic root dilatation and mitral valve prolapse. Life expectancy in patients with MFS is mainly determined by cardiovascular complications, among which aortic dissection or rupture are most dreaded. In recent years, heart failure and ventricular arrhythmia have drawn attention as extra-aortic cardiovascular manifestations and as additional reported causes of death. Imaging studies have provided data supporting a primary myocardial impairment in the absence of valvular disease or cardiovascular surgery, while studies using ambulatory ECG have demonstrated an increased susceptibility to ventricular arrhythmia. In this paper, current literature was reviewed in order to provide insights in characteristics, pathophysiology and evolution of myocardial function, heart failure and ventricular arrhythmia in MFS.

Ambulatory Electrocardiographic Monitoring and Ectopic Beat Detection in Conscious Mice.

Ambulatory electrocardiography (AECG) is a primary diagnostic tool in patients with potential arrhythmic disorders. To study the pathophysiological mechanisms of arrhythmic disorders, mouse models are widely implemented. The use of a technique similar to AECG for mice is thus of great relevance. We have optimized a protocol which allows qualitative, long-term ECG data recording in conscious, freely moving mice. Automated algorithms were developed to efficiently process the large amount of data and calculate the average heart rate (HR), the mean peak-to-peak interval and heart rate variability (HRV) based on peak detection. Ectopic beats are automatically detected based on aberrant peak intervals. As we have incorporated a multiple lead configuration in our ECG set-up, the nature and origin of the suggested ectopic beats can be analyzed in detail. The protocol and analysis tools presented here are promising tools for studies which require detailed, long-term ECG characterization in mouse models with potential arrhythmic disorders.

Paroxysmal atrial fibrillation with high vs. low arrhythmia burden: atrial remodelling and ablation outcome.

AIMS: The relation between atrial tachyarrhythmia (ATA) burden in paroxysmal atrial fibrillation (AF), atrial remodelling, and efficacy of catheter ablation (CA) is unknown. We investigated whether high vs. low-burden paroxysmal AF patients have distinct clinical characteristics or electro-mechanical properties of the left atrium (LA) and whether burden impacts outcome of CA. METHODS AND RESULTS: Atrial tachyarrhythmia burden, defined as the percentage of time spent in ATA, was assessed by insertable cardiac monitors in 105 patients before and after CA. Clinical characteristics and electro-mechanical properties of LA were compared between patients with high vs. low ATA burden. Catheter ablation efficacy was assessed by reduction in ATA burden and 1-year freedom from any ATA. Median ATA burden was 2.7% (highest tertile 9.3%). Clinical characteristics and electrical properties of LA (refractoriness, conduction velocity, low voltage) did not differ between high (≥9.3%) vs. low ATA burden (<9.3%) patients. High ATA burden patients had larger LA diameter (46.5 ± 6 vs. 42.5 ± 6mm, P < 0.01), volume (93.8 ± 22 vs. 80.4 ± 21mL, P = 0.01), and lower LA reservoir and contractile strain (19.7 ± 6 vs. 24.7 ± 6%, P < 0.01; 10.3 ± 3 vs. 12.8 ± 4%, P = 0.01). Catheter ablation reduced ATA burden by 100% (100-100) in both groups (P = 1.0). Freedom from ATA after CA was equally high (83% vs. 89%, P = 0.38). CONCLUSION: Paroxysmal AF patients with high ATA burden have altered LA mechanical properties, reflected by larger size and impaired function. Despite mechanical remodelling of the atria, they are excellent responders to CA. Most likely the lack of fibrosis and/or advanced electrical remodelling explain why pulmonary veins remain the dominant trigger for AF in this patient cohort.

Diagnostic accuracy of R-wave detection by insertable cardiac monitors.

BACKGROUND: Insertable cardiac monitors (ICM) allow prolonged rhythm monitoring, but the diagnostic performance can be hampered by false positive arrhythmia alerts related to inadequate R-wave sensing. This study assesses the prevalence and predictors of inadequate R-wave sensing (both over- and undersensing) among different ICM types. METHODS: Patients implanted with an ICM at Ghent University Hospital between January 2017 and August 2018 were included. ICM tracings recorded at interrogation or transmitted by remote monitoring were reviewed for inadequate R-wave sensing leading to false arrhythmia alerts. Patient and implant characteristics were retrieved from the medical records and implant reports. RESULTS: The study screened 135 patients (age 59 ± 19 years, 44% female) implanted with different ICM types: Reveal LINQ™ and XT (Medtronic): n = 92 (68%), Confirm and Confirm Rx (Abbott): n = 35 (26%), and BioMonitor 2 (Biotronik): n = 8 (6%). ICM tracings were analyzed in 112 patients (83%). False arrhythmia alerts occurred in 22 (20%) patients, most frequently related to undersensing (77%). False diagnosis of bradycardia or pause was documented in 64%, false high ventricular rates in 14%, and false atrial fibrillation alerts in 22%. Occurrence of R-wave changes was not related to patient characteristics or implant R-wave sensing. A trend toward higher number of inadequate R-wave sensing seems to occur with nonparasternal implant sites (P = .074). CONCLUSIONS: False arrhythmia alerts due to inadequate R-wave sensing occurred in 20% of ICM patients independent of implant features and patient characteristics.

Long-term impact of catheter ablation on arrhythmia burden in low-risk patients with paroxysmal atrial fibrillation: The CLOSE to CURE study.

BACKGROUND: Few studies evaluated the impact of catheter ablation (CA) on atrial tachyarrhythmia (ATA) burden in paroxysmal atrial fibrillation (AF). OBJECTIVE: In the prospective, patient-controlled CLOSE to CURE study, we determined the longer-term impact of optimized CA on ATA burden by using an insertable cardiac monitor (ICM). METHODS: A total of 105 patients with paroxysmal AF were implanted with an ICM 65 (interquartile range [IQR] 61-78) days before CA. CA consisted of contact force-guided pulmonary vein isolation targeting an intertag distance of ≤6 mm and a region-specific ablation index. The primary end point was reduction in ICM-detected ATA burden; secondary end points were single-procedure freedom from ATA, quality of life, and adverse events. RESULTS: The mean age was 62 ± 8 years; the median CHA2DS2-VASc score was 1 (IQR 1-2); and the median left atrial diameter was 43 (IQR 39-43) mm. After pulmonary vein isolation (1.13 ± 0.39 procedures per patient), median ATA burden decreased from 2.68% (IQR 0.09%-15.02%) at baseline to 0% (IQR 0%-0%) during the first year and to 0% (IQR 0%-0%) during the second year (reduction in ATA burden 100% [IQR 100%-100%]; P < .001). Single-procedure freedom from any ATA was 87% at 1 year and 78% at 2 years. Quality of life improved significantly across all scores. Adverse events occurred in 5 patients (4.8%). CONCLUSION: CA has become an effective procedure in paroxysmal AF, with a major impact on ICM-detected ATA burden. Whereas conventional survival analysis suggests a progressive decline in efficacy, we observed that burden reduction is maintained at longer follow-up. These data imply that ATA burden is a more optimal end point for assessing ablation efficacy.

Features of Marfan syndrome not listed in the Ghent nosology - the dark side of the disease.

Introduction: The revised Ghent nosology presents the classical features of Marfan syndrome. However, behind its familiar face, Marfan syndrome hides less well-known features.Areas covered: The German Marfan Organization listed unusual symptoms and clinical experts reviewed the literature on clinical features of Marfan syndrome not listed in the Ghent nosology. Thereby we identified the following features: (1) bicuspid aortic valve, mitral valve prolapse, pulmonary valve prolapse, tricuspid valve prolapse, (2) heart failure and cardiomyopathy, (3) supraventricular arrhythmia, ventricular arrhythmia, and abnormal repolarization, (4) spontaneous coronary artery dissection, anomalous coronary arteries, and atherosclerotic coronary artery disease, tortuosity-, aneurysm-, and dissection of large and medium-sized arteries, (5) restrictive lung disease, parenchymal lung disease, and airway disorders, (6) obstructive- and central sleep apnea, (7) liver and kidney cysts, biliary tract disease, diaphragmatic hernia, and adiposity, (8) premature labor, and urinary incontinence, (9) myopathy, reduced bone mineral density, and craniofacial manifestations, (10) atrophic scars, (11) caries, and craniomandibular dysfunction, (12) headache from migraine and spontaneous cerebrospinal fluid leakage, (13) cognitive dysfunction, schizophrenia, depression, fatigue, and pain, (14) and activated fibrinolysis, thrombin, platelets, acquired von Willebrand disease, and platelet dysfunction.Expert commentary: Future research, nosologies, and guidelines may consider less well-known features of Marfan syndrome.

Directed Networks as a Novel Way to Describe and Analyze Cardiac Excitation: Directed Graph Mapping.

Networks provide a powerful methodology with applications in a variety of biological, technological and social systems such as analysis of brain data, social networks, internet search engine algorithms, etc. To date, directed networks have not yet been applied to characterize the excitation of the human heart. In clinical practice, cardiac excitation is recorded by multiple discrete electrodes. During (normal) sinus rhythm or during cardiac arrhythmias, successive excitation connects neighboring electrodes, resulting in their own unique directed network. This in theory makes it a perfect fit for directed network analysis. In this study, we applied directed networks to the heart in order to describe and characterize cardiac arrhythmias. Proof-of-principle was established using in-silico and clinical data. We demonstrated that tools used in network theory analysis allow determination of the mechanism and location of certain cardiac arrhythmias. We show that the robustness of this approach can potentially exceed the existing state-of-the art methodology used in clinics. Furthermore, implementation of these techniques in daily practice can improve the accuracy and speed of cardiac arrhythmia analysis. It may also provide novel insights in arrhythmias that are still incompletely understood.

PulmOnary vein isolation With vs. without continued antiarrhythmic Drug trEatment in subjects with Recurrent Atrial Fibrillation (POWDER AF): results from a multicentre randomized trial.

Aims: Catheter ablation is indicated in patients with symptomatic paroxysmal atrial fibrillation (AF) resistant to antiarrhythmic drug therapy (ADT). We investigated whether continued use of previously ineffective ADT beyond the post-ablation blanking period reduces recurrence of atrial tachyarrhythmia within the 1st year after ablation. Methods and results: This was a multicentre, randomized controlled study in patients undergoing contact force-guided pulmonary vein isolation (PVI) for paroxysmal AF in whom previously ineffective ADT was continued during a blanking period of 3 months. If free of AF at the end of the blanking period, patients were randomly assigned in the ratio of 1:1 to continue ADT (ADT ON group, n = 77) or discontinue ADT (ADT OFF group, n = 76). Patients were followed up until 1 year after PVI, with clinical visits, Holter monitoring, and quality-of-life (QOL) questionnaires at 6 and 12 months post-procedure. Analysis of the primary endpoint (any documented atrial tachyarrhythmia lasting >30 s) was performed according to the modified intention-to-treat principle. Secondary endpoints included repeat ablation, unscheduled visits, and QOL score. Baseline clinical characteristics and initial ablation procedure characteristics were comparable between both groups. Three patients were lost to follow-up in each arm. The primary endpoint was observed in 2 of 74 (2.7%) patients in the ADT ON group vs. 16 of 73 (21.9%) patients in the ADT OFF group (P < 0.001). The ADT ON group had a lower rate of repeat ablation [1.4% vs. 19.2%, hazard ratio (HR) = 0.053; 95% confidence interval (CI) 0.007-0.399; P < 0.01) and less unscheduled arrhythmia-related health care visits (2.7% vs. 20.5%, HR = 0.055, 95% CI 0.007-0.410; P < 0.01). Quality-of-life scores were similar in both groups. Conclusion: In patients free of AF at the end of 3 months of post-ablation blanking period, continued use of previously ineffective ADT significantly reduces the recurrence of atrial tachyarrhythmia in the 1st year after PVI.