Topic: Electrophysiology

Abstract

Outcomes of transcatheter aortic valve replacement without predilation of the aortic valve: Insights from 1544 patients included in the SOURCE 3 registry.

Dumonteil N, Terkelsen C, Frerker C, Collart F, ... Lefèvre T,
Aims
To investigate the impact of transcatheter aortic valve replacement (TAVR) without preliminary balloon aortic valvuloplasty (pre-BAV) on periprocedural outcomes in a large, real-world registry.
Methods and results
The SOURCE 3 registry was an observational, multi-center, single-arm study of patients with severe, symptomatic aortic stenosis at high surgical risk treated with the SAPIEN 3 transcatheter heart valve (THV). Procedural and 30-day outcomes were compared between two groups of 772 patients each (retrospectively matched) with or without pre-BAV. All baseline clinical, echocardiographic, and anatomical valve characteristics were comparable between groups except for Society of Thoracic Surgeons (STS) score, which was lower in the direct TAVR group (6.0 ± 5.9 vs 7.8 ± 8.3; p = 0.003). In the direct TAVR group, there were less post-dilatations (8.1% vs. 13.1%, p = 0.002), shorter procedural time (70.9 ± 39.8 min vs 73.0 ± 32.2 min, p = 0.033) and fluoroscopy time (13.4 ± 7.0 min vs 14.9 ± 7.4 min, p < 0.001). Other procedural outcomes and echocardiographic variables at 30 days did not differ significantly between the two groups: safety endpoint (10.4% with pre-BAV vs 13.5% with direct TAVR, p = 0.059), mortality (2.1% vs 2.3%, p = 0.730), disabling strokes (0.4% vs 0.5%, p = 0.704), and moderate to severe paravalvular leak (PVL) (3.2% vs 2.2%, p = 0.40). Unexpectedly, new permanent pacemaker implantation and life-threatening bleeds were less frequently observed with pre-BAV group than with direct TAVR (10.4% vs 13.9%, p = 0.032 and 3.5% vs 6.5%, p = 0.007, respectively).
Conclusion
In this large TAVR dataset, direct implantation of the SAPIEN 3 THV without pre-BAV was feasible and safe and resulted in shorter procedures, without impact on 30-day prosthesis function and PVL.

Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:32-37
Dumonteil N, Terkelsen C, Frerker C, Collart F, ... Lefèvre T,
Int J Cardiol: 30 Nov 2019; 296:32-37 | PMID: 31256993
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Abstract

The association between pulmonary hypertension and stroke: A systematic review and meta-analysis.

Shah TG, Sutaria JM, Vyas MV
Background
Pulmonary hypertension is associated with atrial fibrillation and paradoxical embolism. Yet, the association between pulmonary hypertension and stroke has not been well studied.
Methods
We reviewed Medline and Embase from inception to December 1, 2018, to identify observational studies reporting prevalence of stroke in adult patients with pulmonary hypertension. We sought studies that included patients with pulmonary hypertension secondary to any etiology except left heart failure, and excluded studies that reported rates of perioperative stroke. We conducted random effects meta-analyses to obtain pooled prevalence of stroke in patients with pulmonary hypertension, and pooled unadjusted odds ratio of stroke in patients with pulmonary hypertension compared to those without.
Results
We included 14 studies including 32,523 participants of which 2976 (9.2%) had pulmonary hypertension, and 727 (2.2%) had a stroke. The pooled prevalence of stroke in patients with pulmonary hypertension was 8.0% [95% confidence interval (CI), 5.1%-10.9%, I 91.9]. The pooled unadjusted odds ratio of stroke in patients with pulmonary hypertension compared to those without was 1.46 (95% CI, 1.07-1.99, I 55.6, n = 7 studies).
Conclusion
Stroke is a major non-cardiac morbidity in patients with pulmonary hypertension, requiring further evaluation to determine its etiology, and measures to reduce its risk.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Nov 2019; 295:21-24
Shah TG, Sutaria JM, Vyas MV
Int J Cardiol: 14 Nov 2019; 295:21-24 | PMID: 31402157
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Abstract

Delayed prolongation of the QRS interval in patients with left ventricular dysfunction.

Rav-Acha M, Nujidat A, Farkash R, Medina A, ... Glikson M, Hasin T
Aims
Patients with left ventricular dysfunction (LVD) and prolonged QRS on surface electrocardiogram are at increased risk for heart failure and death and may benefit from resynchronization therapy. Patients with initial narrow QRS may prolong their QRS during the disease course. The occurrence of delayed QRS prolongation, its predictors and associated risk of heart failure hospitalizations (HFH) or death are currently unknown and the subject of this investigation.
Methods & results
Patients with LVD, QRS < 120 ms and available follow-up ECGs were retrospectively evaluated for persistent unprovoked QRS prolongation >130 ms. Impact on mortality or HFH was assessed using Cox regression with QRS > 130 ms as a time dependent covariate. Following 178 patients for 30 (10;59) median (IQR) months, 28 (16%) patients prolonged their QRS to >130 ms, reaching a QRS duration of 154 ± 29 ms; LBBB pattern was diagnosed among 14 (50%) patients. Patients with delayed QRS prolongation were older (71.9 ± 11.8 vs 64.4 ± 15.1 years p = 0.014), had larger left ventricle and left atrial diameters (6.3 ± 0.9 vs 5.7 ± 0.9 cm p = 0.010; 4.9 ± 0.6 vs 4.5 ± 0.7 cm p = 0.006, respectively) and wider baseline QRS (104.8 ± 12.6 vs 91.4 ± 14.5 ms p < 0.001) which was linearly associated with late QRS prolongation (p for trend<0.0001). In a multivariable model, age, baseline QRS width and left atrial diameter were significantly associated with delayed QRS prolongation. QRS prolongation at follow-up was independently associated with risk of death or HFH (HR 7.426, 95% CI3.017-18.280, p < 0.0001).
Conclusion
QRS prolongation occurs in a significant proportion of patients with LVD and portends adverse outcome. Advanced age, prolonged QRS and larger left atria are potential predictors. Routine monitoring is justified and physicians may choose to plan ahead for resynchronization therapy in patients at risk for QRS prolongation.

Copyright © 2019. Published by Elsevier B.V.

Int J Cardiol: 30 Nov 2019; 296:71-75
Rav-Acha M, Nujidat A, Farkash R, Medina A, ... Glikson M, Hasin T
Int J Cardiol: 30 Nov 2019; 296:71-75 | PMID: 31327517
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Abstract

CMR feature tracking left ventricular strain-rate predicts ventricular tachyarrhythmia, but not deterioration of ventricular function in patients with repaired tetralogy of Fallot.

Hagdorn QAJ, Vos JDL, Beurskens NEG, Gorter TM, ... Berger RMF, Willems TP
Background
Myocardial strain has been shown to predict outcome in various cardiovascular diseases, including congenital heart diseases. The aim of this study was to evaluate the predictive value of cardiac magnetic resonance (CMR) feature-tracking derived strain parameters in repaired tetralogy of Fallot (rTOF) patients for developing ventricular tachycardia (VT) and deterioration of ventricular function.
Methods
Patients with rTOF who underwent CMR investigation were included. Strain and strain-rate of both ventricles were assessed using CMR feature tracking. The primary outcome was a composite of the occurrence of sustained VT or non-sustained VT requiring invasive therapy. The secondary outcome was analyzed in patients that underwent a second CMR after 1.5 to 3.5 years. Deterioration was defined as reduction (≥10%) in right ventricular (RV) ejection fraction, reduction (≥10%) in left ventricular (LV) ejection fraction or increase (≥30 mL/m) in indexed RV end-diastolic volume compared to baseline.
Results
172 patients (median age 24.3 years, 54 patients <18 years) were included. Throughout a median follow-up of 7.4 years, 9 patients (4.5%) experienced the primary endpoint of VT. Multivariate Cox-regression analysis showed that LV systolic circumferential strain-rate was independently predictive of primary outcome (p = 0.023). 70 patients underwent a serial CMR, of whom 14 patients (20%) showed ventricular deterioration. Logistic regression showed no predictive value of strain and strain-rate parameters.
Conclusions
In patients with rTOF, LV systolic circumferential strain-rate is an independent predictor for the development of VT. Ventricular strain parameters did not predict deterioration of ventricular function in the studied population.

Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Nov 2019; 295:1-6
Hagdorn QAJ, Vos JDL, Beurskens NEG, Gorter TM, ... Berger RMF, Willems TP
Int J Cardiol: 14 Nov 2019; 295:1-6 | PMID: 31402156
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Abstract

Incidental abnormal ECG findings and long-term cardiovascular morbidity and all-cause mortality: A population based prospective study.

Goldman A, Hod H, Chetrit A, Dankner R
Background
The additional prognostic value of resting electrocardiogram (ECG) in long-term cardiovascular disease (CVD)-risk-assessment is unclear. We evaluated the association of incidental abnormal ECG findings with long-term CVD-risk and all-cause mortality, and assessed the additional prognostic value of ECG as a screening tool in adults without known CVD.
Methods
A cohort of 2601 Israeli men and women without known CVD were actively followed from 1976 to 1982 for 23-year cumulative CVD-incidence, and until May 2017 for all-cause mortality. At baseline and follow-up, participants underwent interviews, physical examinations, blood tests and ECG.
Results
At baseline, 1199 (46.1%) had incidental abnormal ECG findings (exposed-group). CVD cumulative incidence reached 31.6% among the 930 survivors who participated in the active follow-up (294/930). During a 31-year median follow-up, 1719 (66.1%) of the total cohort died. Incidental abnormal ECG findings were associated with 46% greater CVD-risk (odds ratio = 1.46, 95%CI = 1.09-1.97). The net reclassification improvement (NRI) of CVD-risk was 7.4% (95%CI = 1.5%-13.3%, p = 0.01) following the addition of ECG findings, but the C-index improvement was not statistically significant [C-index = 0.656 (0.619-0.694) vs. C-index = 0.666 (0.629-0.703), p = 0.14]. Multivariable Cox regression demonstrated an all-cause mortality hazard ratio (HR) of 1.18 (95%CI = 1.07-1.30) for exposed vs. unexposed individuals. Non-specific T-wave changes and left-axis deviation are the incidental ECG abnormalities that were associated with all-cause mortality [HR = 1.18 (95%CI = 1.05-1.33) and HR = 1.19 (95%CI = 1.00-1.42), respectively].
Conclusion
Incidental abnormal ECG findings, mainly non-specific T-wave changes and left-axis deviation, were associated with increased long-term CVD-risk and all-cause mortality among individuals without known CVD, and demonstrated net reclassification improvement for CVD-risk.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Nov 2019; 295:36-41
Goldman A, Hod H, Chetrit A, Dankner R
Int J Cardiol: 14 Nov 2019; 295:36-41 | PMID: 31412991
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Abstract

Prognostic value of cardiac metaiodobenzylguanidine imaging and QRS duration in implantable cardioverter defibrillator patients with and without heart failure.

Kawasaki M, Yamada T, Morita T, Furukawa Y, ... Sakata Y, Fukunami M
Background
Cardiac metaiodobenzylguanidine (MIBG) imaging provides prognostic information in patients with heart failure (HF). Recent studies showed that the highest rate of ventricular tachyarrhythmias (VTs) is seen in HF patients with an intermediate decrease in MIBG uptake, rather than in those with the lowest values. However, prolonged QRS duration (QRSd) has been shown to be associated with VTs in HF patients. This study assessed the prognostic value of the combination of an intermediate decrease in MIBG uptake and prolonged QRSd for predicting VTs in patients with implantable cardioverter defibrillators (ICDs) in relation to the presence of heart failure (HF).
Methods and results
A total of 196 outpatients with ICDs (age: 64 ± 14 years, male: 81%, left ventricular ejection fraction [LVEF]: 49% ± 16%) were prospectively enrolled; 135 had HF (NYHA class: 2.0 ± 0.6). At entry, cardiac MIBG imaging was performed, and QRSd was measured on standard 12‑lead electrocardiography. An intermediate decrease in the heart-to-mediastinum ratio on the delayed planar image (ID-H/M) was defined as 1.40-1.89. During the 3.3 ± 2.2-year follow-up, 59 patients had appropriate ICD discharges (ATx) for VTs. On multivariate Cox analysis, ID-H/M and prolonged QRSd (≥147 ms) were significantly and independently associated with ATx. In both patients with and without HF, ATx were significantly more frequent in patients with ID-H/M and/or prolonged QRSd than in those with neither (with HF: 40% vs. 14%, p = 0.020; without HF: 43% vs. 10%, p = 0.0028).
Conclusions
The combination of ID-H/M and prolonged QRSd provided more prognostic information for predicting VTs in ICD patients, with and without HF.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:164-171
Kawasaki M, Yamada T, Morita T, Furukawa Y, ... Sakata Y, Fukunami M
Int J Cardiol: 30 Nov 2019; 296:164-171 | PMID: 31371118
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Abstract

Oral anticoagulation for subclinical atrial tachyarrhythmias detected by implantable cardiac devices: an international survey of the AF-SCREEN Group.

Boriani G, Healey JS, Schnabel RB, Lopes RD, ... Camm JA, Freedman B
Aims
At present, there is little evidence on how to treat subclinical atrial fibrillation (SCAF) or atrial high rate episodes (AHREs) detected by cardiac implantable electronic devices (CIEDs). Our aim was to assess current practice around oral anticoagulation (OAC) in such patients.
Methods
A web-based survey undertaken by 310 physicians: 59 AF-SCREEN International Collaboration members and 251 non-members.
Results
In patients with SCAF/AHRE and a CHADSVASc ≥ 2 in males or ≥ 3 in female the amount of SCAF/AHRE triggering use of OAC was variable but <2% of respondents considered that no AHRE would require OAC. Around one third (34%) considered SCAF/AHRE duration of >5-6 min as the basis for OAC prescription, while 16% and 18% required a burden of at least 5.5 h or 24 h, respectively. The propensity to prescribe OAC for a low burden of AHREs differed according to certain respondent characteristics (greater propensity to prescribe OAC for neurologists). When the clinical scenario included a prior stroke or a prior cardioembolic stroke, stated prescription of OAC was very high. More than 96% felt that any SCAF/AHRE should be treated with OAC.
Conclusions
There is substantial heterogeneity in the perception of the risk of stroke/systemic embolism associated with SCAF/AHRE of variable duration. The threshold of AHRE burden that would trigger initiation of OAC is highly variable, and differs according to the clinical scenario (lower threshold in case of previous stroke). Ongoing trials will clarify the real benefit and risk/benefit ratio of OAC in this specific clinical setting.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:65-70
Boriani G, Healey JS, Schnabel RB, Lopes RD, ... Camm JA, Freedman B
Int J Cardiol: 30 Nov 2019; 296:65-70 | PMID: 31327519
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Abstract

Significance of the CAPRI risk score to predict heart failure hospitalization post-TAVI: The CAPRI-HF study.

Harbaoui B, Durand E, Dupré M, Rabilloud M, ... Eltchaninoff H, Lantelme P
Background
Predictors of heart failure (HF) hospitalization after transcatheter aortic valve implantation (TAVI) are not well defined. CAPRI is a score for predicting 1-year post-TAVI cardiovascular and all-cause mortality. The aim of the present study is to assess the prognostic significance of the CAPRI score for HF hospitalization 1 year after TAVI.
Methods and results
CAPRI-HF is an ancillary study of the C4CAPRI trial, analyzing 409 consecutive patients treated by TAVI. The primary outcome was hospitalization for HF during the first year post-intervention. The prognostic value of the CAPRI score was assessed by multivariable analysis adjusted for diabetes, atrial fibrillation, vascular route, pacemaker implantation, post-TAVI aortic regurgitation, transfusion and pulmonary artery systolic pressure. A subanalysis focused on patients with low-gradient aortic stenosis (LGAS). At 1 year, HF hospitalization occurred in 78 (19.9%) patients. Patients with HF were more prone to have diabetes, atrial fibrillation, renal dysfunction, lower mean aortic gradient, higher logistic EuroSCORE and higher CAPRI score (p < .05 for all associations). In the multivariable analysis, CAPRI score was the sole predictor of HF: hazard ratio (HR) for each 0.1 CAPRI score increase was 1.065, 95% confidence interval (CI) 1.021-1.110. This was confirmed when adjusted for EuroSCORE: HR 1.066, 95% CI 1.024-1.110. The predictive power of the CAPRI score increased for LGAS: HR 1.098, 95% CI 1.028-1.172.
Conclusions
CAPRI score helps predict HF post-TAVI. Including the score in the decision-making process may help selecting candidates for TAVI and identifying patients who need close monitoring post-procedure.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:98-102
Harbaoui B, Durand E, Dupré M, Rabilloud M, ... Eltchaninoff H, Lantelme P
Int J Cardiol: 30 Nov 2019; 296:98-102 | PMID: 31455517
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Abstract

Gene therapy for atrial fibrillation - How close to clinical implementation?

Trivedi A, Hoffman J, Arora R

In this review we examine the current state of gene therapy for the treatment of cardiac arrhythmias. We describe advances and challenges in successfully creating and incorporating gene vectors into the myocardium. After summarizing the current scientific research in gene transfer technology we then focus on the most promising areas of gene therapy, the treatment of atrial fibrillation and ventricular tachyarrhythmias. We review the scientific literature to determine how gene therapy could potentially be used to treat patients with cardiac arrhythmias.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:177-183
Trivedi A, Hoffman J, Arora R
Int J Cardiol: 30 Nov 2019; 296:177-183 | PMID: 31439427
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Abstract

The prognostic value of biventricular long axis strain using standard cardiovascular magnetic resonance imaging in patients with hypertrophic cardiomyopathy.

Yang F, Wang J, Li Y, Li W, ... Han Y, Chen Y
Background
Long axis strain (LAS) is a parameter derived from standard cardiovascular magnetic resonance imaging. However, the prognostic value of biventricular LAS in hypertrophic cardiomyopathy (HCM) is unknown.
Methods
Patients with HCM (n = 384) and healthy volunteers (n = 150) were included in the study. Left ventricular (LV)-LAS was defined as the percentage change in the length measured from the epicardial border of the LV apex to the midpoint of a line connecting the mitral annulus at end-systole and end-diastole. Right ventricular (RV)-LAS represented the percentage change of length between epicardial border of the LV apex to the midpoint of a line connecting the tricuspid annulus at end-systole and end-diastole. The primary endpoint was a combination of all-cause death and sudden cardiac death aborted by appropriate implantable cardioverter-defibrillator discharge and cardiopulmonary resuscitation after syncope. The secondary endpoint was a combination of the primary endpoint and hospitalization for congestive heart failure.
Results
Twenty-nine patients (7.6%) achieved the primary endpoint, and the secondary endpoint occurred in 66 (17.2%) patients. In multivariate Cox regression analysis, RV-LAS was an independent prognostic factor for the primary (hazard ratio (HR), 1.13) and secondary (HR, 1.11) endpoints. In the subgroup of patients with a normal RV ejection fraction (EF) (>45.0%, n = 345), impaired RV-LAS was associated with adverse outcomes and might add incremental prognostic value to RVEF and tricuspid annular plane systolic excursion (TAPSE) (p < 0.01).
Conclusions
RV-LAS is an independent predictor of adverse prognosis in HCM in addition to RVEF and TAPSE.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Oct 2019; 294:43-49
Yang F, Wang J, Li Y, Li W, ... Han Y, Chen Y
Int J Cardiol: 31 Oct 2019; 294:43-49 | PMID: 31405582
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Abstract

Heart failure risk predictions in adult patients with congenital heart disease: a systematic review.

Wang F, Harel-Sterling L, Cohen S, Liu A, ... Paradis G, Marelli AJ

To summarise existing heart failure (HF) risk prediction models and describe the risk factors for HF-related adverse outcomes in adult patients with congenital heart disease (CHD). We performed a systematic search of MEDLINE, EMBASE and Cochrane databases from January 1996 to December 2018. Studies were eligible if they developed multivariable models for risk prediction of decompensated HF in adult patients with CHD (ACHD), death in patients with ACHD-HF or both, or if they reported corresponding predictors. A standardised form was used to extract information from selected studies. Twenty-five studies met the inclusion criteria and all studies were at moderate to high risk of bias. One study derived a model to predict the risk of a composite outcome (HF, death or arrhythmia) with a c-statistic of 0.85. Two studies applied an existing general HF model to patients with ACHD but did not report model performance. Twenty studies presented predictors of decompensated HF, and four examined patient characteristics associated with mortality (two reported predictors of both). A wide variation in population characteristics, outcome of interest and candidate risk factors was observed between studies. Although there were substantial inconsistencies regarding which patient characteristics were predictive of HF-related adverse outcomes, brain natriuretic peptide, New York Heart Association class and CHD lesion characteristics were shown to be important predictors. To date, evidence in the published literature is insufficient to accurately profile patients with ACHD. High-quality studies are required to develop a unique ACHD-HF prediction model and confirm the predictive roles of potential risk factors.

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Oct 2019; 105:1661-1669
Wang F, Harel-Sterling L, Cohen S, Liu A, ... Paradis G, Marelli AJ
Heart: 30 Oct 2019; 105:1661-1669 | PMID: 31350277
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Abstract

A common variant in CCDC93 protects against myocardial infarction and cardiovascular mortality by regulating endosomal trafficking of low-density lipoprotein receptor.

Rimbert A, Dalila N, Wolters JC, Huijkman N, ... van de Sluis B, Kuivenhoven JA
Aims
Genome-wide association studies have previously identified INSIG2 as a candidate gene for plasma low-density lipoprotein cholesterol (LDL-c). However, we suspect a role for CCDC93 in the same locus because of its involvement in the recycling of the LDL-receptor (LDLR).
Methods and results
Characterization of the INSIG2 locus was followed by studies in over 107 000 individuals from the general population, the Copenhagen General Population Study and the Copenhagen City Heart Study, for associations of genetic variants with plasma lipids levels, with risk of myocardial infarction (MI) and with cardiovascular mortality. CCDC93 was furthermore studied in cells and mice. The lead variant of the INSIG2 locus (rs10490626) is not associated with changes in the expression of nearby genes but is a part of a genetic block, which excludes INSIG2. This block includes a coding variant in CCDC93 p.Pro228Leu, which is in strong linkage disequilibrium with rs10490626 (r2 > 0.96). In the general population, separately and combined, CCDC93 p.Pro228Leu is dose-dependently associated with lower LDL-c (P-trend 2.5 × 10-6 to 8.0 × 10-9), with lower risk of MI (P-trend 0.04-0.002) and lower risk of cardiovascular mortality (P-trend 0.005-0.004). These results were validated for LDL-c, risk of both coronary artery disease and MI in meta-analyses including from 194 000 to >700 000 participants. The variant is shown to increase CCDC93 protein stability, while overexpression of human CCDC93 decreases plasma LDL-c in mice. Conversely, CCDC93 ablation reduces LDL uptake as a result of reduced LDLR levels at the cell membrane.
Conclusion
This study provides evidence that a common variant in CCDC93, encoding a protein involved in recycling of the LDLR, is associated with lower LDL-c levels, lower risk of MI and cardiovascular mortality.

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 18 Oct 2019; epub ahead of print
Rimbert A, Dalila N, Wolters JC, Huijkman N, ... van de Sluis B, Kuivenhoven JA
Eur Heart J: 18 Oct 2019; epub ahead of print | PMID: 31630160
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Abstract

Cryoballoon or Radiofrequency Ablation for Atrial Fibrillation Assessed by Continuous Monitoring: A Randomized Clinical Trial.

Andrade JG, Champagne J, Dubuc M, Deyell MW, ... Khairy P,

Advanced generation ablation technologies have been developed to achieve more effective pulmonary vein isolation (PVI) and minimize arrhythmia recurrence following atrial fibrillation (AF) ablation.We randomly assigned 346 patients with drug-refractory paroxysmal AF to contactforce guided RF ablation (CF-RF ablation, 115), 4-minute cryoballoon ablation (CRYO-4, 115), or 2-minute cryoballoon ablation (CRYO-2, 116). Follow-up was 12 months. The primary outcome was time to first documented recurrence of symptomatic or asymptomatic atrial tachyarrhythmia (AF, atrial flutter, or atrial tachycardia) between days 91 and 365 post ablation, or a repeat ablation procedure at any time. Secondary endpoints included freedom from symptomatic arrhythmia, and AF burden. All patients received an implantable loop recorder.One-year freedom from atrial tachyarrhythmia defined by continuous rhythm monitoring, was 53.9%, 52.2%, and 51.7% with CF-RF, CRYO-4, and CRYO-2, respectively; P=0.87. One-year freedom from symptomatic atrial tachyarrhythmia defined by continuous rhythm monitoring, was 79.1%, 78.2%, and 73.3% with CF-RF, CRYO-4, and CRYO-2, respectively; P=0.26. Compared to the pre-ablation monitoring period, AF burden was reduced by a median of 99.3% (IQR 67.8-100.0%) with CF-RF, 99.9% (IQR 65.3-100.0%) with CRYO4, and 98.4% (IQR 56.2-100.0%) with CRYO-2 (P=0.36). Serious adverse events occurred in 2 patients in CF-RF (2.6%), 6 patients in CRYO-4 (5.3%), and 7 patients in CRYO-2 (6.0%), with no significant difference between groups (P=0.24). The CF-RF group had a significantly longer procedure duration but significantly shorter fluoroscopy exposure (P<0.001 vs. cryoballoon groups).In this multicenter, randomized, single-blinded trial, contact-force RF ablation and two different regiments of cryoballoon ablation resulted in no difference in one-year efficacy, which was 53% by time to first recurrence but >98% burden reduction as assessed by continuous cardiac rhythm monitoring.



Circulation: 20 Oct 2019; epub ahead of print
Andrade JG, Champagne J, Dubuc M, Deyell MW, ... Khairy P,
Circulation: 20 Oct 2019; epub ahead of print | PMID: 31630538
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Abstract

Risk of Mortality Following Catheter Ablation of Atrial Fibrillation.

Cheng EP, Liu CF, Yeo I, Markowitz SM, ... Lerman BB, Cheung JW
Background
Although procedure-related deaths during index admission following catheter ablation of AF have been reported to be low, adverse outcomes can occur after discharge. There are limited data on mortality early after AF ablation.
Objectives
This study aimed to identify rates, trends, and predictors of early mortality post-atrial fibrillation (AF) ablation.
Methods
Using the all-payer, nationally representative Nationwide Readmissions Database, we evaluated 60,203 admissions of patients 18 years of age or older for AF ablation between 2010 and 2015. Early mortality was defined as death during initial admission or 30-day readmission. Based on International Classification of Diseases-9th Revision, Clinical Modification codes, we identified comorbidities, procedural complications, and causes of readmission following AF ablation. Multivariable logistic regression was performed to assess predictors of early mortality.
Results
Early mortality following AF ablation occurred in 0.46% cases, with 54.3% of deaths occurring during readmission. From 2010 to 2015, quarterly rates of early mortality post-ablation increased from 0.25% to 1.35% (p < 0.001). Median time from ablation to death was 11.6 (interquartile range [IQR]: 4.2 to 22.7) days. After adjustment for age and comorbidities, procedural complications (adjusted odds ratio [aOR]: 4.06; p < 0.001), congestive heart failure (CHF) (aOR: 2.20; p = 0.011) and low AF ablation hospital volume (aOR: 2.35; p = 0.003) were associated with early mortality. Complications due to cardiac perforation (aOR: 2.98; p = 0.007), other cardiac (aOR: 12.8; p < 0.001), and neurologic etiologies (aOR: 8.72; p < 0.001) were also associated with early mortality.
Conclusions
In a nationally representative cohort, early mortality following AF ablation affected nearly 1 in 200 patients, with the majority of deaths occurring during 30-day readmission. Procedural complications, congestive heart failure, and low hospital AF ablation volume were predictors of early mortality. Prompt management of post-procedure complications and CHF may be critical for reducing mortality rates following AF ablation.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 04 Nov 2019; 74:2254-2264
Cheng EP, Liu CF, Yeo I, Markowitz SM, ... Lerman BB, Cheung JW
J Am Coll Cardiol: 04 Nov 2019; 74:2254-2264 | PMID: 31672181
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Abstract

Direct Current Cardioversion of Atrial Fibrillation in Patients With Left Atrial Appendage Occlusion Devices.

Sharma SP, Turagam MK, Gopinathannair R, Reddy V, ... Natale A, Lakkireddy D
Background
Direct current cardioversion (DCCV) is a common rhythm control strategy in patients with symptomatic atrial fibrillation or flutter. There is no long-term data regarding the safety of DCCV in patients with endocardial left atrial appendage occlusion (LAAO) devices.
Objectives
The purpose of this study was to assess the feasibility and safety of DCCV in patients with an LAAO device.
Methods
This multicenter retrospective study included 148 patients with an LAAO device who underwent DCCV for symptomatic atrial fibrillation or atrial flutter.
Results
The average age of the included patients was 72 ± 7 years and 59% were men. All patients (100%) had a transesophageal echocardiogram prior to DCCV. Device-related thrombus was seen in 2.7%. They were all successfully treated with oral anticoagulation (OAC) and were able to undergo DCCV after 6 to 8 weeks. DCCV restored sinus rhythm in all patients. None of the patients had DCCV-related thromboembolic complications. A total of 22% of patients were newly started on OAC after DCCV. There was no difference in DCCV-related complications between patients treated with or without OAC post-DCCV. Patients receiving OAC post-DCCV were found to undergo cardioversion at an earlier time after implantation (3.6 months [interquartile range (IQR): 0.7 to 8.6 months] vs. 8.6 months [IQR: 2.5 to 13.3 months]; p = 0.003). Three transient ischemic attacks, unrelated to DCCV, were found during follow-up. During a median follow-up of 12.8 months (IQR: 11.8 to 14.2 months), no device or left atrial thrombosis, device dislodgement, or a new device leak were observed. One patient died during follow-up due to noncardiac cause.
Conclusions
DCCV is feasible in high-risk AF patients with an LAAO device without the need for oral anticoagulation if pre-procedural transesophageal echocardiography shows good device position, absence of device-related thrombus, and peridevice leak of ≤5 mm. The preliminary results are encouraging, but further large studies are warranted to establish safety.

Copyright © 2019. Published by Elsevier Inc.

J Am Coll Cardiol: 04 Nov 2019; 74:2267-2274
Sharma SP, Turagam MK, Gopinathannair R, Reddy V, ... Natale A, Lakkireddy D
J Am Coll Cardiol: 04 Nov 2019; 74:2267-2274 | PMID: 31672183
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Impact:
Abstract

Altered fibrin clot properties and fibrinolysis in patients with atrial fibrillation: practical implications.

Undas A

Compelling evidence indicates that a hypercoagulable state occurs in patients with atrial fibrillation (AF) including those in sinus rhythm following paroxysmal and persistent AF. Activation of blood coagulation in AF reflects heightened thrombin generation with the subsequent increased formation of fibrin as evidenced by elevated soluble fibrin monomers and D-dimer. Formation of denser fibrin meshworks, relatively resistant to plasmin-mediated lysis has been demonstrated in patients with AF. The presence of stroke risk factors in AF, such as diabetes, heart failure, hypertension, previous myocardial infarction, or stroke, advanced age have been shown to be linked to the prothrombotic clot characteristics, including reduced clot permeability and lysability. Importantly, biomarkers, including cardiac troponins and N-terminal pro-brain natriuretic peptide, are associated with thrombin generation and fibrin-related markers in AF patients. Recently, increased fibrin clot density (low clot permeability measured in plasma-based assays) and impaired fibrinolysis measured off anticoagulation have been demonstrated to predict ischaemic cerebrovascular events in patients with AF receiving vitamin K antagonists and those on rivaroxaban. The current review summarizes evidence for a role of altered fibrin clot properties and hypofibrinolysis in AF and their prognostic value in terms of adverse events.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Europace: 17 Oct 2019; epub ahead of print
Undas A
Europace: 17 Oct 2019; epub ahead of print | PMID: 31625555
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Impact:
Abstract

Anticoagulation in Concomitant Chronic Kidney Disease and Atrial Fibrillation: JACC Review Topic of the Week.

Kumar S, Lim E, Covic A, Verhamme P, ... Camm AJ, Goldsmith D

Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist as they share multiple risk factors, including hypertension, diabetes mellitus, and coronary artery disease. Although there is irrefutable evidence supporting anticoagulation in AF in the general population, these data may not be transferable to the setting of advanced CKD, where the decision to commence anticoagulation poses a conundrum. In this cohort, there is a progressively increased risk of both ischemic stroke and hemorrhage as renal function declines, complicating the decision to initiate anticoagulation. No definitive clinical guidelines derived from randomized controlled trials exist to aid clinical decision-making, and the findings from observational studies are conflicting. In this review, the authors outline the pathophysiological mechanisms at play and summarize the limited existing data related to anticoagulation in those with concomitant CKD and AF. Finally, the authors suggest how to approach the decision of whether and how to use oral anticoagulation in these patients.

Copyright © 2019. Published by Elsevier Inc.

J Am Coll Cardiol: 28 Oct 2019; 74:2204-2215
Kumar S, Lim E, Covic A, Verhamme P, ... Camm AJ, Goldsmith D
J Am Coll Cardiol: 28 Oct 2019; 74:2204-2215 | PMID: 31648714
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Impact:
Abstract

Safety and efficacy outcomes of double vs. triple antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention: a systematic review and meta-analysis of non-vitamin K antagonist oral anticoagulant-based randomized clinical trials.

Gargiulo G, Goette A, Tijssen J, Eckardt L, ... Vranckx P, Valgimigli M
Aims
To investigate the safety and efficacy of double vs. triple antithrombotic therapy (DAT vs. TAT) in patients with atrial fibrillation (AF) and acute coronary syndrome or who underwent percutaneous coronary intervention (PCI).
Methods and results
A systematic review and meta-analysis was performed using PubMed to search for non-vitamin K antagonist oral anticoagulant (NOAC)-based randomized clinical trials comparing DAT vs. TAT in AF patients undergoing PCI. Four trials encompassing 10 234 patients (DAT = 5496 vs. TAT = 4738) were included. The primary safety endpoint (ISTH major or clinically relevant non-major bleeding) was significantly lower with DAT compared with TAT [risk ratio (RR) 0.66, 95% confidence interval (CI) 0.56-0.78; P < 0.0001; I2 = 69%], which was consistent across all available bleeding definitions. This benefit was counterbalanced by a significant increase of stent thrombosis (RR 1.59, 95% CI 1.01-2.50; P = 0.04; I2 = 0%) and a trend towards higher risk of myocardial infarction with DAT. There were no significant differences in all-cause and cardiovascular death, stroke and major adverse cardiovascular events. The comparison of NOAC-based DAT vs. vitamin K antagonist (VKA)-TAT yielded consistent results and a significant reduction of intracranial haemorrhage (RR 0.33, 95% CI 0.17-0.65; P = 0.001; I2 = 0%).
Conclusion
Double antithrombotic therapy, particularly if consisting of a NOAC instead of VKA and a P2Y12 inhibitor, is associated with a reduction of bleeding, including major and intracranial haemorrhages. This benefit is however counterbalanced by a higher risk of cardiac-mainly stent-related-but not cerebrovascular ischaemic occurrences.

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 24 Oct 2019; epub ahead of print
Gargiulo G, Goette A, Tijssen J, Eckardt L, ... Vranckx P, Valgimigli M
Eur Heart J: 24 Oct 2019; epub ahead of print | PMID: 31651946
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Impact:
Abstract

Subclinical and Device-Detected Atrial Fibrillation: Pondering the Knowledge Gap: A Scientific Statement From the American Heart Association.

Noseworthy PA, Kaufman ES, Chen LY, Chung MK, ... Yao X,

The widespread use of cardiac implantable electronic devices and wearable monitors has led to the detection of subclinical atrial fibrillation in a substantial proportion of patients. There is evidence that these asymptomatic arrhythmias are associated with increased risk of stroke. Thus, detection of subclinical atrial fibrillation may offer an opportunity to reduce stroke risk by initiating anticoagulation. However, it is unknown whether long-term anticoagulation is warranted and in what populations. This scientific statement explores the existing data on the prevalence, clinical significance, and management of subclinical atrial fibrillation and identifies current gaps in knowledge and areas of controversy and consensus.



Circulation: 06 Nov 2019:CIR0000000000000740; epub ahead of print
Noseworthy PA, Kaufman ES, Chen LY, Chung MK, ... Yao X,
Circulation: 06 Nov 2019:CIR0000000000000740; epub ahead of print | PMID: 31694402
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Impact:
Abstract

Impact of the Duration and Degree of Hypertension and Body Weight on New-Onset Atrial Fibrillation: A Nationwide Population-Based Study.

Kim YG, Han KD, Choi JI, Yung Boo K, ... Kim JS, Kim YH

Hypertension and obesity are known risk factors for atrial fibrillation (AF). However, it is unclear whether uncontrolled, long-standing hypertension has a particularly profound effect on AF. Because they have a similar underlying pathophysiology, hypertension and obesity could act synergistically in the context of AF. We evaluated how various stages of hypertension and body weight status affect new-onset AF. We analyzed a total of 9 797 418 participants who underwent a national health checkup. Hypertension was classified into 5 stages: nonhypertension, prehypertension, hypertension without medication, hypertension with medication <5 years, and hypertension with medication ≥5 years. The participants were also stratified based on body mass index and waist circumference. During the 80 130 161 person×years follow-up, a total of 196 136 new-onset AF cases occurred. The incidence of new-onset AF gradually increased among the 5 stages of hypertension: the adjusted hazard ratio for each group was 1 (reference), 1.145, 1.390, 1.853, and 2.344 for each stage of hypertension. A graded escalation in the risk of new-onset AF was also observed in response to increased systolic and diastolic blood pressure. The incidence of new-onset AF correlated with body mass index and waist circumference, with obese people having a higher risk than others. Hypertension and obesity acted synergistically: obese people with hypertension on medication ≥5 years had the highest risk of AF. In conclusion, the degree and duration of hypertension, as well as the presence of hypertension, were important factors for new-onset AF. Body weight status was significantly associated with new-onset AF and acted synergistically with hypertension.



Hypertension: 30 Oct 2019; 74:e45-e51
Kim YG, Han KD, Choi JI, Yung Boo K, ... Kim JS, Kim YH
Hypertension: 30 Oct 2019; 74:e45-e51 | PMID: 31522617
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Impact:
Abstract

Comparison of outcomes in infected cardiovascular implantable electronic devices between complete, partial, and failed lead removal: an ESC-EHRA-EORP ELECTRa (European Lead Extraction ConTrolled) registry.

Nof E, Bongiorni MG, Auricchio A, Butter C, ... Lundqvist CB, Glikson M
Aims
The present study sought to determine predictors for success and outcomes of patients who underwent cardiac implantable electronic devices (CIED) extraction indicated for systemic or local CIED related infection in particular where complete lead removal could not be achieved.
Methods and results
ESC-EORP ELECTRa (European Lead Extraction ConTRolled Registry) is a European prospective lead extraction registry. Out of the total cohort, 1865/3510 (52.5%) patients underwent removal due to CIED related infection. Predictors and outcomes of failure were analysed. Complete removal was achieved in 1743 (93.5%) patients, partial (<4 cm of lead left) in 88 (4.7%), and failed (>4 cm of lead left) in 32 (1.8%) patients. Removal success was unrelated to type of CIED infection (pocket or systemic). Predictors for failure were older leads and older patients [odds ratio (OR) 1.14 (1.08-1.19), P < 0.0001 and OR 2.68 (1.22-5.91), P = 0.0146, respectively]. In analysis by lead, predictors for failure were: pacemaker vs. defibrillator removal and failure to engage the locking stylet all the way to the tip [OR 0.20 (0.04-0.95), P = 0.03 and OR 0.32 (0.13-0.74), P = 0.008, respectively]. Significantly higher complication rates were noted in the failure group (40.6% vs. 15.9 for partial and 8.7% for success groups, P < 0.0001). Failure to remove a lead was a strong predictor for in hospital mortality [hazard ratio of 2.05 (1.01-4.16), P = 0.046].
Conclusion
A total of 6.5% of infected CIED patients failed attempted extraction. Only were >4 cm of lead remained resulted in higher procedural complications and mortality rates.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Europace: 17 Oct 2019; epub ahead of print
Nof E, Bongiorni MG, Auricchio A, Butter C, ... Lundqvist CB, Glikson M
Europace: 17 Oct 2019; epub ahead of print | PMID: 31625553
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Impact:
Abstract

Heightened Risk of Intensive Rate Control in Patients With Atrial Fibrillation Who Are Obese or Have Type 2 Diabetes: A Critical Review and Re-Evaluation.

Packer M

Atrial fibrillation (AF) is common in patients with obesity and diabetes; the arrhythmia (if long-standing) is typically managed by rate-control and anticoagulation. However, the coexistence of these two metabolic disorders complicates therapeutic options for rate-control. The likely pathogenesis of AF in these patients is an expansion of epicardial adipose tissue, whose inflammation is transmitted to the left atrium causing electromechanical remodeling. However, this same process is also transmitted to the left ventricle, impairing its distensibility and its ability to tolerate volume, leading to heart failure with preserved ejection fraction. Unfortunately, the latter diagnosis (although commonly present in patients with AF and a coexistent metabolic disorder) is often ignored. To achieve rate control, physicians prescribe intensive treatment with atrioventricular (AV)-nodal blocking drugs, often at doses that are titrated to blunt exercise as well as resting heart rate responses. However, strict rate control (target rate <80/min) is associated with somewhat worse outcomes than lenient rate control (target rate <110/min). Furthermore, any rate slowing that facilitates diastolic filling may aggravate filling pressures that are already disproportionately increased because the left ventricle is stiff and overfilled as a result of cardiac inflammation. Rate slowing in AF with beta-blockers may not achieve the benefit expected from the blockade of adrenergically-mediated cardiotoxicity, and some AV-nodal blocking drugs (digoxin and dronedarone) can increase the risk of death in patients with AF. Finally, cardiac fibrosis in obesity and diabetes may affect the conduction system, which can predispose to serious bradyarrhythmias if patients are prescribed AV-nodal blocking drugs. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 17 Oct 2019; epub ahead of print
Packer M
J Cardiovasc Electrophysiol: 17 Oct 2019; epub ahead of print | PMID: 31626365
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Impact:
Abstract

Hands On: How to approach patients undergoing lead extraction.

Lewis RK, Pokorney SD, Hegland DD, Piccini JP

Due to the growing number of patients treated with cardiac implantable electronic devices (CIEDs) there is an increased need for lead management, evaluation, and extraction. While CIED lead extraction has many indications, a consistent approach to pre-procedural planning should be applied in all cases, including a thorough consultation with careful review of the patient\'s medical and device history, as well as a discussion of informed consent and shared decision-making with the patient and their loved ones. The use of chest X-ray, echocardiography, and CT scan can further help with risk statification and procedural planning. Intra-procedural echocardiography (transesophageal or intracardiac) is recommended and allows early recognition of cardiothoracic injury. Establishing an extraction team with cardiology/electrophysiology, anesthesiology, and CT surgery is is crucial to a successful and safe CIED extraction practice, including immediately available surgical backup. This hands-on review will address how to approach patients who are undergoing lead extraction, as well as several innovations in pre-procedure and intra-procedural risk assessment. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 17 Oct 2019; epub ahead of print
Lewis RK, Pokorney SD, Hegland DD, Piccini JP
J Cardiovasc Electrophysiol: 17 Oct 2019; epub ahead of print | PMID: 31626390
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Impact:
Abstract

The quest for physiological pacing - does one size fit all?

Kaye G

Pacing is an established and ubiquitous treatment of bradycardias and some types of heart failure. The optimal pacing lead position which maximises cardiac function and minimises deterioration of ventricular function remains controversial. The desire to achieve a physiological pacing system which mimics cardiac function has led to investigation of several potential pacing sites. This editorial provides an overview of past and current pacing lead position and summaries the current and future direction of physiological pacing. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 17 Oct 2019; epub ahead of print
Kaye G
J Cardiovasc Electrophysiol: 17 Oct 2019; epub ahead of print | PMID: 31626353
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Impact:
Abstract

Pericardial access via wire-guided puncture without contrast: The feasibility and safety of a modified approach.

Long DY, Sun LP, Sang CH, Jiang CX, ... Du X, Ma CS
Objective
To investigate the feasibility and safety of wire-guided pericardial access without contrast.
Methods
From January of 2014 to February of 2019, patients who received epicardial mapping and ablation of ventricular tachycardia (VT) in Beijing Anzhen Hospital were entered into the current study. They were divided into contrast-guided access group or wire-guided access group according to the pericardial puncture technique used. The baseline variables, procedure parameters, complications were collected and compared.
Results
During the study period, a consecutive of 73 patients received epicardial access. The initial 32 patients received contrast-guided puncture with success achieved in 30 patients; the remaining 41 patients underwent wire-guided puncture with success achieved in 40 patients (30/32&40/41, P=0.581). Fluoroscopy time (4.45±0.52&4.38±0.46min, P=0.891) and access time (5.14±0.58 &5.34±0.50min, P=0.657) were comparable between the two groups. Inadvertent RV puncture occurred more commonly in contrast-guided group (5/32 &1/41, P=0.038). Though more pericardial effusions (2/32&1/41, P=0.575), tamponade (2/32&1/41, P=0.575), and surgical repair (1/32&0/41, P=0.432) occurred in the contrast-guided group, reached no statistical difference.
Conclusions
Wire-guided pericardial puncture exhibits better safety and similar success rates to contrast-guided technique with a trend towards less complications. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 17 Oct 2019; epub ahead of print
Long DY, Sun LP, Sang CH, Jiang CX, ... Du X, Ma CS
J Cardiovasc Electrophysiol: 17 Oct 2019; epub ahead of print | PMID: 31626367
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Impact:
Abstract

Left Bundle Branch Pacing Utilizing Three Dimensional Mapping.

Vijayaraman P, Panikkath R, Mascarenhas V, Bauch TD
Introduction
Permanent His bundle pacing is feasible and effective in patients with atrioventricular block or left bundle branch block. However, pacing thresholds to capture the distal His bundle is often higher. Recently left bundle branch area pacing (LBBP) has been shown to be feasible by advancing the lead transvenously, deep into the interventricular septum to reach the left ventricular endocardial surface. In this article we describe the utility of three dimensional (3D) mapping to achieve LBBP.
Methods
Ensite Precision (Abbott) mapping system was used to perform LBBP. A decapolar catheter was used to create 3D map of right atrium and right ventricle (RV). Regions of interest (His bundle, potential LBBP sites of interest in RV) were tagged in the 3D map. The LBBP lead was implanted utilizing the 3D map. The lead depth in the septum was assessed in the 3D map.
Results
LBBP was performed in three patients: chronic LBBB and intermittent 2:1 atrioventricular block; AV node ablation and conduction system pacing; and bifascicular block and intermittent AV block in a patient with severe left ventricular hypertrophy. LBBP was successful in all three patients. The lead depth in the interventricular septum was 12, 11 and 21 mm respectively as assessed by 3D mapping.
Conclusions
Three-dimensional mapping was helpful in achieving LBBP in patients with LBBB, severe left ventricular hypertrophy or during AV node ablation. 3D mapping also facilitated easy assessment of lead depth during and after lead fixation. 3D mapping techniques may be a valuable tool to reduce the learning curve of implanters with minimal experience in LBBP. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 17 Oct 2019; epub ahead of print
Vijayaraman P, Panikkath R, Mascarenhas V, Bauch TD
J Cardiovasc Electrophysiol: 17 Oct 2019; epub ahead of print | PMID: 31626377
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Impact:
Abstract

Usage of implantable loop recorder to evaluate absolute effectiveness of cardioneuroablation.

Aksu T, Guler TE, Saygı S, Yalin K

Cardioneuroablation (CNA) is an endocardial ablation technique aiming to prevent the autonomic imbalance occurring in vasovagal syncope (VVS) (1). A 20-year-old female was referred to our centre due to recurrent syncopal episodes. The frequency of episodes was twice a month since the age of 14, but it considerably increased recently. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 17 Oct 2019; epub ahead of print
Aksu T, Guler TE, Saygı S, Yalin K
J Cardiovasc Electrophysiol: 17 Oct 2019; epub ahead of print | PMID: 31626378
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Impact:
Abstract

Effects of Focal Impulse and Rotor Modulation-Guided Ablation on Atrial Arrhythmia Termination and Inducibility: Impact on Outcomes after Treatment of Persistent Atrial Fibrillation.

Kirzner JM, Raelson CA, Liu CF, Thomas G, ... Markowitz SM, Cheung JW
Introduction
The role of focal impulse and rotor modulation (FIRM)-guided ablation for the treatment of atrial fibrillation (AF) remains unclear. Previous studies on the FIRM-guided ablation outcomes have been limited by a focus on AF termination as an endpoint and by patient population heterogeneity. We sought to determine differences in rates of AF termination, inducibility, and recurrence in patients with persistent AF undergoing first-time ablation with a FIRM-guided approach compared with patients undergoing conventional ablation.
Methods and results
Eight-five consecutive patients (38 FIRM, 47 conventional) with persistent AF undergoing first-time ablation were retrospectively analyzed. There were no significant differences in the rates of AF termination in the FIRM group compared to the conventional group (26% vs. 15%; p = 0.15). Rates of inducible AF after ablation were 37% in the FIRM group and 30% in the conventional group (p = 0.32). Over a median follow-up of 2.4 years, the rates of freedom from AF were similar between the FIRM and conventional groups (1-year freedom from AF 65% vs. 50%, respectively; P = 0.18). Procedural termination of AF with either FIRM ablation or conventional ablation was not associated with any significant reduction in AF recurrence.
Conclusion
A FIRM-guided approach was not associated with a significant difference in freedom from AF when compared to conventional ablation. Termination of AF with ablation was not associated with increased freedom from AF. While AF termination using substrate-based ablation may have mechanistic implications for understanding AF rotor physiology, its impact on clinical outcomes remains unclear. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 17 Oct 2019; epub ahead of print
Kirzner JM, Raelson CA, Liu CF, Thomas G, ... Markowitz SM, Cheung JW
J Cardiovasc Electrophysiol: 17 Oct 2019; epub ahead of print | PMID: 31626356
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Impact:
Abstract

Treadmill Stress Test in a 56-Year-Old Man.

Kawji MM, Glancy DL

Several findings on an exercise electrocardiogram predicted left main and/or 3-vessel coronary arterial disease, which was confirmed by coronary arteriography, and the 56-year-old man underwent a multivessel coronary arterial bypass operation the following day.

Copyright © 2019 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Nov 2019; 124:1647-1648
Kawji MM, Glancy DL
Am J Cardiol: 14 Nov 2019; 124:1647-1648 | PMID: 31514967
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Impact:
Abstract

Improving Communication in Heart Failure Patient Care.

Goldstein NE, Mather H, McKendrick K, Gelfman LP, ... Pinney S, Morrison RS
Background
Although implantable cardioverter-defibrillators (ICDs) reduce sudden death, these patients die of heart failure (HF) or other diseases. To prevent shocks at the end of life, clinicians should discuss deactivating the defibrillation function.
Objectives
The purpose of this study was to determine if a clinician-centered teaching intervention and automatic reminders increased ICD deactivation discussions and increased device deactivation.
Methods
In this 6-center, single-blinded, cluster-randomized, controlled trial, primary outcomes were proportion of patients: 1) having ICD deactivation discussions; and 2) having the shocking function deactivated. Secondary outcomes included goals of care conversations and advance directive completion.
Results
A total of 525 subjects were included with advanced HF who had an ICD: 301 intervention and 224 control. At baseline, 52% (n = 272) were not candidates for advanced therapies (i.e., cardiac transplant or mechanical circulatory support). There were no differences in discussions (41 [14%] vs. 26 [12%]) or deactivation (33 [11%] vs. 26 [12%]). In pre-specified subgroup analyses of patients who were not candidates for advanced therapies, the intervention increased deactivation discussions (32 [25%] vs. 16 [11%]; odds ratio: 2.90; p = 0.003). Overall, 99 patients died; there were no differences in conversations or deactivations among decedents.
Secondary outcomes
Among all participants, there was an increase in goals of care conversations (47% intervention vs. 38% control; odds ratio: 1.53; p = 0.04). There were no differences in completion of advance directives.
Conclusions
The intervention increased conversations about ICD deactivation and goals of care. HF clinicians were able to apply new communication techniques based on patients\' severity of illness. (An Intervention to Improve Implantable Cardioverter-Defibrillator Deactivation Conversations [WISDOM]; NCT01459744).

Published by Elsevier Inc.

J Am Coll Cardiol: 01 Oct 2019; 74:1682-1692
Goldstein NE, Mather H, McKendrick K, Gelfman LP, ... Pinney S, Morrison RS
J Am Coll Cardiol: 01 Oct 2019; 74:1682-1692 | PMID: 31558252
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Impact:
Abstract

Approach and Strategy for Repeat Catheter Ablation of Recurrent Atrial Fibrillation.

Tomaiko E, Tseng A, Reichert WB, Su WW

Patients with atrial fibrillation (AF) often undergo repeat catheter ablation for recurrence of tachyarrhythmia. If the pulmonary veins were isolated in prior procedure, the operator should focus on substrate homogenization with identification and ablation of only arrhythmogenic areas. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 17 Oct 2019; epub ahead of print
Tomaiko E, Tseng A, Reichert WB, Su WW
J Cardiovasc Electrophysiol: 17 Oct 2019; epub ahead of print | PMID: 31626351
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Impact:
Abstract

Significance of inducibility of atrial fibrillation after pulmonary vein isolation in patients with healthy left atrium substrate.

Kosiuk J, Gründig S, Dinov B, Müssigbrodt A, ... Hindricks G, Bollmann A
Background
The significance of inducibility of atrial fibrillation (AF) after pulmonary vein isolation (PVI) in patients with AF remains disputable and polarizing. Therefore, we investigated the prognostic value of inducibility of AF on long-term outcome after PVI in patients without low-voltage left atrial (LA) substrate.
Methods
245 patients (mean age 59+/-9years, 72% male) without LA low voltage areas (defined as electrogram amplitudes <0.5 mV) undergoing first PVI procedure were included in the study. Following successful PVI, inducibility was assessed by burst pacing from coronary sinus with a cycle length (CL) of 300, 250 and 200ms or the shortest CL resulting in 1:1 atrial capture. During the follow up period of up to 3 years the rhythm outcome was monitored by serial 7-days Holter ECG.
Results
AF was induced in 38 patients (16%). Atypical atrial flutter (aAFL) was observed in 6 patients (2%), while typical flutter in 3 cases (1%). Within the first 3 months, early recurrence was diagnosed in 39 patients (16%), while late recurrence was detected in 58 patients (24%) after a mean AF free survival of 28±1 months. While there was no impact on early recurrence, AF inducibility affected long-term recurrence (31±1 versus 23±3 months, p=0.001). In multivariate analysis, AF inducibility (HR 2.14; 95%CI 1.03-4.45; p=0.041) and persistent type of AF (HR 2.17; 95%CI 1.06-4.47; p=0.034) were associated with late AF recurrence.
Conclusion
In patients without low-voltage substrate undergoing PVI, AF inducibility is a significant predictor of long-term outcome. The pathomechanisms of this phenomenon must be further studied in order to be addressed by additional treatment. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 17 Oct 2019; epub ahead of print
Kosiuk J, Gründig S, Dinov B, Müssigbrodt A, ... Hindricks G, Bollmann A
J Cardiovasc Electrophysiol: 17 Oct 2019; epub ahead of print | PMID: 31626352
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Impact:
Abstract

\"Feeling\" your way to the pericardium - A new approach to an old space.

Narasimhan B, Tandri H

Percutaneous pericardial access was first performed in 1840 by Frank Schuh, a thoracic surgeon using a left lateral approach for pericardiocentesis. Interest in the pericardium was largely restricted to draining pericardial fluid for over two centuries until interest was renewed in electrophysiology interventions. The epicardial approach for catheter ablation through the subxiphoid space was popularized by Sosa in 1996 in Chagasic cardiomyopathy. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 17 Oct 2019; epub ahead of print
Narasimhan B, Tandri H
J Cardiovasc Electrophysiol: 17 Oct 2019; epub ahead of print | PMID: 31626349
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Impact:
Abstract

Osteoporotic Fractures in Patients With Atrial Fibrillation Treated With Conventional Versus Direct Anticoagulants.

Binding C, Bjerring Olesen J, Abrahamsen B, Staerk L, Gislason G, Nissen Bonde A
Background
Elderly patients in long-term treatment with vitamin K antagonists (VKAs) are at high risk of osteoporotic fractures compared with the background population. It has been speculated that the choice of oral anticoagulant (OAC) may affect the risk of osteoporotic fractures.
Objectives
The risk of osteoporotic fractures was evaluated among patients with atrial fibrillation treated with VKA or direct oral anticoagulants (DOACs).
Methods
Patients were identified using the Danish national registries. Patients were included only if they had no prior use of osteoporosis medication and they had undergone 180 days of OAC treatment. Outcomes were hip fracture, major osteoporotic fracture, any fracture, initiation of osteoporosis medication, and a combined endpoint.
Results
Overall, 37,350 patients were included. The standardized absolute 2-year risk of any fracture was low among DOAC-treated patients (3.1%; 95% CI: 2.9% to 3.3%) and among VKA-treated patients (3.8%; 95% CI: 3.4% to 4.2%). DOAC was associated with a significantly lower relative risk of any fracture (hazard ratio [HR]: 0.85; 95% CI: 0.74 to 0.97), major osteoporotic fractures (HR: 0.85; 95% CI: 0.72 to 0.99), and initiating osteoporotic medication (HR: 0.82; 95% CI: 0.71 to 0.95). A combined endpoint showed that patients treated with DOAC had a significantly lower relative risk of experiencing any fracture or initiating osteoporosis medication (HR: 0.84; 95% CI: 0.76 to 0.93).
Conclusions
In a nationwide population, the absolute risk of osteoporotic fractures was low among patients with atrial fibrillation on OAC, but DOAC was associated with a significantly lower risk of osteoporotic fractures compared with VKA.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 28 Oct 2019; 74:2150-2158
Binding C, Bjerring Olesen J, Abrahamsen B, Staerk L, Gislason G, Nissen Bonde A
J Am Coll Cardiol: 28 Oct 2019; 74:2150-2158 | PMID: 31648707
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Abstract

Infective endocarditis after transcatheter aortic valve implantation: a nationwide study.

Bjursten H, Rasmussen M, Nozohoor S, Götberg M, ... Rück A, Ragnarsson S
Aims 
Transcatheter aortic valve implantation (TAVI), now a common procedure to treat high-risk patients with severe aortic stenosis, has rapidly been expanding into younger and lower-risk populations, creating a need to better understand long-term outcome after TAVI. The aim of the present investigation was to determine the incidence, risk factors for, clinical presentation of, and outcome after prosthetic valve endocarditis (PVE) in patients treated with TAVI in a nationwide study.
Methods and results 
Three registries were used: a national TAVI registry, a national diagnosis registry, and a national infective endocarditis registry. Combining these registries made it possible to perform a nationwide, all-comers study with independent and validated reporting of PVE in 4336 patients between 2008 and mid-2018. The risk for PVE after TAVI was 1.4% (95% confidence interval 1.0-1.8%) the first year and 0.8% (0.6-1.1%) per year thereafter. One-year survival after PVE diagnosis was 58% (49-68%), and 5-year survival was 29% (17-41%). Body surface area, estimated glomerular filtration rate <30 mL/min/1.73 m2, critical pre-operative state, mean pre-procedural valve gradient, amount of contrast dye used, transapical access, and atrial fibrillation were identified as independent risk factors for PVE. Staphylococcus aureus was more common in early (<1 year) PVE. Infection with S. aureus, root abscess, late PVE, and non-community acquisition was associated with higher 6-month mortality.
Conclusion 
The incidence of PVE was similar to that of surgical bioprostheses. Compromised renal function was a strong risk factor for developing PVE. In the context of PVE, TAVI seems to be a safe option for patients.
Clinical trial registration
NCT03768180 (http://clinicaltrials.gov/).

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Eur Heart J: 13 Oct 2019; 40:3263-3269
Bjursten H, Rasmussen M, Nozohoor S, Götberg M, ... Rück A, Ragnarsson S
Eur Heart J: 13 Oct 2019; 40:3263-3269 | PMID: 31433472
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Abstract

Childhood Tobacco Smoke Exposure and Risk of Atrial Fibrillation in Adulthood.

Groh CA, Vittinghoff E, Benjamin EJ, Dupuis J, Marcus GM
Background
Cigarette smoking is known to increase the risk of atrial fibrillation (AF), and a recent cross-sectional analysis suggested that parental smoking may be an AF risk factor.
Objectives
The purpose of this study was to assess if parental smoking predicts offspring AF in the Framingham Heart Study.
Methods
This study analyzed Framingham Offspring cohort participants with parents in the Original cohort with known smoking status during the offspring\'s childhood. Framingham participants were evaluated every 2 to 8 years and were under routine surveillance for incident AF. The authors assessed AF incidence among Offspring participants exposed to parental smoking through age 18 years and performed a mediation analysis to determine the extent to which offspring smoking might explain observed associations.
Results
Of 2,816 Offspring cohort participants with at least 1 parent in the Original cohort, 82% were exposed to parental smoking. For every pack/day increase in parental smoking, there was an 18% increase in offspring AF incidence (adjusted hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 1.00 to 1.39; p = 0.04). Additionally, parental smoking was a risk factor for offspring smoking (adjusted odds ratio [OR]: 1.34; 95% CI: 1.17 to 1.54; p < 0.001). Offspring smoking mediated 17% (95% CI: 1.5% to 103.3%) of the relationship between parental smoking and offspring AF.
Conclusions
Childhood secondhand smoke exposure predicted increased risk for adulthood AF after adjustment for AF risk factors. Some of this relationship may be mediated by a greater propensity among offspring of smoking parents to smoke themselves. These findings highlight potential new pathways for AF risk that begin during childhood, offering new evidence to motivate smoking avoidance and cessation.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 01 Oct 2019; 74:1658-1664
Groh CA, Vittinghoff E, Benjamin EJ, Dupuis J, Marcus GM
J Am Coll Cardiol: 01 Oct 2019; 74:1658-1664 | PMID: 31558248
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Abstract

Transcatheter versus medical treatment of symptomatic severe tricuspid regurgitation.

Taramasso M, Benfari G, van der Bijl P, Alessandrini H, ... Enriquez-Sarano M, Maisano F
Background
Tricuspid Regurgitation (TR) is associated with increased rates of heart failure (HF) and mortality. Transcatheter tricuspid valve interventions (TTVI) are promising, but the clinical benefit is unknown.
Objectives
To investigate the potential benefit of TTVI over medical therapy in a propensity score matched population.
Methods
The TriValve (Transcatheter Tricuspid Valve Therapies) registry collected 472 patients from 22 European and North American centers, who underwent TTVI from 2016 to 2018. A control cohort formed by two large retrospective registries enrolling medically managed patients with ≥moderate TR in Europe and North America (1179 pts) were propensity score 1:1 matched (distance ± 0.2 SD) using age, Euroscore II, and systolic pulmonary artery pressure. Survival was tested with Cox regression analysis. Primary endpoint was 1-year mortality or HF rehospitalization or the composite.
Results
After matching, 268 adequately matched pairs of patients were identified. Compared to controls, TTVI patients had lower 1-year mortality (23 ±3% vs 36 ±3%, p=0.001), rehospitalization (26 ±3% vs 47 ±3% p<0.0001), and composite endpoint (32 ±4% vs 49 ±3%; p=0.0003). TTVI was associated with greater survival and freedom from HF rehospitalization (HR 0.60 [0.46-0.79], p=0.003 unadjusted) which remained significant after adjusting for sex, NYHA class, right ventricular dysfunction and atrial fibrillation (HR 0.39 [0.26-0.59], p<0.0001) and after further adjustment for mitral regurgitation and pacemaker/defibrillator (HR 0.35 [0.23.54], p<0.0001).
Conclusions
In this propensity matched case-control study, TTVI is associated with greater survival and reduced HF rehospitalization compared with medical therapy alone. Randomized trials should be performed to confirm these results.

Copyright © 2019. Published by Elsevier Inc.

J Am Coll Cardiol: 24 Sep 2019; epub ahead of print
Taramasso M, Benfari G, van der Bijl P, Alessandrini H, ... Enriquez-Sarano M, Maisano F
J Am Coll Cardiol: 24 Sep 2019; epub ahead of print | PMID: 31568868
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Impact:
Abstract

Transcatheter aortic valve implantation vs. surgical aortic valve replacement for treatment of symptomatic severe aortic stenosis: an updated meta-analysis.

Siontis GCM, Overtchouk P, Cahill TJ, Modine T, ... Jüni P, Windecker S
Aims 
Owing to new evidence from randomized controlled trials (RCTs) in low-risk patients with severe aortic stenosis, we compared the collective safety and efficacy of transcatheter aortic valve implantation (TAVI) vs. surgical aortic valve replacement (SAVR) across the entire spectrum of surgical risk patients.
Methods and results 
The meta-analysis is registered with PROSPERO (CRD42016037273). We identified RCTs comparing TAVI with SAVR in patients with severe aortic stenosis reporting at different follow-up periods. We extracted trial, patient, intervention, and outcome characteristics following predefined criteria. The primary outcome was all-cause mortality up to 2 years for the main analysis. Seven trials that randomly assigned 8020 participants to TAVI (4014 patients) and SAVR (4006 patients) were included. The combined mean STS score in the TAVI arm was 9.4%, 5.1%, and 2.0% for high-, intermediate-, and low surgical risk trials, respectively. Transcatheter aortic valve implantation was associated with a significant reduction of all-cause mortality compared to SAVR {hazard ratio [HR] 0.88 [95% confidence interval (CI) 0.78-0.99], P = 0.030}; an effect that was consistent across the entire spectrum of surgical risk (P-for-interaction = 0.410) and irrespective of type of transcatheter heart valve (THV) system (P-for-interaction = 0.674). Transcatheter aortic valve implantation resulted in lower risk of strokes [HR 0.81 (95% CI 0.68-0.98), P = 0.028]. Surgical aortic valve replacement was associated with a lower risk of major vascular complications [HR 1.99 (95% CI 1.34-2.93), P = 0.001] and permanent pacemaker implantations [HR 2.27 (95% CI 1.47-3.64), P < 0.001] compared to TAVI.
Conclusion 
Compared with SAVR, TAVI is associated with reduction in all-cause mortality and stroke up to 2 years irrespective of baseline surgical risk and type of THV system.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Eur Heart J: 06 Oct 2019; 40:3143-3153
Siontis GCM, Overtchouk P, Cahill TJ, Modine T, ... Jüni P, Windecker S
Eur Heart J: 06 Oct 2019; 40:3143-3153 | PMID: 31329852
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Abstract

Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients.

Kolte D, Vlahakes GJ, Palacios IF, Sakhuja R, ... Inglessis I, Elmariah S
Background
Transcatheter aortic valve replacement (TAVR) has emerged as a safe and effective therapeutic option for patients with severe aortic stenosis (AS) who are at prohibitive, high, or intermediate risk for surgical aortic valve replacement (SAVR). However, in low-risk patients, SAVR remains the standard therapy in current clinical practice.
Objectives
This study sought to perform a meta-analysis of randomized controlled trials (RCTs) comparing TAVR versus SAVR in low-risk patients.
Methods
Electronic databases were searched from inception to March 20, 2019. RCTs comparing TAVR versus SAVR in low-risk patients (Society of Thoracic Surgeons Predicted Risk of Mortality [STS-PROM] score <4%) were included. Primary outcome was all-cause death at 1 year. Random-effects models were used to calculate pooled risk ratio (RR) and corresponding 95% confidence interval (CI).
Results
The meta-analysis included 4 RCTs that randomized 2,887 patients (1,497 to TAVR and 1,390 to SAVR). The mean age of patients was 75.4 years, and the mean STS-PROM score was 2.3%. Compared with SAVR, TAVR was associated with significantly lower risk of all-cause death (2.1% vs. 3.5%; RR: 0.61; 95% CI: 0.39 to 0.96; p = 0.03; I = 0%) and cardiovascular death (1.6% vs. 2.9%; RR: 0.55; 95% CI: 0.33 to 0.90; p = 0.02; I = 0%) at 1 year. Rates of new/worsening atrial fibrillation, life-threatening/disabling bleeding, and acute kidney injury stage 2/3 were lower, whereas those of permanent pacemaker implantation and moderate/severe paravalvular leak were higher after TAVR versus SAVR. There were no significant differences between TAVR versus SAVR for major vascular complications, endocarditis, aortic valve re-intervention, and New York Heart Association functional class ≥II.
Conclusions
In this meta-analysis of RCTs comparing TAVR versus SAVR in low-risk patients, TAVR was associated with significantly lower risk of all-cause death and cardiovascular death at 1 year. These findings suggest that TAVR may be the preferred option over SAVR in low-risk patients with severe AS who are candidates for bioprosthetic AVR.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 24 Sep 2019; 74:1532-1540
Kolte D, Vlahakes GJ, Palacios IF, Sakhuja R, ... Inglessis I, Elmariah S
J Am Coll Cardiol: 24 Sep 2019; 74:1532-1540 | PMID: 31537261
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Abstract

Novel Transcatheter Mitral Valve Prosthesis for Patients With Severe Mitral Annular Calcification.

Sorajja P, Gössl M, Babaliaros V, Rizik D, ... Cavalcante JL, Sun B
Background
Treatment of mitral regurgitation (MR) in the setting of severe mitral annular calcification (MAC) is challenging due to the high risk for fatal atrioventricular groove disruption and significant paravalvular leak.
Objectives
The objective of this study was to evaluate the potential for transcatheter mitral valve replacement in patients with severe MAC using an anatomically designed mitral prosthesis.
Methods
Nine patients (77 ± 6 years of age; 5 men) were treated with the valve, using transapical delivery performed under general anesthesia and with guidance from transesophageal echocardiography and fluoroscopy.
Results
Device implantation was successful with relief of MR in all 9 patients. There were no procedural deaths. In 1 patient, left ventricular outflow tract obstruction occurred due to malrotation of the prosthesis, and successful alcohol septal ablation was performed. During a median follow-up of 12 months (range 1 to 28 months), there was 1 cardiac death, 1 noncardiac death, no other mortality, and no prosthetic dysfunction, and MR remained absent in all treated patients. Rehospitalization for heart failure occurred in 2 patients who did not die subsequently. Clinical improvement with mild or no symptoms occurred in all patients alive at the end of follow-up.
Conclusions
Transcatheter mitral valve replacement in severe mitral annular calcification with a dedicated prosthesis is feasible and can result in MR relief with symptom improvement. Further evaluation of this approach for these high-risk patients is warranted.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 17 Sep 2019; 74:1431-1440
Sorajja P, Gössl M, Babaliaros V, Rizik D, ... Cavalcante JL, Sun B
J Am Coll Cardiol: 17 Sep 2019; 74:1431-1440 | PMID: 31514943
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Impact:
Abstract

The role of implantable cardioverter-defibrillators and sudden cardiac death prevention: indications, device selection, and outcome.

Goldenberg I, Huang DT, Nielsen JC

Multiple randomized multicentre clinical trials have established the role of the implantable cardioverter-defibrillator (ICD) as the mainstay in the treatment of ventricular tachyarrhythmias and sudden cardiac death (SCD) prevention. These trials have focused mainly on heart failure patients with advanced left ventricular dysfunction and were mostly conducted two decades ago, whereas a more recent trial has provided conflicting results. Therefore, much remains to be determined on how best to balance the identification of patients at high risk of SCD together with who would benefit most from ICD implantation in a contemporary setting. Implantable cardioverter-defibrillators have also evolved from the simple, defibrillation-only devices implanted surgically to more advanced technologies of multi-chamber devices, with physiologic bradycardic pacing, including cardiac resynchronization therapy, atrial and ventricular therapeutic pacing algorithms, and subcutaneous ICDs. These multiple options necessitate individualized approach to device selection and programming. This review will focus on the current knowledge on selection of patients for ICD treatment, device selection and programming, and future directions of implantable device therapy for SCD prevention.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Eur Heart J: 11 Nov 2019; epub ahead of print
Goldenberg I, Huang DT, Nielsen JC
Eur Heart J: 11 Nov 2019; epub ahead of print | PMID: 31713598
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Impact:
Abstract

Atrial fibrillation and cardiac fibrosis.

Sohns C, Marrouche NF

The understanding of atrial fibrillation (AF) evolved from a sole rhythm disturbance towards the complex concept of a cardiomyopathy based on arrhythmia substrates. There is evidence that atrial fibrosis can be visualized using late gadolinium enhancement cardiac magnetic resonance imaging and that it is a powerful predictor for the outcome of AF interventions. However, a strategy of an individual and fibrosis guided management of AF looks promising but results from prospective multicentre trials are pending. This review gives an overview about the relationship between cardiac fibrosis and AF focusing on translational aspects, clinical observations, and fibrosis imaging to emphasize the concept of personalized paths in AF management taking into account the individual amount and distribution of fibrosis.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Eur Heart J: 11 Nov 2019; epub ahead of print
Sohns C, Marrouche NF
Eur Heart J: 11 Nov 2019; epub ahead of print | PMID: 31713590
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Impact:
Abstract

Predicting cardiac electrical response to sodium-channel blockade and Brugada syndrome using polygenic risk scores.

Tadros R, Tan HL, , El Mathari S, ... Wilde AA, Bezzina CR
Aims
Sodium-channel blockers (SCBs) are associated with arrhythmia, but variability of cardiac electrical response remains unexplained. We sought to identify predictors of ajmaline-induced PR and QRS changes and Type I Brugada syndrome (BrS) electrocardiogram (ECG).
Methods and results
In 1368 patients that underwent ajmaline infusion for suspected BrS, we performed measurements of 26 721 ECGs, dose-response mixed modelling and genotyping. We calculated polygenic risk scores (PRS) for PR interval (PRSPR), QRS duration (PRSQRS), and Brugada syndrome (PRSBrS) derived from published genome-wide association studies and used regression analysis to identify predictors of ajmaline dose related PR change (slope) and QRS slope. We derived and validated using bootstrapping a predictive model for ajmaline-induced Type I BrS ECG. Higher PRSPR, baseline PR, and female sex are associated with more pronounced PR slope, while PRSQRS and age are positively associated with QRS slope (P < 0.01 for all). PRSBrS, baseline QRS duration, presence of Type II or III BrS ECG at baseline, and family history of BrS are independently associated with the occurrence of a Type I BrS ECG, with good predictive accuracy (optimism-corrected C-statistic 0.74).
Conclusion
We show for the first time that genetic factors underlie the variability of cardiac electrical response to SCB. PRSBrS, family history, and a baseline ECG can predict the development of a diagnostic drug-induced Type I BrS ECG with clinically relevant accuracy. These findings could lead to the use of PRS in the diagnosis of BrS and, if confirmed in population studies, to identify patients at risk for toxicity when given SCB.

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 30 Sep 2019; 40:3097-3107
Tadros R, Tan HL, , El Mathari S, ... Wilde AA, Bezzina CR
Eur Heart J: 30 Sep 2019; 40:3097-3107 | PMID: 31504448
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Impact:
Abstract

Sudden death in cardiac sarcoidosis: an analysis of nationwide clinical and cause-of-death registries.

Ekström K, Lehtonen J, Nordenswan HK, Mäyränpää MI, ... Kerola T, Kupari M
Aims
The present study was done to assess the role of sudden cardiac death (SCD) among the presenting manifestations of and fatalities from cardiac sarcoidosis (CS).
Methods and results
We analysed altogether 351 cases of CS presenting from year 1998 through 2015 in Finland. There were 262 patients with a clinical diagnosis and treatment of CS, 27 patients with an initial lifetime diagnosis of giant cell myocarditis that was later converted to CS, and 62 cases detected at autopsy and identified by screening >820 000 death certificates from the national cause-of-death registry. The total case series comprised 253 females and 98 males aged on average 52 years at presentation. High-grade atrioventricular block was the most common first sign of CS (n = 147, 42%) followed by heart failure (n = 58, 17%), unexpected fatal (n = 38) or aborted (n = 12) SCD (14%), and sustained ventricular tachycardia (n = 48, 14%). Severe coronary artery disease was found at autopsy concomitant with CS in four of the 38 cases presenting with fatal SCD. Of all deaths recorded till the end of 2015, 64% (n = 54/84) were unexpected SCDs from CS that had either been silent during life or defied all attempts at diagnosis. The Kaplan-Meier estimate (95% CI) of survival from symptom onset was 85% (80-90%) at 5 years and 76% (68-84%) at 10 years.
Conclusion
Together fatal and aborted SCD constitute 14% of the presenting manifestations of CS. Nearly two-thirds of all fatalities from CS are caused by undiagnosed granulomas in the heart.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Eur Heart J: 30 Sep 2019; 40:3121-3128
Ekström K, Lehtonen J, Nordenswan HK, Mäyränpää MI, ... Kerola T, Kupari M
Eur Heart J: 30 Sep 2019; 40:3121-3128 | PMID: 31230070
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Impact:
Abstract

Genetic Risk of Arrhythmic Phenotypes in Patients With Dilated Cardiomyopathy.

Gigli M, Merlo M, Graw SL, Barbati G, ... Sinagra G, Mestroni L
Background
Genotype-phenotype correlations in dilated cardiomyopathy (DCM) and, in particular, the effects of gene variants on clinical outcomes remain poorly understood.
Objectives
The purpose of this study was to investigate the prognostic role of genetic variant carrier status in a large cohort of DCM patients.
Methods
A total of 487 DCM patients were analyzed by next-generation sequencing and categorized the disease genes into functional gene groups. The following composite outcome measures were assessed: 1) all-cause mortality; 2) heart failure-related death, heart transplantation, or destination left ventricular assist device implantation (DHF/HTx/VAD); and 3) sudden cardiac death/sustained ventricular tachycardia/ventricular fibrillation (SCD/VT/VF).
Results
A total of 183 pathogenic/likely pathogenic variants were found in 178 patients (37%): 54 (11%) Titin; 19 (4%) Lamin A/C (LMNA); 24 (5%) structural cytoskeleton-Z disk genes; 16 (3.5%) desmosomal genes; 46 (9.5%) sarcomeric genes; 8 (1.6%) ion channel genes; and 11 (2.5%) other genes. All-cause mortality was no different between variant carriers and noncarriers (p = 0.99). A trend toward worse SCD/VT/VF (p = 0.062) and DHF/HTx/VAD (p = 0.061) was found in carriers. Carriers of desmosomal and LMNA variants experienced the highest rate of SCD/VT/VF, which was independent of the left ventricular ejection fraction.
Conclusions
Desmosomal and LMNA gene variants identify the subset of DCM patients who are at greatest risk for SCD and life-threatening ventricular arrhythmias, regardless of the left ventricular ejection fraction.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 17 Sep 2019; 74:1480-1490
Gigli M, Merlo M, Graw SL, Barbati G, ... Sinagra G, Mestroni L
J Am Coll Cardiol: 17 Sep 2019; 74:1480-1490 | PMID: 31514951
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Impact:
Abstract

Right Atrial Mechanisms of Atrial Fibrillation in a Rat Model of Right Heart Disease.

Hiram R, Naud P, Xiong F, Al-U\'datt D, ... Tardif JC, Nattel S
Background
Conditions affecting the right heart, including diseases of the lungs and pulmonary circulation, promote atrial fibrillation (AF), but the mechanisms are poorly understood.
Objectives
This study sought to determine whether right heart disease promotes atrial arrhythmogenesis in a rat model of pulmonary hypertension (PH) and, if so, to define the underlying mechanisms.
Methods
PH was induced in male Wistar rats with a single intraperitoneal injection of 60 mg/kg of monocrotaline, and rats were studied 21 days later when right heart disease was well developed. AF vulnerability was assessed in vivo and in situ, and mechanisms were defined by optical mapping, histochemistry, and biochemistry.
Results
Monocrotaline-treated rats developed increased right ventricular pressure and mass, along with right atrial (RA) enlargement. AF/flutter was inducible in 32 of 32 PH rats (100%) in vivo and 11 of 12 (92%) in situ, versus 2 of 32 (6%) and 2 of 12 (17%), respectively, in control rats (p < 0.001 vs. PH for each). PH rats had significant RA (16.1 ± 0.5% of cross-sectional area, vs. 3.0 ± 0.6% in control) and left atrial (LA: 11.8 ± 0.5% vs. 5.4 ± 0.8% control) fibrosis. Multiple extracellular matrix proteins, including collagen 1 and 3, fibronectin, and matrix metalloproteinases 2 and 9, were up-regulated in PH rat RA. Optical mapping revealed significant rate-dependent RA conduction slowing and rotor activity, including stable rotors in 4 of 11 PH rats, whereas no significant conduction slowing or rotor activity occurred in the LA of monocrotaline-treated rats. Transcriptomic analysis revealed differentially enriched genes related to hypertrophy, inflammation, and fibrosis in RA of monocrotaline-treated rats versus control. Biochemical results in PH rats were compared with those of AF-prone rats with atrial remodeling in the context of left ventricular dysfunction due to myocardial infarction: myocardial infarction rat LA shared molecular motifs with PH rat RA.
Conclusions
Right heart disease produces a substrate for AF maintenance due to RA re-entrant activity, with an underlying substrate prominently involving RA fibrosis and conduction abnormalities.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 10 Sep 2019; 74:1332-1347
Hiram R, Naud P, Xiong F, Al-U'datt D, ... Tardif JC, Nattel S
J Am Coll Cardiol: 10 Sep 2019; 74:1332-1347 | PMID: 31488271
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Impact:
Abstract

Cardiogenic Shock Classification to Predict Mortality in the Cardiac Intensive Care Unit.

Jentzer JC, van Diepen S, Barsness GW, Henry TD, ... Naidu SS, Baran DA
Background
A new 5-stage cardiogenic shock (CS) classification scheme was recently proposed by the Society for Cardiovascular Angiography and Intervention (SCAI) for the purpose of risk stratification.
Objectives
This study sought to apply the SCAI shock classification in a cardiac intensive care unit (CICU) population.
Methods
The study retrospectively analyzed Mayo Clinic CICU patients admitted between 2007 and 2015. SCAI CS stages A through E were classified retrospectively using CICU admission data based on the presence of hypotension or tachycardia, hypoperfusion, deterioration, and refractory shock. Hospital mortality in each SCAI shock stage was stratified by cardiac arrest (CA).
Results
Among the 10,004 unique patients, 43.1% had acute coronary syndrome, 46.1% had heart failure, and 12.1% had CA. The proportion of patients in SCAI CS stages A through E was 46.0%, 30.0%, 15.7%, 7.3%, and 1.0% and unadjusted hospital mortality in these stages was 3.0%, 7.1%, 12.4%, 40.4%, and 67.0% (p < 0.001), respectively. After multivariable adjustment, each higher SCAI shock stage was associated with increased hospital mortality (adjusted odds ratio: 1.53 to 6.80; all p < 0.001) compared with SCAI shock stage A, as was CA (adjusted odds ratio: 3.99; 95% confidence interval: 3.27 to 4.86; p < 0.001). Results were consistent in the subset of patients with acute coronary syndrome or heart failure.
Conclusions
When assessed at the time of CICU admission, the SCAI CS classification, including presence or absence of CA, provided robust hospital mortality risk stratification. This classification system could be implemented as a clinical and research tool to identify, communicate, and predict the risk of death in patients with, and at risk for, CS.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 17 Sep 2019; epub ahead of print
Jentzer JC, van Diepen S, Barsness GW, Henry TD, ... Naidu SS, Baran DA
J Am Coll Cardiol: 17 Sep 2019; epub ahead of print | PMID: 31548097
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Impact:
Abstract

Nurse-led vs. usual-care for atrial fibrillation.

Wijtvliet EPJP, Tieleman RG, van Gelder IC, Pluymaekers NAHA, ... Tijssen JG, Crijns HJGM
Background
Nurse-led integrated care is expected to improve outcome of patients with atrial fibrillation compared with usual-care provided by a medical specialist.
Methods and results
We randomized 1375 patients with atrial fibrillation (64 ± 10 years, 44% women, 57% had CHA2DS2-VASc ≥ 2) to receive nurse-led care or usual-care. Nurse-led care was provided by specialized nurses using a decision-support tool, in consultation with the cardiologist. The primary endpoint was a composite of cardiovascular death and cardiovascular hospital admissions. Of 671 nurse-led care patients, 543 (81%) received anticoagulation in full accordance with the guidelines against 559 of 683 (82%) usual-care patients. The cumulative adherence to guidelines-based recommendations was 61% under nurse-led care and 26% under usual-care. Over 37 months of follow-up, the primary endpoint occurred in 164 of 671 patients (9.7% per year) under nurse-led care and in 192 of 683 patients (11.6% per year) under usual-care [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.69 to 1.04, P = 0.12]. There were 124 vs. 161 hospitalizations for arrhythmia events (7.0% and 9.4% per year), and 14 vs. 22 for heart failure (0.7% and 1.1% per year), respectively. Results were not consistent in a pre-specified subgroup analysis by centre experience, with a HR of 0.52 (95% CI 0.37-to 0.71) in four experienced centres and of 1.24 (95% CI 0.94-1.63) in four less experienced centres (P for interaction <0.001).
Conclusion
Our trial failed to show that nurse-led care was superior to usual-care. The data suggest that nurse-led care by an experienced team could be clinically beneficial (ClinicalTrials.gov NCT01740037).
Trial registration number
ClinicalTrials.gov (NCT01740037).

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 22 Sep 2019; epub ahead of print
Wijtvliet EPJP, Tieleman RG, van Gelder IC, Pluymaekers NAHA, ... Tijssen JG, Crijns HJGM
Eur Heart J: 22 Sep 2019; epub ahead of print | PMID: 31544925
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Impact:
Abstract

Atrial Fibrillation and Diabetes Mellitus: JACC Review Topic of the Week.

Wang A, Green JB, Halperin JL, Piccini JP

Diabetes mellitus is one of the most common chronic medical conditions, and is a risk factor for the development of atrial fibrillation (AF). The presence of diabetes in patients with AF is associated with increased symptom burden and increased cardiovascular and cerebrovascular mortality. The pathophysiology of diabetes-related AF is not fully understood, but is related to structural, electrical, electromechanical, and autonomic remodeling. This paper reviews the complex interaction between diabetes and AF, and explores its effect on the prevention and treatment of AF.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 27 Aug 2019; 74:1107-1115
Wang A, Green JB, Halperin JL, Piccini JP
J Am Coll Cardiol: 27 Aug 2019; 74:1107-1115 | PMID: 31439220
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Abstract

Anticoagulation After Surgical or Transcatheter Bioprosthetic Aortic Valve Replacement.

Chakravarty T, Patel A, Kapadia S, Raschpichler M, ... Leon MB, Makkar RR
Background
There is paucity of evidence on the impact of anticoagulation (AC) after bioprosthetic aortic valve replacement (AVR) on valve hemodynamics and clinical outcomes.
Objectives
The study aimed to assess the impact of AC after bioprosthetic AVR on valve hemodynamics and clinical outcomes.
Methods
Data on antiplatelet and antithrombotic therapy were collected. Echocardiograms were performed at 30 days and 1 year post-AVR. Linear regression model and propensity-score adjusted cox proportional model were used to assess the impact of AC on valve hemodynamics and clinical outcomes, respectively.
Results
A total of 4,832 patients undergoing bioprosthetic AVR (transcatheter aortic valve replacement [TAVR], n = 3,889 and surgical AVR [SAVR], n = 943) in the pooled cohort of PARTNER2 (Placement of Aortic Transcatheter Valves) randomized trials and nonrandomized registries were studied. Following adjustment for valve size, annular diameter, atrial fibrillation, and ejection fraction at the time of assessment of hemodynamics, there was no significant difference in aortic valve mean gradients or aortic valve areas between patients discharged on AC vs. those not discharged on AC, for either TAVR or SAVR cohorts. A significantly greater proportion of patients not discharged on AC had an increase in mean gradient >10 mm Hg from 30 days to 1 year, compared with those discharged on AC (2.3% vs. 1.1%, p = 0.03). There was no independent association between AC after TAVR and adverse outcomes (death, p = 0.15; rehospitalization, p = 0.16), whereas AC after SAVR was associated with significantly fewer strokes (hazard ratio [HR]: 0.17; 95% confidence interval [CI]: 0.05-0.60; p = 0.006).
Conclusions
In the short term, early AC after bioprosthetic AVR did not result in adverse clinical events, did not significantly affect aortic valve hemodynamics (aortic valve gradients or area), and was associated with decreased rates of stroke after SAVR (but not after TAVR). Whether early AC after bioprosthetic AVR has impact on long-term outcomes remains to be determined. (Placement of AoRTic TraNscathetER Valves [PARTNERII A]; NCT01314313).

Copyright © 2019. Published by Elsevier Inc.

J Am Coll Cardiol: 03 Sep 2019; 74:1190-1200
Chakravarty T, Patel A, Kapadia S, Raschpichler M, ... Leon MB, Makkar RR
J Am Coll Cardiol: 03 Sep 2019; 74:1190-1200 | PMID: 31466616
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Abstract

Management of Conduction Disturbances Associated With Transcatheter Aortic Valve Replacement: JACC Scientific Expert Panel.

Rodés-Cabau J, Ellenbogen KA, Krahn AD, Latib A, ... Windecker S, Philippon F

Despite major improvements in transcatheter aortic valve replacement (TAVR) periprocedural complications in recent years, the occurrence of conduction disturbances has not decreased over time and remains the most frequent complication of the procedure. Additionally, there has been an important lack of consensus on the management of these complications, which has indeed translated into a high degree of uncertainty regarding the most appropriate treatment of a large proportion of such patients along with major differences between centers and studies in pacemaker rates post-TAVR. There is therefore an urgent need for a uniform strategy regarding the management of conduction disturbances after TAVR. The present expert consensus scientific panel document has been formulated by a multidisciplinary group of interventional cardiologists, electrophysiologists, and cardiac surgeons as an initial attempt to provide a guide for the management of conduction disturbances after TAVR based on the best available data and group expertise.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 27 Aug 2019; 74:1086-1106
Rodés-Cabau J, Ellenbogen KA, Krahn AD, Latib A, ... Windecker S, Philippon F
J Am Coll Cardiol: 27 Aug 2019; 74:1086-1106 | PMID: 31439219
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Impact:
Abstract

Quality of life predicting long-term outcomes in cardiac resynchronization therapy patients.

Nagy KV, Merkely B, Rosero S, Geller L, ... Zareba W, Kutyifa V
Aims
While improvement in quality of life (QoL) has been widely reported in cardiac resynchronization therapy (CRT) patients, its predictive value is not well-understood. We aimed to assess the predictive role of baseline QoL on long-term heart failure (HF) or death events in mild HF patients enrolled in Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT).
Methods and results
A total of 1791 of 1820 patients had their QoL evaluated at baseline, using the EuroQol-5 dimensions (EQ-5D) and the Kansas City Cardiomyopathy Questionnaires (KCCQ). Kaplan-Meier survival analyses and multivariate Cox models were utilized. Issues within any of the domains of the baseline EQ-5D questionnaire (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) were associated with long-term mortality (median follow-up 5.6 years) (all P < 0.05). Heart failure or death events were predicted by issues in baseline mobility [hazard ratio (HR) = 1.41, P < 0.001], usual activities (HR = 1.41, P < 0.001), and anxiety/depression (HR = 1.21, P = 0.035). The risk of HF events alone was significantly higher in patients with baseline mobility issues (HR = 1.42, P < 0.001) or usual activity (HR = 1.35, P = 0.003). Every 10% increase in the visual analogue scale (0-100) was associated with an 8% lower risk of all-cause mortality (P = 0.006), and a 6% lower risk of HF/death (P = 0.002). Mobility issues also predicted echocardiographic reverse remodelling (-33.08 mL vs. -31.17 mL, P = 0.043). Using the KCCQ, patients in the lower tertile of the clinical summary or physical limitations score had a significantly higher risk of long-term HF or death (P < 0.05).
Conclusion
In mild HF patients enrolled in MADIT-CRT, multiple baseline QoL questionnaire domains were predictors of echocardiographic remodelling, long-term all-cause mortality, and HF events.

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 15 Oct 2019; epub ahead of print
Nagy KV, Merkely B, Rosero S, Geller L, ... Zareba W, Kutyifa V
Europace: 15 Oct 2019; epub ahead of print | PMID: 31617896
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Impact:
Abstract

Long-Term Results of Mitral Valve Repair for Regurgitation Due to Leaflet Prolapse.

David TE, David CM, Tsang W, Lafreniere-Roula M, Manlhiot C
Background
Mitral valve (MV) repair has become the standard therapy for mitral regurgitation (MR) due to degenerative diseases, but information on late outcomes is limited.
Objectives
The purpose of this study was to examine the late results of MV repair for MR in a large cohort of patients.
Methods
A total of 1,234 consecutive patients (median age 59 years; 70.4% men) had MV repair for MR due to leaflet prolapse and were followed prospectively for a median of 13 years (interquartile range: 8 to 34 years) with periodical echocardiographic studies. There were 163 patients still at risk at 20 years. Cumulative incidences of adverse events and associated factors were examined with death as a competing outcome.
Results
At 20 years, reoperation-free survival was 60.4% (95% confidence interval: 56.2% to 64.2%) and the cumulative incidence of cardiac and valve-related deaths was 12%, noncardiac deaths 21.3%, reoperation on the MV 4.6%, infective endocarditis 1.1%, thromboembolism 10.3%, and bleeding 6.4%. The probability of recurrent moderate or severe MR was 12.5%, persistent or new moderate or severe tricuspid regurgitation (TR) 20.8%, and new atrial fibrillation (AF) 32.4%. Multivariable analysis identified older age, complete heart block, MV repair without annuloplasty ring, and the degree of myxomatous degeneration of the MV to be associated with recurrent MR. The development of AF and TR was unrelated to recurrent MR.
Conclusions
MV reoperation was uncommon after MV repair, but there was an increasing incidence of recurrent MR, TR, and new AF over time.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 27 Aug 2019; 74:1044-1053
David TE, David CM, Tsang W, Lafreniere-Roula M, Manlhiot C
J Am Coll Cardiol: 27 Aug 2019; 74:1044-1053 | PMID: 31439213
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Abstract

Thromboembolic events around the time of cardioversion for atrial fibrillation in patients receiving antiplatelet treatment in the ACTIVE trials.

McIntyre WF, Connolly SJ, Wang J, Masiero S, ... Beresh H, Healey JS
Aims
It is unknown whether cardioversion of atrial fibrillation causes thromboembolic events or is a risk marker. To assess causality, we examined the temporal pattern of thromboembolism in patients having cardioversion.
Methods and results
We studied patients randomized to aspirin or aspirin plus clopidogrel in the ACTIVE trials, comparing the thromboembolic rate in the peri-cardioversion period (30 days before until 30 days after) to the rate during follow-up, remote from cardioversion. Among 962 patients, the 30-day thromboembolic rate remote from cardioversion was 0.16%; while it was 0.73% in the peri-cardioversion period [hazard ratio (HR) 4.1, 95% confidence interval (CI) 2.1-7.9]. The 30-day thromboembolic rates in the periods immediately before and after cardioversion were 0.47% and 0.96%, respectively (HR 2.2, 95% CI 0.7-7.1). Heart failure (HF) hospitalization increased in the peri-cardioversion period (HR 11.5, 95% CI 6.8-19.4). Compared to baseline, the thromboembolic rate in the 30 days following cardioversion was increased both in patients who received oral anticoagulation or a transoesophageal echocardiogram prior to cardioversion (HR 7.9, 95% CI 2.8-22.4) and in those who did not (HR 4.8, 95% CI 1.6-14.9) (interaction P = 0.2); the risk was also increased with successful (HR 4.5; 95% CI 2.0-10.5) and unsuccessful (HR 10.2; 95% CI 2.3-44.9) cardioversion.
Conclusions
Thromboembolic risk increased in the 30 days before cardioversion and persisted until 30 days post-cardioversion, in a pattern similar to HF hospitalization. These data suggest that the increased thromboembolic risk around the time of cardioversion may not be entirely causal, but confounded by the overall clinical deterioration of patients requiring cardioversion.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Eur Heart J: 20 Sep 2019; 40:3026-3032
McIntyre WF, Connolly SJ, Wang J, Masiero S, ... Beresh H, Healey JS
Eur Heart J: 20 Sep 2019; 40:3026-3032 | PMID: 31377776
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Impact:
Abstract

Thromboembolic Risk After Atriopulmonary, Lateral Tunnel, and Extracardiac Conduit Fontan Surgery.

Deshaies C, Hamilton RM, Shohoudi A, Trottier H, ... Khairy P,
Background
Thromboembolic events contribute greatly to morbidity and mortality following Fontan surgery for univentricular hearts.
Objectives
This study sought to evaluate the effect of type of Fontan surgery on thromboembolic risk.
Methods
A North American multicenter retrospective cohort study enrolled 522 patients with Fontan palliation consisting of an atriopulmonary connection (APC) (21.4%), lateral tunnel (LT) (41.8%), or extracardiac conduit (EC) (36.8%). Thromboembolic complications and new-onset atrial arrhythmia were reviewed and classified by a blinded adjudicating committee. Thromboembolic risk across surgical techniques was assessed by multivariable competing-risk survival regression.
Results
Over a median follow-up of 11.6 years, 10- and 20-year freedom from Fontan conversion, transplantation, or death was 94.7% and 78.9%, respectively. New-onset atrial arrhythmias occurred in 4.4, 1.2, and 1.0 cases per 100 person-years with APC, LT, and EC, respectively. APC was associated with a 2.82-fold higher risk of developing atrial arrhythmias (p < 0.001), with no difference between LT and EC (p = 0.95). A total of 71 thromboembolic events, 32 systemic and 39 venous, occurred in 12.8% of subjects, for an overall incidence of 1.1%/year. In multivariable analyses, EC was independently associated with a lower risk of systemic (hazard ratio [HR]: 0.20 vs. LT; 95% confidence interval [CI]: 0.04 to 0.97) and combined (HR: 0.34 vs. LT; 95% CI: 0.13 to 0.91) thromboembolic events. A lower incidence of combined thromboembolic events was also observed with antiplatelet agents (HR: 0.54; 95% CI: 0.32 to 0.92) but not anticoagulation (p = 0.53).
Conclusions
The EC Fontan was independently associated with a lower thromboembolic risk after controlling for time-varying effects of atrial arrhythmias and thromboprophylaxis.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 27 Aug 2019; 74:1071-1081
Deshaies C, Hamilton RM, Shohoudi A, Trottier H, ... Khairy P,
J Am Coll Cardiol: 27 Aug 2019; 74:1071-1081 | PMID: 31439217
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Impact:
Abstract

Implantable cardioverter-defibrillators in previously undiagnosed patients with catecholaminergic polymorphic ventricular tachycardia resuscitated from sudden cardiac arrest.

van der Werf C, Lieve KV, Bos JM, Lane CM, ... Ackerman MJ, Wilde AA
Aims
In patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), implantable cardioverter-defibrillator (ICD) shocks are sometimes ineffective and may even trigger fatal electrical storms. We assessed the efficacy and complications of ICDs placed in patients with CPVT who presented with a sentinel event of sudden cardiac arrest (SCA) while undiagnosed and therefore untreated.
Methods and results
We analysed 136 patients who presented with SCA and in whom CPVT was diagnosed subsequently, leading to the initiation of guideline-directed therapy, including β-blockers, flecainide, and/or left cardiac sympathetic denervation. An ICD was implanted in 79 patients (58.1%). The primary outcome of the study was sudden cardiac death (SCD). The secondary outcomes were composite outcomes of SCD, SCA, appropriate ICD shocks, and syncope. After a median follow-up of 4.8 years, SCD had occurred in three patients (3.8%) with an ICD and none of the patients without an ICD (P = 0.1). SCD, SCA, or appropriate ICD shocks occurred in 37 patients (46.8%) with an ICD and 9 patients (15.8%) without an ICD (P < 0.0001). Inappropriate ICD shocks occurred in 19 patients (24.7%) and other device-related complications in 22 patients (28.9%).
Conclusion
In previously undiagnosed patients with CPVT who presented with SCA, an ICD was not associated with improved survival. Instead, the ICD was associated with both a high rate of appropriate ICD shocks and inappropriate ICD shocks along with other device-related complications. Strict adherence to guideline-directed therapy without an ICD may provide adequate protection in these patients without all the potential disadvantages of an ICD.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Eur Heart J: 13 Sep 2019; 40:2953-2961
van der Werf C, Lieve KV, Bos JM, Lane CM, ... Ackerman MJ, Wilde AA
Eur Heart J: 13 Sep 2019; 40:2953-2961 | PMID: 31145795
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Impact:
Abstract

Stroke Risk in Patients With Atrial Fibrillation Undergoing Electrical Isolation of the Left Atrial Appendage.

Di Biase L, Mohanty S, Trivedi C, Romero J, ... Sanchez JE, Natale A
Background
Loss of contractility leading to stasis of blood flow following left atrial appendage electrical isolation (LAAEI) could lead to thrombus formation.
Objectives
This study evaluated the incidence of thromboembolic events (TE) in post-LAAEI cases \"on\" and \"off\" oral anticoagulation (OAC).
Methods
A total of 1,854 consecutive post-LAAEI patients with follow-up transesophageal echocardiography (TEE) performed in sinus rhythm at 6 months to assess left atrial appendage (LAA) function were included in this analysis.
Results
The TEE at 6 months revealed preserved LAA velocity, contractility, and consistent A waves in 336 (18%) and abnormal parameters in the remaining 1,518 patients. In the post-ablation period, all 336 patients with preserved LAA function were off OAC. At long-term follow-up, patients with normal LAA function did not experience any stroke events. Of the 1,518 patients with abnormal LAA contractility, 1,086 remained on OAC, and the incidence of stroke/transient ischemic attack (TIA) in this population was 18 of 1,086 (1.7%), whereas the number of TE events in the off-OAC patients (n = 432) was 72 (16.7%); p < 0.001. Of the 90 patients with stroke, 84 received left atrial appendage occlusion (LAAO) devices. At median 12.4 months (interquartile range: 9.8 to 15.3 months) of device implantation, 2 (2.4%) patients were on OAC because of high stroke risk or personal preference, whereas 81 patients discontinued OAC after LAAO device implantation without any TE events.
Conclusions
LAAEI is associated with a significant risk of stroke that can be effectively reduced by optimal uninterrupted OAC or LAAO devices.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 27 Aug 2019; 74:1019-1028
Di Biase L, Mohanty S, Trivedi C, Romero J, ... Sanchez JE, Natale A
J Am Coll Cardiol: 27 Aug 2019; 74:1019-1028 | PMID: 31439209
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Impact:
Abstract

How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

Pieske B, Tschöpe C, de Boer RA, Fraser AG, ... Seferovic P, Filippatos G

Making a firm diagnosis of chronic heart failure with preserved ejection fraction (HFpEF) remains a challenge. We recommend a new stepwise diagnostic process, the \'HFA-PEFF diagnostic algorithm\'. Step 1 (P=Pre-test assessment) is typically performed in the ambulatory setting and includes assessment for HF symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes mellitus, elderly, atrial fibrillation), and diagnostic laboratory tests, electrocardiogram, and echocardiography. In the absence of overt non-cardiac causes of breathlessness, HFpEF can be suspected if there is a normal left ventricular ejection fraction, no significant heart valve disease or cardiac ischaemia, and at least one typical risk factor. Elevated natriuretic peptides support, but normal levels do not exclude a diagnosis of HFpEF. The second step (E: Echocardiography and Natriuretic Peptide Score) requires comprehensive echocardiography and is typically performed by a cardiologist. Measures include mitral annular early diastolic velocity (e\'), left ventricular (LV) filling pressure estimated using E/e\', left atrial volume index, LV mass index, LV relative wall thickness, tricuspid regurgitation velocity, LV global longitudinal systolic strain, and serum natriuretic peptide levels. Major (2 points) and Minor (1 point) criteria were defined from these measures. A score ≥5 points implies definite HFpEF; ≤1 point makes HFpEF unlikely. An intermediate score (2-4 points) implies diagnostic uncertainty, in which case Step 3 (F1: Functional testing) is recommended with echocardiographic or invasive haemodynamic exercise stress tests. Step 4 (F2: Final aetiology) is recommended to establish a possible specific cause of HFpEF or alternative explanations. Further research is needed for a better classification of HFpEF.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Eur Heart J: 30 Aug 2019; epub ahead of print
Pieske B, Tschöpe C, de Boer RA, Fraser AG, ... Seferovic P, Filippatos G
Eur Heart J: 30 Aug 2019; epub ahead of print | PMID: 31504452
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Impact:
Abstract

Long-term outcomes of chronic coronary syndrome worldwide: insights from the international CLARIFY registry.

Sorbets E, Fox KM, Elbez Y, Danchin N, ... Vidal-Petiot E, Steg PG
Aims
Over the last decades, the profile of chronic coronary syndrome has changed substantially. We aimed to determine characteristics and management of patients with chronic coronary syndrome in the contemporary era, as well as outcomes and their determinants.
Methods and results
Data from 32 703 patients (45 countries) with chronic coronary syndrome enrolled in the prospective observational CLARIFY registry (November 2009 to June 2010) with a 5-year follow-up, were analysed. The primary outcome [cardiovascular death or non-fatal myocardial infarction (MI)] 5-year rate was 8.0% [95% confidence interval (CI) 7.7-8.3] overall [male 8.1% (7.8-8.5); female 7.6% (7.0-8.3)]. A cox proportional hazards model showed that the main independent predictors of the primary outcome were prior hospitalization for heart failure, current smoking, atrial fibrillation, living in Central/South America, prior MI, prior stroke, diabetes, current angina, and peripheral artery disease. There was an interaction between angina and prior MI (P = 0.0016); among patients with prior MI, angina was associated with a higher primary event rate [11.8% (95% CI 10.9-12.9) vs. 8.2% (95% CI 7.8-8.7) in patients with no angina, P < 0.001], whereas among patients without prior MI, event rates were similar for patients with [6.3% (95% CI 5.4-7.3)] or without angina [6.4% (95% CI 5.9-7.0)], P > 0.99. Prescription rates of evidence-based secondary prevention therapies were high.
Conclusion
This description of the spectrum of chronic coronary syndrome patients shows that, despite high rates of prescription of evidence-based therapies, patients with both angina and prior MI are an easily identifiable high-risk group who may deserve intensive treatment.
Clinical registry
ISRCTN43070564.

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 02 Sep 2019; epub ahead of print
Sorbets E, Fox KM, Elbez Y, Danchin N, ... Vidal-Petiot E, Steg PG
Eur Heart J: 02 Sep 2019; epub ahead of print | PMID: 31504434
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Impact:
Abstract

Calmodulin mutations and life-threatening cardiac arrhythmias: insights from the International Calmodulinopathy Registry.

Crotti L, Spazzolini C, Tester DJ, Ghidoni A, ... Ackerman MJ, Schwartz PJ
Aims
Calmodulinopathies are rare life-threatening arrhythmia syndromes which affect mostly young individuals and are, caused by mutations in any of the three genes (CALM 1-3) that encode identical calmodulin proteins. We established the International Calmodulinopathy Registry (ICalmR) to understand the natural history, clinical features, and response to therapy of patients with a CALM-mediated arrhythmia syndrome.
Methods and results
A dedicated Case Report File was created to collect demographic, clinical, and genetic information. ICalmR has enrolled 74 subjects, with a variant in the CALM1 (n = 36), CALM2 (n = 23), or CALM3 (n = 15) genes. Sixty-four (86.5%) were symptomatic and the 10-year cumulative mortality was 27%. The two prevalent phenotypes are long QT syndrome (LQTS; CALM-LQTS, n = 36, 49%) and catecholaminergic polymorphic ventricular tachycardia (CPVT; CALM-CPVT, n = 21, 28%). CALM-LQTS patients have extremely prolonged QTc intervals (594 ± 73 ms), high prevalence (78%) of life-threatening arrhythmias with median age at onset of 1.5 years [interquartile range (IQR) 0.1-5.5 years] and poor response to therapies. Most electrocardiograms (ECGs) show late onset peaked T waves. All CALM-CPVT patients were symptomatic with median age of onset of 6.0 years (IQR 3.0-8.5 years). Basal ECG frequently shows prominent U waves. Other CALM-related phenotypes are idiopathic ventricular fibrillation (IVF, n = 7), sudden unexplained death (SUD, n = 4), overlapping features of CPVT/LQTS (n = 3), and predominant neurological phenotype (n = 1). Cardiac structural abnormalities and neurological features were present in 18 and 13 patients, respectively.
Conclusion
Calmodulinopathies are largely characterized by adrenergically-induced life-threatening arrhythmias. Available therapies are disquietingly insufficient, especially in CALM-LQTS. Combination therapy with drugs, sympathectomy, and devices should be considered.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Eur Heart J: 13 Sep 2019; 40:2964-2975
Crotti L, Spazzolini C, Tester DJ, Ghidoni A, ... Ackerman MJ, Schwartz PJ
Eur Heart J: 13 Sep 2019; 40:2964-2975 | PMID: 31170290
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Impact:
Abstract

Weight and weight change and risk of atrial fibrillation: the HUNT study.

Feng T, Vegard M, Strand LB, Laugsand LE, ... Mukamal K, Janszky I
Aims
Although obesity has been associated with risk of atrial fibrillation (AF), the associations of long-term obesity, recent obesity, and weight change with AF risk throughout adulthood are uncertain.
Methods and results
An ambispective cohort study was conducted which included 15 214 individuals. The cohort was created from 2006 to 2008 (the baseline) and was followed for incident AF until 2015. Weight and height were directly measured at baseline. Data on previous weight and height were retrieved retrospectively from measurements conducted 10, 20, and 40 years prior to baseline. Average body mass index (BMI) over time and weight change was calculated. During follow-up, 1149 participants developed AF. The multivariable-adjusted hazard ratios were 1.2 (95% confidence interval 1.0-1.4) for average BMI 25.0-29.9 kg/m2 and 1.6 (1.2-2.0) for average BMI ≥30 kg/m2 when compared with normal weight. The association of average BMI with AF risk was only slightly attenuated after adjustment for most recent BMI. In contrast, current BMI was not strongly associated with the risk of AF after adjustment for average BMI earlier in life. Compared with stable BMI, both loss and gain in BMI were associated with increased AF risk. After adjustment for most recent BMI, the association of BMI gain with AF risk was largely unchanged, while the association of BMI loss with AF risk was weakened.
Conclusion
Long-term obesity and BMI change are associated with AF risk. Obesity earlier in life and weight gain over time exert cumulative effects on AF development even after accounting for most recent BMI.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Eur Heart J: 06 Sep 2019; 40:2859-2866
Feng T, Vegard M, Strand LB, Laugsand LE, ... Mukamal K, Janszky I
Eur Heart J: 06 Sep 2019; 40:2859-2866 | PMID: 31209455
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Impact:
Abstract

Maximum-fixed energy shocks for cardioverting atrial fibrillation.

Schmidt AS, Lauridsen KG, Torp P, Bach LF, Rickers H, Løfgren B
Aims
Direct-current cardioversion is one of the most commonly performed procedures in cardiology. Low-escalating energy shocks are common practice but the optimal energy selection is unknown. We compared maximum-fixed and low-escalating energy shocks for cardioverting atrial fibrillation.
Methods and results
In a single-centre, single-blinded, randomized trial, we allocated elective atrial fibrillation patients to cardioversion using maximum-fixed (360-360-360 J) or low-escalating (125-150-200 J) biphasic truncated exponential shocks. The primary endpoint was sinus rhythm 1 min after cardioversion. Safety endpoints were any arrhythmia, myocardial injury, skin burns, and patient-reported pain after cardioversion. We randomized 276 patients, and baseline characteristics were well-balanced between groups (mean ± standard deviation age: 68 ± 9 years, male: 72%, atrial fibrillation duration >1 year: 30%). Sinus rhythm 1 min after cardioversion was achieved in 114 of 129 patients (88%) in the maximum-fixed energy group, and in 97 of 147 patients (66%) in the low-escalating energy group (between-group difference; 22 percentage points, 95% confidence interval 13-32, P < 0.001). Sinus rhythm after first shock occurred in 97 of 129 patients (75%) in the maximum-fixed energy group compared to 50 of 147 patients (34%) in the low-escalating energy group (between-group difference; 41 percentage points, 95% confidence interval 30-51). There was no significant difference between groups in any safety endpoint.
Conclusion
Maximum-fixed energy shocks were more effective compared with low-escalating energy shocks for cardioverting atrial fibrillation. We found no difference in any safety endpoint.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Eur Heart J: 30 Aug 2019; epub ahead of print
Schmidt AS, Lauridsen KG, Torp P, Bach LF, Rickers H, Løfgren B
Eur Heart J: 30 Aug 2019; epub ahead of print | PMID: 31504412
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Impact:
Abstract

Incidence of heart failure after pacemaker implantation: a nationwide Danish Registry-based follow-up study.

Tayal B, Fruelund P, Sogaard P, Riahi S, ... Kober L, Kragholm KH
Aims
The objective of the current study is to investigate the risk of heart failure (HF) after implantation of a pacemaker (PM) with a right ventricular pacing (RVP) lead in comparison to a matched cohort without a PM and factors associated with this risk.
Methods and results
All patients without a known history of HF who had a PM implanted with an RVP lead between 2000 and 2014 (n = 27 704) were identified using Danish nationwide registries. An age- and gender-matched control cohort (matched 1:5, n = 138 520) without PM and HF was identified to compare the risk. Outcome was the cumulative incidence of HF including fatal HF within the first 2 years of PM implantation, with all-cause mortality and myocardial infarction (MI) as competing risks. Due to violation of proportional hazards, the follow-up period was divided into three time-intervals: <30 days, 30-180 days, and >180 days-2 years. The cumulative incidence of HF including fatal HF was observed in 2937 (10.6%) PM patients. Risks for the three time-intervals were <30 days [hazard ratio (HR) 5.98, 95% CI 5.19-6.90], 30-180 days (HR 1.84, 95% CI 1.71-1.98), and >180 days (HR 1.11, 95% CI 1.04-1.17). Among patients with a PM device, factors associated with increased risk of HF were male sex (HR 1.33, 95% CI 1.24-1.43), presence of chronic kidney disease (CKD) (HR 1.64, 95% CI 1.29-2.09), and prior MI (1.77, 95% 1.50-2.09).
Conclusions
Pacemaker with an RVP lead is strongly associated with risk of HF specifically within the first 6 months. Patients with antecedent history of MI and CKD had substantially increased risk.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Eur Heart J: 25 Aug 2019; epub ahead of print
Tayal B, Fruelund P, Sogaard P, Riahi S, ... Kober L, Kragholm KH
Eur Heart J: 25 Aug 2019; epub ahead of print | PMID: 31504437
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Impact:
Abstract

Comparison of Events Across Bleeding Scales in the ENGAGE AF-TIMI 48 Trial.

Bergmark BA, Kamphuisen PW, Wiviott SD, Ruff CT, ... Braunwald E, Giugliano RP

Numerous scales exist for classification of major bleeding events. There are limited data comparing the most commonly used bleeding scales within a single at-risk cohort of patients with atrial fibrillation (AF). Here we analyze bleeding outcomes according to the ISTH, TIMI, GUSTO, and BARC bleeding scales in the ENGAGE AF (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation)-TIMI 48 trial of edoxaban vs warfarin.21,105 patients with AF at risk for stroke (CHADS ≥2) were enrolled in the ENGAGE AF-TIMI 48 trial (NCT00781391) comparing warfarin to a higher (HDER; 60/30 mg daily) or lower (LDER; 30/15 mg daily) dose edoxaban regimen. Median follow-up was 2.8 years. Bleeding events occurring among on-treatment patients were examined. Annualized event rates were calculated by the ISTH, TIMI, GUSTO, and BARC scales and compared across treatment arms. Cox proportional hazards for a first bleeding event of each type were calculated for HDER vs warfarin and LDER vs warfarin.10,311 total bleeding events were reported. Comparing the most severe events in each scale, ISTH Major bleeding was the most common (n=1,289) followed by TIMI Major (n=548), GUSTO Severe/Life-Threatening (n=347), and BARC 3c+5 (n=276). Lower bleeding risk with edoxaban as compared with warfarin was seen regardless of bleeding scale (HDER range: HR 0.47 [0.35-0.62] for BARC 3c+5 to HR 0.80 [0.71-0.91] for ISTH Major; LDER range: HR 0.32 [0.23-0.45] for BARC 3c+5 to HR 0.47 [0.41-0.55] for ISTH Major). Further, a gradient of more pronounced risk reduction with edoxaban was observed for with greater severity of first bleeding event (HDER: HR 0.47 [0.35-0.62] for BARC 3c+5 bleeds vs HR 0.86 [0.81-0.91] for any BARC bleed; LDER: HR 0.32 [0.23-0.45] for BARC 3c+5 bleeds vs HR 0.68 [0.63-0.72] for any BARC bleed). The direction of this trend was consistent for both gastrointestinal and non-gastrointestinal bleeding.Among patients with AF at risk for stroke, there was an approximately four-fold difference in the frequency of the most severe bleeding events across commonly used bleeding scales. Further, the relative safety of edoxaban as compared with warfarin tended to increase with greater severity of bleeding.URL: https://clinicaltrials.gov Unique Identifier: NCT00781391.



Circulation: 09 Oct 2019; epub ahead of print
Bergmark BA, Kamphuisen PW, Wiviott SD, Ruff CT, ... Braunwald E, Giugliano RP
Circulation: 09 Oct 2019; epub ahead of print | PMID: 31597460
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Impact:
Abstract

Stroke Risk as a Function of Atrial Fibrillation Duration and CHADS-VASc Score.

Kaplan RM, Koehler J, Ziegler PD, Sarkar S, Zweibel S, Passman RS

Studies of patients with cardiovascular implantable electronic devices (CIED) show a relationship between atrial fibrillation (AF) duration and stroke risk, though the interaction with CHADS-VASc score is poorly defined. The objective of this study is to evaluate rates of stroke and systemic embolism (SSE) in CIED patients as a function of both CHADS-VASc score and AF duration.Data from the Optum electronic health record (EHR) de-identified database (2007-2017) were linked to the Medtronic CareLink database of CIEDs capable of continuous AF monitoring. An index date was assigned as the later of 6 months after device implant or 1 year after EHR data availability. CHADS-VASc score was assessed via EHR data prior to the index date. Maximum daily AF burden (No AF, 6 minutes-23.5 hours, and >23.5 hours) was assessed over the 6 months prior to index date. SSE rates were computed post-index date.Among 21,768 non-anticoagulated CIED patients (68.6±12.7 years, 63% male), increasing AF duration (p<0.001) and increasing CHADS-VASc score (p<0.001) were both significantly associated with annualized risk of SSE. SSE rates were low in CHADS-VASc 0-1 patients regardless of device-detected AF duration. However, stroke risk crossed an actionable threshold defined as >1%/year in CHADS-VASc 2 patients with >23.5 hours of AF, CHADS-VASc 3-4 patients with >6 minutes of AF, and in CHADS-VASc ≥5 patients even with no AF.There is an interaction between AF duration and CHADS-VASc score which can further risk stratify AF patients for SSE and may be useful in guiding anticoagulation therapy.



Circulation: 29 Sep 2019; epub ahead of print
Kaplan RM, Koehler J, Ziegler PD, Sarkar S, Zweibel S, Passman RS
Circulation: 29 Sep 2019; epub ahead of print | PMID: 31564126
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Impact:
Abstract

Transcatheter aortic valve replacement versus surgical aortic valve replacement in low-surgical-risk patients: An updated meta-analysis.

Goel S, Pasam RT, Wats K, Patel J, ... Shani J, Gidwani U
Objective
The purpose of this meta-analysis is to compare the safety and efficacy of transcatheter aortic-valve replacement (TAVR) to surgical aortic valve replacement (SAVR) in low-surgical-risk patients.
Background
TAVR is proven to be safe and effective in patients with high- and intermediate-risk aortic stenosis. However, there is limited data on the safety and efficacy of TAVR in patients with low surgical risk.
Methods
We conducted an electronic database search of all published data for studies that compared TAVR to SAVR in low-surgical-risk patients (mean society for thoracic surgery [STS] score <4% and/or logistic EuroScore <10%) and reported on subsequent all-cause mortality, cardiac mortality, stroke rates, and other outcomes of interest. Event rates were compared with a forest plot of odds ratio using a random-effects model assuming interstudy heterogeneity.
Results
A total of seven studies (n = 6,293 patients; TAVR = 2,912; and SAVR = 3,381) were included in the final analysis. There was no significant difference between TAVR and SAVR in terms of all-cause mortality (OR 0.82; 95% CI 0.50-1.36, I = 51%), cardiac mortality (OR 0.57; 95% CI 0.32-1.02, I = 0%), new pacemaker implantation (OR = 3.11; 95% CI 0.58-16.60, I = 89%), moderate/severe paravalvular leak (PVL; OR 3.50; 95% CI 0.64-19.10, I = 54%) and rate of stroke (OR 0.63; 95% CI 0.34-1.15, I = 39%) at 1-year follow-up. TAVR was found to have a significantly lower incidence of atrial fibrillation (AF; OR 0.15, 95% CI 0.10-0.24, I = 38%) as compared to SAVR.
Conclusion
The results of our meta-analysis demonstrate similar rates of all-cause mortality, cardiac mortality, and stroke at 1-year follow-up in patients undergoing TAVR and SAVR. TAVR is associated with a lower incidence of AF relative to SAVR. However, there was a significantly higher incidence of PVL with TAVR compared to SAVR.

© 2019 Wiley Periodicals, Inc.

Catheter Cardiovasc Interv: 20 Oct 2019; epub ahead of print
Goel S, Pasam RT, Wats K, Patel J, ... Shani J, Gidwani U
Catheter Cardiovasc Interv: 20 Oct 2019; epub ahead of print | PMID: 31631514
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Impact:
Abstract

Prediction of mortality benefit based on periodic repolarisation dynamics in patients undergoing prophylactic implantation of a defibrillator: a prospective, controlled, multicentre cohort study.

Bauer A, Klemm M, Rizas KD, Hamm W, ... Zabel M,
Background
A small proportion of patients undergoing primary prophylactic implantation of implantable cardioverter defibrillators (ICDs) experiences malignant arrhythmias. We postulated that periodic repolarisation dynamics, a novel marker of sympathetic-activity-associated repolarisation instability, could be used to identify electrically vulnerable patients who would benefit from prophylactic implantation of ICDs by way of a reduction in mortality.
Methods
We did a prespecified substudy of EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD), a prospective, investigator-initiated, non-randomised, controlled cohort study done at 44 centres in 15 EU countries. Patients aged 18 years or older with ischaemic or non-ischaemic cardiomyopathy and reduced left ventricular ejection fraction (≤35%) were eligible for inclusion if they met guideline-based criteria for primary prophylactic implantation of ICDs. Periodic repolarisation dynamics from 24-h Holter recordings were assessed blindly in patients the day before ICD implantation or on the day of study enrolment in patients who were conservatively managed. The primary endpoint was all-cause mortality. Propensity scoring and multivariable models were used to assess the interaction between periodic repolarisation dynamics and the treatment effect of ICDs on mortality.
Findings
Between May 12, 2014, and Sept 7, 2018, 1371 patients were enrolled in our study. 968 of these patients underwent ICD implantation, and 403 were treated conservatively. During follow-up (median 2·7 years [IQR 2·0-3·3] in the ICD group and 1·2 years [0·8-2·7] in the control group), 138 (14%) patients died in the ICD group and 64 (16%) patients died in the control group. We noted a 43% reduction in mortality in the ICD group compared with the control group (adjusted hazard ratio [HR] 0·57 [95% CI 0·41-0·79]; p=0·0008). Periodic repolarisation dynamics significantly predicted the treatment effect of ICDs on mortality (adjusted p=0·0307). The mortality benefits associated with ICD implantation were greater in patients with periodic repolarisation dynamics of 7·5 deg or higher (n=199; adjusted HR 0·25 [95% CI 0·13-0·47] for the ICD group vs the control group; p<0·0001) than in those with periodic repolarisation dynamics less than 7·5 deg (n=1166; adjusted HR 0·69 [95% CI 0·47-1·00]; p=0·0492; p=0·0056). The number needed to treat was 18·3 (95% CI 10·6-4895·3) in patients with periodic repolarisation dynamics less than 7·5 deg and 3·1 (2·6-4·8) in those with periodic repolarisation dynamics of 7·5 deg or higher.
Interpretation
Periodic repolarisation dynamics predict mortality reductions associated with prophylactic implantation of ICDs in contemporarily treated patients with ischaemic or non-ischaemic cardiomyopathy. Periodic repolarisation dynamics could help to guide treatment decisions about prophylactic ICD implantation.
Funding
The European Community\'s 7th Framework Programme.

Copyright © 2019 Elsevier Ltd. All rights reserved.

Lancet: 11 Oct 2019; 394:1344-1351
Bauer A, Klemm M, Rizas KD, Hamm W, ... Zabel M,
Lancet: 11 Oct 2019; 394:1344-1351 | PMID: 31488371
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Impact:
Abstract

Meta-Analysis Evaluating Outcomes of Surgical Left Atrial Appendage Occlusion During Cardiac Surgery.

Ibrahim AM, Tandan N, Koester C, Al-Akchar M, ... Maini R, Labedi M

Surgical left atrial appendage occlusion (S-LAAO) has become a common procedure performed in patients undergoing cardiac surgery; however, evidence to support this procedure remains inconclusive. This meta-analysis aims to assess the efficacy of S-LAAO in terms of ischemic stroke, postoperative atrial fibrillation, and all-cause mortality. A thorough literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We identified 10 relevant studies for our meta-analysis. It included 6,779 patients who underwent S-LAAO and 6,573 who did not undergo LAAO. In terms of ischemic stroke, the S-LAAO cohort had a lower events (pooled odds ratio [OR] 0.655 (0.518 to 0.829), p = 0.0004) compared with the non-LAAO cohort. S-LAAO cohort also had lower events of all-cause mortality (pooled OR 0.74 (95% confidence interval 0.55 to 0.99), p = 0.0408) when compared with the non-LAAO cohort. In regards to postoperative atrial fibrillation, there was no difference between the 2 groups (pooled OR 1.29 (95% confidence interval 0.81 to 2.06), p = 0.2752). In conclusion, S-LAAO was associated with lower events of ischemic stroke or systemic embolism and all-cause mortality when compared to the non-LAAO group.

Copyright © 2019 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Oct 2019; 124:1218-1225
Ibrahim AM, Tandan N, Koester C, Al-Akchar M, ... Maini R, Labedi M
Am J Cardiol: 14 Oct 2019; 124:1218-1225 | PMID: 31474327
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Impact:
Abstract

Edoxaban-based versus vitamin K antagonist-based antithrombotic regimen after successful coronary stenting in patients with atrial fibrillation (ENTRUST-AF PCI): a randomised, open-label, phase 3b trial.

Vranckx P, Valgimigli M, Eckardt L, Tijssen J, ... Zierhut W, Goette A
Background
We aimed to assess the safety of edoxaban in combination with P2Y12 inhibition in patients with atrial fibrillation who had percutaneous coronary intervention (PCI).
Methods
ENTRUST-AF PCI was a randomised, multicentre, open-label, non-inferiority phase 3b trial with masked outcome evaluation, done at 186 sites in 18 countries. Patients had atrial fibrillation requiring oral anticoagulation, were aged at least 18 years, and had a successful PCI for stable coronary artery disease or acute coronary syndrome. Participants were randomly assigned (1:1) from 4 h to 5 days after PCI using concealed, stratified, and blocked web-based central randomisation to either edoxaban (60 mg once daily) plus a P2Y12 inhibitor for 12 months or a vitamin K antagonist (VKA) in combination with a P2Y12 inhibitor and aspirin (100 mg once daily, for 1-12 months). The edoxaban dose was reduced to 30 mg per day if one or more factors (creatinine clearance 15-50 mL/min, bodyweight ≤60 kg, or concomitant use of specified potent P-glycoprotein inhibitors) were present. The primary endpoint was a composite of major or clinically relevant non-major (CRNM) bleeding within 12 months. The primary analysis was done in the intention-to-treat population and safety was assessed in all patients who received at least one dose of their assigned study drug. This trial is registered with ClinicalTrials.gov, NCT02866175, is closed to new participants, and follow-up is completed.
Findings
From Feb 24, 2017, through May 7, 2018, 1506 patients were enrolled and randomly assigned to the edoxaban regimen (n=751) or VKA regimen (n=755). Median time from PCI to randomisation was 45·1 h (IQR 22·2-76·2). Major or CRNM bleeding events occurred in 128 (17%) of 751 patients (annualised event rate 20·7%) with the edoxaban regimen and 152 (20%) of 755 patients (annualised event rate 25·6%) patients with the VKA regimen; hazard ratio 0·83 (95% CI 0·65-1·05; p=0·0010 for non-inferiority, margin hazard ratio 1·20; p=0·1154 for superiority).
Interpretation
In patients with atrial fibrillation who had PCI, the edoxaban-based regimen was non-inferior for bleeding compared with the VKA-based regimen, without significant differences in ischaemic events.
Funding
Daiichi Sankyo.

Copyright © 2019 Elsevier Ltd. All rights reserved.

Lancet: 11 Oct 2019; 394:1335-1343
Vranckx P, Valgimigli M, Eckardt L, Tijssen J, ... Zierhut W, Goette A
Lancet: 11 Oct 2019; 394:1335-1343 | PMID: 31492505
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Impact:
Abstract

Incident Atrial Fibrillation Among American Indians in California.

Sanchez JM, Jolly SE, Dewland TA, Tseng ZH, ... Vittinghoff E, Marcus GM

Members of the white race have consistently exhibited a higher prevalence and incidence of atrial fibrillation (AF). This observation has been referred to as the racial paradox, given that minorities often experience more traditional AF risk factors than whites. Although American Indians exhibit high rates of AF risk factors, they have not been included in previous research that has examined the relationship between race and incident AF. We used the Healthcare Cost and Utilization Project (HCUP) California State Databases to identify California residents ({greater than or equal to}18 years of age) who received care in an emergency department, inpatient hospital unit, or ambulatory surgery setting between January 1, 2005, and December 31, 2011. Patients entered the cohort at first healthcare encounter, were followed up prospectively, and were censored on diagnosis of AF, time of inpatient death, or end of the study period. Certification to use deidentified HCUP data was obtained from the University of California, San Francisco, Institutional Review Board.



Circulation: 20 Oct 2019; epub ahead of print
Sanchez JM, Jolly SE, Dewland TA, Tseng ZH, ... Vittinghoff E, Marcus GM
Circulation: 20 Oct 2019; epub ahead of print | PMID: 31630530
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Impact:
Abstract

The ADP/ATP translocase drives mitophagy independent of nucleotide exchange.

Hoshino A, Wang WJ, Wada S, McDermott-Roe C, ... Holzbaur ELF, Arany Z

Mitochondrial homeostasis vitally depends on mitophagy, the programmed degradation of mitochondria. The roster of proteins known to participate in mitophagy remains small. We devised here a multidimensional CRISPR/Cas9 genetic screen, using multiple mitophagy reporter systems and pro-mitophagy triggers, and uncover numerous new components of Parkin-dependent mitophagy. Unexpectedly, we identify the adenine nucleotide translocator (ANT) complex as required for mitophagy in multiple cell types. While pharmacological inhibition of ANT-mediated ADP/ATP exchange promotes mitophagy, genetic ablation of ANT paradoxically suppresses mitophagy. Importantly, ANT promotes mitophagy independently of its nucleotide translocase catalytic activity. Instead, the ANT complex is required for inhibition of the presequence translocase TIM23, leading to PINK1 stabilization, in response to bioenergetic collapse. ANT modulates TIM23 indirectly via interaction with TIM44, known to regulate peptide import through TIM23. Mice lacking ANT1 reveal blunted mitophagy and consequent profound accumulation of aberrant mitochondria. Disease-causing human mutations in ANT1 abrogate binding to TIM44 and TIM23 and inhibit mitophagy. Together, these data identify a novel and essential function for ANT as a fundamental mediator of mitophagy in health and disease.



Nature: 15 Oct 2019; epub ahead of print
Hoshino A, Wang WJ, Wada S, McDermott-Roe C, ... Holzbaur ELF, Arany Z
Nature: 15 Oct 2019; epub ahead of print | PMID: 31618756
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Impact:
Abstract

Antithrombotic Therapy in Patients with Atrial Fibrillation and Acute Coronary Syndrome Treated Medically or with Percutaneous Coronary Intervention or Undergoing Elective Percutaneous Coronary Intervention: Insights from the AUGUSTUS Trial.

Windecker S, Lopes RD, Massaro T, Jones-Burton C, ... Alexander JH,

The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation (AF) who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI.Using a 2×2 factorial design we compared apixaban with vitamin K antagonists (VKA) and aspirin with placebo in patients with AF who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death, and hospitalization as well as death and ischemic events by antithrombotic strategy in three pre-specified subgroups: patients with ACS treated medically, ACS treated with PCI, and those undergoing elective PCI.Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with VKA reduced ISTH major or CRNM bleeding in patients with ACS treated medically (HR 0.44, 95% CI 0.28-0.68), ACS treated with PCI (HR 0.68, 95% CI 0.52-0.89), and undergoing elective PCI (HR 0.82, 95% CI 0.64-1.04) (p=0.052); and reduced death or hospitalization in ACS treated medically (HR 0.71, 95% CI 0.54-0.92), ACS treated with PCI (HR 0.88, 95% CI 0.74-1.06), and elective PCI (HR 0.87, 95% CI 0.72-1.04) (p=0.345). Compared with VKA, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (p=0.356). Compared with placebo, aspirin had a higher rate of bleeding than placebo in patients with ACS treated medically (HR 1.49, 95% CI 0.98-2.26), ACS treated with PCI (HR 2.02, 95% CI 1.53-2.67) and elective PCI groups (HR 1.91, 95% CI 1.48-2.47) (p=0.479). For the same comparison, there was no difference in outcomes among the three groups for the composite of death or hospitalization (p=0.787) and death and ischemic events (p=0.710).An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with AF who have ACS, whether managed medically or with PCI, or those undergoing elective PCI than regimens that include VKAs, aspirin, or both.URL: https://clinicaltrials.gov Unique Identifier: NCT02415400.



Circulation: 25 Sep 2019; epub ahead of print
Windecker S, Lopes RD, Massaro T, Jones-Burton C, ... Alexander JH,
Circulation: 25 Sep 2019; epub ahead of print | PMID: 31557056
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Impact:
Abstract

Hospitalization among Patients with Atrial Fibrillation and a Recent Acute Coronary Syndrome or Percutaneous Coronary Intervention Treated with Apixaban or Aspirin: Insights from the AUGUSTUS Trial.

Vora AN, Alexander JH, Wojdyla D, Aronson R, ... Goodman SG, Lopes RD

The optimal antithrombotic therapy among patients with atrial fibrillation (AF) who present with acute coronary syndrome (ACS) or require percutaneous coronary intervention (PCI) can be challenging, with combination therapy including both dual antiplatelet therapy (DAPT) and oral anticoagulation (OAC) markedly increasing bleeding risk. Recent trials with rivaroxaban and dabigatran have demonstrated the safety of using a non-vitamin K oral anticoagulant (NOAC) with a P2Y12 inhibitor, without aspirin or with reduced-dose aspirin, after PCI. The AUGUSTUS study demonstrated that apixaban resulted in less bleeding than vitamin K antagonist (VKA), with lower rates of the composite of death or all-cause hospitalization. Rates of bleeding were higher among patients treated with aspirin than with placebo, but rates of death or all-cause hospitalization were not different. This analysis evaluated rates and causes ofhospitalization, a key secondary outcome, overall and by randomized treatment.



Circulation: 24 Sep 2019; epub ahead of print
Vora AN, Alexander JH, Wojdyla D, Aronson R, ... Goodman SG, Lopes RD
Circulation: 24 Sep 2019; epub ahead of print | PMID: 31553201
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Impact:
Abstract

Clinical characteristics and long-term clinical course of patients with Brugada syndrome without previous cardiac arrest: a multiparametric risk stratification approach.

Letsas KP, Bazoukis G, Efremidis M, Georgopoulos S, ... Stavrakis S, Sideris A
Aims
Risk stratification in Brugada syndrome (BrS) still represents an unsettled issue. In this multicentre study, we aimed to evaluate the clinical characteristics and the long-term clinical course of patients with BrS.
Methods and results
A total of 111 consecutive patients (86 males; aged 45.3 ± 13.3 years) diagnosed with BrS were included and followed-up in a prospective fashion. Thirty-seven patients (33.3%) were symptomatic at enrolment (arrhythmic syncope). An electrophysiological study (EPS) was performed in 59 patients (53.2%), and ventricular arrhythmias were induced in 32 (54.2%). A cardioverter defibrillator was implanted in 34 cases (30.6%). During a mean follow-up period of 4.6 ± 3.5 years, appropriate device therapies occurred in seven patients. Event-free survival analysis (log-rank test) showed that spontaneous type-1 electrocardiogram pattern (P = 0.008), symptoms at presentation (syncope) (P = 0.012), family history of sudden cardiac death (P < 0.001), positive EPS (P = 0.024), fragmented QRS (P = 0.004), and QRS duration in lead V2 > 113 ms (P < 0.001) are predictors of future arrhythmic events. Event rates were 0%, 4%, and 60% among patients with 0-1 risk factor, 2-3 risk factors, and 4-5 risk factors, respectively (P < 0.001). Current multiparametric score models exhibit an excellent negative predictive value and perform well in risk stratification of BrS patients.
Conclusions
Multiparametric models including common risk factors appear to provide better risk stratification of BrS patients than single factors alone.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Europace: 21 Oct 2019; epub ahead of print
Letsas KP, Bazoukis G, Efremidis M, Georgopoulos S, ... Stavrakis S, Sideris A
Europace: 21 Oct 2019; epub ahead of print | PMID: 31638693
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Impact:
Abstract

Transcatheter aspiration of large pacemaker and implantable cardioverter-defibrillator lead vegetations facilitating safe transvenous lead extraction.

Starck CT, Schaerf RHM, Breitenstein A, Najibi S, ... Dreizler T, Falk V
Aims
Treatment of patients with systemic cardiac implantable electronic device (CIED) infection with large lead vegetations is challenging and associated with relevant morbidity and mortality. To avoid complications from open surgical extraction, a novel approach with percutaneous aspiration of large vegetations prior to transvenous lead extraction was instituted. The results of this treatment concept were retrospectively analysed in this multicentre study.
Methods and results
One hundred and one patients [mean age 68.2 ± 13.1 (30-92) years] were treated in four centres for endovascular CIED infection with large lead vegetations. Mean lead vegetation size was 30.7 ± 13.5 mm. Two hundred and forty-seven leads were targeted for extraction (170 pacemaker leads, 77 implantable cardioverter-defibrillator leads). Mean lead implant duration was 81.7 (1-254) months. The transcatheter aspiration system with a specialized long venous drainage cannula and a funnel-shaped tip was based on a veno-venous extracorporeal circuit with an in-line filter. The aspiration of vegetations showed complete procedural success in 94.0% (n = 95), partial success in 5.0% (n = 5). Three major complications (3.0%) were encountered. Complete procedural success (per lead) of the subsequently performed transvenous lead extraction procedure was 99.2% (n = 245). Thirty-day mortality was 3.0% (n = 3). Five patients (5.0%) died in the further course on Days 51, 54, 68, 134, and 182 post-procedure (septic complications: n = 4; heart failure: n = 1).
Conclusion
The percutaneous aspiration procedure is highly effective and is associated with a low complication profile. The aspiration of vegetations immediately prior and during the lead extraction procedure may avoid septic embolization into the pulmonary circulation. This may potentially lead to a long-term survival benefit.

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 21 Oct 2019; epub ahead of print
Starck CT, Schaerf RHM, Breitenstein A, Najibi S, ... Dreizler T, Falk V
Europace: 21 Oct 2019; epub ahead of print | PMID: 31638648
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Impact:
Abstract

Meta-Analysis Comparing Transcatheter Aortic Valve Implantation With Balloon Versus Self-Expandable Valves.

Osman M, Ghaffar YA, Saleem M, Kheiri B, ... Munir MB, Alkhouli M

Two transcatheter aortic valve systems are currently in use in the United States; balloon-expandable valves (BEV) and the self-expanding valve (SEV). However, comparative data outcomes between the 2 systems are limited, as only one randomized trial (RCT) performed a head-to-head comparison between BEVs and SEVs. However, there are several RCTs comparing BEV or SEV to surgical valve replacement. In this analysis, we used Bayesian network meta-analysis techniques to compare BEVs and SEVs. The primary outcome was all-cause mortality at maximum follow-up. Secondary outcomes were cardiovascular mortality, stroke, pacemaker implantation, reintervention, heart failure hospitalization, and moderate-severe paravalvular leak (PVL.). Eight RCTs with 8,095 patients were included. With the exception of less pacemaker implantation in BEV versus SEV (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.11 to 0.77, I = 51%), there was no difference between BEV and SEV in 30-day outcomes. During long-term follow-up (mean 3 ± 2 years); there was no difference between BEV and SEV in all-cause mortality (hazard ratio [HR] 1.1, 95% CI 0.87 to 1.5, I = 19.6%), cardiovascular mortality (HR 1.1, 95% CI 0.73 to 1.6, I = 18.5%), stroke (HR 1.3, 95% CI 0.73 to 2.1, I = 16.9%), hospitalization (HR 0.87, 95% CI 0.41 to 1.6, I = 62%), and reintervention (HR 0.68, 95% CI 0.2 to 2.3, I = 62%). New pacemaker implantation and PVL were significantly less in BEV group (HR 0.45, 95% CI 0.24 to 0.80, I = 38.2%), and (HR 0.03, 95% CI 0.0004 to 0.28, I = 79%), respectively. In conclusion, similar outcomes were seen following transcatheter aortic valve implantation with BEV and SEV with the exception of higher rates of pacemaker implantation and PVL in SEV group.

Copyright © 2019 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Oct 2019; 124:1252-1256
Osman M, Ghaffar YA, Saleem M, Kheiri B, ... Munir MB, Alkhouli M
Am J Cardiol: 14 Oct 2019; 124:1252-1256 | PMID: 31470973
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Impact:
Abstract

Preeclampsia and Cardiovascular Disease in a Large UK Pregnancy Cohort of Linked Electronic Health Records: A CALIBER Study.

Leon LJ, McCarthy FP, Direk K, Gonzalez-Izquierdo A, ... Casas JP, Chappell L
Background
The associations between pregnancy hypertensive disorders and common cardiovascular disorders have not been investigated at scale in a contemporaneous population. We aimed to investigate the association between preeclampsia, hypertensive disorders of pregnancy, and subsequent diagnosis of 12 different cardiovascular disorders.
Methods
We used linked electronic health records from 1997 to 2016 to recreate a UK population-based cohort of 1.3 million women, mean age at delivery 28 years, with nearly 1.9 million completed pregnancies. We used multivariable Cox models to determine the associations between hypertensive disorders of pregnancy, and preeclampsia alone (term and preterm), with 12 cardiovascular disorders in addition to chronic hypertension. We estimated the cumulative incidence of a composite end point of any cardiovascular disorder according to preeclampsia exposure.
Results
During the 20-year study period, 18 624 incident cardiovascular disorders were observed, 65% of which had occurred in women under 40 years. Compared to women without hypertension in pregnancy, women who had 1 or more pregnancies affected by preeclampsia had a hazard ratio of 1.9 (95% confidence interval 1.53-2.35) for any stroke, 1.67 (1.54-1.81) for cardiac atherosclerotic events, 1.82 (1.34-2.46) for peripheral events, 2.13 (1.64-2.76) for heart failure, 1.73 (1.38-2.16) for atrial fibrillation, 2.12 (1.49-2.99) for cardiovascular deaths, and 4.47 (4.32-4.62) for chronic hypertension. Differences in cumulative incidence curves, according to preeclampsia status, were apparent within 1 year of the first index pregnancy. Similar patterns of association were observed for hypertensive disorders of pregnancy, while preterm preeclampsia conferred slightly further elevated risks.
Conclusions
Hypertensive disorders of pregnancy, including preeclampsia, have a similar pattern of increased risk across all 12 cardiovascular disorders and chronic hypertension, and the impact was evident soon after pregnancy. Hypertensive disorders of pregnancy should be considered as a natural screening tool for cardiovascular events, enabling cardiovascular risk prevention through national initiatives.



Circulation: 23 Sep 2019; 140:1050-1060
Leon LJ, McCarthy FP, Direk K, Gonzalez-Izquierdo A, ... Casas JP, Chappell L
Circulation: 23 Sep 2019; 140:1050-1060 | PMID: 31545680
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Abstract

Atypical Electrocardiographic Presentations in Need of Primary Percutaneous Coronary Intervention.

Tzimas G, Antiochos P, Monney P, Eeckhout E, ... Muller O, Schläpfer J

Early initiation of reperfusion therapy remains the cornerstone of successful management for ST-elevation myocardial infarction (STEMI). Rapid restoration of coronary blood flow relies on prompt recognition of the typical ST-segment elevation on a 12-lead electrocardiogram (ECG)-a surrogate for coronary occlusion or critical stenosis-allowing timely activation of the STEMI protocol cascade, with a major positive impact in mortality and clinical outcomes. However, atypical, very high risk ECG patterns-known as \"STEMI equivalents\"-are present in 10% to 25% of patients with ongoing myocardial ischemia in need of urgent primary percutaneous coronary intervention. Though briefly mentioned in the current recommendations, structured clinical data on those specific ECG presentations are lacking. By thoroughly searching MEDLINE and EMBASE we conducted a structured review of non-STEMI, albeit very high risk, ECG patterns of acute coronary syndrome, often associated with coronary occlusion or critical stenosis. After screening 997 studies, we identified the following distinct \"STEMI equivalent\" ECG patterns: Wellens\' syndrome, de Winter sign, hyperacute T waves, left bundle branch block-including paced rhythm-and right bundle branch block. For each pattern, a brief summary of the existing evidence, together with the sensitivity, specificity, and positive predictive value-whenever available-are presented. In conclusion, prompt recognition of \"STEMI equivalent\" ECG patterns is crucial for every physician or paramedic dealing with acute coronary syndrome patients in the emergency department or the prehospital setting, as misinterpretation of those high risk presentations can lead to reperfusion delays and worse outcomes.

Copyright © 2019 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Oct 2019; 124:1305-1314
Tzimas G, Antiochos P, Monney P, Eeckhout E, ... Muller O, Schläpfer J
Am J Cardiol: 14 Oct 2019; 124:1305-1314 | PMID: 31455501
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Impact:
Abstract

Catheter ablation of ventricular arrhythmias and in-hospital mortality: insights from the German-wide Helios hospital network of 5052 cases.

König S, Ueberham L, Müller-Röthing R, Wiedemann M, ... Hindricks G, Bollmann A
Aims
Catheter ablation (CA) of ventricular arrhythmias is one of the most challenging electrophysiological interventions with an increasing use over the last years. Several benefits must be weighed against the risk of potentially life-threatening complications which necessitates a steady reevaluation of safety endpoints. Therefore, the aims of this study were (i) to investigate overall in-hospital mortality in patients undergoing such procedures and (ii) to identify variables associated with in-hospital mortality in a German-wide hospital network.
Methods and results
Between January 2010 and September 2018, administrative data provided by 85 Helios hospitals were screened for patients with main or secondary discharge diagnosis of ventricular tachycardia (VT) or premature ventricular contractions (PVCs) in combination with an arrhythmia-related CA using ICD- and OPS codes. In 5052 cases (mean age 60.9 ± 14.3 years, 30.1% female) of 30 different hospitals, in-hospital mortality was 1.27% with a higher mortality in patients ablated for VT (1.99%, n = 2, 955) compared to PVC (0.24%, n = 2, 097, P < 0.01). Mortality rates were 2.06% in patients with ischaemic heart disease (IHD, n = 2, 137), 1.47% in patients with non-ischaemic structural heart disease (NIHD, n = 1, 224), and 0.12% in patients without structural heart disease (NSHD, n = 1, 691). Considering different types of hospital admission, mortality rates were 0.35% after elective (n = 2, 825), 1.60% after emergency admission/hospital transfer <24 h (n = 1, 314) and 3.72% following delayed hospital transfer >24 h after initial admission (n = 861, P < 0.01 vs. elective admission and emergency admission/hospital transfer <24 h). In multivariable analysis, a delayed hospital transfer >24 h [odds ratio (OR) 2.28, 95% confidence interval (CI) 1.59-3.28, P < 0.01], the occurrence of procedure-related major adverse events (OR 6.81, 95% CI 2.90-16.0, P < 0.01), Charlson Comorbidity Index (CCI, OR 2.39, 95% CI 1.56-3.66, P < 0.01) and its components congestive heart failure (OR 8.04, 95% CI 1.71-37.8, P < 0.01), and diabetes mellitus (OR 1.59, 95% CI 1.13-2.22, P < 0.01) were significantly associated with in-hospital death.
Conclusions
We reported in-hospital mortality rates after CA of ventricular arrhythmias in the largest multicentre, administrative dataset in Germany which can be implemented in quality management programs. Aside from comorbidities, a delayed hospital transfer to a CA performing centre is associated with an increased in-hospital mortality. This deserves further studies to determine the optimal management strategy.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Europace: 21 Oct 2019; epub ahead of print
König S, Ueberham L, Müller-Röthing R, Wiedemann M, ... Hindricks G, Bollmann A
Europace: 21 Oct 2019; epub ahead of print | PMID: 31638643
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Abstract

Stent Thrombosis in Patients with Atrial Fibrillation Undergoing Coronary Stenting in the AUGUSTUS Trial.

Lopes RD, Leonardi S, Wojdyla DM, Vora AN, ... Mehran R, Alexander JH

We describe the incidence, timing, and characteristics of stent thrombosis and its consequences in patients with atrial fibrillation (AF) in the AUGUSTUS trial who received a coronary stent during their qualifying admission (acute coronary syndrome [ACS] or elective percutaneous coronary intervention [PCI]) and the randomized treatment effects of low-dose aspirin (compared with placebo) and apixaban (compared with vitamin K antagonist [VKA]) on the risk of stent thrombosis. We included patients who received a stent during their qualifying admission. We excluded patients with medically-managed ACS (n=1097) or an unknown qualifying index event (n=19). The protocol was approved by appropriate ethics committees; patients provided written informed consent prior to participation.



Circulation: 10 Nov 2019; epub ahead of print
Lopes RD, Leonardi S, Wojdyla DM, Vora AN, ... Mehran R, Alexander JH
Circulation: 10 Nov 2019; epub ahead of print | PMID: 31707833
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Impact:
Abstract

Mapping and Ablation of Ventricular Fibrillation Associated with Early Repolarization Syndrome.

Nademanee K, Haissaguerre M, Hocini M, Nogami A, ... Khongphatthanayothin A, Veerakul G

We conducted a multicenter study to evaluate mapping and ablation of ventricular fibrillation (VF) substrates or VF triggers in early repolarization syndromes (ERS) or J-wave syndrome (JWS).We studied 52 ERS patients (4 females; median age, 35 years) with recurrent VF episodes. Body-surface electrocardiographic imaging (ECGI) along with endocardial and epicardial electroanatomic mapping of both ventricles were performed during sinus rhythm and VF for localization of triggers, substrates, and drivers. Ablations were performed on:1) VF substrates defined as areas that had late depolarization abnormalities characterized by low voltage fractionated late potentials and 2) VF triggers.Fifty-one of the 52 patients had detailed mapping which revealed two phenotypes: 1) Group 1 had late depolarization abnormalities predominantly at the right ventricular (RV) epicardium (n=40); and 2) Group 2 had no depolarization abnormalities (n=11). Group 1 can be subcategorized into 2 groups: Group 1A included 33 ERS patients with Brugada ECG pattern, and Group 1B included 7 ERS patients without Brugada ECG pattern. Late depolarization areas co-localize with VF driver areas. The anterior RV outflow tract (RVOT)/RV epicardium and the RV inferior epicardium are the major substrate sites for Group 1. The Purkinje network is the leading underlying VF trigger in Group 2 that had no substrates. Ablations were performed in 43 patients: 33 and 5 Group 1 patients had only VF substrate ablation and VF substrates plus VF trigger, respectively (mean 1.4 ± 0.6 sessions); 5 Group 2 patients and 1 without group classification had only Purkinje VF trigger ablation (mean 1.2 ± 0.4 sessions). Ablations were successful in reducing VF recurrences (p<0.0001). After follow-up of 31 ± 26 months, 39 (91%) had no VF recurrences.There are 2 phenotypes of ERS/JWS: 1) one with late depolarization abnormality as the underlying mechanism of high amplitude J-wave elevation that predominantly resides in the RVOT and RV inferolateral epicardium, serving as an excellent target for ablation; and 2) the other with pure ERS devoid of VF substrates, but with VF triggers that are associated with Purkinje sites. Ablation is effective in treating symptomatic ERS/JWS patients with frequent VF episodes.



Circulation: 22 Sep 2019; epub ahead of print
Nademanee K, Haissaguerre M, Hocini M, Nogami A, ... Khongphatthanayothin A, Veerakul G
Circulation: 22 Sep 2019; epub ahead of print | PMID: 31542949
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Abstract

Internal Versus External Electrical Cardioversion of Atrial Arrhythmia in Patients With Implantable Cardioverter-Defibrillator: A Randomized Clinical Trial.

Lüker J, Kuhr K, Sultan A, Nölker G, ... Sanders P, Steven D
Background
Atrial arrhythmias are common in patients with implantable cardioverter-defibrillator (ICD). External shocks and internal cardioversion through commanded ICD shock for electrical cardioversion are used for rhythm-control. However, there is a paucity of data on efficacy of external versus internal cardioversion and on the risk of lead and device malfunction. We hypothesized that external cardioversion is noninferior to internal cardioversion for safety, and superior for successful restoration of sinus rhythm.
Methods
Consecutive patients with ICD undergoing elective cardioversion for atrial arrhythmias at 13 centers were randomized in 1:1 fashion to either internal or external cardioversion. The primary safety end point was a composite of surrogate events of lead or device malfunction. Conversion of atrial arrhythmia to sinus rhythm was the primary efficacy end point. Myocardial damage was studied by measuring troponin release in both groups.
Results
N=230 patients were randomized. Shock efficacy was 93% in the external cardioversion group and 65% in the internal cardioversion group (<0.001). Clinically relevant adverse events caused by external or internal cardioversion were not observed. Three cases of pre-existing silent lead malfunction were unmasked by internal shock, resulting in lead failure. Troponin release did not differ between groups.
Conclusions
This is the first randomized trial on external vs internal cardioversion in patients with ICDs. External cardioversion was superior for the restoration of sinus rhythm. The unmasking of silent lead malfunction in the internal cardioversion group suggests that an internal shock attempt may be reasonable in selected ICD patients presenting for electrical cardioversion.
Clinical trial registration
URL: https://www.clinicaltrials.gov. Unique identifier: NCT03247738.



Circulation: 23 Sep 2019; 140:1061-1069
Lüker J, Kuhr K, Sultan A, Nölker G, ... Sanders P, Steven D
Circulation: 23 Sep 2019; 140:1061-1069 | PMID: 31466479
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Abstract

Change in mitral regurgitation severity impacts survival after transcatheter aortic valve replacement.

Feldt K, De Palma R, Bjursten H, Petursson P, ... Rück A, Settergren M
Background
The impact of a change in mitral regurgitation (MR) following TAVR is unknown. We studied the impact of baseline MR and early post-procedural change in MR on survival following TAVR.
Methods
The SWEDEHEART registry included all TAVRs performed in Sweden. Patients were dichotomized into no/mild and moderate/severe MR groups. Vital status, echocardiographic data at baseline and within 7 days after TAVR were analyzed.
Results
1712 patients were included. 1404 (82%) had no/mild MR and 308 (18%) had moderate/severe MR. Baseline moderate/severe MR conferred a higher mortality rate at 5-year follow-up (adjusted HR 1.29, CI 1.01-1.65, p = 0.04). Using persistent ≤mild MR as the reference, when moderate/severe MR persisted or if MR worsened from ≤mild at baseline to moderate/severe after TAVR, higher 5-year mortality rates were seen (adjusted HR 1.66, CI 1.17-2.34, p = 0.04; adjusted HR 1.97, CI 1.29-3.00, p = 0.002, respectively). If baseline moderate/severe MR improved to ≤mild after TAVR no excess mortality was seen (HR 1.09, CI 0.75-1.58, p = 0.67). Paravalvular aortic regurgitation (PVL) was inversely associated with MR improvement after TAVR (OR 0.4, 95%: CI 0.17-0.94; p = 0.034). Atrial fibrillation (OR 2.1, 95% CI: 1.27-3.39, p = 0.004), self-expanding valve (OR 3.8, 95% CI: 2.08-7.14, p < 0.0001), and PVL (4.3, 95% CI 2.32-7.78. p < 0.0001) were associated with MR worsening.
Conclusions
Moderate/severe baseline MR in patients undergoing TAVR is associated with a mortality increase during 5 years of follow-up. This risk is offset if MR improves to ≤mild, whereas worsening of MR after TAVR is associated with a 2-fold mortality increase.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Oct 2019; 294:32-36
Feldt K, De Palma R, Bjursten H, Petursson P, ... Rück A, Settergren M
Int J Cardiol: 31 Oct 2019; 294:32-36 | PMID: 31399298
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Abstract

Targeted Ablation of Ventricular Tachycardia Guided by Wavefront Discontinuities During Sinus Rhythm: A New Functional Substrate Mapping Strategy.

Aziz Z, Shatz D, Raiman M, Upadhyay GA, ... Nayak HM, Tung R

Accurate and expedited identification of scar regions most prone to reentry is needed to guide ventricular tachycardia (VT) ablation. We aimed to prospectively assess outcomes of VT ablation guided primarily by the targeting of deceleration zones (DZ) identified by propagational analysis of ventricular activation during sinus rhythm.Patients with scar-related VT were prospectively enrolled in the UChicago VT Ablation Registry between 2016-2018. Isochronal late activation maps annotated to the latest local electrogram deflection were created with high-density multielectrode mapping catheters. Targeted ablation of DZ (>3 isochrones within 1 cm radius) was performed, prioritizing later activated regions with maximal isochronal crowding. When possible, activation mapping of VT was performed and successful ablation sites were compared with DZ locations for mechanistic correlation. Patients were prospectively followed for VT recurrence and mortality.120 patients (median age 65 years (59-71), 15% female, 50% nonischemic, median EF 31%) underwent 144 ablation procedures for scar-related VT. 57% of patients had previous ablation and epicardial access was employed in 59% of cases. High-density mapping during baseline rhythm was performed (2,518 points (1615-3752) endo, 5049 ± 2580 points epi) and identified an average of 2±1 DZ, which co-localized to successful termination sites in 95% of cases. The median total RF application duration was 29 min (21-38 min) to target DZ, representing ablation of 18% of the low voltage area. At 12±10 months, 70% freedom from VT recurrence (80% in ICM and 63% in NICM) was achieved. The overall survival rate was 87%.A novel voltage-independent high-density mapping display can identify the functional substrate for VT during sinus rhythm and guide targeted ablation, obviating the need for extensive radiofrequency delivery. Regions with isochronal crowding during the baseline rhythm were predictive of VT termination sites, providing mechanistic evidence that deceleration zones are highly arrhythmogenic, functioning as niduses for reentry.



Circulation: 18 Sep 2019; epub ahead of print
Aziz Z, Shatz D, Raiman M, Upadhyay GA, ... Nayak HM, Tung R
Circulation: 18 Sep 2019; epub ahead of print | PMID: 31533463
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Abstract

Mitral Valve Prolapse, Ventricular Arrhythmias, and Sudden Death.

Basso C, Iliceto S, Thiene G, Perazzolo Marra M

Despite a 2% to 3% prevalence of echocardiographically defined mitral valve prolapse (MVP) in the general population, the actual burden, risk stratification, and treatment of the so-called arrhythmic MVP are unknown. The clinical profile is characterized by a patient, usually female, with mostly bileaflet myxomatous disease, mid-systolic click, repolarization abnormalities in the inferior leads, and complex ventricular arrhythmias with polymorphic/right bundle branch block morphology, without significant regurgitation. Among the various pathophysiologic mechanisms of electrical instability, left ventricular fibrosis in the papillary muscles and inferobasal wall, mitral annulus disjunction, and systolic curling have been recently described by pathological and cardiac magnetic resonance studies in sudden death victims and patients with arrhythmic MVP. In addition, premature ventricular beats arising from the Purkinje tissue as ventricular fibrillation triggers have been documented by electrophysiologic studies in MVP patients with aborted sudden death. The genesis of malignant ventricular arrhythmias in MVP probably recognizes the combination of the substrate (regional myocardial hypertrophy and fibrosis, Purkinje fibers) and the trigger (mechanical stretch) eliciting premature ventricular beats because of a primary morphofunctional abnormality of the mitral valve annulus. The main clinical challenge is how to identify patients with arrhythmic MVP (which imaging technique and in which patient) and how to treat them to prevent sudden death. Thus, there is a necessity for prospective multicenter studies focusing on the prognostic role of cardiac magnetic resonance and electrophysiologic studies and on the therapeutic efficacy of targeted catheter ablation and mitral valve surgery in reducing the risk of life-threatening arrhythmias, as well as the role of implantable cardioverter defibrillators for primary prevention.



Circulation: 09 Sep 2019; 140:952-964
Basso C, Iliceto S, Thiene G, Perazzolo Marra M
Circulation: 09 Sep 2019; 140:952-964 | PMID: 31498700
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Abstract

Disruption of Ca Homeostasis and Connexin 43 Hemichannel Function in the Right Ventricle Precedes Overt Arrhythmogenic Cardiomyopathy in Plakophilin-2-Deficient Mice.

Kim JC, Pérez-Hernández M, Alvarado FJ, Maurya SR, ... Cerrone M, Delmar M
Background
Plakophilin-2 (PKP2) is classically defined as a desmosomal protein. Mutations in PKP2 associate with most cases of gene-positive arrhythmogenic right ventricular cardiomyopathy. A better understanding of PKP2 cardiac biology can help elucidate the mechanisms underlying arrhythmic and cardiomyopathic events consequent to PKP2 deficiency. Here, we sought to capture early molecular/cellular events that can act as nascent arrhythmic/cardiomyopathic substrates.
Methods
We used multiple imaging, biochemical and high-resolution mass spectrometry methods to study functional/structural properties of cells/tissues derived from cardiomyocyte-specific, tamoxifen-activated, PKP2 knockout mice (PKP2cKO) 14 days post-tamoxifen injection, a time point preceding overt electrical or structural phenotypes. Myocytes from right or left ventricular free wall were studied separately.
Results
Most properties of PKP2cKO left ventricular myocytes were not different from control; in contrast, PKP2cKO right ventricular (RV) myocytes showed increased amplitude and duration of Ca transients, increased Ca in the cytoplasm and sarcoplasmic reticulum, increased frequency of spontaneous Ca release events (sparks) even at comparable sarcoplasmic reticulum load, and dynamic Ca accumulation in mitochondria. We also observed early- and delayed-after transients in RV myocytes and heightened susceptibility to arrhythmias in Langendorff-perfused hearts. In addition, ryanodine receptor 2 in PKP2cKO-RV cells presented enhanced Ca sensitivity and preferential phosphorylation in a domain known to modulate Ca gating. RNAseq at 14 days post-tamoxifen showed no relevant difference in transcript abundance between RV and left ventricle, neither in control nor in PKP2cKO cells. Instead, we found an RV-predominant increase in membrane permeability that can permit Ca entry into the cell. Connexin 43 ablation mitigated the membrane permeability increase, accumulation of cytoplasmic Ca, increased frequency of sparks and early stages of RV dysfunction. Connexin 43 hemichannel block with GAP19 normalized [Ca] homeostasis. Similarly, protein kinase C inhibition normalized spark frequency at comparable sarcoplasmic reticulum load levels.
Conclusions
Loss of PKP2 creates an RV-predominant arrhythmogenic substrate (Ca dysregulation) that precedes the cardiomyopathy; this is, at least in part, mediated by a Connexin 43-dependent membrane conduit and repressed by protein kinase C inhibitors. Given that asymmetric Ca dysregulation precedes the cardiomyopathic stage, we speculate that abnormal Ca handling in RV myocytes can be a trigger for gross structural changes observed at a later stage.



Circulation: 16 Sep 2019; 140:1015-1030
Kim JC, Pérez-Hernández M, Alvarado FJ, Maurya SR, ... Cerrone M, Delmar M
Circulation: 16 Sep 2019; 140:1015-1030 | PMID: 31315456
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Impact:
Abstract

An artificial intelligence-enabled ECG algorithm for the identification of patients with atrial fibrillation during sinus rhythm: a retrospective analysis of outcome prediction.

Attia ZI, Noseworthy PA, Lopez-Jimenez F, Asirvatham SJ, ... Kapa S, Friedman PA
Background
Atrial fibrillation is frequently asymptomatic and thus underdetected but is associated with stroke, heart failure, and death. Existing screening methods require prolonged monitoring and are limited by cost and low yield. We aimed to develop a rapid, inexpensive, point-of-care means of identifying patients with atrial fibrillation using machine learning.
Methods
We developed an artificial intelligence (AI)-enabled electrocardiograph (ECG) using a convolutional neural network to detect the electrocardiographic signature of atrial fibrillation present during normal sinus rhythm using standard 10-second, 12-lead ECGs. We included all patients aged 18 years or older with at least one digital, normal sinus rhythm, standard 10-second, 12-lead ECG acquired in the supine position at the Mayo Clinic ECG laboratory between Dec 31, 1993, and July 21, 2017, with rhythm labels validated by trained personnel under cardiologist supervision. We classified patients with at least one ECG with a rhythm of atrial fibrillation or atrial flutter as positive for atrial fibrillation. We allocated ECGs to the training, internal validation, and testing datasets in a 7:1:2 ratio. We calculated the area under the curve (AUC) of the receiver operatoring characteristic curve for the internal validation dataset to select a probability threshold, which we applied to the testing dataset. We evaluated model performance on the testing dataset by calculating the AUC and the accuracy, sensitivity, specificity, and F1 score with two-sided 95% CIs.
Findings
We included 180 922 patients with 649 931 normal sinus rhythm ECGs for analysis: 454 789 ECGs recorded from 126 526 patients in the training dataset, 64 340 ECGs from 18 116 patients in the internal validation dataset, and 130 802 ECGs from 36 280 patients in the testing dataset. 3051 (8·4%) patients in the testing dataset had verified atrial fibrillation before the normal sinus rhythm ECG tested by the model. A single AI-enabled ECG identified atrial fibrillation with an AUC of 0·87 (95% CI 0·86-0·88), sensitivity of 79·0% (77·5-80·4), specificity of 79·5% (79·0-79·9), F1 score of 39·2% (38·1-40·3), and overall accuracy of 79·4% (79·0-79·9). Including all ECGs acquired during the first month of each patient\'s window of interest (ie, the study start date or 31 days before the first recorded atrial fibrillation ECG) increased the AUC to 0·90 (0·90-0·91), sensitivity to 82·3% (80·9-83·6), specificity to 83·4% (83·0-83·8), F1 score to 45·4% (44·2-46·5), and overall accuracy to 83·3% (83·0-83·7).
Interpretation
An AI-enabled ECG acquired during normal sinus rhythm permits identification at point of care of individuals with atrial fibrillation.
Funding
None.

Copyright © 2019 Elsevier Ltd. All rights reserved.

Lancet: 06 Sep 2019; 394:861-867
Attia ZI, Noseworthy PA, Lopez-Jimenez F, Asirvatham SJ, ... Kapa S, Friedman PA
Lancet: 06 Sep 2019; 394:861-867 | PMID: 31378392
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Impact:
Abstract

Long-Term Incidence of Atrial Fibrillation and Stroke Among Cross-Country Skiers.

Svedberg N, Sundström J, James S, Hållmarker U, Hambraeus K, Andersen K
Background
Studies have revealed a higher incidence of atrial fibrillation among well-trained athletes. We aim to investigate associations of endurance training with incidence of atrial fibrillation and stroke and to establish potential sex differences of such associations in a cohort of endurance trained athletes.
Methods
All Swedish skiers (208 654) completing 1 or more races in the 30 to 90 km cross-country skiing event Vasaloppet (1989-2011) and a matched sample (n=527 448) of nonskiers were followed until first event of atrial fibrillation or stroke. Cox regression was used to investigate associations of number of completed races and finishing time with incidence of atrial fibrillation and stroke.
Results
Female skiers in Vasaloppet had a lower incidence of atrial fibrillation than did female nonskiers (hazard ratio [HR], 0.55; 95% CI, 0.48-0.64), independent of finishing time and number of races. Male skiers had a similar incidence to that of nonskiers (HR, 0.98; 95% CI, 0.93-1.03). Skiers with the highest number of races or fastest finishing times had the highest incidence. Skiers of either sex had a lower incidence of stroke than did nonskiers (HR, 0.64; 95% CI, 0.60-0.67), independent of the number of races and finishing time. Skiers with atrial fibrillation had higher incidence of stroke than did skiers and nonskiers without atrial fibrillation (men: HR, 2.28; 95% CI, 1.93-2.70; women: HR, 3.51; 95% CI, 2.17-5.68; skiers with atrial fibrillation vs. skiers without atrial fibrillation). After diagnosis of atrial fibrillation, skiers with atrial fibrillation had a lower incidence of stroke (HR, 0.73; 95% CI, 0.50-0.91) and lower mortality compared with nonskiers with atrial fibrillation (HR, 0.57; 95% CI, 0.49-0.65).
Conclusions
Female skiers in Vasaloppet had lower incidence of atrial fibrillation and stroke. Male skiers had similar incidence of atrial fibrillation and lower risk of stroke. Men with higher number of races and faster finishing times had the highest incidence of atrial fibrillation. After diagnosis of atrial fibrillation, skiers had lower incidence of stroke and death than did nonskiers with atrial fibrillation. This indicates that although on an individual level atrial fibrillation in well-trained individuals is associated with higher incidence of stroke, on population level, risk of stroke is low and that exercise should not be avoided.



Circulation: 09 Sep 2019; 140:910-920
Svedberg N, Sundström J, James S, Hållmarker U, Hambraeus K, Andersen K
Circulation: 09 Sep 2019; 140:910-920 | PMID: 31446766
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Abstract

Laparoscopic supracervical hysterectomy versus endometrial ablation for women with heavy menstrual bleeding (HEALTH): a parallel-group, open-label, randomised controlled trial.

Cooper K, Breeman S, Scott NW, Scotland G, ... Bhattacharya S,
Background
Heavy menstrual bleeding affects 25% of women in the UK, many of whom require surgery to treat it. Hysterectomy is effective but has more complications than endometrial ablation, which is less invasive but ultimately leads to hysterectomy in 20% of women. We compared laparoscopic supracervical hysterectomy with endometrial ablation in women seeking surgical treatment for heavy menstrual bleeding.
Methods
In this parallel-group, multicentre, open-label, randomised controlled trial in 31 hospitals in the UK, women younger than 50 years who were referred to a gynaecologist for surgical treatment of heavy menstrual bleeding and who were eligible for endometrial ablation were randomly allocated (1:1) to either laparoscopic supracervical hysterectomy or second generation endometrial ablation. Women were randomly assigned by either an interactive voice response telephone system or an internet-based application with a minimisation algorithm based on centre and age group (<40 years vs ≥40 years). Laparoscopic supracervical hysterectomy involves laparoscopic (keyhole) surgery to remove the upper part of the uterus (the body) containing the endometrium. Endometrial ablation aims to treat heavy menstrual bleeding by destroying the endometrium, which is responsible for heavy periods. The co-primary clinical outcomes were patient satisfaction and condition-specific quality of life, measured with the menorrhagia multi-attribute quality of life scale (MMAS), assessed at 15 months after randomisation. Our analysis was based on the intention-to-treat principle. The trial was registered with the ISRCTN registry, number ISRCTN49013893.
Findings
Between May 21, 2014, and March 28, 2017, we enrolled and randomly assigned 660 women (330 in each group). 616 (93%) of 660 women were operated on within the study period, 588 (95%) of whom received the allocated procedure and 28 (5%) of whom had an alternative surgery. At 15 months after randomisation, more women allocated to laparoscopic supracervical hysterectomy were satisfied with their operation compared with those in the endometrial ablation group (270 [97%] of 278 women vs 244 [87%] of 280 women; adjusted percentage difference 9·8, 95% CI 5·1-14·5; adjusted odds ratio [OR] 2·53, 95% CI 1·83-3·48; p<0·0001). Women randomly assigned to laparoscopic supracervical hysterectomy were also more likely to have the best possible MMAS score of 100 than women assigned to endometrial ablation (180 [69%] of 262 women vs 146 [54%] of 268 women; adjusted percentage difference 13·3, 95% CI 3·8-22·8; adjusted OR 1·87, 95% CI 1·31-2·67; p=0·00058). 14 (5%) of 309 women in the laparoscopic supracervical hysterectomy group and 11 (4%) of 307 women in the endometrial ablation group had at least one serious adverse event (adjusted OR 1·30, 95% CI 0·56-3·02; p=0·54).
Interpretation
Laparoscopic supracervical hysterectomy is superior to endometrial ablation in terms of clinical effectiveness and has a similar proportion of complications, but takes longer to perform and is associated with a longer recovery.
Funding
UK National Institute for Health Research Health Technology Assessment Programme.

Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Lancet: 11 Sep 2019; epub ahead of print
Cooper K, Breeman S, Scott NW, Scotland G, ... Bhattacharya S,
Lancet: 11 Sep 2019; epub ahead of print | PMID: 31522846
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Abstract

Light-entrained and brain-tuned circadian circuits regulate ILC3s and gut homeostasis.

Godinho-Silva C, Domingues RG, Rendas M, Raposo B, ... Carvalho T, Veiga-Fernandes H

Group 3 innate lymphoid cells (ILC3s) are major regulators of inflammation, infection, microbiota composition and metabolism. ILC3s and neuronal cells have been shown to interact at discrete mucosal locations to steer mucosal defence. Nevertheless, it is unclear whether neuroimmune circuits operate at an organismal level, integrating extrinsic environmental signals to orchestrate ILC3 responses. Here we show that light-entrained and brain-tuned circadian circuits regulate enteric ILC3s, intestinal homeostasis, gut defence and host lipid metabolism in mice. We found that enteric ILC3s display circadian expression of clock genes and ILC3-related transcription factors. ILC3-autonomous ablation of the circadian regulator Arntl led to disrupted gut ILC3 homeostasis, impaired epithelial reactivity, a deregulated microbiome, increased susceptibility to bowel infection and disrupted lipid metabolism. Loss of ILC3-intrinsic Arntl shaped the gut \'postcode receptors\' of ILC3s. Strikingly, light-dark cycles, feeding rhythms and microbial cues differentially regulated ILC3 clocks, with light signals being the major entraining cues of ILC3s. Accordingly, surgically or genetically induced deregulation of brain rhythmicity led to disrupted circadian ILC3 oscillations, a deregulated microbiome and altered lipid metabolism. Our work reveals a circadian circuitry that translates environmental light cues into enteric ILC3s, shaping intestinal health, metabolism and organismal homeostasis.



Nature: 29 Sep 2019; 574:254-258
Godinho-Silva C, Domingues RG, Rendas M, Raposo B, ... Carvalho T, Veiga-Fernandes H
Nature: 29 Sep 2019; 574:254-258 | PMID: 31534216
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