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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Initial Imaging-Guided Strategy Versus Routine Care in Patients With Non-ST-Segment Elevation Myocardial Infarction.

Smulders MW, Kietselaer BLJH, Wildberger JE, Dagnelie PC, ... Crijns HJGM, Bekkers SCAM
Background
Patients with non-ST-segment elevation myocardial infarction and elevated high-sensitivity cardiac troponin levels often routinely undergo invasive coronary angiography (ICA), but many do not have obstructive coronary artery disease.
Objectives
This study investigated whether cardiovascular magnetic resonance imaging (CMR) or computed tomographic angiography (CTA) may serve as a safe gatekeeper for ICA.
Methods
This randomized controlled trial (NCT01559467) in 207 patients (age 64 years; 62% male patients) with acute chest pain, elevated high-sensitivity cardiac troponin T levels (>14 ng/l), and inconclusive electrocardiogram compared a CMR- or CTA-first strategy with a control strategy of routine clinical care. Follow-up ICA was recommended when initial CMR or CTA suggested myocardial ischemia, infarction, or obstructive coronary artery disease (≥70% stenosis). Primary efficacy and secondary safety endpoints were referral to ICA during hospitalization and 1-year outcomes (major adverse cardiac events and complications), respectively.
Results
The CMR- and CTA-first strategies reduced ICA compared with routine clinical care (87% [p = 0.001], 66% [p < 0.001], and 100%, respectively), with similar outcome (hazard ratio: CMR vs. routine, 0.78 [95% confidence interval: 0.37 to 1.61]; CTA vs. routine, 0.66 [95% confidence interval: 0.31 to 1.42]; and CMR vs. CTA, 1.19 [95% confidence interval: 0.53 to 2.66]). Obstructive coronary artery disease after ICA was found in 61% of patients in the routine clinical care arm, in 69% in the CMR-first arm (p = 0.308 vs. routine), and in 85% in the CTA-first arm (p = 0.006 vs. routine). In the non-CMR and non-CTA arms, follow-up CMR and CTA were performed in 67% and 13% of patients and led to a new diagnosis in 33% and 3%, respectively (p < 0.001).
Conclusions
A novel strategy of implementing CMR or CTA first in the diagnostic process in non-ST-segment elevation myocardial infarction is a safe gatekeeper for ICA.

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

J Am Coll Cardiol: 18 Nov 2019; 74:2466-2477
Smulders MW, Kietselaer BLJH, Wildberger JE, Dagnelie PC, ... Crijns HJGM, Bekkers SCAM
J Am Coll Cardiol: 18 Nov 2019; 74:2466-2477 | PMID: 31727284
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Time trends in sudden cardiac death risk in heart failure patients with cardiac resynchronization therapy: a systematic review.

Barra S, Providência R, Narayanan K, Boveda S, ... Levy WC, Marijon E
Aims
While data from randomized trials suggest a declining incidence of sudden cardiac death (SCD) among heart failure patients, the extent to which such a trend is present among patients with cardiac resynchronization therapy (CRT) has not been evaluated. We therefore assessed changes in SCD incidence, and associated factors, in CRT recipients over the last 20 years.
Methods and results
Literature search from inception to 30 April 2018 for observational and randomized studies involving CRT patients, with or without defibrillator, providing specific cause-of-death data. Sudden cardiac death was the primary endpoint. For each study, rate of SCD per 1000 patient-years of follow-up was calculated. Trend line graphs were subsequently constructed to assess change in SCD rates over time, which were further analysed by device type, patient characteristics, and medical therapy. Fifty-three studies, comprising 22 351 patients with 60 879 patient-years of follow-up and a total of 585 SCD, were included. There was a gradual decrease in SCD rates since the early 2000s in both randomized and observational studies, with rates falling more than four-fold. The rate of decline in SCD was steeper than that of all-cause mortality, and accordingly, the proportion of deaths which were due to SCD declined over the years. The magnitude of absolute decline in SCD was more prominent among CRT-pacemaker (CRT-P) patients compared to those receiving CRT-defibrillator (CRT-D), with the difference in SCD rates between CRT-P and CRT-D decreasing considerably over time. There was a progressive increase in age, use of beta-blockers, and left ventricular ejection fraction, and conversely, a decrease in QRS duration and antiarrhythmic drug use.
Conclusion
Sudden cardiac death rates have progressively declined in the CRT heart failure population over time, with the difference between CRT-D vs. CRT-P recipients narrowing considerably.

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 Nov 2019; epub ahead of print
Barra S, Providência R, Narayanan K, Boveda S, ... Levy WC, Marijon E
Eur Heart J: 20 Nov 2019; epub ahead of print | PMID: 31750896
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Echocardiographic Features of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction.

Shah AM, Cikes M, Prasad N, Li G, ... Solomon SD,
Background
The PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction) trial tested the efficacy of sacubitril-valsartan in patients with heart failure with preserved ejection fraction (HFpEF). Existing data on cardiac structure and function in patients with HFpEF suggest significant heterogeneity.
Objectives
The aim of this study was to characterize cardiac structure and function, quantify their associations with clinical outcomes, and contextualize these findings with other HFpEF studies.
Methods
Echocardiography was performed in 1,097 of 4,822 PARAGON-HF patients within 6 months of enrollment. Associations with incident first heart failure hospitalization or cardiovascular death were assessed using Cox proportional hazards models adjusted for age, sex, region of enrollment, randomized treatment, N-terminal pro-brain natriuretic peptide, and clinical risk factors.
Results
Average age was 74 ± 8 years, 53% of patients were women, median N-terminal pro-brain natriuretic peptide level was 918 pg/ml (interquartile range: 485 to 1,578 pg/ml), 94% had hypertension, and 35% had atrial fibrillation. The mean left ventricular (LV) ejection fraction was 58.6 ± 9.8%, prevalence of LV hypertrophy was 21%, prevalence of left atrial enlargement was 83%, prevalence of elevated E/e\' ratio was 53%, and prevalence of pulmonary hypertension was 31%. Heart failure hospitalization or cardiovascular death occurred in 288 patients at 2.8-year median follow-up. In fully adjusted models, higher LV mass index (hazard ratio [HR]: 1.05 per 10 g/m; 95% confidence interval [CI]: 1.00 to 1.10; p = 0.03), E/e\' ratio (HR: 1.04 per unit; 95% CI: 1.02 to 1.06; p < 0.001), pulmonary artery systolic pressure (HR: 1.51 per 10 mm Hg; 95% CI: 1.29 to 1.76; p < 0.001), and right ventricular end-diastolic area (HR: 1.04 per cm; 95% CI: 1.01 to 1.07; p = 0.003) were each associated with this composite, while LV ejection fraction and left atrial size were not (p > 0.05 for all). Appreciable differences were observed in cardiac structure compared with other HFpEF clinical trials, despite similar E/e\' ratio, pulmonary artery systolic pressure, and event rates.
Conclusions
Diastolic dysfunction, left atrial enlargement, and pulmonary hypertension were common in PARAGON-HF. LV hypertrophy, elevated left- and right-sided pressures, and right ventricular enlargement were independently predictive of incident heart failure hospitalization or cardiovascular death. Echocardiographic differences among HFpEF trials despite similar clinical event rates highlight the heterogeneity of this syndrome. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).

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

J Am Coll Cardiol: 09 Dec 2019; 74:2858-2873
Shah AM, Cikes M, Prasad N, Li G, ... Solomon SD,
J Am Coll Cardiol: 09 Dec 2019; 74:2858-2873 | PMID: 31806129
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Natural History of Subclinical Atrial Fibrillation Detected by Implanted Loop Recorders.

Diederichsen SZ, Haugan KJ, Brandes A, Lanng MB, ... Højberg S, Svendsen JH
Background
As new heart rhythm monitoring technologies emerge, subclinical atrial fibrillation (AF) signifies a future challenge to health care systems. The pathological characteristics of this condition are largely unknown.
Objectives
This study sought to characterize the natural history of subclinical AF in at-risk patients from the general population.
Methods
The authors studied 590 individuals ≥70 years of age with ≥1 of hypertension, diabetes, previous stroke, or heart failure, without history of AF, undergoing long-term implantable loop recorder monitoring as part of the LOOP (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-risk Individuals) study. Baseline assessments included N-terminal pro-B-type natriuretic peptide (NT-proBNP). All day-to-day heart rhythm and symptom data were extracted from the device. Endpoints included AF burden, AF progression, symptom reports, and heart rate during AF.
Results
A total of 685,445 monitoring days were available for analysis. Adjudicated AF episodes lasting ≥6 min were detected in 205 participants (35%). The AF burden was median 0.13% (interquartile range: 0.03% to 1.05%) of the monitoring time and changed by a factor of 1.31 (95% CI: 1.02 to 1.68) per doubling of NT-proBNP. AF episodes were present 2.7% (interquartile range: 1.0% to 15.7%) of monitoring days after debut. Progression to 24-h episodes was seen in 33 of the AF patients (16%), whereas 46 (22%) had no AF episodes in the last 6 months of monitoring or longer. Symptoms were absent in 185 (90%) at debut, and 178 (87%) never reported AF-related symptoms during follow-up. The averaged heart rate during AF was 96 (interquartile range: 83 to 114) beats/min, 24 (interquartile range: 9 to 41) beats/min faster than daytime sinus rates.
Conclusions
Although previously unknown AF was highly prevalent, the burden was low, and progression was limited. In addition, symptoms were scarce, and the heart rate was only modestly elevated. (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-risk Individuals [LOOP]; NCT02036450).

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

J Am Coll Cardiol: 02 Dec 2019; 74:2771-2781
Diederichsen SZ, Haugan KJ, Brandes A, Lanng MB, ... Højberg S, Svendsen JH
J Am Coll Cardiol: 02 Dec 2019; 74:2771-2781 | PMID: 31779791
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus.

Kapur J, Elm J, Chamberlain JM, Barsan W, ... Silbergleit R,
Background
The choice of drugs for patients with status epilepticus that is refractory to treatment with benzodiazepines has not been thoroughly studied.
Methods
In a randomized, blinded, adaptive trial, we compared the efficacy and safety of three intravenous anticonvulsive agents - levetiracetam, fosphenytoin, and valproate - in children and adults with convulsive status epilepticus that was unresponsive to treatment with benzodiazepines. The primary outcome was absence of clinically evident seizures and improvement in the level of consciousness by 60 minutes after the start of drug infusion, without additional anticonvulsant medication. The posterior probabilities that each drug was the most or least effective were calculated. Safety outcomes included life-threatening hypotension or cardiac arrhythmia, endotracheal intubation, seizure recurrence, and death.
Results
A total of 384 patients were enrolled and randomly assigned to receive levetiracetam (145 patients), fosphenytoin (118), or valproate (121). Reenrollment of patients with a second episode of status epilepticus accounted for 16 additional instances of randomization. In accordance with a prespecified stopping rule for futility of finding one drug to be superior or inferior, a planned interim analysis led to the trial being stopped. Of the enrolled patients, 10% were determined to have had psychogenic seizures. The primary outcome of cessation of status epilepticus and improvement in the level of consciousness at 60 minutes occurred in 68 patients assigned to levetiracetam (47%; 95% credible interval, 39 to 55), 53 patients assigned to fosphenytoin (45%; 95% credible interval, 36 to 54), and 56 patients assigned to valproate (46%; 95% credible interval, 38 to 55). The posterior probability that each drug was the most effective was 0.41, 0.24, and 0.35, respectively. Numerically more episodes of hypotension and intubation occurred in the fosphenytoin group and more deaths occurred in the levetiracetam group than in the other groups, but these differences were not significant.
Conclusions
In the context of benzodiazepine-refractory convulsive status epilepticus, the anticonvulsant drugs levetiracetam, fosphenytoin, and valproate each led to seizure cessation and improved alertness by 60 minutes in approximately half the patients, and the three drugs were associated with similar incidences of adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ESETT ClinicalTrials.gov number, NCT01960075.).

Copyright © 2019 Massachusetts Medical Society.

N Engl J Med: 27 Nov 2019; 381:2103-2113
Kapur J, Elm J, Chamberlain JM, Barsan W, ... Silbergleit R,
N Engl J Med: 27 Nov 2019; 381:2103-2113 | PMID: 31774955
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cardiac Pacing in Sub-Saharan Africa: JACC International.

Jouven X, Diop BI, Narayanan K, Adoubi A, ... Marijon E,

Many parts of the developing world, especially Sub-Saharan Africa, completely lack access to cardiac pacing. The authors initiated a multinational program to implement cardiac pacing in 14 countries in Sub-Saharan Africa (1996 to 2018), aiming to eventually build self-sustainable capacity in each country. This was based on an \"on-site training\" approach of performing procedures locally and educating local health care teams to work within resource-limited settings, with prospective evaluation of the program. In 64 missions, a total of 542 permanent pacemakers were implanted. In 11 of these countries, the first pacemaker implant in the country was through the mission. More than one-half of those initially listed as suitable died before the mission(s) arrived. The proportion of implantations that were completely handled by local teams increased from 3% in 1996 to 98% in 2018. These findings demonstrate the feasibility and effectiveness of a proctorship-based approach to the development of local cardiac pacing capabilities in Sub-Saharan African nations.

Copyright © 2019. Published by Elsevier Inc.

J Am Coll Cardiol: 25 Nov 2019; 74:2652-2660
Jouven X, Diop BI, Narayanan K, Adoubi A, ... Marijon E,
J Am Coll Cardiol: 25 Nov 2019; 74:2652-2660 | PMID: 31753207
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Long-Term Safety and Efficacy in Continued Access Left Atrial Appendage Closure Registries.

Holmes DR, Reddy VY, Gordon NT, Delurgio D, ... Stone JE, Kar S
Background
Long-term data on the safety and efficacy of left atrial appendage closure (LAAC) for stroke prevention in patients with nonvalvular atrial fibrillation remain limited.
Objectives
The purpose of this study was to evaluate 4.5- to 5-year data in 2 U.S. Food and Drug Association LAAC mandated registries (CAP [Continued Access to PROTECT-AF] and CAP2 [Continued Access to PREVAIL]) for safety and efficacy.
Methods
Two registries of patients implanted with LAAC devices provide the largest source of follow-up data. Both accompanied their respective randomized clinical trials, PROTECT-AF (Watchman Left Atrial Appendage System for Embolic PROTECTion in Patients With Atrial Fibrillation) and PREVAIL (Prospective Randomized Evaluation of the WATCHMAN LAA Closure Device In Patients with Atrial Fibrillation versus Long Term Warfarin Therapy), which used the same endpoints (primary efficacy of composite of stroke, systemic embolism, cardiovascular/unexplained death, and safety).
Results
CAP included 566 patients with an average follow-up of 50.1 months (2,293 patient-years), and CAP2 included 578 patients with an average follow-up of 50.3 months (2,227 patient-years). CAP2 patients were significantly older and had higher CHADS-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, sex category) scores (4.51 vs. 3.88; p < 0.001). Procedural success was similar in both (94%). The primary composite endpoint occurred at a rate of 3.05 per 100 patient-years in CAP and 4.80 per 100 patient-years in CAP2; events contributing to this endpoint were most commonly cardiovascular/unexplained death (1.69 per 100 patient-years for CAP and 2.92 per 100 patient-years for CAP2). Hemorrhagic stroke was significantly less than ischemic stroke (0.17 per 100 patient-years in CAP and 0.09 per 100 patient-years in CAP2), and total stroke rates were significantly less than predicted by CHADS-VASc score (78% reduction with CAP, 69% reduction with CAP2).
Conclusions
These registries, which contain the longest and largest follow-up data of patients with the Watchman device, support LAAC as a safe and effective therapy for long-term anticoagulation in patients with nonvalvular atrial fibrillation, and document the lowest rate of hemorrhagic stroke identified in this population.

Copyright © 2019. Published by Elsevier Inc.

J Am Coll Cardiol: 09 Dec 2019; 74:2878-2889
Holmes DR, Reddy VY, Gordon NT, Delurgio D, ... Stone JE, Kar S
J Am Coll Cardiol: 09 Dec 2019; 74:2878-2889 | PMID: 31806131
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cabins, castles, and constant hearts: rhythm control therapy in patients with atrial fibrillation.

Willems S, Meyer C, de Bono J, Brandes A, ... Wegscheider K, Kirchhof P

Recent innovations have the potential to improve rhythm control therapy in patients with atrial fibrillation (AF). Controlled trials provide new evidence on the effectiveness and safety of rhythm control therapy, particularly in patients with AF and heart failure. This review summarizes evidence supporting the use of rhythm control therapy in patients with AF for different outcomes, discusses implications for indications, and highlights remaining clinical gaps in evidence. Rhythm control therapy improves symptoms and quality of life in patients with symptomatic AF and can be safely delivered in elderly patients with comorbidities (mean age 70 years, 3-7% complications at 1 year). Atrial fibrillation ablation maintains sinus rhythm more effectively than antiarrhythmic drug therapy, but recurrent AF remains common, highlighting the need for better patient selection (precision medicine). Antiarrhythmic drugs remain effective after AF ablation, underpinning the synergistic mechanisms of action of AF ablation and antiarrhythmic drugs. Atrial fibrillation ablation appears to improve left ventricular function in a subset of patients with AF and heart failure. Data on the prognostic effect of rhythm control therapy are heterogeneous without a clear signal for either benefit or harm. Rhythm control therapy has acceptable safety and improves quality of life in patients with symptomatic AF, including in elderly populations with stroke risk factors. There is a clinical need to better stratify patients for rhythm control therapy. Further studies are needed to determine whether rhythm control therapy, and particularly AF ablation, improves left ventricular function and reduces AF-related complications.

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

Eur Heart J: 21 Nov 2019; epub ahead of print
Willems S, Meyer C, de Bono J, Brandes A, ... Wegscheider K, Kirchhof P
Eur Heart J: 21 Nov 2019; epub ahead of print | PMID: 31755940
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Incidence and Risk Factors for Permanent Pacemaker Implantation Following Mitral or Aortic Valve Surgery.

Moskowitz G, Hong KN, Giustino G, Gillinov AM, ... Gelijns AC, Egorova NN
Background
Risk factors for post-operative conduction disturbances after cardiac valve surgery requiring a permanent pacemaker (PPM) are poorly characterized.
Objectives
The aim of this study was to investigate the timing and risk factors for PPM implantation after mitral or aortic valve surgery.
Methods
All patients who underwent open aortic or mitral valve surgery between January 1996 and December 2014 were reviewed using New York State\'s mandatory hospital discharge database. Patients with prior cardiac surgery or pre-existing PPM were excluded. The primary endpoint was PPM implantation within 1 year.
Results
Among 77,882 patients, 63.8% (n = 49,706) underwent aortic valve replacement (AVR), 18.9% (n = 14,686) underwent mitral valve replacement (MVR), 10.5% (n = 8,219) underwent mitral valve repair (MVr), 5.4% (n = 4,202) underwent AVR plus MVR, and 1.4% (n = 1,069) underwent AVR plus MVr. The 1-year PPM implantation rate was 4.5% after MVr, 6.6% after AVR, 9.3% after AVR plus MVr, 10.5% after MVR, and 13.3% after AVR plus MVR (p < 0.001). Across all groups, the majority of PPMs were implanted during the index hospitalization (79.9%). MVr was associated with the lowest risk for PPM and AVR plus MVR with the highest risk. Older age, history of arrhythmias, pre-operative conduction disturbances, and concomitant index procedures were associated with increased risk for PPM during the index hospitalization. Conversely, beyond 30 days, chronic comorbidities were associated with increased risk for PPM.
Conclusions
Conduction disturbances requiring PPM remain a common adverse event after valve surgery. Identifying patients at risk for PPM will help facilitate perioperative planning and inform clinical decision making regarding post-operative rhythm surveillance.

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

J Am Coll Cardiol: 25 Nov 2019; 74:2607-2620
Moskowitz G, Hong KN, Giustino G, Gillinov AM, ... Gelijns AC, Egorova NN
J Am Coll Cardiol: 25 Nov 2019; 74:2607-2620 | PMID: 31753204
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Primary Aldosteronism: JACC State-of-the-Art Review.

Rossi GP

Primary aldosteronism (PA) is a common, but frequently overlooked, cause of arterial hypertension and excess cardiovascular events, particularly atrial fibrillation. As timely diagnosis and treatment can provide a cure of hyperaldosteronism and hypertension, even when the latter is resistant to drug treatment, strategies to screen patients for PA early with a simplified diagnostic algorithm are justified. They can be particularly beneficial in some subgroups of hypertensive patients, as those who are at highest cardiovascular risk. However, identification of the surgically curable cases of PA and achievement of optimal results require subtyping with adrenal vein sampling, which, as it is technically challenging and currently performed only in tertiary referral centers, represents the bottleneck in the work-up of PA. Measures aimed at improving the clinical use of adrenal vein sampling and at developing alternative techniques for subtyping, alongside recommendations for drug treatment, including new development in the field, and for follow-up are discussed.

Copyright © 2019. Published by Elsevier Inc.

J Am Coll Cardiol: 02 Dec 2019; 74:2799-2811
Rossi GP
J Am Coll Cardiol: 02 Dec 2019; 74:2799-2811 | PMID: 31779795
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Impact of Renal Impairment on Beta-Blocker Efficacy in Patients With Heart Failure.

Kotecha D, Gill SK, Flather MD, Holmes J, ... Coats AJS,
Background
Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy.
Objectives
This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR).
Methods
Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm.
Results
Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR.
Conclusions
Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction.

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

J Am Coll Cardiol: 09 Dec 2019; 74:2893-2904
Kotecha D, Gill SK, Flather MD, Holmes J, ... Coats AJS,
J Am Coll Cardiol: 09 Dec 2019; 74:2893-2904 | PMID: 31806133
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Evaluation, Management, and Outcomes of Patients Poorly Responsive to Cardiac Resynchronization Device Therapy.

Varma N, Boehmer J, Bhargava K, Yoo D, ... Gill J, Auricchio A
Background
\"Nonresponse\" to cardiac resynchronization therapy (CRT) is recognized, but definition(s) applied in practice, treatment(s), and their consequences are little known.
Objectives
The authors sought to assess nonresponse in the prospective, international, ADVANCE CRT registry (Advance Cardiac Resynchronization Therapy Registry).
Methods
Each subject\'s response was assessed at 6 months post-implantation using site-specific definitions and compared with the independently derived clinical composite score (CCS). Treatment(s) and hospitalization(s) were tracked during the following 6 months.
Results
Of 1,524 subjects enrolled in 69 centers (68 ± 12 years of age, 32% female, ischemic disease 39%), 74.3% received CRT-defibrillator devices, using mainly quadripolar LV leads (75%) deployed laterally (78%). Indications for CRT were wider than past trials. Among 1,327 evaluable subjects, site-defined nonresponse was 20.0% (greater age, comorbidities, ischemic cardiomyopathy, non-left bundle branch block, and lower %CRT pacing vs. responders). Site definitions used mainly clinical criteria (echocardiography infrequently), and underestimated nonresponders by 35% compared with CCS (58% sensitivity vs. CCS). Overall, more site-defined nonresponders received treatment (55.9% vs. 38.3% of responders; p < 0.001) using medication changes and heart failure education, but device programming less frequently. Intensification of in-clinic/remote evaluations and involvement of heart failure specialists remained minimal. Remarkably, 44% of site-defined nonresponders received no additional treatment. Frequency and duration of hospitalizations, and death, among site-defined nonresponders was significantly higher than responders.
Conclusions
A high incidence of CRT nonresponders persists despite good patient selection and LV lead position, but site identification methods have modest sensitivity. Following diagnosis, nonresponders are often passively managed, without specialty care, with poor outcome. ADVANCE CRT exposes a vulnerable group of heart failure patients. (Advance Cardiac Resynchronization Therapy Registry [ADVANCE CRT]; NCT01805154).

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

J Am Coll Cardiol: 05 Nov 2019; epub ahead of print
Varma N, Boehmer J, Bhargava K, Yoo D, ... Gill J, Auricchio A
J Am Coll Cardiol: 05 Nov 2019; epub ahead of print | PMID: 31748196
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Screening for atrial fibrillation: a call for evidence.

Jones NR, Taylor CJ, Hobbs FDR, Bowman L, Casadei B

Atrial fibrillation (AF) is the most common cardiac arrhythmia and prevalence is predicted to double over the next 30 years due to changing demographics and the rise in prevalence of risk factors such as hypertension and diabetes. Atrial fibrillation is associated with a five-fold increased stroke risk, but anticoagulation in eligible patients can reduce this risk by around 65%. Many people with AF currently go undetected and therefore untreated, either because they are asymptomatic or because they have paroxysmal AF. Screening has been suggested as one approach to increase AF detection rates and reduce the incidence of ischaemic stroke by earlier initiation of anticoagulation therapy. However, international taskforces currently recommend against screening, citing the cost implications and uncertainty over the benefits of a systematic screening programme compared to usual care. A number of large randomized controlled trials have commenced to determine the cost-effectiveness and clinical benefit of screening using a range of devices and across different populations. The recent AppleWatch study demonstrates how advances in technology are providing the public with self-screening devices that are increasingly affordable and accessible. Health care professionals should be aware of the implications of these emerging data for diagnostic pathways and treatment. This review provides an overview of the gaps in the current evidence and a summary of the arguments for and against screening.

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

Eur Heart J: 06 Dec 2019; epub ahead of print
Jones NR, Taylor CJ, Hobbs FDR, Bowman L, Casadei B
Eur Heart J: 06 Dec 2019; epub ahead of print | PMID: 31811716
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The cardiac sympathetic co-transmitter neuropeptide Y is pro-arrhythmic following ST-elevation myocardial infarction despite beta-blockade.

Kalla M, Hao G, Tapoulal N, Tomek J, ... Paterson DJ, Herring N
Aims
ST-elevation myocardial infarction is associated with high levels of cardiac sympathetic drive and release of the co-transmitter neuropeptide Y (NPY). We hypothesized that despite beta-blockade, NPY promotes arrhythmogenesis via ventricular myocyte receptors.
Methods and results
In 78 patients treated with primary percutaneous coronary intervention, sustained ventricular tachycardia (VT) or fibrillation (VF) occurred in 6 (7.7%) within 48 h. These patients had significantly (P < 0.05) higher venous NPY levels despite the absence of classical risk factors including late presentation, larger infarct size, and beta-blocker usage. Receiver operating curve identified an NPY threshold of 27.3 pg/mL with a sensitivity of 0.83 and a specificity of 0.71. RT-qPCR demonstrated the presence of NPY mRNA in both human and rat stellate ganglia. In the isolated Langendorff perfused rat heart, prolonged (10 Hz, 2 min) stimulation of the stellate ganglia caused significant NPY release. Despite maximal beta-blockade with metoprolol (10 μmol/L), optical mapping of ventricular voltage and calcium (using RH237 and Rhod2) demonstrated an increase in magnitude and shortening in duration of the calcium transient and a significant lowering of ventricular fibrillation threshold. These effects were prevented by the Y1 receptor antagonist BIBO3304 (1 μmol/L). Neuropeptide Y (250 nmol/L) significantly increased the incidence of VT/VF (60% vs. 10%) during experimental ST-elevation ischaemia and reperfusion compared to control, and this could also be prevented by BIBO3304.
Conclusions
The co-transmitter NPY is released during sympathetic stimulation and acts as a novel arrhythmic trigger. Drugs inhibiting the Y1 receptor work synergistically with beta-blockade as a new anti-arrhythmic therapy.

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

Eur Heart J: 12 Dec 2019; epub ahead of print
Kalla M, Hao G, Tapoulal N, Tomek J, ... Paterson DJ, Herring N
Eur Heart J: 12 Dec 2019; epub ahead of print | PMID: 31834357
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

One-year outcomes in atrial fibrillation presenting during infections: a nationwide registry-based study.

Gundlund A, Olesen JB, Butt JH, Christensen MA, ... Kümler T, Fosbøl EL
Aims
Thromboprophylaxis guidelines for patients with concurrent atrial fibrillation (AF) during infections are unclear and not supported by data. We compared 1-year outcomes in patients with infection-related AF and infection without AF.
Methods and results
By crosslinking Danish nationwide registry data, AF naïve patients admitted with infection (1996-2016) were identified. Those with AF during the infection (infection-related AF) were matched 1:3 according to age, sex, type of infection, and year with patients with infection without AF. Outcomes (AF, thromboembolic events) were assessed by multivariable Cox regression. The study population comprised 30 307 patients with infection-related AF and 90 912 patients with infection without AF [median age 79 years (interquartile range 71-86), 47.6% males in both groups]. The 1-year absolute risk of AF and thromboembolic events were 36.4% and 7.6%, respectively (infection-related AF) and 1.9% and 4.4%, respectively (infection without AF). In the multivariable analyses, infection-related AF was associated with an increased long-term risk of AF and thromboembolic events compared with infection without AF: hazard ratio (HR) 25.98, 95% confidence interval (CI) 24.64-27.39 for AF and HR 2.10, 95% CI 1.98-2.22 for thromboembolic events. Further, differences in risks existed across different subtypes of infections.
Conclusion
During the first year after discharge, 36% of patients with infection-related AF had a new hospital contact with AF. Infection-related AF was associated with increased risk of thromboembolic events compared with infection without AF and our results suggest that AF related to infection may merit treatment and follow-up similar to that of AF not related to infection.

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: 16 Dec 2019; epub ahead of print
Gundlund A, Olesen JB, Butt JH, Christensen MA, ... Kümler T, Fosbøl EL
Eur Heart J: 16 Dec 2019; epub ahead of print | PMID: 31848584
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Chimeric Antigen Receptor T-Cell Therapy for Cancer and Heart: JACC Council Perspectives.

Ganatra S, Carver JR, Hayek SS, Ky B, ... Barac A, Liu JE

Chimeric antigen receptor (CAR) T-cell therapy has significantly advanced the treatment of patients with relapsed and refractory hematologic malignancies and is increasingly investigated as a therapeutic option of other malignancies. The main adverse effect of CAR T-cell therapy is potentially life-threatening cytokine release syndrome (CRS). Clinical cardiovascular (CV) manifestations of CRS include tachycardia, hypotension, troponin elevation, reduced left ventricular ejection fraction, pulmonary edema, and cardiogenic shock. Although insults related to CRS toxicity might be transient and reversible in most instances in patients with adequate CV reserve, they can be particularly challenging in higher-risk, often elderly patients with pre-existing CV disease. As the use of CAR T-cell therapy expands to include a wider patient population, careful patient selection, pre-treatment cardiac evaluation, and CV risk stratification should be considered within the CAR T-cell treatment protocol. Early diagnosis and management of CV complications in patients with CRS require awareness and multidisciplinary collaboration.

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

J Am Coll Cardiol: 23 Dec 2019; 74:3153-3163
Ganatra S, Carver JR, Hayek SS, Ky B, ... Barac A, Liu JE
J Am Coll Cardiol: 23 Dec 2019; 74:3153-3163 | PMID: 31856973
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Patients with Atrial Fibrillation Taking Nonsteroidal Anti-Inflammatory Drugs and Oral Anticoagulants in the ARISTOTLE Trial.

Dalgaard F, Mulder H, Wojdyla DM, Lopes RD, ... Granger CB, Al-Khatib SM

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) with oral anticoagulants has been associated with an increased risk of bleeding. We investigated the risk of bleeding and major cardiovascular outcomes in patients with atrial fibrillation (AF) taking NSAIDs and apixaban or warfarin.The ARISTOTLE trial (n=18,201) compared apixaban with warfarin in patients with AF at increased risk of stroke. Patients in ARISTOTLE without severe renal (creatine clearance ≤30 mL/min) or liver disease were included in this analysis (n=17,423). NSAID use at baseline, NSAID use during the trial (incident NSAID use) and never users were described. The primary outcome was major bleeding. Secondary outcomes included clinically relevant non-major (CRNM) bleeding, gastrointestinal bleeding, heart failure hospitalization, stroke or systemic embolism, and all-cause mortality. NSAID use during the trial and the interaction between randomized treatment and was analyzed using time dependent Cox proportional hazards models.Those with baseline NSAID use (n=832 [4.8%]), incident NSAID use (n=2185 [13.2%]), and never users were similar in median age [25th, 75th] (70 [64, 77] vs. 70 [63, 75] vs. 70 [62, 76]). Those with NSAID use at baseline and incident NSAID use were more likely to have a history of bleeding (24.5% vs. 21.0% vs 15.6%) than never users. During a median follow-up [25th, 75th] of 1.8 [1.4, 2.3]) years and when excluding those taking NSAID at baseline, we found that incident NSAID use was associated with an increased risk of major bleeding (hazard ratio [HR] 1.61, 95% CI 1.11-2.33) and clinically relevant non-major bleeding (HR 1.70, 95% CI 1.16-2.48), but not gastrointestinal bleeding. No significant interaction was observed between NSAID use and randomized treatment for any outcome.A substantial number of patients in the ARISTOTLE trial took NSAIDs. Incident NSAID use was associated with major and CRNM bleeding, but not gastrointestinal bleeding. The safety and efficacy of apixaban versus warfarin appeared not significantly to be altered by NSAID use. This study warrants more investigation of the effect of NSAIDs on the outcomes of patients treated with apixaban.URL: https://clinicaltrials.gov Unique Identifier: NCT00412984.



Circulation: 20 Nov 2019; epub ahead of print
Dalgaard F, Mulder H, Wojdyla DM, Lopes RD, ... Granger CB, Al-Khatib SM
Circulation: 20 Nov 2019; epub ahead of print | PMID: 31747786
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Impact of Sapien 3 Balloon-Expandable Versus Evolut R Self-Expandable Transcatheter Aortic Valve Implantation in Patients with Aortic Stenosis: Data from a Nationwide Analysis.

Deharo P, Bisson A, Herbert J, Lacour T, ... Cuisset T, Fauchier L

Two competing Transcatheter aortic valve replacement (TAVR) technologies are currently available. Head-to-head comparisons of the relative performances of these two devices have been published. However, long-term clinical outcome evaluation remains limited by the number of patients analyzed, particularly for recent generation devices.Based on the French administrative hospital-discharge database, the study collected information for all consecutive patients treated with TAVR device commercialized in France between 2014 and 2018. Propensity score matching was used for the analysis of outcomes during follow-up. The objective of this study was to analyze the outcomes of TAVR according to Sapien 3 balloon-expandable (BE) versus Evolut R self-expanding (SE) TAVR technology at a nationwide level in France.A total of 31 113 patients treated with either Sapien 3 BE or Evolut R SE TAVR were found in the database. After matching on baseline characteristics, 20 918 patients were analyzed (10 459 in each group with BE or SE valves). During follow-up (mean [SD] 358 [384], median [IQR] 232 [10-599] days), BE TAVR was associated with lower yearly incidence of all-cause death (relative risk [RR] 0.88, corrected p=0.005), cardiovascular death (RR 0.82, corrected p=0.002) and rehospitalization for heart failure (RR 0.84, corrected p<0.0001). BE TAVR was also associated with lower rates of pacemaker implantation after the procedure (RR 0.72, corrected p<0.0001).Based on the largest cohort available, we observed that Sapien 3 BE valves were associated with lower rates of all-cause death, cardiovascular death, rehospitalization for heart failure, and pacemaker implantation after a TAVR procedure.



Circulation: 15 Nov 2019; epub ahead of print
Deharo P, Bisson A, Herbert J, Lacour T, ... Cuisset T, Fauchier L
Circulation: 15 Nov 2019; epub ahead of print | PMID: 31736332
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

A Metastable Atrial State Underlies The Primary Genetic Substrate for MYL4 Mutation-Associated Atrial Fibrillation.

Ghazizadeh Z, Kiviniemi TO, Olafsson S, Plotnick D, ... Hollmén M, MacRae CA

Atrial fibrillation (AF) is the most common clinical arrhythmia and is associated with heart failure, stroke and increased mortality. The myocardial substrate for AF is poorly understood due to limited access to primary human tissue and mechanistic questions around existingormodels.Using anknock-in reporter line we developed a protocol to generate and highly purify human pluripotent stem cell-derived cardiomyocytes displaying physiological and molecular characteristics of atrial cells (hESC-atrial cells). We modeled humanmutants, one of the few definitive genetic causes of AF. To explore non cell-autonomous components of AF substrate, we also created a zebrafishKO model, which exhibited molecular, cellular and physiologic abnormalities that parallel those in humans bearing the cognate mutations.There was evidence of increased retinoic acid signaling in both hESC and zebrafish mutant models, as well as abnormal expression and localization of cytoskeletal proteins, and loss of intracellular NAD and NADH. To identify potentially druggable proximate mechanisms, we performed a chemical suppressor screen integrating multiple human cellular and zebrafishendpoints. This screen identified connexin 43 hemichannel (HC) blockade, as a robust suppressor of the abnormal phenotypes in both models of MYL4-related atrial cardiomyopathy. Immunofluorescence and co-immunoprecipitation studies revealed an interaction between MYL4 and Cx43 with altered localization of Cx43 HCs to the lateral membrane inmutants, as well as in atrial biopsies from unselected forms of human AF. The membrane fraction from -/- hESC-atrial cells demonstrated increased phospho-Cx43 which was further accentuated by retinoic acid (RA) treatment and by the presence of risk alleles at the Pitx2 locus. Protein kinase C was induced by RA, and PKC inhibition also rescued the abnormal phenotypes in the atrial cardiomyopathy models.These data establish a mechanistic link between the transcriptional, metabolic and electrical pathways previously implicated in AF substrate and suggest novel avenues for the prevention or therapy of this common arrhythmia.



Circulation: 15 Nov 2019; epub ahead of print
Ghazizadeh Z, Kiviniemi TO, Olafsson S, Plotnick D, ... Hollmén M, MacRae CA
Circulation: 15 Nov 2019; epub ahead of print | PMID: 31735076
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Alcohol Abstinence in Drinkers with Atrial Fibrillation.

Voskoboinik A, Kalman JM, De Silva A, Nicholls T, ... Taylor AJ, Kistler PM
Background
Excessive alcohol consumption is associated with incident atrial fibrillation and adverse atrial remodeling; however, the effect of abstinence from alcohol on secondary prevention of atrial fibrillation is unclear.
Methods
We conducted a multicenter, prospective, open-label, randomized, controlled trial at six hospitals in Australia. Adults who consumed 10 or more standard drinks (with 1 standard drink containing approximately 12 g of pure alcohol) per week and who had paroxysmal or persistent atrial fibrillation in sinus rhythm at baseline were randomly assigned in a 1:1 ratio to either abstain from alcohol or continue their usual alcohol consumption. The two primary end points were freedom from recurrence of atrial fibrillation (after a 2-week \"blanking period\") and total atrial fibrillation burden (proportion of time in atrial fibrillation) during 6 months of follow-up.
Results
Of 140 patients who underwent randomization (85% men; mean [±SD] age, 62±9 years), 70 were assigned to the abstinence group and 70 to the control group. Patients in the abstinence group reduced their alcohol intake from 16.8±7.7 to 2.1±3.7 standard drinks per week (a reduction of 87.5%), and patients in the control group reduced their alcohol intake from 16.4±6.9 to 13.2±6.5 drinks per week (a reduction of 19.5%). After a 2-week blanking period, atrial fibrillation recurred in 37 of 70 patients (53%) in the abstinence group and in 51 of 70 patients (73%) in the control group. The abstinence group had a longer period before recurrence of atrial fibrillation than the control group (hazard ratio, 0.55; 95% confidence interval, 0.36 to 0.84; P = 0.005). The atrial fibrillation burden over 6 months of follow-up was significantly lower in the abstinence group than in the control group (median percentage of time in atrial fibrillation, 0.5% [interquartile range, 0.0 to 3.0] vs. 1.2% [interquartile range, 0.0 to 10.3]; P = 0.01).
Conclusions
Abstinence from alcohol reduced arrhythmia recurrences in regular drinkers with atrial fibrillation. (Funded by the Government of Victoria Operational Infrastructure Support Program and others; Australian New Zealand Clinical Trials Registry number, ACTRN12616000256471.).

Copyright © 2020 Massachusetts Medical Society.

N Engl J Med: 01 Jan 2020; 382:20-28
Voskoboinik A, Kalman JM, De Silva A, Nicholls T, ... Taylor AJ, Kistler PM
N Engl J Med: 01 Jan 2020; 382:20-28 | PMID: 31893513
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Heart Failure Risk Stratification and Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes Mellitus.

Berg DD, Wiviott SD, Scirica BM, Gurmu Y, ... Braunwald E, Sabatine MS
Background
Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing heart failure. Sodium-glucose cotransporter-2 inhibitors reduce the risk of hospitalization for heart failure (HHF) in patients with T2DM. We aimed to develop and validate a practical clinical risk score for HHF in patients with T2DM and assess whether this score can identify high-risk patients with T2DM who have the greatest reduction in risk for HHF with a sodium-glucose cotransporter-2 inhibitor.
Methods
We developed a clinical risk score for HHF in 8212 patients with T2DM in the placebo arm of SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53). Candidate variables were assessed using multivariable Cox regression, and independent clinical risk indicators achieving statistical significance of <0.001 were included in the risk score. We externally validated the score in 8578 patients with T2DM in the placebo arm of DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58). The relative and absolute risk reductions in HHF with the sodium-glucose cotransporter-2 inhibitor dapagliflozin were assessed by baseline HHF risk.
Results
Five clinical variables were independent risk predictors of HHF: prior heart failure, history of atrial fibrillation, coronary artery disease, estimated glomerular filtration rate, and urine albumin-to-creatinine ratio. A simple integer-based score (0-7 points) using these predictors identified a >20-fold gradient of HHF risk ( for trend <0.001) in both the derivation and validation cohorts, with C indices of 0.81 and 0.78, respectively. Although relative risk reductions with dapagliflozin were similar for patients across the risk scores (25%-34%), absolute risk reductions were greater in those at higher baseline risk (1-sidedfor trend=0.04), with high-risk (2 points) and very-high-risk (≥3 points) patients having 1.5% and 2.7% absolute reductions in Kaplan-Meier estimates of HHF risk at 4 years, respectively.
Conclusions
Risk stratification using a novel clinical risk score for HHF in patients with T2DM identifies patients at higher risk for HHF who derive greater absolute benefit from sodium-glucose cotransporter-2 inhibition.
Clinical trial registration
URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01107886 and NCT01730534.



Circulation: 04 Nov 2019; 140:1569-1577
Berg DD, Wiviott SD, Scirica BM, Gurmu Y, ... Braunwald E, Sabatine MS
Circulation: 04 Nov 2019; 140:1569-1577 | PMID: 31474116
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Monogenic and Polygenic Contributions to Atrial Fibrillation Risk: Results from a National Biobank.

Choi SH, Jurgens SJ, Weng LC, Pirruccello JP, ... Lubitz SA, Ellinor PT

Genome-wide association studies have identified over 100 genetic loci for atrial fibrillation (AF); recent work described an association between loss-of-function (LOF) variants in TTN and early-onset AF.We sought to determine the contribution of rare and common genetic variation to AF risk in the general population.The UK Biobank is a population-based study of 500,000 individuals including a subset with genome-wide genotyping and exome sequencing. In this case-control study, we included AF cases and controls of genetically determined white-European ancestry; analyses were performed using a logistic mixed-effects model adjusting for age, sex, the first 4 principal components of ancestry, empirical relationships and case-control imbalance. An exome wide, gene-based burden analysis was performed to examine the relationship between AF and rare, high-confidence LOF variants in genes with {greater than or equal to} 10 LOF carriers. A polygenic risk score (PRS) for AF was estimated using the LDpred algorithm. We then compared the contribution of AF PRS and LOF variants to AF risk. The study included 1,546 AF cases and 41,593 controls. In an analysis of 9,099 genes with sufficient LOF variant carriers, a significant association between AF and rare LOF variants was observed in a single gene, TTN (OR 2.71, P=2.50x10). The association with AF was more significant (OR 6.15, P=3.26x10) when restricting to LOF variants located in exons highly expressed in cardiac tissue (TTN). Overall, 0.44% of individuals carried TTN variants, of whom 14% had AF. Among individuals in the highest 0.44% of the AF PRS, only 9.3% had AF. In contrast, an AF PRS explained 4.7% of the variance in AF susceptibility, while TTN variants only accounted for 0.2%.Both monogenic and polygenic factors contribute to AF risk in the general population. While monogenic TTNLOF variants confer a substantial AF penetrance, polygenic risk explains a larger proportion of genetic susceptibility to AF.



Circ Res: 05 Nov 2019; epub ahead of print
Choi SH, Jurgens SJ, Weng LC, Pirruccello JP, ... Lubitz SA, Ellinor PT
Circ Res: 05 Nov 2019; epub ahead of print | PMID: 31691645
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Left Bundle Branch Pacing: JACC Review Topic of the Week.

Zhang S, Zhou X, Gold MR

Right ventricular pacing causes electric and mechanical dyssynchrony, which is associated with an increased risk for heart failure and atrial fibrillation. Cardiac resynchronization therapy with biventricular pacing reduces ventricular dyssynchrony and results in clinical benefits in subsets of patients with heart failure with QRS prolongation. Recently, His bundle pacing has increased in use as a physiological pacing modality but is limited by difficult implantation, lower success rates in patients with QRS prolongation, and high, often unstable, pacing capture threshold. Thus, the concept of pacing the conduction system distal to the His bundle to bypass the region of conduction block was proposed. Early clinical studies demonstrated the procedural feasibility of left bundle branch pacing using a transventricular septal approach that generates narrow paced QRS duration, fast synchronized left ventricular activation, and correction of left bundle branch block. The current status and future direction of left bundle branch pacing are summarized in this paper.

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

J Am Coll Cardiol: 16 Dec 2019; 74:3039-3049
Zhang S, Zhou X, Gold MR
J Am Coll Cardiol: 16 Dec 2019; 74:3039-3049 | PMID: 31865972
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Research Needs and Priorities for Catheter Ablation of Atrial Fibrillation: A Report from a National Heart, Lung, and Blood Institute Virtual Workshop.

Al-Khatib SM, Benjamin EJ, Buxton AE, Calkins H, ... Cooper LS, Go AS

Catheter ablation has brought major advances in the management of patients with atrial fibrillation (AF). As evidenced by multiple randomized trials, AF catheter ablation can reduce the risk of recurrent AF and improve quality of life. In some studies, AF ablation significantly reduced cardiovascular hospitalizations. Despite the existing data on AF catheter ablation, numerous knowledge gaps remain in relation to this intervention. This report is based on a recent virtual workshop convened by the National Heart, Lung, and Blood Institute to identify key research opportunities in AF ablation. We outline knowledge gaps related to emerging technologies, the relationship between cardiac structure and function and the success of AF ablation, patient subgroups in whom clinical benefit from ablation varies, and potential platforms to advance clinical research in this area. This report also considers the potential value and challenges of a sham ablation randomized trial. Prioritized research opportunities are identified and highlighted to empower relevant stakeholders to collaborate in designing and conducting effective, cost-efficient, and transformative research to optimize the use and outcomes of AF ablation.



Circulation: 19 Nov 2019; epub ahead of print
Al-Khatib SM, Benjamin EJ, Buxton AE, Calkins H, ... Cooper LS, Go AS
Circulation: 19 Nov 2019; epub ahead of print | PMID: 31744331
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Ischemic Stroke Risk in Patients With Nonvalvular Atrial Fibrillation: JACC Review Topic of the Week.

Alkhouli M, Friedman PA

The last decade has witnessed remarkable advances in pharmacological and nonpharmacological strategies for stroke prevention in patients with atrial fibrillation. However, the currently available clinical stroke risk prediction models do not account for key nonclinical factors (arrhythmia burden, left atrial physiology and anatomy, chemical and electrocardiographic markers) and other competing clinical risks. Hence, their ability to identify patients who will derive the most benefit from pharmacological and mechanical risk prevention strategies remain limited. In this paper, the authors review the current and evolving ischemic stroke risk prediction schemes in patients with nonvalvular atrial fibrillation, highlight the strengths and weaknesses of the models, and discuss the unmet needs in this field.

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

J Am Coll Cardiol: 16 Dec 2019; 74:3050-3065
Alkhouli M, Friedman PA
J Am Coll Cardiol: 16 Dec 2019; 74:3050-3065 | PMID: 31865973
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Clinical impact of conduction disturbances in transcatheter aortic valve replacement recipients: a systematic review and meta-analysis.

Faroux L, Chen S, Muntané-Carol G, Regueiro A, ... Nazif T, Rodés-Cabau J
Aims
The clinical impact of new-onset persistent left bundle branch block (NOP-LBBB) and permanent pacemaker implantation (PPI) on transcatheter aortic valve replacement (TAVR) recipients remains controversial. We aimed to evaluate the impact of (i) periprocedural NOP-LBBB and PPI post-TAVR on 1-year all-cause death, cardiac death, and heart failure hospitalization and (ii) NOP-LBBB on the need for PPI at 1-year follow-up.
Methods and results
We performed a systematic search from PubMed and EMBASE databases for studies reporting raw data on 1-year clinical impact of NOP-LBBB or periprocedural PPI post-TAVR. Data from 30 studies, including 7792 patients (12 studies) and 42 927 patients (21 studies) for the evaluation of the impact of NOP-LBBB and PPI after TAVR were sourced, respectively. NOP-LBBB was associated with an increased risk of all-cause death [risk ratio (RR) 1.32, 95% confidence interval (CI) 1.17-1.49; P < 0.001], cardiac death (RR 1.46, 95% CI 1.20-1.78; P < 0.001), heart failure hospitalization (RR 1.35, 95% CI 1.05-1.72; P = 0.02), and PPI (RR 1.89, 95% CI 1.58-2.27; P < 0.001) at 1-year follow-up. Periprocedural PPI after TAVR was associated with a higher risk of all-cause death (RR 1.17, 95% CI 1.11-1.25; P < 0.001) and heart failure hospitalization (RR 1.18, 95% CI 1.03-1.36; P = 0.02). Permanent pacemaker implantation was not associated with an increased risk of cardiac death (RR 0.84, 95% CI 0.67-1.05; P = 0.13).
Conclusion
NOP-LBBB and PPI after TAVR are associated with an increased risk of all-cause death and heart failure hospitalization at 1-year follow-up. Periprocedural NOP-LBBB also increased the risk of cardiac death and PPI within the year following the procedure. Further studies are urgently warranted to enhance preventive measures and optimize the management of conduction disturbances post-TAVR.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J: 02 Jan 2020; epub ahead of print
Faroux L, Chen S, Muntané-Carol G, Regueiro A, ... Nazif T, Rodés-Cabau J
Eur Heart J: 02 Jan 2020; epub ahead of print | PMID: 31899484
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Searching for Atrial Fibrillation Poststroke: A White Paper of the AF-SCREEN International Collaboration.

Schnabel RB, Haeusler KG, Healey JS, Freedman B, ... Wijeratne T, Yan B

Cardiac thromboembolism attributed to atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes. Stroke may be the first manifestation of previously undetected AF. Given the efficacy of oral anticoagulants in preventing AF-related ischemic strokes, strategies of searching for AF after a stroke using ECG monitoring followed by oral anticoagulation (OAC) treatment have been proposed to prevent recurrent cardioembolic strokes. This white paper by experts from the AF-SCREEN International Collaboration summarizes existing evidence and knowledge gaps on searching for AF after a stroke by using ECG monitoring. New AF can be detected by routine plus intensive ECG monitoring in approximately one-quarter of patients with ischemic stroke. It may be causal, a bystander, or neurogenically induced by the stroke. AF after a stroke is a risk factor for thromboembolism and a strong marker for atrial myopathy. After acute ischemic stroke, patients should undergo 72 hours of electrocardiographic monitoring to detect AF. The diagnosis requires an ECG of sufficient quality for confirmation by a health professional with ECG rhythm expertise. AF detection rate is a function of monitoring duration and quality of analysis, AF episode definition, interval from stroke to monitoring commencement, and patient characteristics including old age, certain ECG alterations, and stroke type. Markers of atrial myopathy (eg, imaging, atrial ectopy, natriuretic peptides) may increase AF yield from monitoring and could be used to guide patient selection for more intensive/prolonged poststroke ECG monitoring. Atrial myopathy without detected AF is not currently sufficient to initiate OAC. The concept of embolic stroke of unknown source is not proven to identify patients who have had a stroke benefitting from empiric OAC treatment. However, some embolic stroke of unknown source subgroups (eg, advanced age, atrial enlargement) might benefit more from non-vitamin K-dependent OAC therapy than aspirin. Fulfilling embolic stroke of unknown source criteria is an indication neither for empiric non-vitamin K-dependent OAC treatment nor for withholding prolonged ECG monitoring for AF. Clinically diagnosed AF after a stroke or a transient ischemic attack is associated with significantly increased risk of recurrent stroke or systemic embolism, in particular, with additional stroke risk factors, and requires OAC rather than antiplatelet therapy. The minimum subclinical AF duration required on ECG monitoring poststroke/transient ischemic attack to recommend OAC therapy is debated.



Circulation: 25 Nov 2019; 140:1834-1850
Schnabel RB, Haeusler KG, Healey JS, Freedman B, ... Wijeratne T, Yan B
Circulation: 25 Nov 2019; 140:1834-1850 | PMID: 31765261
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Patch repair of deep wounds by mobilized fascia.

Correa-Gallegos D, Jiang D, Christ S, Ramesh P, ... Volz T, Rinkevich Y

Mammals form scars to quickly seal wounds and ensure survival by an incompletely understood mechanism. Here we show that skin scars originate from prefabricated matrix in the subcutaneous fascia. Fate mapping and live imaging revealed that fascia fibroblasts rise to the skin surface after wounding, dragging their surrounding extracellular jelly-like matrix, including embedded blood vessels, macrophages and peripheral nerves, to form the provisional matrix. Genetic ablation of fascia fibroblasts prevented matrix from homing into wounds and resulted in defective scars, whereas placing an impermeable film beneath the skin-preventing fascia fibroblasts from migrating upwards-led to chronic open wounds. Thus, fascia contains a specialized prefabricated kit of sentry fibroblasts, embedded within a movable sealant, that preassemble together diverse cell types and matrix components needed to heal wounds. Our findings suggest that chronic and excessive skin wounds may be attributed to the mobility of the fascia matrix.



Nature: 26 Nov 2019; epub ahead of print
Correa-Gallegos D, Jiang D, Christ S, Ramesh P, ... Volz T, Rinkevich Y
Nature: 26 Nov 2019; epub ahead of print | PMID: 31776510
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Trends in U.S. Ambulatory Cardiovascular Care 2013 to 2017: JACC Review Topic of the Week.

Maddox TM, Song Y, Allen J, Chan PS, ... Virani SS, Masoudi FA

The National Cardiovascular Data Registry PINNACLE (Practice Innovation and Clinical Excellence) Registry is the largest outpatient cardiovascular practice registry in the world. It tracks real-world management and quality of 4 common cardiovascular conditions: heart failure, coronary artery disease, atrial fibrillation, and hypertension. In 2013, the PINNACLE Registry contained information on 2,898,505 patients, cared for by 4,859 providers in 431 practices. By 2017, the registry contained information on 6,040,996 patients, cared for by 8,853 providers in 724 practices. During this time period, care processes for PINNACLE patients generally improved. Among patients with heart failure, combined beta-blocker and renin-angiotensin antagonist medication rates increased from 60.7% to 72.8%. Among patients with coronary artery disease, statin medication rates increased from 66% to 80.1%. Among patients with atrial fibrillation, oral anticoagulation rates increased from 52.7% to 65.2%. In contrast, blood pressure control rates among patients with hypertension were largely stable. PINNACLE data also fueled a variety of quality measurement programs and 51 peer-reviewed publications.

Copyright © 2020 American College of Cardiology Foundation. All rights reserved.

J Am Coll Cardiol: 06 Jan 2020; 75:93-112
Maddox TM, Song Y, Allen J, Chan PS, ... Virani SS, Masoudi FA
J Am Coll Cardiol: 06 Jan 2020; 75:93-112 | PMID: 31918838
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association between physical activity and risk of incident arrhythmias in 402 406 individuals: evidence from the UK Biobank cohort.

Elliott AD, Linz D, Mishima R, Kadhim K, ... La Gerche A, Sanders P
Aims
Physical activity reduces cardiovascular disease burden and mortality, although its relationship with cardiac arrhythmias is less certain. The aim of this study was to assess the association between self-reported physical activity and atrial fibrillation (AF), ventricular arrhythmias and bradyarrhythmias, across the UK Biobank cohort.
Methods and results
We included 402 406 individuals (52.5% female), aged 40-69 years, with over 2.8 million person-years of follow-up who underwent self-reported physical activity assessment computed in metabolic equivalent-minutes per week (MET-min/wk) at baseline, detailed physical assessment and medical history evaluation. Arrhythmia episodes were diagnosed through hospital admissions and death reports. Incident AF risk was lower amongst physically active participants, with a more pronounced reduction amongst female participants [hazard ratio (HR) for 1500 vs. 0 MET-min/wk: 0.85, 95% confidence interval (CI) 0.74-0.98] than males (HR for 1500 vs. 0 MET-min/wk: 0.90, 95% CI 0.82-1.0). Similarly, we observed a significantly lower risk of ventricular arrhythmias amongst physically active participants (HR for 1500 MET-min/wk 0.78, 95% CI 0.64-0.96) that remained relatively stable over a broad range of physical activity levels between 0 and 2500 MET-min/wk. A lower AF risk amongst female participants who engaged in moderate levels of vigorous physical activity was observed (up to 2500 MET-min/wk). Vigorous physical activity was also associated with reduced ventricular arrhythmia risk. Total or vigorous physical activity was not associated with bradyarrhythmias.
Conclusion
The risk of AF and ventricular arrhythmias is lower amongst physically active individuals. These findings provide observational support that physical activity is associated with reduced risk of atrial and ventricular arrhythmias.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J: 16 Jan 2020; epub ahead of print
Elliott AD, Linz D, Mishima R, Kadhim K, ... La Gerche A, Sanders P
Eur Heart J: 16 Jan 2020; epub ahead of print | PMID: 31951255
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Incidence, Trends and Outcomes of Type 2 Myocardial Infarction in a Community Cohort.

Raphael CE, Roger VL, Sandoval Y, Singh M, ... Jaffe AS, Gulati R

Type 2 myocardial infarction (T2MI) occurs due to an acute imbalance in myocardial oxygen supply and demand in the absence of athero-thrombosis. Despite being frequently encountered in clinical practice, the population-based incidence and trends remain unknown and the long-term outcomes incompletely characterized.We prospectively recruited residents of Olmsted County, Minnesota who experienced an event associated with a cardiac troponin T (cTnT) >99th percentile of a normal reference population (≥0.01 ng/mL) between 1/1/2003 and 12/31/2012. Events were retrospectively classified into type 1 MI (T1MI, atherothombotic event), T2MI or myocardial injury (troponin rise not meeting criteria for MI) using the universal definition. Outcomes were long term all-cause and cardiovascular mortality and recurrent MI. T2MI was further subclassified by inciting event for supply/demand mismatch.A total of 5460 patients had at least one cTnT ≥0.01 ng/mL, of whom 1365 were classified as index T1MI (age 68.5±14.8 years, 63% male) and 1054 T2MI (age 73.7±15.8 years, 46% male). The annual incidence of T1MI decreased markedly from 202 to 84 per 100,000 persons between 2003 and 2012 (p<0.001), while the incidence of T2MI declined from 130 to 78 per 100,000 persons (p=0.02). Compared to T1MI, patients with T2MI had higher long-term all-cause mortality after adjustment for age and sex, driven by early and non-cardiovascular death. Rates of cardiovascular death were similar after either type of MI (HR 0.8, 95% CI 0.7-1.0, p=0.11). Sub-classification of T2MI by etiology demonstrated a more favorable prognosis when the principal provoking mechanism was arrhythmia, compared with post-operative status, hypotension, anemia and hypoxia. After index T2MI, the most common MI during follow-up was a recurrent T2MI while the occurrence of a new T1MI was relatively rare (estimated rates 9.7% and 1.7% at 5 years).There has been an evolution in type of MI occurring in the community over a decade, with the incidence of T2MI now being similar to T1MI. Mortality after T2MI is higher and driven by early and non-cardiovascular death. The provoking mechanism of supply/demand mismatch affects long-term survival. These findings underscore the healthcare burden of T2MI and provide benchmarks for clinical trial design.



Circulation: 05 Jan 2020; epub ahead of print
Raphael CE, Roger VL, Sandoval Y, Singh M, ... Jaffe AS, Gulati R
Circulation: 05 Jan 2020; epub ahead of print | PMID: 31902228
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Results of a 6-week treatment with 10 mg prednisolone in patients with hand osteoarthritis (HOPE): a double-blind, randomised, placebo-controlled trial.

Kroon FPB, Kortekaas MC, Boonen A, Böhringer S, ... Allaart CF, Kloppenburg M
Background
Hand osteoarthritis is a prevalent joint condition that has a high burden of disease and an unmet medical need for effective therapeutic options. Since local inflammation is recognised as contributing to osteoarthritic complaints, the Hand Osteoarthritis Prednisolone Efficacy (HOPE) study aimed to investigate the efficacy and safety of short-term prednisolone in patients with painful hand osteoarthritis and synovial inflammation.
Methods
The HOPE study is a double-blind, randomised, placebo-controlled trial. We recruited eligible adults from rheumatology outpatient clinics at two sites in the Netherlands. Patients were considered eligible if they had symptomatic hand osteoarthritis and signs of inflammation in their distal and proximal interphalangeal (DIP/PIP) joints. For inclusion, patients were required to have four or more DIP/PIP joints with osteoarthritic nodes; at least one DIP/PIP joint with soft swelling or erythema; at least one DIP/PIP joint with a positive power Doppler signal or synovial thickening of at least grade 2 on ultrasound; and finger pain of at least 30 mm on a 100-mm visual analogue scale (VAS) that flared up during a 48-h non-steroidal anti-inflammatory drug (NSAID) washout (defined as worsening of finger pain by at least 20 mm on the VAS). Eligible patients were randomly assigned (1:1) to receive 10 mg prednisolone or placebo orally once daily for 6 weeks, followed by a 2-week tapering scheme, and a 6-week follow-up without study medication. The patients and study team were masked to treatment assignment. The primary endpoint was finger pain, assessed on a VAS, at 6 weeks in participants who had been randomly assigned to groups and attended the baseline visit. This study is registered with the Netherlands Trial Registry, number NTR5263.
Findings
We screened patients for enrolment between Dec 3, 2015, and May 31, 2018. Patients completed baseline visits and started treatment between Dec 14, 2015, and July 2, 2018, and the last study visit of the last patient was Oct 4, 2018. Of 149 patients assessed for eligibility, 57 (38%) patients were excluded (predominantly because they did not meet one or several inclusion criteria, most often because of an absence of synovial inflammation or of flare-ups after NSAID washout) and 92 (62%) patients were eligible for inclusion. We randomly assigned 46 (50%) patients to receive prednisolone and 46 (50%) patients to receive placebo, all of whom were included in the modified intention-to-treat analysis of the primary endpoint. 42 (91%) patients in the prednisolone group and 42 (91%) in the placebo group completed the 14-week study. The mean change between baseline and week 6 on VAS-reported finger pain was -21·5 (SD 21·7) in the prednisolone group and -5·2 (24·3) in the placebo group, with a mean between-group difference (of prednisolone vs placebo) of -16·5 (95% CI -26·1 to -6·9; p=0·0007). The number of non-serious adverse events was similar between the groups. Five serious adverse events were reported during our study: one serious adverse event in the prednisolone group (a myocardial infarction) and four serious adverse events in the placebo group (an infected traumatic leg haematoma that required surgery, bowel surgery, atrial fibrillation that required a pacemaker implantation, and symptomatic uterine myomas that required a hysterectomy). Four (4%) patients discontinued the study because of an adverse event: one (2%) patient receiving prednisolone (for a myocardial infarction) and three (7%) patients receiving placebo (for surgery of the bowel and for an infected leg haematoma and for Lyme disease arthritis of the knee).
Interpretation
Treatment with 10 mg prednisolone for 6 weeks is efficacious and safe for the treatment of patients with painful hand osteoarthritis and signs of inflammation. The results of our study provide clinicians with a new short-term treatment option for patients with hand osteoarthritis who report a flare-up of their disease.
Funding
Dutch Arthritis Society.

Copyright © 2019 Elsevier Ltd. All rights reserved.

Lancet: 07 Nov 2019; epub ahead of print
Kroon FPB, Kortekaas MC, Boonen A, Böhringer S, ... Allaart CF, Kloppenburg M
Lancet: 07 Nov 2019; epub ahead of print | PMID: 31727410
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Improved Survival with Extracorporeal Cardiopulmonary Resuscitation Despite Progressive Metabolic Derangement Associated with Prolonged Resuscitation.

Bartos JA, Grunau B, Carlson C, Duval S, ... Aufderheide TP, Yannopoulos D

Likelihood of neurologically favorable survival declines with prolonged resuscitation. However, the ability of extracorporeal cardiopulmonary resuscitation (ECPR) to modulate this decline is unknown. We aimed to examine the effects of resuscitation duration on survival and metabolic profile in patients who undergo ECPR for refractory ventricular fibrillation/ventricular tachycardia out-of-hospital cardiac arrest (VF/VT OHCA).We retrospectively evaluated survival in 160 consecutive adults with refractory VF/VT OHCA treated with the UMN-ECPR protocol (transport with ongoing CPR to the cardiac catheterization laboratory for ECPR) compared with 654 adults who had received standard CPR in the amiodarone arm of the ALPS trial. We evaluated the metabolic changes and rate of survival in relation to duration of CPR in UMN-ECPR patients.Neurologically favorable survival was significantly higher in UMN-ECPR patients vs. ALPS patients (33% vs. 23%; p = 0.01) overall. The mean duration of CPR was also significantly longer for UMN-ECPR patients vs. ALPS patients (60 vs. 35 min; p < 0.001). Analysis of the effect of CPR duration on neurologically favorable survival demonstrated significantly higher neurologically favorable survival for UMN-ECPR patients compared to ALPS patients at each CPR duration interval less than 60 minutes; however, longer CPR duration was associated with progressive decline in neurologically favorable survival in both groups. All UMN-ECPR patients with 20-29 minutes of CPR (8/8) survived with neurologically favorable status compared to 24% (24/102) for ALPS patients with the same duration of CPR. There were no neurologically favorable survivors in the ALPS cohort with CPR {greater than or equal to}40 minutes, whereas neurologically favorable survival was 25% (9/36) for UMN-ECPR patients with 50-59 minutes of CPR and 19% with {greater than or equal to}60 minutes. Relative risk of mortality or poor neurologic function was significantly reduced in UMN-ECPR patients with CPR duration {greater than or equal to} 60 minutes, Significant metabolic changes included decline in pH, increased lactic acid and paCO2, and thickened left ventricular wall with prolonged professional CPR.ECPR was associated with improved neurologically favorable survival at all CPR durations less than 60 minutes despite severe progressive metabolic derangement. However, CPR duration remains a critical determinate of survival.



Circulation: 02 Jan 2020; epub ahead of print
Bartos JA, Grunau B, Carlson C, Duval S, ... Aufderheide TP, Yannopoulos D
Circulation: 02 Jan 2020; epub ahead of print | PMID: 31896278
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Oral Anticoagulation for Patients With Atrial Fibrillation on Long-Term Hemodialysis.

Kuno T, Takagi H, Ando T, Sugiyama T, ... Burger A, Bangalore S
Background
Patients on long-term dialysis are at increased risk of bleeding. Although oral anticoagulants (OACs) are recommended for atrial fibrillation (AF) to reduce the risk of stroke, randomized trials have excluded these populations. As such, the net clinical benefit of OACs among patients on dialysis is unknown.
Objectives
This study aimed to investigate the efficacy and safety of OACs in patients with AF on long-term dialysis.
Methods
MEDLINE and EMBASE were searched through June 10, 2019, for studies that investigated the efficacy and safety of different OAC strategies in patients with AF on long-term dialysis. The efficacy outcomes were ischemic stroke and/or systemic thromboembolism, all-cause mortality, and the safety outcome was major bleeding.
Results
This study identified 16 eligible observational studies (N = 71,877) regarding patients on long-term dialysis who had AF. Only 2 of 16 studies investigated direct OACs. Outcomes for dabigatran and rivaroxaban were limited to major bleeding events. Compared with no anticoagulants, apixaban and warfarin were not associated with a significant decrease in stroke and/or systemic thromboembolism (apixaban 5 mg, hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.30 to 1.17; apixaban 2.5 mg, HR: 1.00; 95% CI: 0.52 to 1.93; warfarin, HR: 0.91; 95% CI: 0.72 to 1.16). Apixaban 5 mg was associated with a significantly lower risk of mortality (vs. warfarin, HR: 0.65; 95% CI: 0.45 to 0.93; vs. apixaban 2.5 mg, HR: 0.62; 95% CI: 0.42 to 0.90; vs. no anticoagulant, HR: 0.61; 95% CI: 0.41 to 0.90). Warfarin was associated with a significantly higher risk of major bleeding than apixaban 5 min/2.5 mg and no anticoagulant (vs. apixaban 5 mg, HR: 1.41; 95% CI: 1.07 to 1.88; vs. apixaban 2.5 mg, HR: 1.40; 95% CI: 1.07 to 1.82; vs. no anticoagulant, HR: 1.31; 95% CI: 1.15 to 1.50). Dabigatran and rivaroxaban were also associated with significantly higher risk of major bleeding than apixaban and no anticoagulant.
Conclusions
This meta-analysis showed that OACs were not associated with a reduced risk of thromboembolism in patients with AF on long-term dialysis. Warfarin, dabigatran, and rivaroxaban were associated with significantly higher bleeding risk compared with apixaban and no anticoagulant. The benefit-to-risk ratio of OACs in patients with AF on long-term dialysis warrants validation in randomized clinical trials.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 27 Jan 2020; 75:273-285
Kuno T, Takagi H, Ando T, Sugiyama T, ... Burger A, Bangalore S
J Am Coll Cardiol: 27 Jan 2020; 75:273-285 | PMID: 31976865
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

An International Multi-Center Evaluation of Type 5 Long QT Syndrome: A Low Penetrant Primary Arrhythmic Condition.

Roberts JD, Asaki SY, Mazzanti A, Bos JM, ... Priori SG, Ackerman MJ

Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic features associated with rarevariants implicated in LQT5 was sought through an international multi-center collaboration.Patients with either presumed autosomal dominant LQT5 (N = 229) or the recessive Type 2 Jervell and Lange-Nielsen syndrome (JLNS2, N = 19) were enrolled from 22 genetic arrhythmia clinics and 4 registries from 9 countries.variants were evaluated for ECG penetrance (defined as QTc > 460ms on presenting ECG) and genotype-phenotype segregation. Multivariable Cox regression was used to compare the associations between clinical and genetic variables with a composite primary outcome of definite arrhythmic events, including appropriate implantable cardioverter-defibrillator shocks, aborted cardiac arrest, and sudden cardiac death.A total of 32 distinctrare variants were identified in 89 probands and 140 genotype positive family members with presumed LQT5 and an additional 19 JLNS2 patients. Among presumed LQT5 patients, the mean QTc on presenting ECG was significantly longer in probands (476.9 ± 38.6ms) compared to genotype positive family members (441.8 ± 30.9ms, p<0.001). ECG penetrance for heterozygous genotype positive family members was 20.7% (29/140). A definite arrhythmic event was experienced in 16.9% (15/89) of heterozygous probands in comparison with 1.4% (2/140) of family members (adjusted hazard ratio [HR]: 11.6, 95% confidence interval [CI]: 2.6-52.2; p=0.001). Event incidence did not differ significantly for JLNS2 patients relative to the overall heterozygous cohort (10.5% [2/19]; HR: 1.7, 95% CI: 0.3-10.8, p=0.590). The cumulative prevalence of the 32variants in the Genome Aggregation Database (gnomAD), which is a human database of exome and genome sequencing data from now over 140,000 individuals, was 238-fold greater than the anticipated prevalence of all LQT5 combined (0.238% vs. 0.001%).The present study suggests that putative/confirmed loss-of-functionvariants predispose to QT-prolongation, however the low ECG penetrance observed suggests they do not manifest clinically in the majority of individuals, aligning with the mild phenotype observed for JLNS2 patients.



Circulation: 15 Jan 2020; epub ahead of print
Roberts JD, Asaki SY, Mazzanti A, Bos JM, ... Priori SG, Ackerman MJ
Circulation: 15 Jan 2020; epub ahead of print | PMID: 31941373
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Survival After Intravenous Versus Intraosseous Amiodarone, Lidocaine or Placebo in Out-of-Hospital Shock-Refractory Cardiac Arrest.

Daya MR, Leroux BG, Dorian P, Rea TD, ... Kudenchuk PJ,

Antiarrhythmic drugs have not proven to significantly improve overall survival after out-of-hospital cardiac arrest (OHCA) from shock-refractory ventricular fibrillation/pulseless ventricular tachycardia (VF/VT). How this might be influenced by the route of drug administration is not known.In this pre-specified analysis of a randomized, placebo-controlled clinical trial, we compared differences in survival to hospital discharge in adults with shock-refractory VF/VT OHCA who were randomized by emergency medical services (EMS) personnel to an antiarrhythmic drug versus placebo in the Resuscitation Outcomes Consortium Amiodarone, Lidocaine or Placebo Study (ALPS), when stratified by the intravenous (IV) versus intraosseous (IO) route of administration.Of 3,019 randomized patients with known vascular access site, 2,358 received ALPS drugs IV and 661 patients by IO route. IO and IV groups differed in sex, time-to-EMS arrival, and some CPR characteristics, but were similar in others, including time-to-IV/IO-drug receipt. Overall hospital discharge survival was 23%. Compared to placebo, discharge survival was significantly higher in recipients of IV amiodarone ((adjusted risk ratio (RR) 1.26 (95% confidence interval (CI) 1.06, 1.50); adjusted absolute survival difference 5.5% (95% CI 1.5, 9.5)) and IV lidocaine (RR 1.21 (95% CI 1.02, 1.45)); absolute survival difference 4.7% (95% CI 0.7, 8.8)); but not in recipients of IO amiodarone (RR 0.94 (95% CI 0.66, 1.32)) or IO lidocaine (RR 1.03 (95% CI 0.74, 1.44)). Survival to hospital admission also increased significantly when drugs were given IV but not IO, and favored improved neurological outcome at discharge. There were no outcome differences between IV and IO placebo, indicating the access route itself did not demarcate patients with poor prognosis. The study was underpowered to assess IV/IO-drug interactions, which were not statistically significant.We found no significant effect modification by drug administration route for amiodarone or lidocaine compared to placebo during OHCA. However, point estimates for the effects of both drugs compared to placebo were greater for the IV than IO route across all outcomes and beneficial only for IV. Given that the study was underpowered to statistically assess interactions, these findings signal the potential importance of the drug administration route during resuscitation that merits further investigation.



Circulation: 15 Jan 2020; epub ahead of print
Daya MR, Leroux BG, Dorian P, Rea TD, ... Kudenchuk PJ,
Circulation: 15 Jan 2020; epub ahead of print | PMID: 31941354
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Medical Therapies for Heart Failure With Preserved Ejection Fraction.

Kjeldsen SE, von Lueder TG, Smiseth OA, Wachtell K, ... Devereux RB, Zannad F

Current cardiovascular pharmacotherapy targets maladaptive overactivation of the renin-angiotensin-aldosterone system (RAAS), which occurs throughout the continuum of cardiovascular disease spanning from hypertension to heart failure with reduced ejection fraction. Over the past 16 years, 4 prospective, randomized, placebo-controlled clinical trials using candesartan, perindopril, irbesartan, and spironolactone in patients with heart failure with preserved ejection fraction (HFpEF) failed to demonstrate increased efficacy of RAAS blockade added to guideline-directed medical therapy. We reappraise these trials and their weaknesses, which precluded statistically significant findings. Recently, dual-acting RAAS blockade with sacubitril-valsartan relative to stand-alone valsartan failed to improve outcome in the PARAGON-HF trial (Efficacy and Safety of LCZ696 Compared with Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction). The majority of patients with HFpEF experience hypertension, frequently with subclinical left ventricular dysfunction, contributed to by comorbidities such as coronary disease, diabetes mellitus, overweight, and atrial fibrillation. Contrasting the findings in HFpEF, trials evaluating RAAS blockade on either side of HFpEF on the cardiovascular continuum in patients with high-risk hypertension and heart failure with reduced ejection fraction, respectively, showed positive outcomes. We do not have a biologically plausible explanation for such divergent efficacy of RAAS blockade. Based on considerations of well-established clinical efficacy in hypertension and heart failure with reduced ejection fraction and the shortcomings of aforementioned clinical trials in HFpEF, we argue that RAAS blockers including MRAs (mineralocorticoid receptor antagonists; aldosterone antagonists) should be used in the treatment of patients with HFpEF.



Hypertension: 01 Dec 2019:HYPERTENSIONAHA11914057; epub ahead of print
Kjeldsen SE, von Lueder TG, Smiseth OA, Wachtell K, ... Devereux RB, Zannad F
Hypertension: 01 Dec 2019:HYPERTENSIONAHA11914057; epub ahead of print | PMID: 31786973
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells.

Zhang B, Ma S, Rachmin I, He M, ... Fisher DE, Hsu YC

Empirical and anecdotal evidence has associated stress with accelerated hair greying (formation of unpigmented hairs), but so far there has been little scientific validation of this link. Here we report that, in mice, acute stress leads to hair greying through the fast depletion of melanocyte stem cells. Using a combination of adrenalectomy, denervation, chemogenetics, cell ablation and knockout of the adrenergic receptor specifically in melanocyte stem cells, we find that the stress-induced loss of melanocyte stem cells is independent of immune attack or adrenal stress hormones. Instead, hair greying results from activation of the sympathetic nerves that innervate the melanocyte stem-cell niche. Under conditions of stress, the activation of these sympathetic nerves leads to burst release of the neurotransmitter noradrenaline (also known as norepinephrine). This causes quiescent melanocyte stem cells to proliferate rapidly, and is followed by their differentiation, migration and permanent depletion from the niche. Transient suppression of the proliferation of melanocyte stem cells prevents stress-induced hair greying. Our study demonstrates that neuronal activity that is induced by acute stress can drive a rapid and permanent loss of somatic stem cells, and illustrates an example in which the maintenance of somatic stem cells is directly influenced by the overall physiological state of the organism.



Nature: 21 Jan 2020; epub ahead of print
Zhang B, Ma S, Rachmin I, He M, ... Fisher DE, Hsu YC
Nature: 21 Jan 2020; epub ahead of print | PMID: 31969699
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Blood Pressure Variability and Incidence of New-Onset Atrial Fibrillation: A Nationwide Population-Based Study.

Lee SR, Choi YJ, Choi EK, Han KD, ... Oh S, Lip GYH

Blood pressure variability is a well-known risk factor for cardiovascular disease, but its association with atrial fibrillation (AF) is uncertain. We aimed to evaluate the association between visit-to-visit blood pressure variability and incident AF. This population-based cohort study used database from the Health Screening Cohort, which contained a complete set of medical claims and a biannual health checkup information of the Koran population. A total of 8 063 922 individuals who had at least 3 health checkups with blood pressure measurement between 2004 and 2010 were collected after excluding subjects with preexisting AF. Blood pressure variability was defined as variability independence of the mean and was divided into 4 quartiles. During a mean follow-up of 6.8 years, 140 086 subjects were newly diagnosed with AF. The highest blood pressure variability (fourth quartile) was associated with an increased risk of AF (hazard ratio, 95% CI; systolic blood pressure: 1.06, 1.05-1.08; diastolic blood pressure: 1.07, 1.05-1.08) compared with the lowest (first quartile). Among subjects in the fourth quartile in both systolic and diastolic blood pressure variability, the risk of AF was 7.6% higher than those in the first quartile. Moreover, this result was consistent in both patients with or without prevalent hypertension. In subgroup analysis, the impact of high blood pressure variability on AF development was stronger in high-risk subjects, who were older (≥65 years), with diabetes mellitus or chronic kidney disease. Our findings demonstrated that higher blood pressure variability was associated with a modestly increased risk of AF.



Hypertension: 15 Dec 2019:HYPERTENSIONAHA11913708; epub ahead of print
Lee SR, Choi YJ, Choi EK, Han KD, ... Oh S, Lip GYH
Hypertension: 15 Dec 2019:HYPERTENSIONAHA11913708; epub ahead of print | PMID: 31838903
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

High Blood Pressure and Cardiovascular Disease.

Fuchs FD, Whelton PK

Fragmented investigation has masked the overall picture for causes of cardiovascular disease (CVD). Among the risk factors for CVD, high blood pressure (BP) is associated with the strongest evidence for causation and it has a high prevalence of exposure. Biologically, normal levels of BP are considerably lower than what has typically been characterized as normal in research and clinical practice. We propose that CVD is primarily caused by a right-sided shift in the population distribution of BP. Our view that BP is the predominant risk factor for CVD is based on conceptual postulates that have been tested in observational investigations and clinical trials. Large cohort studies have demonstrated that high BP is an important risk factor for heart failure, atrial fibrillation, chronic kidney disease, heart valve diseases, aortic syndromes, and dementia, in addition to coronary heart disease and stroke. In multivariate modeling, the presumed attributable risk of high BP for stroke and coronary heart disease has increased steadily with progressive use of lower values for normal BP. Meta-analysis of BP-lowering randomized controlled trials has demonstrated a benefit which is almost identical to that predicted from BP risk relationships in cohort studies. Prevention of age-related increases in BP would, in large part, reduce the vascular consequences usually attributed to aging, and together with intensive treatment of established hypertension would eliminate a large proportion of the population burden of BP-related CVD.



Hypertension: 22 Dec 2019:HYPERTENSIONAHA11914240; epub ahead of print
Fuchs FD, Whelton PK
Hypertension: 22 Dec 2019:HYPERTENSIONAHA11914240; epub ahead of print | PMID: 31865786
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Ang II (Angiotensin II) Conversion to Angiotensin-(1-7) in the Circulation Is POP (Prolyloligopeptidase)-Dependent and ACE2 (Angiotensin-Converting Enzyme 2)-Independent.

Serfozo P, Wysocki J, Gulua G, Schulze A, ... García-Horsman JA, Batlle D

The Ang II (Angiotensin II)-Angiotensin-(1-7) axis of the Renin Angiotensin System encompasses 3 enzymes that form Angiotensin-(1-7) [Ang-(1-7)] directly from Ang II: ACE2 (angiotensin-converting enzyme 2), PRCP (prolylcarboxypeptidase), and POP (prolyloligopeptidase). We investigated their relative contribution to Ang-(1-7) formation in vivo and also ex vivo in serum, lungs, and kidneys using models of genetic ablation coupled with pharmacological inhibitors. In wild-type (WT) mice, infusion of Ang II resulted in a rapid increase of plasma Ang-(1-7). In / mice, Ang II infusion resulted in a similar increase in Ang-(1-7) as in WT (563±48 versus 537±70 fmol/mL, respectively), showing that the bulk of Ang-(1-7) formation in circulation is essentially independent of ACE2 and PRCP. By contrast, a POP inhibitor, Z-Pro-Prolinal reduced the rise in plasma Ang-(1-7) after infusing Ang II to control WT mice. In POP mice, the increase in Ang-(1-7) was also blunted as compared with WT mice (309±46 and 472±28 fmol/mL, respectively =0.01), and moreover, the rate of recovery from acute Ang II-induced hypertension was delayed (=0.016). In ex vivo studies, POP inhibition with ZZP reduced Ang-(1-7) formation from Ang II markedly in serum and in lung lysates. By contrast, in kidney lysates, the absence of ACE2, but not POP, obliterated Ang-(1-7) formation from added Ang II. We conclude that POP is the main enzyme responsible for Ang II conversion to Ang-(1-7) in the circulation and in the lungs, whereas Ang-(1-7) formation in the kidney is mainly ACE2-dependent.



Hypertension: 01 Dec 2019:HYPERTENSIONAHA11914071; epub ahead of print
Serfozo P, Wysocki J, Gulua G, Schulze A, ... García-Horsman JA, Batlle D
Hypertension: 01 Dec 2019:HYPERTENSIONAHA11914071; epub ahead of print | PMID: 31786979
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Should This Patient Be Screened for Atrial Fibrillation?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Burns RB, Zimetbaum P, Lubitz SA, Smetana GW

Atrial fibrillation (AFib) is the most common type of cardiac arrhythmia, affecting 2.7 million to 6.1 million persons in the United States. Although some persons with AFib have no symptoms, others do. For those without symptoms, AFib may be detected by 12-lead electrocardiogram (ECG), single-lead monitors (such as ambulatory blood pressure monitors and pulse oximeters), or consumer devices (such as wearable monitors and smartphones). Pulse palpation and heart auscultation also may detect AFib. In a systematic review, screening with ECG identified more new cases of AFib than no screening. Atrial fibrillation is an important cause of stroke, and without anticoagulant treatment, patients with AFib have approximately a 5-fold increased risk for stroke. The U.S. Preventive Services Task Force reviewed the benefits and harms of ECG screening for AFib in adults aged 65 years or older and found inadequate evidence that ECG identifies AFib more effectively than usual care. This conclusion is in contrast to guidelines from the European Society of Cardiology and the National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand, which found that active screening for AFib in patients older than 65 years may be useful. Here, 2 cardiologists discuss the risks and benefits of screening for AFib, if and when they would recommend screening, and whether they would recommend anticoagulation for a patient with screen-detected AFib.



Ann Intern Med: 02 Dec 2019; 171:828-836
Burns RB, Zimetbaum P, Lubitz SA, Smetana GW
Ann Intern Med: 02 Dec 2019; 171:828-836 | PMID: 31791056
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Sex differences in cardiometabolic disorders.

Gerdts E, Regitz-Zagrosek V

The prevalence of cardiometabolic disorders in both women and men has increased worldwide and is linked to a rise in obesity and obesity-associated associated clustering of other cardiometabolic risk factors such as hypertension, impaired glucose regulation and dyslipidemia. However, the predominance of common types of cardiometabolic disorders such as heart failure, atrial fibrillation and ischemic heart disease is sex specific, and our identification of these and the underlying mechanisms is only just emerging. New evidence suggests that sex hormones, sex-specific molecular mechanisms and gender influence glucose and lipid metabolisms, as well as cardiac energy metabolism, and function. Here we review sex differences in cardiometabolic risk factors, associated preclinical and clinical cardiac disorders and potential therapeutic avenues.



Nat Med: 06 Nov 2019; epub ahead of print
Gerdts E, Regitz-Zagrosek V
Nat Med: 06 Nov 2019; epub ahead of print | PMID: 31700185
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Keyhole hysterectomy is effective for women with heavy menstrual bleeding.

Cook R, Lyon-Maris J, Davidson P

The studyCooper K, Breeman S, Scott NW, et al. Laparoscopic supracervical hysterectomy versus endometrial ablation for women with heavy menstrual bleeding (HEALTH): a parallel-group, open-label, randomised controlled trial.2019;394:1425-36.The study was funded by the NIHR Health Technology Assessment Programme (project number 12/35/23).To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000837/keyhole-hysterectomy-is-effective-for-women-with-heavy-menstrual-bleeding.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

BMJ: 02 Jan 2020; 368:l6764
Cook R, Lyon-Maris J, Davidson P
BMJ: 02 Jan 2020; 368:l6764 | PMID: 31900245
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prevalence and Risk Factors of White Matter Lesions in Tibetan Patients Without Acute Stroke.

Jin H, Ding Z, Lian S, Zhao Y, ... Yan G, Sun Y

Background and Purpose- Studies on the prevalence and risk factors of white matter lesions (WMLs) in Tibetans living at high altitudes are scarce. We conducted this study to determine the prevalence and risks of WMLs in Tibetan patients without or with nonacute stroke. Methods- We undertook a retrospective analysis of medical records of patients treated at the People\'s Hospital of Tibetan Autonomous Region and identified a total of 301 Tibetan patients without acute stroke. WML severity was graded by the Fazekas Scale. We assessed the overall and age-specific prevalence of WMLs and analyzed associations between WMLs and related factors with univariate and multivariate methods. Results- Of the 301 patients, 87 (28.9%) had peripheral vertigo, 83 (27.3%) had primary headache, 52 (17.3%) had a history of stroke, 36 (12.0%) had an anxiety disorder, 29 (9.6%) had epilepsy, 12 (4.0%) had infections of the central nervous system, and 3 (1.0%) had undetermined diseases. WMLs were present in 245 (81.4%) patients, and 54 (17.9%) were younger than 40 years. Univariate analysis showed that age, history of cerebral infarction, hypertension, the thickness of the common carotid artery intima, and plaque within the intracarotid artery were related risks for WMLs. Ordered logistic analysis showed that age, history of cerebral ischemic stroke, hypertension, male sex, and atrial fibrillation were associated with WML severity. Conclusions- Risk factors for WMLs appear similar for Tibetans residing at high altitudes and individuals living in the plains. Further investigations are needed to determine whether Tibetans residing at high altitudes have a higher burden of WMLs than inhabitants of the plains.



Stroke: 03 Nov 2019:STROKEAHA119027115; epub ahead of print
Jin H, Ding Z, Lian S, Zhao Y, ... Yan G, Sun Y
Stroke: 03 Nov 2019:STROKEAHA119027115; epub ahead of print | PMID: 31679502
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association of Premature Natural and Surgical Menopause With Incident Cardiovascular Disease.

Honigberg MC, Zekavat SM, Aragam K, Finneran P, ... Scott NS, Natarajan P
Importance
Recent guidelines endorse using history of menopause before age 40 years to refine atherosclerotic cardiovascular disease risk assessments among middle-aged women. Robust data on cardiovascular disease risk in this population are lacking.
Objective
To examine the development of cardiovascular diseases and cardiovascular risk factors in women with natural and surgical menopause before age 40 years.
Design, setting, and participants
Cohort study (UK Biobank), with adult residents of the United Kingdom recruited between 2006 and 2010. Of women who were 40 to 69 years old and postmenopausal at study enrollment, 144 260 were eligible for inclusion. Follow-up occurred through August 2016.
Exposures
Natural premature menopause (menopause before age 40 without oophorectomy) and surgical premature menopause (bilateral oophorectomy before age 40). Postmenopausal women without premature menopause served as the reference group.
Main outcomes and measures
The primary outcome was a composite of incident coronary artery disease, heart failure, aortic stenosis, mitral regurgitation, atrial fibrillation, ischemic stroke, peripheral artery disease, and venous thromboembolism. Secondary outcomes included individual components of the primary outcome, incident hypertension, hyperlipidemia, and type 2 diabetes.
Results
Of 144 260 postmenopausal women included (mean [SD] age at enrollment, 59.9 [5.4] years), 4904 (3.4%) had natural premature menopause and 644 (0.4%) had surgical premature menopause. Participants were followed up for a median of 7 years (interquartile range, 6.3-7.7). The primary outcome occurred in 5415 women (3.9%) with no premature menopause (incidence, 5.70/1000 woman-years), 292 women (6.0%) with natural premature menopause (incidence, 8.78/1000 woman-years) (difference vs no premature menopause, +3.08/1000 woman-years [95% CI, 2.06-4.10]; P < .001), and 49 women (7.6%) with surgical premature menopause (incidence, 11.27/1000 woman-years) (difference vs no premature menopause, +5.57/1000 woman-years [95% CI, 2.41-8.73]; P < .001). For the primary outcome, natural and surgical premature menopause were associated with hazard ratios of 1.36 (95% CI, 1.19-1.56; P < .001) and 1.87 (95% CI, 1.36-2.58; P < .001), respectively, after adjustment for conventional cardiovascular disease risk factors and use of menopausal hormone therapy.
Conclusions and relevance
Natural and surgical premature menopause (before age 40 years) were associated with a small but statistically significant increased risk for a composite of cardiovascular diseases among postmenopausal women. Further research is needed to understand the mechanisms underlying these associations.



JAMA: 17 Nov 2019; epub ahead of print
Honigberg MC, Zekavat SM, Aragam K, Finneran P, ... Scott NS, Natarajan P
JAMA: 17 Nov 2019; epub ahead of print | PMID: 31738818
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Lifestyle modifications for treatment of atrial fibrillation.

Middeldorp ME, Ariyaratnam J, Lau D, Sanders P

The management of atrial fibrillation (AF) has focused on anticoagulation, rhythm control and ventricular rate control. Recently, a fourth pillar of AF management has been incorporated recognising the importance of risk factor management (RFM). There are several risk factors that contribute to the development and progression of AF, these include traditional risk factors such as age, hypertension, heart failure, diabetes and valvular heart disease. However, increasingly it is recognised that obesity, sleep apnoea, hyperlipidaemia, smoking, alcohol, physical inactivity, genetics, aortic stiffness are associated with the development of AF. Importantly, several of these risk factors are modifiable. We have seen the evolution of RFM programmes which have demonstrated promising results. Indeed, the evidence is now so compelling that major clinical guidelines strongly advocate that aggressive treatment of these risk factors as a key component of AF management. Patients with AF who comprehensively managed their risk factors demonstrate greater reduction in symptoms, AF burden, more successful ablations and improved outcomes with greater AF freedom. In this article, we will review the evidence for the association between cardiac risk factors and AF and assess the burgeoning evidence for improved AF outcomes associated with aggressive cardiac RFM.

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

Heart: 10 Nov 2019; epub ahead of print
Middeldorp ME, Ariyaratnam J, Lau D, Sanders P
Heart: 10 Nov 2019; epub ahead of print | PMID: 31712316
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Usefulness of Red Cells Distribution Width to Predict Worse Outcomes in Patients With Atrial Fibrillation.

Malavasi VL, Proietti M, Spagni S, Valenti AC, ... Lip GY, Boriani G

Red cells distribution width (RDW) is a measure of red cell size variability, but little is known about the relation between RDW and outcomes in atrial fibrillation (AF).The aims of our study were to evaluate the association between RDW values, AF patients\' profile and outcomes. Consecutive patients with ECG-confirmed AF were divided in 3 groups according to tertiles of RDW values (≤13.5%, 13.6% to 14.6%, >14.6%).We enrolled 457 patients, 61.9% males, median (interquartile range) age 74 (66 to 80). Both CHADS-VASc and HAS-BLED scores increased progressively according to RDW tertiles. During follow-up, there was an increased risk for all-cause death and the composite end point in the highest RDW tertile (p <0.001 for both outcomes). On multivariate Cox regression analysis, the highest RDW tertile was independently associated with all-cause death (hazard ratio [HR] 3.23, 95% confidence interval [CI] 1.04 to 10.00) and the composite end point (HR 2.04, 95% CI 1.12 to 3.70). RDW as a continuous variable was also independently associated with all cause death and the composite outcome (HR 1.16, 95% CI 1.02 to 1.31 and HR 1.16, 95% CI 1.05 to 1.27, respectively). In conclusion, in a real-life AF population, RDW is associated with clinical factors indicating a worse profile and is independently associated with increased risks of all-cause death and other clinical events.

Copyright © 2019 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Nov 2019; 124:1561-1567
Malavasi VL, Proietti M, Spagni S, Valenti AC, ... Lip GY, Boriani G
Am J Cardiol: 14 Nov 2019; 124:1561-1567 | PMID: 31521256
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Significantly increased risk of all-cause mortality among cardiac patients feeling lonely.

Christensen AV, Juel K, Ekholm O, Thrysøe L, ... Rasmussen TB, Berg SK
Objective
To explore whether living alone and loneliness 1) are associated with poor patient-reported outcomes at hospital discharge and 2) predict cardiac events and mortality 1 year after hospital discharge in women and men with ischaemic heart disease, arrhythmia, heart failure or heart valve disease.
Methods
A national cross-sectional survey including patients with known cardiac disease at hospital discharge combined with national register data at baseline and 1-year follow-up. Loneliness was evaluated using one self-reported question, and information on cohabitation was available from national registers. Patient-reported outcomes were Short Form-12, Hospital Anxiety and Depression Scale and HeartQoL. Clinical outcomes were 1-year cardiac events (myocardial infarction, stroke, cardiac arrest, ventricular tachycardia/fibrillation) and all-cause mortality from national registers.
Results
A total of 13 443 patients (53%) with ischaemic heart disease, arrhythmia, heart failure or heart valve disease completed the survey. Of these, 70% were male, and mean age was 66.1 among women and 64.9 among men. Across cardiac diagnoses, loneliness was associated with significantly poorer patient-reported outcomes in men and women. Loneliness predicted all-cause mortality among women and men (HR 2.92 (95% CI 1.55 to 5.49) and HR 2.14 (95% CI 1.43 to 3.22), respectively). Living alone predicted cardiac events in men only (HR 1.39 (95% CI 1.05 to 1.85)).
Conclusions
A strong association between loneliness and poor patient-reported outcomes and 1-year mortality was found in both men and women across cardiac diagnoses. The results suggest that loneliness should be a priority for public health initiatives, and should also be included in clinical risk assessment in cardiac patients.

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

Heart: 03 Nov 2019; epub ahead of print
Christensen AV, Juel K, Ekholm O, Thrysøe L, ... Rasmussen TB, Berg SK
Heart: 03 Nov 2019; epub ahead of print | PMID: 31685646
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

External Performance of the HAVOC Score for the Prediction of New Incident Atrial Fibrillation.

Ntaios G, Perlepe K, Lambrou D, Sirimarco G, ... Vemmos K, Michel P

Background and Purpose- The HAVOC score (hypertension, age, valvular heart disease, peripheral vascular disease, obesity, congestive heart failure, coronary artery disease) was proposed for the prediction of atrial fibrillation (AF) after cryptogenic stroke. It showed good model discrimination (area under the curve, 0.77). Only 2.5% of patients with a low-risk HAVOC score (ie, 0-4) were diagnosed with new incident AF. We aimed to assess its performance in an external cohort of patients with embolic stroke of undetermined source. Methods- In the AF-embolic stroke of undetermined source dataset, we assessed the discriminatory power, calibration, specificity, negative predictive value, and accuracy of the HAVOC score to predict new incident AF. Patients with a HAVOC score of 0 to 4 were considered as low-risk, as proposed in its original publication. Results- In 658 embolic stroke of undetermined source patients (median age, 67 years; 44% women), the median HAVOC score was 2 (interquartile range, 3). There were 540 (82%) patients with a HAVOC score of 0 to 4 and 118 (18%) with a score of ≥5. New incident AF was diagnosed in 95 (14.4%) patients (28.8% among patients with HAVOC score ≥5 and 11.3% among patients with HAVOC score 0-4 [age- and sex-adjusted odds ratio, 2.29 (95% CI,1.37-3.82)]). The specificity of low-risk HAVOC score to identify patients without new incident AF was 88.7%. The negative predictive value of low-risk HAVOC score was 85.1%. The accuracy was 78.0%, and the area under the curve was 68.7% (95% CI, 62.1%-73.3%). Conclusions- The previously reported low rate of AF among embolic stroke of undetermined source patients with low-risk HAVOC score was not confirmed in our cohort. Further assessment of the HAVOC score is warranted before it is routinely implemented in clinical practice.



Stroke: 11 Dec 2019:STROKEAHA119027990; epub ahead of print
Ntaios G, Perlepe K, Lambrou D, Sirimarco G, ... Vemmos K, Michel P
Stroke: 11 Dec 2019:STROKEAHA119027990; epub ahead of print | PMID: 31826729
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

An N-/L-type calcium channel blocker, cilnidipine, suppresses autonomic, electrical, and structural remodelling associated with atrial fibrillation.

Tajiri K, Guichard JB, Qi X, Xiong F, ... Aonuma K, Nattel S
Aims
Autonomic dysfunction can promote atrial fibrillation (AF) and results from AF-related remodelling. N-type Ca2+-channels (NTCCs) at sympathetic nerve terminals mediate Ca2+-entry that triggers neurotransmitter release. AF-associated remodelling plays an important role in AF pathophysiology but the effects of NTCC inhibition on such remodelling is unknown. Here, we investigated the ability of a clinically available Ca2+-channel blocker (CCB) with NTCC-blocking activity to suppress the arrhythmogenic effects of AF-promoting remodelling in dogs.
Methods and results
Mongrel dogs were kept in AF by right atrial tachypacing at 600 bpm. Four groups were studied under short-term AF (7 days): (i) Shams, instrumented but without tachypacing (n = 5); (ii) a placebo group, tachypaced while receiving placebo (n = 6); (iii) a control tachypacing group receiving nifedipine (10 mg orally twice-daily; n = 5), an L-type CCB; and (iv) a cilnidipine group, subjected to tachypacing and treatment with cilnidipine (10 mg orally twice-daily; n = 7), an N-/L-type CCB. With cilnidipine therapy, dogs with 1-week AF showed significantly reduced autonomic changes reflected by heart rate variability (decreases in RMSSD and pNN50) and plasma norepinephrine concentrations. In addition, cilnidipine-treated dogs had decreased extracellular matrix gene expression vs. nifedipine-dogs. As in previous work, atrial fibrosis had not yet developed after 1-week AF, so three additional groups were studied under longer-term AF (21 days): (i) Shams, instrumented without tachypacing or drug therapy (n = 8); (ii) a placebo group, tachypaced while receiving placebo (n = 8); (iii) a cilnidipine group, subjected to tachypacing during treatment with cilnidipine (10 mg twice-daily; n = 8). Cilnidipine attenuated 3-week AF effects on AF duration and atrial conduction, and suppressed AF-induced increases in fibrous-tissue content, decreases in connexin-43 expression and reductions in sodium-channel expression.
Conclusions
Cilnidipine, a commercially available NTCC-blocking drug, prevents AF-induced autonomic, electrical and structural remodelling, along with associated AF promotion.

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

Cardiovasc Res: 30 Nov 2019; 115:1975-1985
Tajiri K, Guichard JB, Qi X, Xiong F, ... Aonuma K, Nattel S
Cardiovasc Res: 30 Nov 2019; 115:1975-1985 | PMID: 31119260
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Increased Incidence of Ischemic Cerebrovascular Events in Cardiovascular Patients With Elevated Apolipoprotein CIII.

Olivieri O, Cappellari M, Turcato G, Bonetti B, ... Castagna A, Martinelli N

Background and Purpose- Apo CIII (apolipoprotein CIII), a crucial regulator of lipoprotein metabolism, has been associated with increased activity of coagulation factors and thrombin generation and, in turn, with an increased risk of thromboembolic events in both arterial and venous districts. Thus, we hypothesized that it may affect the risk of acute ischemic cerebrovascular events in cardiovascular patients. Methods- We systematically checked medical records and quantified cerebral ischemic events in a cohort of 950 subjects (median age 65 with interquartile range, 55-79 years; 30.7% females) with or without angiographically defined coronary artery disease (CAD: 774 CAD and 176 CAD-free, respectively). All the subjects, enrolled between May 1999 and December 2006, were prospectively followed until death or July 31, 2018. Assessments of complete plasma lipid and apolipoprotein profiles, including Apo A-I, B, CIII, and E, were available for all subjects at enrollment. Results- After a median follow-up of 130 months (interquartile range, 69-189), 95 subjects (10%) suffered ischemic stroke/transient ischemic attack (TIA) events. Stroke/TIA subjects had higher Apo CIII plasma concentration (11.4; interquartile range: 9.3-14.4 mg/dL) at enrollment than those without stroke/TIA (10.4, interquartile range: 8.7-13.0 mg/dL). Subjects with Apo CIII levels above the median value (10.6 mg/dL) exhibited an ≈2-fold increased risk of stroke/TIA, even after adjustment for potential confounders, including sex, age, CAD diagnosis, hypertension, atrial fibrillation, oral anticoagulant treatment, and all plasma lipid parameters (hazard ratio: 2.23 [95% CI, 1.21-4.13]). This result was confirmed in CAD and CAD-free populations, separately, and even by a propensity score matching method, in which 98 CAD and 98 CAD-free subjects were one-to-one matched for all clinical and laboratory characteristics. Conclusions- These findings suggest that a high Apo CIII plasma concentration may predict an increased risk of ischemic stroke/TIA in cardiovascular patients.



Stroke: 03 Dec 2019:STROKEAHA119026811; epub ahead of print
Olivieri O, Cappellari M, Turcato G, Bonetti B, ... Castagna A, Martinelli N
Stroke: 03 Dec 2019:STROKEAHA119026811; epub ahead of print | PMID: 31795904
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Sex differences in implantable cardiac defibrillator therapy according to arrhythmia detection times.

Gasparini M, Kloppe A, Lunati M, Varma N, ... Mangoni di Santo Stefano L, Proclemer A
Objective
In implantable cardiac defibrillators (ICDs), long-detection times safely reduce unnecessary and inappropriate therapies. We aimed to evaluate ICD treatment of ventricular arrhythmias in women, compared with men, also taking into account ICD detection.
Methods
The Advance III trial randomised patients implanted with an ICD for primary or secondary prevention in two arms-long and nominal ventricular arrhythmias detection times before therapy delivering (number of intervals needed to detect (NID) 30/40 and 18/24, respectively). The main endpoint of this post hoc analysis was the incidence of ICD therapies evaluated through Kaplan-Meier method and univariate Cox regression models.
Results
Overall, 1902 patients (304 women, 65±11 years) were randomised. Women showed a lower risk of ICD therapy (HR 0.63, 95% CI 0.43 to 0.93, p=0.022); this difference was observed only in the long-detection arm (HR 0.37, p=0.013) and not in the short detection arm (HR 0.82, p=0.414). No significant sex differences were observed concerning inappropriate therapies and mortality rate. Long-detection settings significantly reduced overall ICD therapies and appropriate ICD therapies, both in women (overall HR 0.31, p=0.007; appropriate HR 0.33, p=0.033) and in men (overall HR 0.69, p=0.006; appropriate HR 0.73, p=0.048).
Conclusions
In patients with ICDs, the strategy of setting a long-detection time to treat ventricular arrhythmias (NID 30/40) reduces overall delivered therapies, both in women and men, when compared with nominal setting (NID 18/24). The reduction was significantly higher in women. Overall, women were less likely to experience ICD therapies than men; this result was only observed in the long-detection arm.
Clinical trial registration
NCT00617175.

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

Heart: 10 Dec 2019; epub ahead of print
Gasparini M, Kloppe A, Lunati M, Varma N, ... Mangoni di Santo Stefano L, Proclemer A
Heart: 10 Dec 2019; epub ahead of print | PMID: 31826936
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

A 63-year-old woman with multiple secondary tumours.

Muresan ID, Agoston-Coldea L, Dumitrascu DL

Clinical introductionA 63-year-old woman recently diagnosed with lung metastasis, after routine chest radiography, was admitted to our hospital for unspecified symptoms, such as dyspnoea on minimal exertion and dry cough. Physical examination showed uncommon signs. The electrocardiogram showed sinus rhythm and incomplete left bundle branch block. Thoracic CT scan revealed bilateral lung and pleural metastases and pelvic CT showed a right femoral bone mass. Transthoracic echocardiography revealed a heterogeneous mass, lateral to the right ventricle, with pericardial effusion. Further, cardiac MRI (cMRI) was performed (figure 1A,B). Diagnosis was completed with an ultrasound-guided biopsy and histopathological examination (figure 1C,D).heartjnl;106/3/202/F1F1F1Figure 1(A,B) Cardiac MRI: asterisk is suggestive of fluid and the white arrow indicates fibrous encapsulation by LGE, (C) H&E stain:white arrow indicating a tumoral cell with atypical mitosis and (D) immunohistochemical staining for smooth muscle actin antibody. QUESTION: Which of the following is the most likely diagnosis?Pericardial lymphoma.Pericardial leiomyosarcoma.Pericardial cyst.Secondary malignant cardiac tumour.Pericardial teratoma.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Jan 2020; 106:202-241
Muresan ID, Agoston-Coldea L, Dumitrascu DL
Heart: 30 Jan 2020; 106:202-241 | PMID: 31915242
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Integrative Omics Approach to Identifying Genes Associated with Atrial Fibrillation.

Wang B, Lunetta K, Dupuis J, Lubitz SA, ... Benjamin EJ, Lin H

Genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with atrial fibrillation (AF). However, these loci explain only a small proportion of AF heritability.To develop an approach to identify additional AF-related genes by integrating multiple omics data.Three types of omics data were integrated: 1) summary statistics from the AFGen 2017 GWAS; 2) a whole blood epigenome-wide association study (EWAS) of AF; and 3) a whole blood transcriptome-wide association study (TWAS) of AF. The variant-level GWAS results were collapsed into gene-level associations using fast set-based association analysis (fastBAT). The CpG-level EWAS results were also collapsed into gene-level associations by an adapted SNP-set Kernel Association Test (SKAT) approach. Both GWAS and EWAS gene-based associations were then meta-analyzed with TWAS using a fixed-effects model weighted by the sample size of each data set. A tissue-specific network was subsequently constructed using the Network-wide association study (NetWAS). The identified genes were then compared with the AFGen 2018 GWAS that contained twice the number of AF cases compared to AFGen 2017 GWAS. We observed that the multi-omics approach identified many more relevant AF-related genes than using AFGen 2018 GWAS alone (1931 vs. 206 genes). Many of these genes are involved in the development and regulation of heart and muscle related biological processes. Moreover, the gene set identified by multi-omics approach explained much more AF variance than those identified by GWAS alone (10.4% vs 3.5%).We developed a strategy to integrate multiple omics data to identify AF-related genes. Our integrative approach may be useful to improve the power of traditional GWAS, which might be particularly useful for rare traits and diseases with limited sample size.



Circ Res: 04 Dec 2019; epub ahead of print
Wang B, Lunetta K, Dupuis J, Lubitz SA, ... Benjamin EJ, Lin H
Circ Res: 04 Dec 2019; epub ahead of print | PMID: 31801406
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Impact of oral anticoagulation in patients with atrial fibrillation at very low thromboembolic risk.

Verbrugge FH, Martin AC, Siegal D, Pieper K, ... Camm AJ, Fox KAA
Objective
To investigate reasons for and impact of oral anticoagulation (OAC) in patients with atrial fibrillation (AF) at very low thromboembolic risk.
Methods
Individuals with CHADS-VASc score 0 (men) or 1 (women) from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) were studied. Baseline characteristics according to OAC use were evaluated by logistic regression analysis. Non-haemorrhagic stroke or systemic embolism, major bleeding, cardiovascular and all-cause mortality were compared.
Results
From 2224 low CHADS-VASc patients in GARFIELD-AF, 44% received OAC. In an adjusted model, increasing age up to 65 years (OR (95% CI)=1.31 (1.19 to 1.44)) and persistent AF (OR (95% CI)=3.25 (2.44 to 4.34)) or permanent AF (OR (95% CI)=2.29 (1.59 to 3.30)) versus paroxysmal/unclassified AF were associated with OAC use. Concomitant antiplatelet therapy (OR (95% CI)=0.21 (0.17 to 0.27)) was inversely associated. Crude incidence rates per 100 person-years over 2 years in patients on OAC versus not on OAC were 0.32 (95% CI 0.14 to 0.71) vs 0.30 (95% CI 0.14 to 0.63) for non-haemorrhagic stroke or systemic embolism, 0.21 (95% CI 0.08 to 0.57) vs 0.17 (95% CI 0.06 to 0.46) for major bleeding, 0.26 (95% CI 0.11 to 0.64) vs 0.26 (95% CI 0.12 to 0.57) for cardiovascular mortality and 0.74 (95% CI 0.44 to 1.25) vs 0.99 (95% CI 0.66 to 1.49) for all-cause mortality.
Conclusions
In contrast to guideline recommendations, almost half of real-world patients with AF at a very low thromboembolic risk according to the CHADS-VASc score receive OAC. Persistent or permanent AF and increasing age up to 65 years are associated with OAC use, while concomitant antiplatelet therapy shows an inverse association. Regardless whether patients received OAC therapy, few thromboembolic and bleeding events occur, highlighting the low risk of this population.

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

Heart: 04 Dec 2019; epub ahead of print
Verbrugge FH, Martin AC, Siegal D, Pieper K, ... Camm AJ, Fox KAA
Heart: 04 Dec 2019; epub ahead of print | PMID: 31806700
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Blood pressure measurement in atrial fibrillation: review and meta-analysis of evidence on accuracy and clinical relevance.

Stergiou GS, Kyriakoulis KG, Stambolliu E, Destounis A, ... Kalogeropoulos P, Kollias A

: Atrial fibrillation (AF) often coexists with hypertension in the elderly and multiplies the risk of stroke and death. Blood pressure (BP) measurement in patients with AF is difficult and uncertain and has been a classic exclusion criterion in hypertension clinical trials leading to limited research data. This article reviews the evidence on the accuracy of BP measurement in AF performed using different methods (office, ambulatory, home) and devices (auscultatory, oscillometric) and its clinical relevance in predicting cardiovascular damage. The current evidence suggests the following: (i) Interobserver and intra-observer variation in auscultatory BP measurement is increased in AF because of increased beat-to-beat BP variability and triplicate measurement is required; (ii) Data from validation studies of automated electronic BP monitors in AF are limited and methodologically heterogeneous and suggest reasonable accuracy in measuring SBP and a small yet consistent overestimation of DBP; (iii) 24-h ambulatory BP monitoring is feasible in AF, with similar proportion of errors as in individuals without AF; (iv) both auscultatory and automated oscillometric BP measurements appear to be clinically relevant in AF, providing similar associations with intra-arterial BP measurements and with indices of preclinical cardiac damage as in patients without AF, and predict cardiovascular events and death; (v) Screening for AF in the elderly using an AF-specific algorithm during routine automated office, home or ambulatory BP measurement has high diagnostic accuracy. In conclusion, in AF patients, BP measurement is important, reliable, and clinically relevant and should not be neglected in clinical research and in practice.



J Hypertens: 29 Nov 2019; 37:2430-2441
Stergiou GS, Kyriakoulis KG, Stambolliu E, Destounis A, ... Kalogeropoulos P, Kollias A
J Hypertens: 29 Nov 2019; 37:2430-2441 | PMID: 31408028
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Atrial Cardiopathy and Nonstenosing Large Artery Plaque in Patients With Embolic Stroke of Undetermined Source.

Kamel H, Pearce LA, Ntaios G, Gladstone DJ, ... Hart RG, Healey JS

Background and Purpose- Atrial cardiopathy and atherosclerotic plaque are two potential mechanisms underlying embolic strokes of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear. A better understanding of their association may inform targeted secondary prevention strategies. Methods- We examined the association between atrial cardiopathy and atherosclerotic plaque in the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), which enrolled 7213 patients with recent ESUS during 2014 to 2017. For this analysis, we included patients with data on left atrial dimension, location of brain infarction, and cervical large artery plaque. The variables of primary interest were left atrial diameter and cervical plaque ipsilateral to brain infarction. Secondary markers of atrial cardiopathy were premature atrial contractions on Holter monitoring and newly diagnosed atrial fibrillation. For descriptive purposes, left atrial enlargement was defined as ≥4.7 cm. Multivariable logistic regression was used to examine the association between atrial cardiopathy markers and ipsilateral plaque after adjustment for age, sex, body mass index, hypertension, diabetes mellitus, current smoking, and hyperlipidemia. Results- Among 3983 eligible patients, 235 (5.9%) had left atrial enlargement, 939 (23.6%) had ipsilateral plaque, and 94 (2.4%) had both. Shared risk factors for left atrial enlargement and ipsilateral plaque were male sex, white race, hypertension, tobacco use, and coronary artery disease. Despite shared risk factors, increasing left atrial dimension was not associated with ipsilateral plaque after adjustment for covariates (odds ratio per cm, 1.1 [95% CI, 1.0-1.2]; =0.08). We found no consistent associations between secondary markers of atrial cardiopathy and ipsilateral plaque. Conclusions- In a large population of patients with ESUS, we did not observe a notable association between atrial cardiopathy and atherosclerotic plaque, and few patients had both conditions. These findings suggest that atrial cardiopathy and atherosclerotic plaque may be distinct, nonoverlapping risk factors for stroke among ESUS patients.



Stroke: 01 Jan 2020:STROKEAHA119028154; epub ahead of print
Kamel H, Pearce LA, Ntaios G, Gladstone DJ, ... Hart RG, Healey JS
Stroke: 01 Jan 2020:STROKEAHA119028154; epub ahead of print | PMID: 31893985
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Sex differences of resource utilisation and outcomes in patients with atrial arrhythmias and heart failure.

Ueberham L, König S, Hohenstein S, Mueller-Roething R, ... Bollmann A,
Objective
Atrial fibrillation or atrial flutter (AF) and heart failure (HF) often go hand in hand and, in combination, lead to an increased risk of death compared with patients with just one of both entities. Sex-specific differences in patients with AF and HF are under-reported. Therefore, the aim of this study was to investigate sex-specific catheter ablation (CA) use and acute in-hospital outcomes in patients with AF and concomitant HF in a retrospective cohort study.
Methods
Using International Statistical Classification of Diseases and Related Health Problems and Operations and Procedures codes, administrative data of 75 hospitals from 2010 to 2018 were analysed to identify cases with AF and HF. Sex differences were compared for baseline characteristics, right and left atrial CA use, procedure-related adverse outcomes and in-hospital mortality.
Results
Of 54 645 analysed cases with AF and HF, 46.2% were women. Women were significantly older (75.4±9.5 vs 68.7±11.1 years, p<0.001), had different comorbidities (more frequently: cerebrovascular disease (2.4% vs 1.8%, p<0.001), dementia (5.3% vs 2.2%, p<0.001), rheumatic disease (2.1% vs 0.8%, p<0.001), diabetes with chronic complications (9.7% vs 9.1%, p=0.033), hemiplegia or paraplegia (1.7% vs 1.2%, p<0.001) and chronic kidney disease (43.7% vs 33.5%, p<0.001); less frequently: myocardial infarction (5.4% vs 10.5%, p<0.001), peripheral vascular disease (6.9% vs 11.3%, p<0.001), mild liver disease (2.0% vs 2.3%, p=0.003) or any malignancy (1.0% vs 1.3%, p<0.001), underwent less often CA (12.0% vs 20.7%, p<0.001), had longer hospitalisations (6.6±5.8 vs 5.2±5.2 days, p<0.001) and higher in-hospital mortality (1.6% vs 0.9%, p<0.001). However, in the multivariable generalised linear mixed model for in-hospital mortality, sex did not remain an independent predictor (OR 0.96, 95% CI 0.82 to 1.12, p=0.579) when adjusted for age and comorbidities. Vascular access complications requiring interventions (4.8% vs 4.2%, p=0.001) and cardiac tamponade (0.3% vs 0.1%, p<0.001) occurred more frequently in women, whereas stroke (0.6% vs 0.5%, p=0.179) and death (0.3% vs 0.1%, p=0.101) showed no sex difference in patients undergoing CA.
Conclusions
There are sex differences in patients with AF and HF with respect to demographics, resource utilisation and in-hospital outcomes. This needs to be considered when treating women with AF and HF, especially for a sufficient patient informed decision making in clinical practice.

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

Heart: 18 Dec 2019; epub ahead of print
Ueberham L, König S, Hohenstein S, Mueller-Roething R, ... Bollmann A,
Heart: 18 Dec 2019; epub ahead of print | PMID: 31857353
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Risk of Arterial Ischemic Events After Intracerebral Hemorrhage.

Murthy SB, Diaz I, Wu X, Merkler AE, ... Navi BB, Kamel H

Background and Purpose- The risk of arterial ischemic events after intracerebral hemorrhage (ICH) is poorly understood given the lack of a control group in prior studies. This study aimed to evaluate the risk of acute ischemic stroke and myocardial infarction (MI) among patients with and without ICH. Methods- We performed a retrospective cohort study using claims data from Medicare beneficiaries from 2008 to 2014. Our exposure was acute ICH, identified using validateddiagnosis codes. Our primary outcome was a composite of acute ischemic stroke and MI, whereas secondary outcomes were ischemic stroke alone and MI alone. We used Cox regression analysis to compute hazard ratios during 1-month intervals after ICH. Sensitivity analyses entailed exclusion of patients with atrial fibrillation and valvular heart disease. Results- Among 1 760 439 Medicare beneficiaries, 5924 had ICH. The 1-year cumulative incidence of an arterial ischemic event was 5.7% (95% CI, 4.8-6.8) in patients with ICH and 1.8% (95% CI, 1.7-1.9) in patients without ICH. After adjusting for potential confounders, the risk of an arterial ischemic event remained significantly increased for the first 6 months after ICH and was especially high in the first month (hazard ratio, 6.7 [95% CI, 5.0-8.6]). In secondary analysis, the risk of ischemic stroke was increased in the first 6 months after ICH (hazard ratio, 6.1 [95% CI, 3.5-9.3]) but the risk of MI was not (hazard ratio, 1.6 [95% CI, 0.3-2.9]). In sensitivity analyses excluding patients with atrial fibrillation and valvular heart disease, the association between ICH and arterial ischemic events was similar to that of the primary analysis. Conclusions- In a large population-based cohort, we found that elderly patients with ICH had a substantially increased risk of ischemic stroke in the first 6 months after diagnosis. Further exploration of this risk is needed to determine optimal secondary prevention strategies for these patients.



Stroke: 26 Nov 2019:STROKEAHA119026207; epub ahead of print
Murthy SB, Diaz I, Wu X, Merkler AE, ... Navi BB, Kamel H
Stroke: 26 Nov 2019:STROKEAHA119026207; epub ahead of print | PMID: 31771458
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effect of Heart Rate on Stroke Recurrence and Mortality in Acute Ischemic Stroke With Atrial Fibrillation.

Lee KJ, Kim BJ, Han MK, Kim JT, ... Bae HJ,

Background and Purpose- There is a paucity of information about the role of resting heart rate in the prediction of outcome events in patients with ischemic stroke with atrial fibrillation. We aimed to investigate the relationships between the level and variability of heart rate in the acute stroke period and stroke recurrence and mortality after acute ischemic stroke in patients with atrial fibrillation. Methods- Acute patients with ischemic stroke who had atrial fibrillation and were hospitalized within 48 hours of stroke onset were identified from a multicenter prospective stroke registry database. The acute stroke period was divided into early (within 24 hours of hospitalization) and late (72 hours to 7 days from onset) stages, and data on heart rate in both stages were collected. Moreover, the level and variability of heart rate were assessed using mean values and coefficients of variation. Outcome events were prospectively monitored up to 1 year after the index stroke. Results- Among 2046 patients eligible for the early acute stage analysis, 102 (5.0%) had a stroke recurrence, and 440 (21.5%) died during the first year after stroke. A statistically significant nonlinear J-shaped association was observed between mean heart rate and mortality (<0.04 for quadratic and overall effect) but not between mean heart rate and stroke recurrence (>0.1 for quadratic and overall effect). The nonlinear and overall effects of the coefficients of variation of heart rate were not significant for all outcome variables. The same results were observed in the late acute stage analysis (n=1576). Conclusions- In patients with atrial fibrillation hospitalized for acute ischemic stroke, the mean heart rate during the acute stroke period was not associated with stroke recurrence but was associated with mortality (nonlinear, J-shaped association). The relationships between heart rate and outcomes were not observed with respect to heart rate variability.



Stroke: 03 Dec 2019:STROKEAHA119026847; epub ahead of print
Lee KJ, Kim BJ, Han MK, Kim JT, ... Bae HJ,
Stroke: 03 Dec 2019:STROKEAHA119026847; epub ahead of print | PMID: 31795905
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Nitric oxide modulates cardiomyocyte pH control through a biphasic effect on sodium/hydrogen exchanger-1.

Richards MA, Simon JN, Ma R, Loonat AA, ... Fliegel L, Swietach P
Aims
When activated, Na+/H+ exchanger-1 (NHE1) produces some of the largest ionic fluxes in the heart. NHE1-dependent H+ extrusion and Na+ entry strongly modulate cardiac physiology through the direct effects of pH on proteins and by influencing intracellular Ca2+ handling. To attain an appropriate level of activation, cardiac NHE1 must respond to myocyte-derived cues. Among physiologically-important cues is nitric oxide (NO), which regulates a myriad of cardiac functions, but its actions on NHE1 are unclear.
Methods and results
NHE1 activity was measured using pH-sensitive cSNARF1 fluorescence after acid-loading adult ventricular myocytes by an ammonium prepulse solution manoeuvre. NO signalling was manipulated by knockout of its major constitutive synthase nNOS, adenoviral nNOS gene delivery, nNOS inhibition, and application of NO-donors. NHE1 flux was found to be activated by low [NO], but inhibited at high [NO]. These responses involved cGMP-dependent signalling, rather than S-nitros(yl)ation. Stronger cGMP signals, that can inhibit phosphodiesterase enzymes, allowed [cAMP] to rise, as demonstrated by a FRET-based sensor. Inferring from the actions of membrane-permeant analogues, cGMP was determined to activate NHE1, whereas cAMP was inhibitory, which explains the biphasic regulation by NO. Activation of NHE1-dependent Na+ influx by low [NO] also increased the frequency of spontaneous Ca2+ waves, whereas high [NO] suppressed these aberrant forms of Ca2+ signalling.
Conclusions
Physiological levels of NO stimulation increase NHE1 activity, which boosts pH control during acid-disturbances and results in Na+-driven cellular Ca2+ loading. These responses are positively inotropic but also increase the likelihood of aberrant Ca2+ signals, and hence arrhythmia. Stronger NO signals inhibit NHE1, leading to a reversal of the aforementioned effects, ostensibly as a potential cardioprotective intervention to curtail NHE1 overdrive.
Translational perspective
NHE1 regulates intracellular [H+] and [Na+], but its over-activation can drive ionic imbalances that affect cardiac contractility and rhythm. Pharmacological control of NHE1 (e.g. with cariporide) has been proposed as cardioprotective in conditions such as ischemia/reperfusion injury, but trials (e.g. GUARDIAN) failed to demonstrate overall clinical benefit. A confounding factor in these analyses is NHE1 modulation by endogenous factors. We demonstrate that NO signalling fine-tunes NHE1, producing stimulation at low levels, turning into inhibition as the signal grows stronger. Thus, evaluations of the therapeutic efficacy of NHE1-blocking drugs should consider NO signalling, a pathway known to undergo changes in disease.

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

Cardiovasc Res: 18 Nov 2019; epub ahead of print
Richards MA, Simon JN, Ma R, Loonat AA, ... Fliegel L, Swietach P
Cardiovasc Res: 18 Nov 2019; epub ahead of print | PMID: 31742355
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Classification of Covert Brain Infarct Subtype and Risk of Death and Vascular Events.

Gutierrez J, Gil-Guevara A, Ramaswamy S, DeRosa J, ... Wright CB, Elkind MSV

Background and Purpose- To test the hypothesis that covert brain infarcts (CBIs) are more likely to be located in noneloquent brain areas compared with clinical strokes and that CBI etiological subtypes carry a differential risk of vascular events compared with people without CBI. Methods- We used brain magnetic resonance imaging from 1290 stroke-free participants in the NOMAS (Northern Manhattan Study) to evaluate for CBI. We classified CBI as cardioembolic (ie, known atrial fibrillation), large artery atherosclerosis (extracranial and intracranial), penetrating artery disease, and cryptogenic (no apparent cause). CBI localized in the nonmotor areas of the right hemisphere were considered noneloquent. We then evaluated risk of events by CBI subtype with adjusted Cox proportional models. Results- At the time of magnetic resonance imaging, 236 participants (18%) had CBI (144 [61%] distal cryptogenic, 29 [12%] distal cardioembolic, 26 [11%] large artery atherosclerosis, and 37 [16%] penetrating artery disease). Smaller (per mm, odds ratio, 0.8 [0.8-0.9]) and nonbrain stem infarcts (odds ratio, 0.2 [0.1-0.6]) were more likely to be covert. During the follow-up period (10.4±3.1 years), 398 (31%) died (162 [13%] of vascular death) and 117 (9%) had a stroke (99 [85%]) were ischemic. Risks of events varied by CBI subtype, with the highest risk of stroke (hazard ratio, 2.2 [1.3-3.7]) and vascular death (hazard ratio, 2.24 [1.29-3.88]) noted in participants with intracranial large artery atherosclerosis-related CBI. Conclusions- CBI can be classified into subtypes that have differential outcomes. Certain CBI subtypes such as those related to intracranial large artery atherosclerosis have a high risk of adverse vascular outcomes and could warrant consideration of treatment trials.



Stroke: 25 Nov 2019:STROKEAHA119026068; epub ahead of print
Gutierrez J, Gil-Guevara A, Ramaswamy S, DeRosa J, ... Wright CB, Elkind MSV
Stroke: 25 Nov 2019:STROKEAHA119026068; epub ahead of print | PMID: 31766980
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Stroke Risk Analysis, a System With a High Detection Rate of Atrial Fibrillation in Stroke and Transient Ischemic Attack.

Gomis M, Dávalos A, Purroy F, Cardona P, ... van de Groep A, Molina C

Background and Purpose- Stroke Risk Analysis (SRA) comprises an algorithm for automated analysis of ECG monitoring, enabling the detection of paroxysmal atrial fibrillation (pxAF) and identifying patterns indicating a high risk of atrial fibrillation (R_AF). We compared Holter-enabled continuous ECG monitoring in combination with SRA (hSRA) with standard continuous ECG monitoring for pxAF detection in patients with acute ischemic stroke. Also, we sought to identify whether the detection of R_AF patterns during the first cycle (first 2 hours) of hSRA recording was associated with the detection of pxAF during the Stroke Unit stay. Methods- We enrolled 524 consecutive patients admitted in the Stroke Unit with acute ischemic stroke or transient ischemic attack with neither history of AF nor AF at admission into a prospective multicentric observational analytic clinical study with intrapatient comparison, who received both continuous ECG monitoring as well as hSRA up to 7 days. Investigators were blinded to hSRA results unless pxAF was detected on SRA. Results- Of the 524 consecutive acute stroke patients (median age, 70.0 years; 60% male; acute ischemic stroke 93%, transient ischemic attack 7%), 462 were eligible and included in the study. Among 462 patients with hSRA available for 66 hours, AF was documented by hSRA in 79 patients (17.1%). From this group, 45 AF cases (9.7%) were confirmed after review by an independent and blinded cardiologist. continuous ECG monitoring detected 21 AF cases (4.3%; <0.0001). hSRA detected R_AF patterns in 92 patients. 35 out of the 92 R_AF patients showed an episode of AF during the Stroke Unit stay. Predictive values of R_AF patterns within the first cycle of hSRA were: sensitivity 71%, specificity 86%, positive predictive value 38%, and negative predictive value 96%. Conclusions- Automated analysis using SRA technology strongly improves pxAF detection in acute ischemic stroke patients compared with continuous ECG monitoring. The predictive value of a R_AF pattern, as detected by hSRA during the first few hours after admission, deserves further investigation.



Stroke: 16 Dec 2019:STROKEAHA119026354; epub ahead of print
Gomis M, Dávalos A, Purroy F, Cardona P, ... van de Groep A, Molina C
Stroke: 16 Dec 2019:STROKEAHA119026354; epub ahead of print | PMID: 31842722
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Risks of Stroke and Mortality in Atrial Fibrillation Patients Treated With Rivaroxaban and Warfarin.

Alberts M, Chen YW, Lin JH, Kogan E, Twyman K, Milentijevic D

Background and Purpose- Oral anticoagulation therapy is standard of care for patients with nonvalvular atrial fibrillation to prevent stroke. This study compared rivaroxaban and warfarin for stroke and all-cause mortality risk reduction in a real-world setting. Methods- This retrospective cohort study (2011-2017) included de-identified patients from the Optum Clinformatics Database who started treatment with rivaroxaban or warfarin within 30 days following initial diagnosis of nonvalvular atrial fibrillation. Before nonvalvular atrial fibrillation diagnosis, patients had 6 months of continuous health plan enrollment and CHADS-VASc score ≥2. Stroke severity was determined by the National Institutes of Health Stroke Scale, imputed based on machine learning algorithms. Stroke and all-cause mortality risks were compared by treatment using Cox proportional hazard regression, with inverse probability of treatment weighting to balance cohorts for baseline risk factors. Stratified analysis by treatment duration was also performed. Results- During a mean follow-up of 27 months, 175 (1.33/100 patient-years [PY]) rivaroxaban-treated and 536 (1.66/100 PY) warfarin-treated patients developed stroke. The inverse probability of treatment weighting model showed that rivaroxaban reduced stroke risk by 19% (hazard ratio [HR], 0.81 [95% CI, 0.73-0.91]). Analysis by stroke severity revealed risk reductions by rivaroxaban of 48% for severe stroke (National Institutes of Health Stroke Scale score, 16-42; HR, 0.52 [95% CI, 0.33-0.82]) and 19% for minor stroke (National Institutes of Health Stroke Scale score, 1 to <5; HR, 0.81 [95% CI, 0.68-0.96]), but no difference for moderate stroke (National Institutes of Health Stroke Scale score, 5 to <16; HR, 0.93 [95% CI, 0.78-1.10]). A total of 41 (0.31/100 PY) rivaroxaban-treated and 147 (0.44/100 PY) warfarin-treated patients died poststroke, 12 (0.09/100 PY) and 67 (0.20/100 PY) of whom died within 30 days, representing mortality risk reductions by rivaroxaban of 24% (HR, 0.76 [95% CI, 0.61-0.95]) poststroke and 59% (HR, 0.41 [95% CI, 0.28-0.60]) within 30 days. Conclusions- After the initial diagnosis of atrial fibrillation, patients treated with rivaroxaban versus warfarin had significant risk reduction for stroke, especially severe stroke, and all-cause mortality after a stroke. Findings from this observational study may help inform anticoagulant choice for stroke prevention in patients with nonvalvular atrial fibrillation.



Stroke: 30 Dec 2019:STROKEAHA119025554; epub ahead of print
Alberts M, Chen YW, Lin JH, Kogan E, Twyman K, Milentijevic D
Stroke: 30 Dec 2019:STROKEAHA119025554; epub ahead of print | PMID: 31888412
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Brain Natriuretic Peptide and Discovery of Atrial Fibrillation After Stroke: A Subanalysis of the Find-AF Trial.

Wasser K, Weber-Krüger M, Gröschel S, Uphaus T, ... Gröschel K, Wachter R

Background and Purpose- Diagnosing paroxysmal atrial fibrillation (pAF) can be challenging after acute ischemic stroke. Enhanced and prolonged Holter-ECG monitoring (EPM) improves the detection rate but is not feasible for all patients. We hypothesized that brain natriuretic peptide (BNP) may help to identify patients with stroke at high risk for pAF to select patients for EPM more effectively. Methods- Patients with acute cerebral ischemia ≥60 years presenting in sinus rhythm and without history of AF were included into a prospective, randomized multicenter study to receive either EPM (3× 10-day Holter-ECG) or usual stroke care diagnostic work-up. BNP plasma levels were measured on randomization and 3 months thereafter. Levels were compared between patients with and without pAF detected by means of EPM or usual care. Furthermore, the number needed to screen for EPM depending on BNP cut offs was calculated. Results- A total of 398 patients were analyzed. In 373 patients (93.7%), BNP was measured at baseline and in 275 patients (69.1%) after 3 months. pAF was found in 27 patients by means of EPM and in 9 patients by means of usual care (=0.002). Median BNP was higher in patients with pAF as compared to patients without AF in both study arms at baseline (57.8 versus 28.3 pg/mL in the EPM arm, =0.0003; 46.2 versus 27.7 pg/mL, =0.28 in the control arm) and after 3 months (74.9 versus 31.3 pg/mL, =0.012 in the EPM arm, 99.3 versus 26.3 pg/mL, =0.02 in the control arm). Applying a cut off of 100 pg/mL, the number needed to screen was reduced from 18 by usual care to 3 by EPM. Conclusions- BNP measured early after ischemic stroke identifies a subgroup of patients with stroke at increased risk for AF, in whom EPM is particularly efficacious. Clinical trial registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01855035.



Stroke: 08 Dec 2019:STROKEAHA119026496; epub ahead of print
Wasser K, Weber-Krüger M, Gröschel S, Uphaus T, ... Gröschel K, Wachter R
Stroke: 08 Dec 2019:STROKEAHA119026496; epub ahead of print | PMID: 31813354
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Oral Anticoagulation in Asian Patients With Atrial Fibrillation and a History of Intracranial Hemorrhage.

Lee SR, Choi EK, Kwon S, Jung JH, ... Oh S, Lip GYH

Background and Purpose- Warfarin is associated with a better net clinical benefit compared with no treatment in patients with nonvalvular atrial fibrillation (AF) and history of intracranial hemorrhage (ICH). There are limited data on nonvitamin K antagonist oral anticoagulants (NOACs) in these patients, especially in the Asian population. We aimed to compare the effectiveness and safety of NOACs to warfarin in a large-scale nationwide Asian population with AF and a history of ICH. Methods- Using the Korean Health Insurance Review and Assessment database from January 2010 to April 2018, we identified patients with oral anticoagulant naïve nonvalvular AF with a prior spontaneous ICH. For the comparisons, warfarin and NOAC groups were balanced using propensity score weighting. Ischemic stroke, ICH, composite outcome (ischemic stroke+ICH), fatal ischemic stroke, fatal ICH, death from composite outcome, and all-cause death were evaluated as clinical outcomes. Results- Among 5712 patients with AF with prior ICH, 2434 were treated with warfarin and 3278 were treated with NOAC. Baseline characteristics were well-balanced after propensity score weighting (mean age 72.5 years and CHADS-VASc score 4.0). Compared with warfarin, NOAC was associated with lower risks of ischemic stroke (hazard ratio [HR], 0.77 [95% CI, 0.61-0.97]), ICH (HR, 0.66 [95% CI, 0.47-0.92]), and composite outcome (HR, 0.73 [95% CI, 0.60-0.88]). NOAC was associated with lower risks of fatal stroke (HR, 0.54 [95% CI, 0.32-0.89]), death from composite outcome (HR, 0.53 [95% CI, 0.34-0.81]), and all-cause death (HR, 0.83 [95% CI, 0.69-0.99]) than warfarin. NOAC showed nonsignificant trends toward to reduce fatal ICH compared with warfarin (HR, 0.47 [95% CI, 0.20-1.03]). Conclusions- NOAC was associated with a significant lower risk of ICH and ischemic stroke compared with warfarin. NOAC might be a more effective and safer treatment option for Asian patients with nonvalvular AF and a prior history of ICH.



Stroke: 08 Dec 2019:STROKEAHA119028030; epub ahead of print
Lee SR, Choi EK, Kwon S, Jung JH, ... Oh S, Lip GYH
Stroke: 08 Dec 2019:STROKEAHA119028030; epub ahead of print | PMID: 31813363
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Identification of novel pheno-groups in heart failure with preserved ejection fraction using machine learning.

Hedman ÅK, Hage C, Sharma A, Brosnan MJ, ... Ziemek D, Lund L
Objective
Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. We aimed to derive HFpEF phenotype-based groups (\'phenogroups\') based on clinical and echocardiogram data using machine learning, and to compare clinical characteristics, proteomics and outcomes across the phenogroups.
Methods
We applied model-based clustering to 32 echocardiogram and 11 clinical and laboratory variables collected in stable condition from 320 HFpEF outpatients in the Karolinska-Rennes cohort study (56% female, median 78 years (IQR: 71-83)). Baseline proteomics and the composite end point of all-cause mortality or heart failure (HF) hospitalisation were used in secondary analyses.
Results
We identified six phenogroups, for which significant differences in the prevalence of concomitant atrial fibrillation (AF), anaemia and kidney disease were observed (p<0.05). Fifteen out of 86 plasma proteins differed between phenogroups (false discovery rate, FDR<0.05), including biomarkers of HF, AF and kidney function. The composite end point was significantly different between phenogroups (log-rank p<0.001), at short-term (100 days), mid-term (18 months) and longer-term follow-up (1000 days). Phenogroup 2 was older, with poorer diastolic and right ventricular function and higher burden of risk factors as AF (85%), hypertension (83%) and chronic obstructive pulmonary disease (30%). In this group a third experienced the primary outcome to 100 days, and two-thirds to 18 months (HR (95% CI) versus phenogroups 1, 3, 4, 5, 6: 1.5 (0.8-2.9); 5.7 (2.6-12.8); 2.9 (1.5-5.6); 2.7 (1.6-4.6); 2.1 (1.2-3.9)).
Conclusions
Using machine learning we identified distinct HFpEF phenogroups with differential characteristics and outcomes, as well as differential levels of inflammatory and cardiovascular proteins.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 06 Jan 2020; epub ahead of print
Hedman ÅK, Hage C, Sharma A, Brosnan MJ, ... Ziemek D, Lund L
Heart: 06 Jan 2020; epub ahead of print | PMID: 31911501
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Accuracy of a smartwatch based single-lead electrocardiogram device in detection of atrial fibrillation.

Rajakariar K, Koshy AN, Sajeev JK, Nair S, Roberts L, Teh AW
Objective
The AliveCor KardiaBand (KB) is an Food and Drug Administration-approved smartwatch-based cardiac rhythm monitor that records a lead-Intelligent ECG (iECG). Despite the appeal of wearable integrated ECG devices, there is a paucity of data evaluating their accuracy in diagnosing atrial fibrillation (AF). We evaluated whether a smartwatch-based device for AF detection is an accurate tool for diagnosing AF when compared with 12-lead ECG.
Methods
A prospective, multi-centre, validation study was conducted in an inpatient hospital setting. The KB paired with a smartwatch, generated an automated diagnosis of AF or sinus rhythm (SR). This was compared with a 12-lead ECG performed immediately after iECG tracing. Where an unclassified or no-analysis tracing was generated, repeat iECG was performed.
Results
439 ECGs (iECGs (n=239) and 12-lead ECG (n=200)) were recorded in 200 patients (AF: n=38; SR: n=162) from three tertiary centres. Sensitivity and specificity using KB was 94.4% and 81.9% respectively, with a positive predictive value of 54.8% and negative predictive value of 98.4%. Agreement between 12-lead ECG and KB diagnosis was moderate when unclassified tracings were included (κ=0.60, 95% CI 0.47 to 0.72). Combining the automated device diagnosis with blinded electrophysiologists (EP) interpretation of unclassified tracings improved overall agreement (EP1: κ=0.76, 95% CI 0.65 to 0.87; EP2: κ=0.74, 95% CI 0.63 to 0.86).
Conclusion
The KB demonstrated moderate diagnostic accuracy when compared with a 12-lead ECG. Combining the automated device diagnosis with EP interpretation of unclassified tracings yielded improved accuracy. However, even with future improvements in automated algorithms, physician involvement will likely remain an essential component when exploring the utility of these devices for arrhythmia screening.
Clinical trial registration
URL: https://www.anzctr.org.au/ Unique identifier: ACTRN12616001374459.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 06 Jan 2020; epub ahead of print
Rajakariar K, Koshy AN, Sajeev JK, Nair S, Roberts L, Teh AW
Heart: 06 Jan 2020; epub ahead of print | PMID: 31911507
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Safety and Outcomes of Intravenous Thrombolysis in Posterior Versus Anterior Circulation Stroke: Results From the Safe Implementation of Treatments in Stroke Registry and Meta-Analysis.

Keselman B, Gdovinová Z, Jatuzis D, Melo TPE, ... Lees KR, Mazya MV

Background and Purpose- Posterior circulation stroke (PCS) accounts for 5% to 19% of patients with acute stroke receiving intravenous thrombolysis. We aimed to compare safety and outcomes following intravenous thrombolysis between patients with PCS and anterior circulation stroke (ACS) and incorporate the results in a meta-analysis. Methods- We included patients in the Safe Implementation of Treatments in Stroke Thrombolysis Registry 2013 to 2017 with computed tomography/magnetic resonance angiographic occlusion data. Outcomes were parenchymal hematoma, symptomatic intracerebral hemorrhage (SICH) per SITS-MOST (Safe Implementation of Thrombolysis in Stroke Monitoring Study), ECASS II (Second European Co-operative Stroke Study) and NINDS (Neurological Disorders and Stroke definition), 3-month modified Rankin Scale score, and death. Adjustment for SICH risk factors (age, sex, National Institutes of Health Stroke Scale, blood pressure, glucose, and atrial fibrillation) and center was done using inverse probability treatment weighting, after which an average treatment effect (ATE) was calculated. Meta-analysis of 13 studies comparing outcomes in PCS versus ACS after intravenous thrombolysis was conducted. Results- Of 5146 patients, 753 had PCS (14.6%). Patients with PCS had lower median National Institutes of Health Stroke Scale: 7 (interquartile range, 4-13) versus 13 (7-18), <0.001 and fewer cerebrovascular risk factors. In patients with PCS versus ACS, parenchymal hematoma occurred in 3.2% versus 7.9%, ATE (95% CI): -4.7% (-6.3% to 3.0%); SICH SITS-MOST in 0.6% versus 1.9%, ATE: -1.4% (-2.2% to -0.7%); SICH NINDS in 3.1% versus 7.8%, ATE: -3.0% (-6.3% to 0.3%); SICH ECASS II in 1.8% versus 5.4%, ATE: -2.3% (-5.3% to 0.7%). In PCS versus ACS, 3-month outcomes (70% data availability) were death 18.5% versus 20.5%, ATE: 6.0% (0.7%-11.4%); modified Rankin Scale score 0-1, 45.2% versus 37.5%, ATE: 1.7% (-6.6% to 3.2%); modified Rankin Scale score 0-2, 61.3% versus 49.4%, ATE: 2.4% (3.1%-7.9%). Meta-analysis showed relative risk for SICH in PCS versus ACS being 0.49 (95% CI, 0.32-0.75). Conclusions- The risk of bleeding complications after intravenous thrombolysis in PCS was half that of ACS, with similar functional outcomes and higher risk of death, acknowledging limitations of the National Institutes of Health Stroke Scale for stroke severity or infarct size adjustment.



Stroke: 08 Jan 2020:STROKEAHA119027071; epub ahead of print
Keselman B, Gdovinová Z, Jatuzis D, Melo TPE, ... Lees KR, Mazya MV
Stroke: 08 Jan 2020:STROKEAHA119027071; epub ahead of print | PMID: 31914885
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Decline in renal function and oral anticoagulation dose reduction among patients with atrial fibrillation.

Inohara T, Holmes DN, Pieper K, Blanco RG, ... Piccini JP,
Objective
Non-vitamin K oral anticoagulants (NOACs) require dose adjustment for renal function. We sought to investigate change in renal function over time in patients with atrial fibrillation (AF) and whether those on NOACs have appropriate dose adjustments according to its decline.
Methods
We included patients with AF enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II registry treated with oral anticoagulation. Worsening renal function (WRF) was defined as a decrease of >20% in creatinine clearance (CrCl) from baseline. The US Food and Drug Administration (FDA)-approved package inserts were used to define the reduction criteria of NOACs dosing.
Results
Among 6682 patients with AF from 220 sites (median age (25th, 75th): 72.0 years (65.0, 79.0); 57.1% male; median CrCl at baseline: 80.1 mL/min (57.4, 108.5)), 1543 patients (23.1%) experienced WRF with mean decline in CrCl during 2 year follow-up of -6.63 mL/min for NOACs and -6.16 mL/min for warfarin. Among 4120 patients on NOACs, 154 (3.7%) patients had a CrCl decline sufficient to warrant FDA-recommended dose reductions. Of these, NOACs dosing was appropriately reduced in only 31 (20.1%) patients. Compared with patients with appropriately reduced NOACs, those without were more likely to experience bleeding complications (major bleeding: 1.7% vs 0%; bleeding hospitalisation: 2.6% vs 0%) at 1 year.
Conclusions
In the US practice, about one-fourth of patients with AF had >20% decline in CrCl over time during 2 year follow-up. As a result, about 3.7% of those treated with NOACs met guideline criteria for dose reduction, but of these, only 20.1% actually had a reduction.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 06 Jan 2020; epub ahead of print
Inohara T, Holmes DN, Pieper K, Blanco RG, ... Piccini JP,
Heart: 06 Jan 2020; epub ahead of print | PMID: 31911503
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Accuracy of HAS-BLED and other bleeding risk assessment tools in predicting major bleeding events in atrial fibrillation: a network meta-analysis.

Chang G, Xie Q, Ma L, Hu K, ... Mu G, Cui Y
Background
Preventing thrombosis is an important part of atrial fibrillation (AF) treatment. However, it may increase the risk of bleeding, and bleeding risk assessment tools\' predictive value remains unclear. This network meta-analysis investigated the sensitivity and specificity of HAS-BLED, and other bleeding risk assessment tools, to predicting major bleeding events in AF patients.
Methods
The PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched using keywords, including \"AF,\" \"bleeding,\" and \"HAS-BLED,\" for results published through 30 Nov 2018. The predictive sensitivity and specificity of each bleeding risk assessment tool was analyzed by network meta-analysis.
Results
Our analysis included 18 studies, recruiting a total of 321,888 people. The bleeding risk assessment tools analyzed in this study included the ABC-bleeding score, ATRIA, European score, GARFIELD-AF, HAS-BLED, HEMORR2HAGES, ORBIT, Shireman, and mOBRI. A comprehensive analysis of sensitivity and specificity, based on an inconsistency model, showed that European score, ABC and mOBRI have relatively high sensitivity but low specificity, whereas HAS-BLED and HEMORR2HAGES have balanced sensitivity and specificity. ORBIT, ATRIA, Shireman, and GARFIELD-AF had relatively high specificity but low sensitivity. A consistency model analysis showed similar results.
Conclusions
HAS-BLED is a balanced bleeding risk assessment tool in terms of sensitivity and specificity, whereas the European score, ABC, and mOBRI are high sensitivity tools and ORBIT, ATRIA, Shireman, and GARFIELD-AF are high specificity tools.

© 2019 International Society on Thrombosis and Haemostasis.

J Thromb Haemost: 28 Nov 2019; epub ahead of print
Chang G, Xie Q, Ma L, Hu K, ... Mu G, Cui Y
J Thromb Haemost: 28 Nov 2019; epub ahead of print | PMID: 31782613
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Older ...

This program is still in alpha version.