Topic: Electrophysiology

Abstract

Atrial Fibrillation: JACC Council Perspectives.

Chung MK, Refaat M, Shen WK, Kutyifa V, ... Lakkireddy DR,

Atrial fibrillation (AF) is an increasingly prevalent arrhythmia; its pathophysiology and progression are well studied. Stroke and bleeding risk models have been created and validated. Decision tools for stroke prophylaxis are evolving, with better options at hand. Utilization of various diagnostic tools offer insight into AF burden and thromboembolic risk. Rate control, rhythm control, and stroke prophylaxis are the cornerstones of AF therapy. Although antiarrhythmic drugs are useful, AF ablation has become a primary therapeutic strategy. Pulmonary vein isolation is the cornerstone of AF ablation, and methods to improve ablation safety and efficacy continue to progress. Ablation of nonpulmonary vein sites is increasingly being recognized as an important strategy for treating nonparoxysmal AF. Several new ablation techniques and technologies and stroke prophylaxis are being explored. This is a contemporary review on the prevalence, pathophysiology, risk prediction, prophylaxis, treatment options, new insights for optimizing treatment outcomes, and emerging concepts of AF.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 13 Apr 2020; 75:1689-1713
Chung MK, Refaat M, Shen WK, Kutyifa V, ... Lakkireddy DR,
J Am Coll Cardiol: 13 Apr 2020; 75:1689-1713 | PMID: 32273035
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Abstract

Genetic predisposition to smoking in relation to 14 cardiovascular diseases.

Larsson SC, Mason AM, Bäck M, Klarin D, ... Michaëlsson K, Burgess S
Aims
The aim of this study was to use Mendelian randomization (MR) to determine the causality of the association between smoking and 14 different cardiovascular diseases (CVDs).
Methods and results
Our primary genetic instrument comprised 361 single-nucleotide polymorphisms (SNPs) associated with smoking initiation (ever smoked regularly) at genome-wide significance. Data on the associations between the SNPs and 14 CVDs were obtained from the UK Biobank study (N = 367 643 individuals), CARDIoGRAMplusC4D consortium (N = 184 305 individuals), Atrial Fibrillation Consortium (2017 dataset; N = 154 432 individuals), and Million Veteran Program (MVP; N = 190 266 individuals). The main analyses were conducted using the random-effects inverse-variance weighted method and complemented with multivariable MR analyses and the weighted median and MR-Egger approaches. Genetic predisposition to smoking initiation was most strongly and consistently associated with higher odds of coronary artery disease, heart failure, abdominal aortic aneurysm, ischaemic stroke, transient ischaemic attack, peripheral arterial disease, and arterial hypertension. Genetic predisposition to smoking initiation was additionally associated with higher odds of deep vein thrombosis and pulmonary embolism in the UK Biobank but not with venous thromboembolism in the MVP. There was limited evidence of causal associations of smoking initiation with atrial fibrillation, aortic valve stenosis, thoracic aortic aneurysm, and intracerebral and subarachnoid haemorrhage.
Conclusion
This MR study supports a causal association between smoking and a broad range of CVDs, in particular, coronary artery disease, heart failure, abdominal aortic aneurysm, ischaemic stroke, transient ischaemic attack, peripheral arterial disease, and arterial hypertension.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 15 Apr 2020; epub ahead of print
Larsson SC, Mason AM, Bäck M, Klarin D, ... Michaëlsson K, Burgess S
Eur Heart J: 15 Apr 2020; epub ahead of print | PMID: 32300774
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Abstract

Supracardiac atherosclerosis in embolic stroke of undetermined source: the underestimated source.

Ntaios G, Wintermark M, Michel P

The term \'embolic stroke of undetermined source\' (ESUS) is used to describe patients with a non-lacunar ischaemic stroke without any identified embolic source from the heart or the arteries supplying the ischaemic territory, or any other apparent cause. When the ESUS concept was introduced, covert atrial fibrillation was conceived to be the main underlying cause in the majority of ESUS patients. Another important embolic source in ESUS is the atherosclerotic plaque in the carotid, vertebrobasilar, and intracranial arteries, or the aortic arch-collectively described as supracardiac atherosclerosis. There is emerging evidence showing that the role of supracardiac atherosclerosis is larger than it was initially perceived. Advanced imaging methods are available to identify plaques which high embolic risk. The role of novel antithrombotic strategies in these patients needs to be assessed in randomized controlled trials. This review presents the evidence which points towards a major aetiological association between atherosclerotic plaques and ESUS, summarizes the imaging features which may aid to identify plaques more likely to be associated with ESUS, discusses strategies to reduce the associated stroke risk, and highlights the rationale for future research in this field.

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: 15 Apr 2020; epub ahead of print
Ntaios G, Wintermark M, Michel P
Eur Heart J: 15 Apr 2020; epub ahead of print | PMID: 32300781
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Abstract

Primary and Secondary Prevention of Ischemic Stroke and Cerebral Hemorrhage: JACC Focus Seminar.

Diener HC, Hankey GJ

Stroke is a leading cause of permanent disability. Therefore, primary prevention of first stroke and secondary prevention of recurrent stroke are a high priority. Primary prevention of ischemic stroke includes lifestyle modification and diet, treatment of risk factors including hypertension, diabetes mellitus and lipid disorders, antiplatelet therapy for high vascular risk patients, and anticoagulation in atrial fibrillation. Secondary prevention of ischemic stroke includes additional carotid surgery or stenting in selected symptomatic patients, closure of patent foramen ovale after cryptogenic stroke, treatment of insulin resistance, and best medical treatment of intracranial stenosis. The most important preventive strategies in the primary and secondary prevention of cerebral hemorrhage include the treatment of hypertension, reduction in alcohol intake, and occlusion of the left atrial appendage in patients with atrial fibrillation and permanent contraindications for oral anticoagulation.

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

J Am Coll Cardiol: 20 Apr 2020; 75:1804-1818
Diener HC, Hankey GJ
J Am Coll Cardiol: 20 Apr 2020; 75:1804-1818 | PMID: 32299593
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Abstract

Natural History and Risk Stratification in Andersen-Tawil Syndrome Type 1.

Mazzanti A, Guz D, Trancuccio A, Pagan E, ... Bagnardi V, Priori SG
Background
Andersen-Tawil Syndrome type 1 (ATS1) is a rare arrhythmogenic disorder, caused by loss-of-function mutations in the KCNJ2 gene. We present here the largest cohort of patients with ATS1 with outcome data reported.
Objectives
This study sought to define the risk of life-threatening arrhythmic events (LAE), identify predictors of such events, and define the efficacy of antiarrhythmic therapy in patients with ATS1.
Methods
Clinical and genetic data from consecutive patients with ATS1 from 23 centers were entered in a database implemented at ICS Maugeri in Pavia, Italy, and pooled for analysis.
Results
We enrolled 118 patients with ATS1 from 57 families (age 23 ± 17 years at enrollment). Over a median follow-up of 6.2 years (interquartile range: 2.7 to 16.5 years), 17 patients experienced a first LAE, with a cumulative probability of 7.9% at 5 years. An increased risk of LAE was associated with a history of syncope (hazard ratio [HR]: 4.54; p = 0.02), with the documentation of sustained ventricular tachycardia (HR 9.34; p = 0.001) and with the administration of amiodarone (HR: 268; p < 0.001). The rate of LAE without therapy (1.24 per 100 person-years [py]) was not reduced by beta-blockers alone (1.37 per 100 py; p = 1.00), or in combination with Class Ic antiarrhythmic drugs (1.46 per 100 py, p = 1.00).
Conclusions
Our data demonstrate that the clinical course of patients with ATS1 is characterized by a high rate of LAE. A history of unexplained syncope or of documented sustained ventricular tachycardia is associated with a higher risk of LAE. Amiodarone is proarrhythmic and should be avoided in patients with ATS1.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 20 Apr 2020; 75:1772-1784
Mazzanti A, Guz D, Trancuccio A, Pagan E, ... Bagnardi V, Priori SG
J Am Coll Cardiol: 20 Apr 2020; 75:1772-1784 | PMID: 32299589
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Abstract

Functional tricuspid regurgitation of degenerative mitral valve disease: a crucial determinant of survival.

Essayagh B, Antoine C, Benfari G, Maalouf J, ... Avierinos JF, Enriquez-Sarano M
Aims 
To assess functional tricuspid regurgitation (FTR) determinants, consequences, and independent impact on outcome in degenerative mitral regurgitation (DMR).
Methods and results 
All patients diagnosed with isolated DMR 2003-2011, with structurally normal tricuspid leaflets, prospective FTR grading and systolic pulmonary artery pressure (sPAP) estimation by Doppler echocardiography at diagnosis were identified and long-term outcome analysed. The 5083 DMR eligible patients [63 ± 16 years, 47% female, ejection fraction (EF) 63 ± 7%, and sPAP 35 ± 13 mmHg] presented with FTR graded trivial in 45%, mild in 37%, moderate in 15%, and severe in 3%. While pulmonary hypertension (PHTN-sPAP ≥ 50 mmHg) was the most powerful FTR severity determinant, other strong FTR determinants were older age, female sex, lower left ventricle EF, DMR, and particularly atrial fibrillation (AFib) (all P ≤ 0.002). Functional tricuspid regurgitation moderate/severe was independently linked to more severe clinical presentation, more oedema, lower stroke volume, and impaired renal function (P ≤ 0.01). Survival (95% confidence interval) throughout follow-up [70% (69-72%) at 10 years] was strongly associated with FTR severity [82% (80-84%) for trivial, 69% (66-71%) for mild, 51% (47-57%) for moderate, and 26% (19-35%) for severe, P < 0.0001]. Excess mortality persisted after comprehensive adjustment [adjusted hazard ratio 1.40 (1.18-1.67) for moderate FTR and 2.10 (1.63-2.70) for severe FTR, P ≤ 0.01]. Excess mortality persisted adjusting for sPAP/right ventricular function (P < 0.0001), by matching [adjusted hazard ratios 2.08 (1.50-2.89), P < 0.0001] and vs. expected survival [risk ratio 1.79 (1.48-2.16), P < 0.0001]. Within 5-year of diagnosis valve surgery was performed in 73% (70-75%) and 15% (13-17%) of severe and moderate DMR and in only 26% (19-34%) and 6% (4-8%) of severe and moderate FTR. Valvular surgery improved outcome without alleviating completely higher mortality associated with FTR (P < 0.0001).
Conclusion 
In this large DMR cohort, FTR was frequent and causally, not only linked to PHTN but also to other factors, particularly AFib. Higher FTR severity is associated at diagnosis with more severe clinical presentation. Long term, FTR is independently of all confounders, associated with considerably worse mortality. Functional tricuspid regurgitation moderate and even severe is profoundly undertreated. Thus careful assessment, consideration for tricuspid surgery, and testing of new transcatheter therapy is warranted.

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: 15 Apr 2020; epub ahead of print
Essayagh B, Antoine C, Benfari G, Maalouf J, ... Avierinos JF, Enriquez-Sarano M
Eur Heart J: 15 Apr 2020; epub ahead of print | PMID: 32300779
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Abstract

KCNQ1 Antibodies for Immunotherapy of Long QT Syndrome Type 2.

Maguy A, Kucera JP, Wepfer JP, Forest V, Charpentier F, Li J
Background
Patients with long QT syndrome (LQTS) are predisposed to life-threatening arrhythmias. A delay in cardiac repolarization is characteristic of the disease. Pharmacotherapy, implantable cardioverter-defibrillators, and left cardiac sympathetic denervation are part of the current treatment options, but no targeted therapy for LQTS exists to date. Previous studies indicate that induced autoimmunity against the voltage-gated KCNQ1 K channels accelerates cardiac repolarization.
Objectives
However, a causative relationship between KCNQ1 antibodies and the observed electrophysiological effects has never been demonstrated, and thus presents the aim of this study.
Methods
The authors purified KCNQ1 antibodies and performed whole-cell patch clamp experiments as well as single-channel recordings on Chinese hamster ovary cells overexpressing I channels. The effect of purified KCNQ1 antibodies on human cardiomyocytes derived from induced pluripotent stem cells was then studied.
Results
The study demonstrated that KCNQ1 antibodies underlie the previously observed increase in repolarizing I current. The antibodies shift the voltage dependence of activation and slow the deactivation of I. At the single-channel level, KCNQ1 antibodies increase the open time and probability of the channel. In models of LQTS type 2 (LQTS2) using human induced pluripotent stem cell-derived cardiomyocytes, KCNQ1 antibodies reverse the prolonged cardiac repolarization and abolish arrhythmic activities.
Conclusions
Here, the authors provide the first direct evidence that KCNQ1 antibodies act as agonists on I channels. Moreover, KCNQ1 antibodies were able to restore alterations in cardiac repolarization and most importantly to suppress arrhythmias in LQTS2. KCNQ1 antibody therapy may thus present a novel promising therapeutic approach for LQTS2.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 04 May 2020; 75:2140-2152
Maguy A, Kucera JP, Wepfer JP, Forest V, Charpentier F, Li J
J Am Coll Cardiol: 04 May 2020; 75:2140-2152 | PMID: 32354382
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Abstract

Repeat Transcatheter Aortic Valve Replacement for Transcatheter Prosthesis Dysfunction.

Landes U, Webb JG, De Backer O, Sondergaard L, ... Leon MB, Barbanti M
Background
Transcatheter aortic valve replacement (TAVR) use is increasing in patients with longer life expectancy, yet robust data on the durability of transcatheter heart valves (THVs) are limited. Redo-TAVR may play a key strategy in treating patients in whom THVs fail.
Objectives
The authors sought to examine outcomes following redo-TAVR.
Methods
The Redo-TAVR registry collected data on consecutive patients who underwent redo-TAVR at 37 centers. Patients were classified as probable TAVR failure or probable THV failure if they presented within or beyond 1 year of their index TAVR, respectively.
Results
Among 63,876 TAVR procedures, 212 consecutive redo-TAVR procedures were identified (0.33%): 74 within and 138 beyond 1 year of the initial procedure. For these 2 groups, TAVR-to-redo-TAVR time was 68 (38 to 154) days and 5 (3 to 6) years. The indication for redo-TAVR was THV stenosis in 12 (16.2%) and 51 (37.0%) (p = 0.002) and regurgitation or combined stenosis-regurgitation in 62 (83.8%) and 86 (62.3%) (p = 0.028), respectively. Device success using VARC-2 criteria was achieved in 180 patients (85.1%); most failures were attributable to high residual gradients (14.1%) or regurgitation (8.9%). At 30-day and 1-year follow-up, residual gradients were 12.6 ± 7.5 mm Hg and 12.9 ± 9.0 mm Hg; valve area 1.63 ± 0.61 cm and 1.51 ± 0.57 cm; and regurgitation ≤mild in 91% and 91%, respectively. Peri-procedural complication rates were low (3 stroke [1.4%], 7 valve malposition [3.3%], 2 coronary obstruction [0.9%], 20 new permanent pacemaker [9.6%], no mortality), and symptomatic improvement was substantial. Survival at 30 days was 94.6% and 98.5% (p = 0.101) and 83.6% and 88.3% (p = 0.335) at 1 year for patients presenting with early and late valve dysfunction, respectively.
Conclusions
Redo-TAVR is a relatively safe and effective option for selected patients with valve dysfunction after TAVR. These results are important for applicability of TAVR in patients with long life expectancy in whom THV durability may be a concern.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 27 Apr 2020; 75:1882-1893
Landes U, Webb JG, De Backer O, Sondergaard L, ... Leon MB, Barbanti M
J Am Coll Cardiol: 27 Apr 2020; 75:1882-1893 | PMID: 32327098
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Abstract

A Population-Based Registry of Patients With Inherited Cardiac Conditions and Resuscitated Cardiac Arrest.

Rucinski C, Winbo A, Marcondes L, Earle N, ... Martin A, Skinner JR
Background
The relative proportion of each cardiac inherited disease (CID) causing resuscitated sudden cardiac arrest (RSCA) on a population basis is unknown.
Objectives
This study describes the profile of patients with CIDs presenting with RSCA; their data were collected by the national Cardiac Inherited Diseases Registry New Zealand (CIDRNZ).
Methods
Data were collated from CIDRNZ probands presenting with RSCA (2002 to 2018).
Results
CID was identified in 115 (51%) of 225 RSCA cases: long QT syndrome (LQTS) (n = 48 [42%]), hypertrophic cardiomyopathy (HCM) (n = 28 [24%]), Brugada syndrome (BrS) (n = 16 [14%]), catecholaminergic polymorphic ventricular tachycardia (CPVT) (n = 9 [8%]), arrhythmogenic right ventricular cardiomyopathy (ARVC) (n = 9 [8%]), and dilated cardiomyopathy (n = 5 [4%]). Seventy-one (62%) of 115 were male. Of 725 probands from the CIDRNZ with CID, the proportion presenting with RSCA was: CPVT, 9 (53%) of 17; BrS, 16 (33%) of 49; ARVC, 9 (25%) of 36; LQTS, 48 (20%) of 238; dilated cardiomyopathy, 5 (9%) of 58; and HCM, 28 (8%) of 354. Incident activity was: normal everyday activities, 44 (40%); exercising, 33 (30%); concurrent illness, 13 (12%); sleeping, 10 (9%); drugs/medication, 9 (8%); and emotion, 2 (2%). LQTS and CPVT predominated in those <24 years of age, 30 (77%) of 39; cardiomyopathies and BrS predominated in those >24 years of age, 49 (64%) of 76. For those >40 years of age, HCM was the most common (33%) CID. A genetic diagnosis in patients with CID was made in 48 (49%) of 98 tested. Diagnosis by age range was as follows: age 1 to 14 years, 78%; age 15 to 24 years, 53%; age 25 to 39 years, 54%; and age >40 years, 26%.
Conclusions
The commonest CID identified after RSCA was LQTS; the most common CID cause of RSCA for those >40 years of age was HCM. CPVT was the CID most likely to present with RSCA and HCM the least. Genetic yield decreases with age. Only one-third of RSCA cases due to CID occurred while exercising.

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

J Am Coll Cardiol: 01 Jul 2020; 75:2698-2707
Rucinski C, Winbo A, Marcondes L, Earle N, ... Martin A, Skinner JR
J Am Coll Cardiol: 01 Jul 2020; 75:2698-2707 | PMID: 32466885
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Abstract

Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19.

Mehra MR, Desai SS, Kuy S, Henry TD, Patel AN
Background
Coronavirus disease 2019 (Covid-19) may disproportionately affect people with cardiovascular disease. Concern has been aroused regarding a potential harmful effect of angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in this clinical context.
Methods
Using an observational database from 169 hospitals in Asia, Europe, and North America, we evaluated the relationship of cardiovascular disease and drug therapy with in-hospital death among hospitalized patients with Covid-19 who were admitted between December 20, 2019, and March 15, 2020, and were recorded in the Surgical Outcomes Collaborative registry as having either died in the hospital or survived to discharge as of March 28, 2020.
Results
Of the 8910 patients with Covid-19 for whom discharge status was available at the time of the analysis, a total of 515 died in the hospital (5.8%) and 8395 survived to discharge. The factors we found to be independently associated with an increased risk of in-hospital death were an age greater than 65 years (mortality of 10.0%, vs. 4.9% among those ≤65 years of age; odds ratio, 1.93; 95% confidence interval [CI], 1.60 to 2.41), coronary artery disease (10.2%, vs. 5.2% among those without disease; odds ratio, 2.70; 95% CI, 2.08 to 3.51), heart failure (15.3%, vs. 5.6% among those without heart failure; odds ratio, 2.48; 95% CI, 1.62 to 3.79), cardiac arrhythmia (11.5%, vs. 5.6% among those without arrhythmia; odds ratio, 1.95; 95% CI, 1.33 to 2.86), chronic obstructive pulmonary disease (14.2%, vs. 5.6% among those without disease; odds ratio, 2.96; 95% CI, 2.00 to 4.40), and current smoking (9.4%, vs. 5.6% among former smokers or nonsmokers; odds ratio, 1.79; 95% CI, 1.29 to 2.47). No increased risk of in-hospital death was found to be associated with the use of ACE inhibitors (2.1% vs. 6.1%; odds ratio, 0.33; 95% CI, 0.20 to 0.54) or the use of ARBs (6.8% vs. 5.7%; odds ratio, 1.23; 95% CI, 0.87 to 1.74).
Conclusions
Our study confirmed previous observations suggesting that underlying cardiovascular disease is associated with an increased risk of in-hospital death among patients hospitalized with Covid-19. Our results did not confirm previous concerns regarding a potential harmful association of ACE inhibitors or ARBs with in-hospital death in this clinical context. (Funded by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women\'s Hospital.).

Copyright © 2020 Massachusetts Medical Society.

N Engl J Med: 30 Apr 2020; epub ahead of print
Mehra MR, Desai SS, Kuy S, Henry TD, Patel AN
N Engl J Med: 30 Apr 2020; epub ahead of print | PMID: 32356626
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Abstract

Infections Associated with Resterilized Pacemakers and Defibrillators.

Khairy TF, Lupien MA, Nava S, Baez FV, ... Macle L, Khairy P
Background
Access to pacemakers and defibrillators is problematic in places with limited resources. Resterilization and reuse of implantable cardiac devices obtained post mortem from patients in wealthier nations have been undertaken, but uncertainty around the risk of infection is a concern.
Methods
A multinational program was initiated in 1983 to provide tested and resterilized pacemakers and defibrillators to underserved nations; a prospective registry was established in 2003. Patients who received reused devices in this program were matched in a 1:3 ratio with control patients who received new devices implanted in Canada. The primary outcome was infection or device-related death, with mortality from other causes modeled as a competing risk.
Results
Resterilized devices were implanted in 1051 patients (mean [±SD] age, 63.2±18.5 years; 43.6% women) in Mexico (36.0%), the Dominican Republic (28.1%), Guatemala (26.6%), and Honduras (9.3%). Overall, 85% received pacemakers and 15% received defibrillators, with one (55.5%), two (38.8%), or three (5.7%) leads. Baseline characteristics did not differ between these patients and the 3153 matched control patients. At 2 years of follow-up, infections had occurred in 21 patients (2.0%) with reused devices and in 38 (1.2%) with new devices (hazard ratio, 1.66; 95% confidence interval, 0.97 to 2.83; P = 0.06); there were no device-related deaths. The most common implicated pathogens wereand .
Conclusions
Among patients in underserved countries who received a resterilized and reused pacemaker or defibrillator, the incidence of infection or device-related death at 2 years was 2.0%, an incidence that did not differ significantly from that seen among matched control patients with new devices in Canada.

Copyright © 2020 Massachusetts Medical Society.

N Engl J Med: 06 May 2020; 382:1823-1831
Khairy TF, Lupien MA, Nava S, Baez FV, ... Macle L, Khairy P
N Engl J Med: 06 May 2020; 382:1823-1831 | PMID: 32374963
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Abstract

Evaluation and Management of Premature Ventricular Complexes.

Marcus GM

Premature ventricular complexes (PVCs) are extremely common, found in the majority of individuals undergoing long-term ambulatory monitoring. Increasing age, a taller height, a higher blood pressure, a history of heart disease, performance of less physical activity, and smoking each predict a greater PVC frequency. Although the fundamental causes of PVCs remain largely unknown, potential mechanisms for any given PVC include triggered activity, automaticity, and reentry. PVCs are commonly asymptomatic but can also result in palpitations, dyspnea, presyncope, and fatigue. The history, physical examination, and 12-lead ECG are each critical to the diagnosis and evaluation of a PVC. An echocardiogram is indicated in the presence of symptoms or particularly frequent PVCs, and cardiac magnetic resonance imaging is helpful when the evaluation suggests the presence of associated structural heart disease. Ambulatory monitoring is required to assess PVC frequency. The prognosis of those with PVCs is variable, with ongoing uncertainty regarding the most informative predictors of adverse outcomes. An increased PVC frequency may be a risk factor for heart failure and death, and the resolution of systolic dysfunction after successful catheter ablation of PVCs demonstrates that a causal relationship can be present. Patients with no or mild symptoms, a low PVC burden, and normal ventricular function may be best served with simple reassurance. Either medical treatment or catheter ablation are considered first-line therapies in most patients with PVCs associated with symptoms or a reduced left ventricular ejection fraction, and patient preference plays a role in determining which to try first. If medical treatment is selected, either β-blockers or nondihydropyridine calcium channel blockers are reasonable drugs in patients with normal ventricular systolic function. Other antiarrhythmic drugs should be considered if those initial drugs fail and ablation has been declined, has been unsuccessful, or has been deemed inappropriate. Catheter ablation is the most efficacious approach to eradicate PVCs but may confer increased upfront risks. Original research remains necessary to identify individuals at risk for PVC-induced cardiomyopathy and to identify preventative and therapeutic approaches targeting the root causes of PVCs to maximize effectiveness while minimizing risk.



Circulation: 27 Apr 2020; 141:1404-1418
Marcus GM
Circulation: 27 Apr 2020; 141:1404-1418 | PMID: 32339046
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Abstract

Characteristics and outcomes of patients hospitalized for COVID-19 and cardiac disease in Northern Italy.

Inciardi RM, Adamo M, Lupi L, Cani DS, ... Bezzi M, Metra M
Aims
To compare demographic characteristics, clinical presentation, and outcomes of patients with and without concomitant cardiac disease, hospitalized for COVID-19 in Brescia, Lombardy, Italy.
Methods and results
The study population includes 99 consecutive patients with COVID-19 pneumonia admitted to our hospital between 4 March and 25 March 2020. Fifty-three patients with a history of cardiac disease were compared with 46 without cardiac disease. Among cardiac patients, 40% had a history of heart failure, 36% had atrial fibrillation, and 30% had coronary artery disease. Mean age was 67 ± 12 years, and 80 (81%) patients were males. No differences were found between cardiac and non-cardiac patients except for higher values of serum creatinine, N-terminal probrain natriuretic peptide, and high sensitivity troponin T in cardiac patients. During hospitalization, 26% patients died, 15% developed thrombo-embolic events, 19% had acute respiratory distress syndrome, and 6% had septic shock. Mortality was higher in patients with cardiac disease compared with the others (36% vs. 15%, log-rank P = 0.019; relative risk 2.35; 95% confidence interval 1.08-5.09). The rate of thrombo-embolic events and septic shock during the hospitalization was also higher in cardiac patients (23% vs. 6% and 11% vs. 0%, respectively).
Conclusions
Hospitalized patients with concomitant cardiac disease and COVID-19 have an extremely poor prognosis compared with subjects without a history of cardiac disease, with higher mortality, thrombo-embolic events, and septic shock rates.

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: 07 May 2020; epub ahead of print
Inciardi RM, Adamo M, Lupi L, Cani DS, ... Bezzi M, Metra M
Eur Heart J: 07 May 2020; epub ahead of print | PMID: 32383763
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Abstract

Summary of Updated Recommendations for Primary Prevention of Cardiovascular Disease in Women: JACC State-of-the-Art Review.

Cho L, Davis M, Elgendy I, Epps K, ... Volgman AS,

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality for women in the United States and worldwide. There has been no American College of Cardiology (ACC)/American Heart Association guideline update specifically for the prevention of CVD in women since 2011. Since then, the body of sex-specific data has grown, in addition to updated hypertension, cholesterol, diabetes, atrial fibrillation, and primary prevention guidelines. The ACC CVD in Women Committee undertook a review of the recent guidelines and major studies to summarize recommendations pertinent to women. In this update, the authors address special topics, particularly the risk factors and treatments that have led to some controversies and confusion. Specifically, sex-related risk factors, hypertension, diabetes, hyperlipidemia, anticoagulation for atrial fibrillation, use of aspirin, perimenopausal hormone therapy, and psychosocial issues are highlighted.

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

J Am Coll Cardiol: 25 May 2020; 75:2602-2618
Cho L, Davis M, Elgendy I, Epps K, ... Volgman AS,
J Am Coll Cardiol: 25 May 2020; 75:2602-2618 | PMID: 32439010
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Abstract

Cardiovascular outcomes, bleeding risk, and achieved blood pressure in patients on long-term anticoagulation with the thrombin antagonist dabigatran or warfarin: data from the RE-LY trial.

Böhm M, Brueckmann M, Eikelboom JW, Ezekowitz M, ... Wallentin L, Yusuf S
Aims 
A J-shaped association of cardiovascular events to achieved systolic (SBP) and diastolic (DBP) blood pressure was shown in high-risk patients. This association on oral anticoagulation is unknown. This analysis from RELY assessed the risks of death, stroke or systemic emboli, and bleeding according to mean achieved SBP and DBP in atrial fibrillation on oral anticoagulation.
Methods and results 
RE-LY patients were followed for 2 years and recruited between 22 December 2005 until 15 December 2007. 18.113 patients were randomized in 951 centres in 54 countries and 18,107 patients with complete blood pressure (BP) data were analysed with a median follow-up of 2.0 years and a complete follow-up in 99.9%. The association between achieved mean SBP and DBP on all-cause death, stroke and systemic embolic events (SSE), major, and any bleeding were explored. On treatment, SBP >140 mmHg and <120 mmHg was associated with all-cause death compared with SBP 120-130 mmHg (reference). For SSE, risk was unchanged at SBP <110 mmHg but increased at 140-160 mmHg (adjusted hazard ratio (HR) 1.81; 1.40-2.33) and SBP ≥160 mmHg (HR 3.35; 2.09-5.36). Major bleeding events were also increased at <110 mmHg and at 110 to <120 mmHg. Interestingly, there was no increased risk of major bleeding at SBP >130 mmHg. Similar patterns were observed for DBP with an increased risk at <70 mmHg (HR 1.55; 1.35-1.78) and >90 mmHg (HR 1.88; 1.43-2.46) for all-cause death compared to 70 to <80 mmHg (reference). Risk for any bleeding was increased at low DBP <70 mmHg (HR 1.46; 1.37-1.56) at DBP 80 to <90 mmHg (HR 1.13; 1.06-1.31) without increased risk at higher achieved DBP. Dabigatran 150 mg twice daily showed an advantage in all patients for all-cause death and SSE and there was an advantage for 110 mg dabigatran twice daily for major bleeding and any bleeding irrespective of SBP or DBP achieved. Similar results were obtained for baseline BP, time-updated BP, and BP as time-varying covariate.
Conclusion 
Low achieved SBP associates with increased risk of death, SSE, and bleeding in patients with atrial fibrillation on oral anticoagulation. Major bleeding events did not occur at higher BP. Low BP might identify high-risk patients not only for death but also for high bleeding risks.
Clinical trial registration
 ClinicalTrials.gov-Identifier: NCT00262600.

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: 07 May 2020; epub ahead of print
Böhm M, Brueckmann M, Eikelboom JW, Ezekowitz M, ... Wallentin L, Yusuf S
Eur Heart J: 07 May 2020; epub ahead of print | PMID: 32385506
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Abstract

Personalised Rate-Response Programming Improves Exercise Tolerance After Six Months in People with Cardiac Implantable Electronic Devices and Heart Failure: A Phase II Study.

Gierula J, Lowry JE, Paton MF, Cole CA, ... Kearney MT, Witte KK

Heart failure with reduced ejection fraction (HFrEF) is characterised by blunting of the positive relationship between heart rate (HR) and left ventricular (LV) contractility known as the force frequency relationship (FFR). We have previously described that tailoring the rate-response programming of cardiac implantable electronic devices (CIED) in patients with HFrEF based upon individual\'s non-invasive FFR data acutely improves exercise capacity. We sought to examine whether using FFR data to tailor HR response in HFrEF patients with CIEDs, favourably influences exercise capacity and LV function 6 months later.We conducted a single-centre, double-blind, randomized, parallel group trial in patients with stable symptomatic HFrEF, taking optimal guideline-directed medical therapy and with a CIED (cardiac resynchronisation therapy (CRT) or implantable cardioverter defibrillator (ICD)). Participants were randomized on a 1:1 basis between tailored rate-response programming based upon individuals\' FFR data, and conventional age-guided rate-response programming. The primary outcome measure was change in walk time on a treadmill walk test. Secondary outcomes included changes in LV systolic function, peak oxygen consumption and quality of life.We randomized 83 patients with a mean ± SD age 74.6 ± 8.7 years, and mean LV ejection fraction (LVEF) 35.2 ± 10.5. Mean (95%CI) change in exercise time at 6 months was 75.4 (23.4 to 127.5) seconds for FFR-guided rate adaptive pacing and 3.1 (-44.1 to 50.3) seconds for conventional settings (ANCOVA p=0.044 between groups) despite lower peak mean (± SD) heart rates (98.6 ± 19.4 v 112.0 ± 20.3 bts/min). FFR-guided HR settings had no adverse effect on LV structure or function, whilst conventional settings were associated with a reduction in LVEF.In this phase II study, FFR-guided rate-response programming determined using a reproducible, non-invasive method appears to improve exercise time and limit changes to left ventricular function in people with HFrEF and CIEDs. Further work is ongoing to confirm our findings in a multi-centre setting and on longer term clinical outcomes.URL: https://clinicaltrials.gov Unique Identifier: NCT02964650.



Circulation: 16 Apr 2020; epub ahead of print
Gierula J, Lowry JE, Paton MF, Cole CA, ... Kearney MT, Witte KK
Circulation: 16 Apr 2020; epub ahead of print | PMID: 32299222
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Abstract

Prognostic Value of Magnetic Resonance Phenotype in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

Aquaro GD, De Luca A, Cappelletto C, Raimondi F, ... Di Bella G, Sinagra G
Background
Cardiac magnetic resonance (CMR) is widely used to assess tissue and functional abnormalities in arrhythmogenic right ventricular cardiomyopathy (ARVC). Recently, a ARVC risk score was proposed to predict the 5-year risk of malignant ventricular arrhythmias in patients with ARVC. However, CMR features such as fibrosis, fat infiltration, and left ventricular (LV) involvement were not considered.
Objectives
The authors sought to evaluate the prognostic role of CMR phenotype in patients with definite ARVC and to evaluate the effectiveness of the novel 5-year ARVC risk score to predict cardiac events in different CMR presentations.
Methods
A total of 140 patients with definite ARVC were enrolled (mean age 42 ± 17 years, 97 males) in this multicenter prospective registry. As per study design, CMR was performed in all the patients at enrollment. The novel 5-year ARVC risk score was retrospectively calculated using the patient\'s characteristics at the time of enrollment. During a median follow-up of 5 years (2 to 8 years), the combined endpoint of sudden cardiac death, appropriate implantable cardioverter-defibrillator intervention, and aborted cardiac arrest was considered.
Results
CMR was completely negative in 14 patients (10%), isolated right ventricular (RV) involvement was found in 58 (41%), biventricular in 52 (37%), and LV dominant in 16 (12%). During the follow-up, 48 patients (34%) had major events, but none occurred in patients with negative CMR. At Kaplan-Meier analysis, patients with LV involvement (LV dominant and biventricular) had a worse prognosis than those with lone RV (p < 0.0001). At multivariate analysis, the LV involvement, a LV-dominant phenotype, and the 5-year ARVC risk score were independent predictors of major events. The estimated 5-year risk was able to predict the observed risk in patients with lone RV but underestimated the risk in those with LV involvement.
Conclusions
Different CMR presentations of ARVC are associated with different prognoses. The 5-year ARVC risk score is valid for the estimation of risk in patients with lone-RV presentation but underestimated the risk when LV is involved.

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

J Am Coll Cardiol: 08 Jun 2020; 75:2753-2765
Aquaro GD, De Luca A, Cappelletto C, Raimondi F, ... Di Bella G, Sinagra G
J Am Coll Cardiol: 08 Jun 2020; 75:2753-2765 | PMID: 32498802
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Abstract

Desmoplakin Cardiomyopathy, a Fibrotic and Inflammatory Form of Cardiomyopathy Distinct from Typical Dilated or Arrhythmogenic Right Ventricular Cardiomyopathy.

Smith ED, Lakdawala NK, Papoutsidakis N, Aubert G, ... McNally EM, Helms AS

Mutations in desmoplakin (), the primary force transducer between cardiac desmosomes and intermediate filaments, cause an arrhythmogenic form of cardiomyopathy that has been variably associated with arrhythmogenic right ventricular cardiomyopathy (ARVC). Clinical correlates ofcardiomyopathy have been limited to small case series.Clinical and genetic data were collected on 107 patients with pathogenicmutations and 81 patients with pathogenicmutations as a comparison cohort. A composite outcome of severe ventricular arrhythmia was assessed.andcohorts included similar proportions of probands (41% vs. 42%) and patients with truncating mutations (98% vs. 100%). Left ventricular (LV) predominant cardiomyopathy was exclusively present amongpatients (55% vs. 0% for , p<0.001), whereas right ventricular (RV) cardiomyopathy was present in only 14% ofpatients vs. 40% for(p<0.001). ARVC diagnostic criteria had poor sensitivity forcardiomyopathy. LV late gadolinium enhancement (LGE) was present in a primarily subepicardial distribution in 40% ofpatients (23/57 with MRIs). LV LGE occurred with normal LV systolic function in 35% (8/23) ofpatients. Episodes of acute myocardial injury (chest pain with troponin elevation and normal coronary angiography) occurred in 15% ofpatients and were strongly associated with LV LGE (90%), even in cases of acute myocardial injury with normal ventricular function (4/5, 80% with LGE). In 4cases with F-fluorodeoxyglucose positron emission tomography scans, acute LV myocardial injury was associated with myocardial inflammation misdiagnosed initially as cardiac sarcoidosis or myocarditis. LVEF <55% was strongly associated with severe ventricular arrhythmias forcases (p<0.001, sensitivity 85%, specificity 53%). RVEF <45% was associated with severe arrhythmias forcases (p<0.001) but was poorly associated forcases (p=0.8). Frequent PVCs were common among patients with severe arrhythmias for both(80%) and(91%) groups (p=NS).cardiomyopathy is a distinct form of arrhythmogenic cardiomyopathy characterized by episodic myocardial injury, left ventricular fibrosis that precedes systolic dysfunction, and a high incidence of ventricular arrhythmias. A genotype specific approach for diagnosis and risk stratification should be used.



Circulation: 05 May 2020; epub ahead of print
Smith ED, Lakdawala NK, Papoutsidakis N, Aubert G, ... McNally EM, Helms AS
Circulation: 05 May 2020; epub ahead of print | PMID: 32372669
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Abstract

Renal Denervation in High-Risk Patients With Hypertension.

Mahfoud F, Mancia G, Schmieder R, Narkiewicz K, ... Fahy M, Böhm M
Background
Renal denervation (RDN) is under investigation for treatment of uncontrolled hypertension and might represent an attractive treatment for patients with high cardiovascular (CV) risk. It is important to determine whether baseline CV risk affects the efficacy of RDN.
Objectives
The purpose of this study was to assess blood pressure (BP) reduction and event rates after RDN in patients with various comorbidities, testing the hypothesis that RDN is effective and durable in these high-risk populations.
Methods
BP reduction and adverse events over 3 years were evaluated for several high-risk subgroups in the GSR (Global proSpective registrY for syMPathetic renaL denervatIon in seleCted IndicatIons Through 3 Years Registry), an international registry of RDN in patients with uncontrolled hypertension (n = 2,652). Comparisons were made for patients age ≥65 years versus age <65 years, with versus without isolated systolic hypertension, with versus without atrial fibrillation, and with versus without diabetes mellitus. Baseline cardiovascular risk was estimated using the American Heart Association (AHA)/American College of Cardiology (ACC) atherosclerosis cardiovascular disease (ASCVD) risk score.
Results
Reduction in 24-h systolic BP at 3 years was -8.9 ± 20.1 mm Hg for the overall cohort, and for high-risk subgroups, BP reduction was -10.4 ± 21.0 mm Hg for resistant hypertension, -8.7 ± 17.4 mm Hg in patients age ≥65 years, -10.2 ± 17.9 mm Hg in patients with diabetes, -8.6 ± 18.7 mm Hg in isolated systolic hypertension, -10.1 ± 20.3 mm Hg in chronic kidney disease, and -10.0 ± 19.1 mm Hg in atrial fibrillation (p < 0.0001 compared with baseline for all). BP reduction in patients with measurements at 6, 12, 24, and 36 months showed similar reductions in office and 24-h BP for patients with varying baseline ASCVD risk scores, which was sustained to 3 years. Adverse event rates at 3 years were higher for patients with higher baseline CV risk.
Conclusions
BP reduction after RDN was similar for patients with varying high-risk comorbidities and across the range of ASCVD risk scores. The impact of baseline risk on clinical event reduction by RDN-induced BP changes could be evaluated in further studies. (Global proSpective registrY for syMPathetic renaL denervatIon in seleCted IndicatIons Through 3 Years Registry; NCT01534299).

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 15 Jun 2020; 75:2879-2888
Mahfoud F, Mancia G, Schmieder R, Narkiewicz K, ... Fahy M, Böhm M
J Am Coll Cardiol: 15 Jun 2020; 75:2879-2888 | PMID: 32527396
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Abstract

Ramipril in High Risk Patients with COVID-19.

Amat-Santos IJ, Santos-Martinez S, López-Otero D, Nombela-Franco L, ... Ibañez B, San Román JA
Background
The coronavirus disease 2019 (COVID-19) is caused by SARS-CoV2 that interfaces with the renin-angiotensin-aldosterone system (RAAS) through angiotensin-converting enzyme 2 (ACE-2). This interaction has been proposed as a potential risk factor in patients treated with RAAS-inhibitors.
Objectives
To analyze if RAAS-inhibitors modify the risk for COVID-19.
Methods
RASTAVI (NCT03201185) is an ongoing randomized clinical trial randomly allocating Ramipril or control after successful transcatheter aortic valve replacement at 14 centers is Spain. We performed a non-pre-specified interim analysis to evaluate its impact on COVID-19 risk in this vulnerable population.
Results
As in April 1 2020, 102 patients (50 Ramipril and 52 controls) were included in the trial. Mean age was 82.3±6.1 years, 56.9% males. Median time of Ramipril treatment was 6 months [IQR:2.9-11.4]. Eleven patients (10.8%) have been diagnosed with COVID-19 (6 in control group and 5 receiving Ramipril, HR=1.150 [95%CI: 0.351-3.768]). The risk of COVID-19 was increased in older patients (p=0.019), those with atrial fibrillation (p=0.066), lower hematocrit (p=0.084), and more comorbidities according to Society of thoracic surgeons score (p=0.065). Admission and oxygen supply was required in 4.9% (2 patients in the Ramipril and 3 in control), and 4 of them died (two in each randomized group). A higher body mass index was the only factor increasing the mortality rate (p=0.039).
Conclusions
In a high risk population of old patients with cardiovascular disease, randomization to Ramipril had no impact in the incidence or severity of COVID-19. This analysis supports the maintenance of RAAS-inhibitor treatment during COVID-19 crisis.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 21 May 2020; epub ahead of print
Amat-Santos IJ, Santos-Martinez S, López-Otero D, Nombela-Franco L, ... Ibañez B, San Román JA
J Am Coll Cardiol: 21 May 2020; epub ahead of print | PMID: 32470515
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Abstract

An autoantibody profile detects Brugada syndrome and identifies abnormally expressed myocardial proteins.

Chatterjee D, Pieroni M, Fatah M, Charpentier F, ... Saguner AM, Hamilton RM
Aims
Brugada syndrome (BrS) is characterized by a unique electrocardiogram (ECG) pattern and life-threatening arrhythmias. However, the Type 1 Brugada ECG pattern is often transient, and a genetic cause is only identified in <25% of patients. We sought to identify an additional biomarker for this rare condition. As myocardial inflammation may be present in BrS, we evaluated whether myocardial autoantibodies can be detected in these patients.
Methods and results
For antibody (Ab) discovery, normal human ventricular myocardial proteins were solubilized and separated by isoelectric focusing (IEF) and molecular weight on two-dimensional (2D) gels and used to discover Abs by plating with sera from patients with BrS and control subjects. Target proteins were identified by mass spectrometry (MS). Brugada syndrome subjects were defined based on a consensus clinical scoring system. We assessed discovery and validation cohorts by 2D gels, western blots, and ELISA. We performed immunohistochemistry on myocardium from BrS subjects (vs. control). All (3/3) 2D gels exposed to sera from BrS patients demonstrated specific Abs to four proteins, confirmed by MS to be α-cardiac actin, α-skeletal actin, keratin, and connexin-43, vs. 0/8 control subjects. All (18/18) BrS subjects from our validation cohorts demonstrated the same Abs, confirmed by western blots, vs. 0/24 additional controls. ELISA optical densities for all Abs were elevated in all BrS subjects compared to controls. In myocardium obtained from BrS subjects, each protein, as well as SCN5A, demonstrated abnormal protein expression in aggregates.
Conclusion
A biomarker profile of autoantibodies against four cardiac proteins, namely α-cardiac actin, α-skeletal actin, keratin, and connexin-43, can be identified from sera of BrS patients and is highly sensitive and specific, irrespective of genetic cause for BrS. The four involved proteins, along with the SCN5A-encoded Nav1.5 alpha subunit are expressed abnormally in the myocardium of patients with BrS.

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: 11 Jun 2020; epub ahead of print
Chatterjee D, Pieroni M, Fatah M, Charpentier F, ... Saguner AM, Hamilton RM
Eur Heart J: 11 Jun 2020; epub ahead of print | PMID: 32533187
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Abstract

A Validated Model for Sudden Cardiac Death Risk Prediction in Pediatric Hypertrophic Cardiomyopathy.

Miron A, Lafreniere-Roula M, Fan CS, Armstrong KR, ... Ho CY, Mital S

Hypertrophic cardiomyopathy (HCM) is the leading cause of sudden cardiac death (SCD) in children and young adults. Our objective was to develop and validate a SCD risk prediction model in pediatric HCM to guide SCD prevention strategies.In an international multi-center observational cohort study, phenotype-positive patients with isolated HCM <18 years at diagnosis were eligible. The primary outcome variable was the time from diagnosis to a composite of SCD events at 5-year follow-up: SCD, resuscitated sudden cardiac arrest (SCA), and aborted SCD, i.e. appropriate shock following primary prevention ICD. Competing risk models with cause-specific hazard regression were used to identify and quantify clinical and genetic factors associated with SCD. The cause-specific regression model was implemented using boosting, and tuned with ten repeated four-fold cross-validations. The final model was fitted using all data with the tuned hyperparameter value that maximizes the c-statistic, and its performance was characterized using c-statistic for competing risk models. The final model was validated in an independent external cohort (SHaRe, n=285).Overall, 572 patients met eligibility criteria with 2855 patient-years of follow-up. The 5-year cumulative proportion of SCD events was 9.1% (14 SCD, 25 resuscitated SCA, 14 aborted SCD). Risk predictors included age at diagnosis, documented non-sustained ventricular tachycardia, unexplained syncope, septal diameter z-score, LV posterior wall diameter z-score, LA diameter z-score, peak LV outflow tract (LVOT) gradient, and presence of a pathogenic variant. Unlike adults, LVOT gradient had an inverse association, and family history of SCD had no association with SCD. Clinical and clinical/genetic models were developed to predict 5-year freedom from SCD. Both models adequately discriminated patients with and without SCD events with a c-statistic of 0.75 and 0.76 respectively and demonstrated good agreement between predicted and observed events in the primary and validation cohorts (validation c-statistic 0.71 and 0.72 respectively). Our study provides a validated SCD risk prediction model with over 70% prediction accuracy and incorporates risk factors that are unique to pediatric HCM. An individualized risk prediction model has the potential to improve the application of clinical practice guidelines and shared decision-making for ICD insertion. URL: https://clinicaltrials.gov Unique Identifier: NCT04036799.



Circulation: 17 May 2020; epub ahead of print
Miron A, Lafreniere-Roula M, Fan CS, Armstrong KR, ... Ho CY, Mital S
Circulation: 17 May 2020; epub ahead of print | PMID: 32418493
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Abstract

Prevalence and Impact of Myocardial Injury in Patients Hospitalized with COVID-19 Infection.

Lala A, Johnson KW, Januzzi JL, Russak AJ, ... Fuster V,
Background
The degree of myocardial injury, as reflected by troponin elevation, and associated outcomes among US hospitalized patients with Coronavirus Disease 2019 (COVID-19) are unknown.
Objectives
To describe the degree of myocardial injury and associated outcomes in a large hospitalized cohort with laboratory-confirmed COVID-19.
Methods
Patients with COVID-19 admitted to one of five Mount Sinai Health System hospitals in New York City between February 27th and April 12th, 2020 with troponin-I (normal value <0.03ng/mL) measured within 24 hours of admission were included (n=2,736). Demographics, medical history, admission labs, and outcomes were captured from the hospitals\' EHR.
Results
The median age was 66.4 years, with 59.6% men. Cardiovascular disease (CVD) including coronary artery disease, atrial fibrillation, and heart failure, was more prevalent in patients with higher troponin concentrations, as were hypertension and diabetes. A total of 506 (18.5%) patients died during hospitalization. In all, 985 (36%) patients had elevated troponin concentrations. After adjusting for disease severity and relevant clinical factors, even small amounts of myocardial injury (e.g. troponin I 0.03-0.09ng/mL, n=455, 16.6%) were significantly associated with death (adjusted HR: 1.75, 95% CI 1.37-2.24; P<0.001) while greater amounts (e.g. troponin I>0.09 ng/dL, n=530, 19.4%) were significantly associated with higher risk (adjusted HR 3.03, 95% CI 2.42-3.80; P<0.001).
Conclusions
Myocardial injury is prevalent among patients hospitalized with COVID-19 however troponin concentrations were generally present at low levels. Patients with CVD are more likely to have myocardial injury than patients without CVD. Troponin elevation among patients hospitalized with COVID-19 is associated with higher risk of mortality.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 04 Jun 2020; epub ahead of print
Lala A, Johnson KW, Januzzi JL, Russak AJ, ... Fuster V,
J Am Coll Cardiol: 04 Jun 2020; epub ahead of print | PMID: 32517963
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Abstract

Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome.

Lahrouchi N, Tadros R, Crotti L, Mizusawa Y, ... Tanck MWT, Bezzina CR

Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility.We conducted genome-wide association studies (GWAS) followed by transethnic meta-analysis in 1,656 unrelated LQTS patients of European or Japanese ancestry and 9,890 controls to identify susceptibility single nucleotide polymorphisms (SNPs). We estimated the SNP heritability () of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 SNPs previously associated with QTc in the general population using a polygenic risk score (PRS).Genome-wide association analysis identified three loci associated with LQTS at genome-wide statistical significance (P<5x10) near ,and , and one missense variant in(p.Asp85Asn) at the suggestive threshold (P<10). Heritability analyses showed that ~15% of variance in overall LQTS susceptibility was attributable to common genetic variation ( 0.148; standard error [SE] 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT interval in the general population (r=0.40, P=3.2x10). PRS was greater in LQTS cases compared to controls (P<10), and notably, among LQTS patients PRS was greater in genotype negative compared to genotype positive patients (P<0.005).This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.



Circulation: 19 May 2020; epub ahead of print
Lahrouchi N, Tadros R, Crotti L, Mizusawa Y, ... Tanck MWT, Bezzina CR
Circulation: 19 May 2020; epub ahead of print | PMID: 32429735
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Abstract

Use of Administrative Claims to Assess Outcomes and Treatment Effect in Randomized Clinical Trials for Transcatheter Aortic Valve Replacement: Findings from the Extending Trial-Based Evaluations of Medical Therapies Using Novel Sources of Data (EXTEND) Study.

Strom JB, Faridi KF, Butala NM, Zhao Y, ... Kazi DS, Yeh RW

Whether passively collected data can substitute for adjudicated outcomes to reproduce the magnitude and direction of treatment effect observed in cardiovascular clinical trials is not well known.We linked adults aged ≥65 in the US CoreValve Pivotal High Risk (HiR) and Surgical or Transcatheter Aortic Valve Replacement in Intermediate-Risk Patients (SURTAVI) Trials to 100% Medicare inpatient claims, 1/1/2003-12/31/2016. Primary (e.g. death and stroke) and secondary trial endpoints, were compared across treatment arms (e.g. TAVR vs. SAVR) using trial-adjudicated outcomes versus outcomes derived from claims at 1-year (HiR) or 2-years (SURTAVI).Among 600 linked CoreValve HiR participants (linkage rate 80.0%), the rate of the trial\'s primary endpoint of all-cause mortality occurred in 13.7% of patients receiving TAVR and 16.4% of patients receiving SAVR at 1-year using both trial data (HR 0.84, 95% CI 0.65-1.09; p= 0.33) and claims data (HR 0.86, 95% CI 0.66-1.11; p = 0.34; interaction p-value = 0.80). Noninferiority of TAVR relative to SAVR was seen using both trial and claims-based outcomes (p < 0.001 for both). Among 1005 linked SURTAVI trial participants (linkage rate 60.5%), the trial\'s primary endpoint was 12.9% for TAVR and 13.1% for SAVR using trial data (HR 1.08, 95% CI 0.79-1.48, p = 0.90), and 11.3% for TAVR and 12.5% for SAVR patients using claims data (HR 1.02, 95% CI 0.73-1.41, p = 0.58; interaction p-value = 0.89). TAVR was noninferior to SAVR when compared using both trial and claims (p < 0.001 for both). Rates of procedural secondary outcomes (e.g. aortic valve reintervention, pacemaker rates) were more closely concordant between trial and claims data than non-procedural outcomes (e.g., stroke, bleeding, cardiogenic shock).In the CoreValve HiR and SURTAVI trials, ascertainment of trial primary endpoints using claims reproduced both the magnitude and direction of treatment effect compared with adjudicated event data, but non-fatal and non-procedural secondary outcomes were not as well reproduced. Use of claims to substitute for adjudicated outcomes in traditional trial treatment comparisons may be valid and feasible for all-cause mortality and certain procedural outcomes, but may be less suitable for other endpoints.



Circulation: 20 May 2020; epub ahead of print
Strom JB, Faridi KF, Butala NM, Zhao Y, ... Kazi DS, Yeh RW
Circulation: 20 May 2020; epub ahead of print | PMID: 32436390
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Abstract

Outcomes in Patients With Hypertrophic Cardiomyopathy and Left Ventricular Systolic Dysfunction.

Rowin EJ, Maron BJ, Carrick RT, Patel PP, ... Wells S, Maron MS
Background
End-stage (ES) hypertrophic cardiomyopathy (HCM) has been considered a particularly grim and unfavorable disease complication, associated with substantial morbidity and mortality, frequently requiring heart transplant. Previous reports have included small numbers of patients with relatively short follow-up, predominantly in prior treatment eras.
Objectives
The purpose of this study was to re-evaluate clinical profile and prognosis for end-stage heart failure in a large HCM cohort with contemporary management strategies.
Methods
Patients at Tufts HCM Institute, from 2004 to 2017, were identified with ES and systolic dysfunction (ejection fraction [EF] <50%), followed for 5.8 ± 4.7 years (up to 18 years).
Results
Of the 2,447 patients, 118 (4.8%) had ES-HCM (EF 39 ± 9%; range 12% to 49%) at age 48 ± 15 years. Notably, over follow-up, 57 patients (48%) achieved clinical stability in New York Heart Association functional classes I/II with medical treatment (or cardiac resynchronization therapy), including 6 patients ≥10 years from ES diagnosis (up to 14 years). In total, 61 other patients (52%) developed refractory heart failure to disabling New York Heart Association functional classes III/IV (5.2%/year); 67% have survived, including 31 with heart transplant. Of the 118 ES patients, 21 had appropriate implantable cardioverter-defibrillator (ICD) therapy terminating potentially lethal tachyarrhythmias, with no difference in frequency of events in patients with EF 35% to 49% versus EF <35% (17% vs. 19%; p = 0.80). With all available treatment modalities, ES-related mortality was 1.9%/year, with 10-year survival of 85% (95% confidence interval: 77% to 94%). Mortality was 4-fold lower than previously reported for ES (8.0%/year), but exceeded 10-fold HCM with preserved EF (0.2%/year; p < 0.001).
Conclusions
Although ES remains an important complication of HCM, contemporary treatment strategies, including ICDs and heart transplant, are associated with significantly lower mortality than previously considered. Primary prevention ICDs should be considered when EF is <50% in HCM. Rapid heart failure progression is not an inevitable consequence of ES, and some patients experience extended periods of clinical stability.

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

J Am Coll Cardiol: 22 Jun 2020; 75:3033-3043
Rowin EJ, Maron BJ, Carrick RT, Patel PP, ... Wells S, Maron MS
J Am Coll Cardiol: 22 Jun 2020; 75:3033-3043 | PMID: 32553256
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Abstract

The Natural History of Severe Calcific Mitral Stenosis.

Kato N, Padang R, Scott CG, Guerrero M, Pislaru SV, Pellikka PA
Background
Prevalence of calcific mitral stenosis (MS) increases with age; however, its natural history and relation to cardiac symptoms or comorbidities are not well defined.
Objectives
This study assessed the prevalence of symptoms, comorbidities, and determinants of all-cause mortality in patients with severe calcific MS.
Methods
The authors retrospectively investigated adults with isolated severe calcific MS and mitral valve area ≤1.5 cm from July 2003 to December 2017. Inactivity was defined as requirement for assistance with activities of daily living.
Results
Of 491 patients with isolated severe MS, calcific MS was present in 200 (41%; age 78 ± 11 years, 18% men, 32% with atrial fibrillation). Charlson Comorbidity Index was 5.1 ± 1.7 and 14 (7%) were inactive. Mitral valve area and transmitral gradient (TMG) were 1.26 ± 0.19 cm and 8.1 ± 3.8 mm Hg, respectively. Symptoms were present at baseline in 120 (60%); 20 (10%) developed symptoms during follow-up of 2.8 ± 3.0 years. Kaplan-Meier survival at 1 year was 72% without intervention. Inactivity (hazard ratio [HR]: 6.59; 95% confidence interval [CI]: 3.54 to 12.3; p < 0.01), Charlson Comorbidity Index >5 (HR: 1.53; 95% CI: 1.04 to 2.26; p < 0.01), TMG ≥8 mm Hg (HR: 1.68; 95% CI: 1.12 to 2.51; p = 0.012), and right ventricular systolic pressure ≥50 mm Hg (HR: 2.27; 95% CI: 1.50 to 3.43; p < 0.01) were independently associated with mortality. Symptoms were not associated with mortality.
Conclusion
Patients with isolated severe calcific MS had a high burden of comorbidities, resulting in high mortality without intervention. Symptoms were reported in 60%, but not associated with mortality. TMG ≥8 mm Hg and right ventricular systolic pressure ≥50 mm Hg were independently associated with mortality.

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

J Am Coll Cardiol: 22 Jun 2020; 75:3048-3057
Kato N, Padang R, Scott CG, Guerrero M, Pislaru SV, Pellikka PA
J Am Coll Cardiol: 22 Jun 2020; 75:3048-3057 | PMID: 32553258
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Impact:
Abstract

Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis.

Mehra MR, Desai SS, Ruschitzka F, Patel AN
Background
Hydroxychloroquine or chloroquine, often in combination with a second-generation macrolide, are being widely used for treatment of COVID-19, despite no conclusive evidence of their benefit. Although generally safe when used for approved indications such as autoimmune disease or malaria, the safety and benefit of these treatment regimens are poorly evaluated in COVID-19.
Methods
We did a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19. The registry comprised data from 671 hospitals in six continents. We included patients hospitalised between Dec 20, 2019, and April 14, 2020, with a positive laboratory finding for SARS-CoV-2. Patients who received one of the treatments of interest within 48 h of diagnosis were included in one of four treatment groups (chloroquine alone, chloroquine with a macrolide, hydroxychloroquine alone, or hydroxychloroquine with a macrolide), and patients who received none of these treatments formed the control group. Patients for whom one of the treatments of interest was initiated more than 48 h after diagnosis or while they were on mechanical ventilation, as well as patients who received remdesivir, were excluded. The main outcomes of interest were in-hospital mortality and the occurrence of de-novo ventricular arrhythmias (non-sustained or sustained ventricular tachycardia or ventricular fibrillation).
Findings
96 032 patients (mean age 53·8 years, 46·3% women) with COVID-19 were hospitalised during the study period and met the inclusion criteria. Of these, 14 888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81 144 patients were in the control group. 10 698 (11·1%) patients died in hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9·3%), hydroxychloroquine (18·0%; hazard ratio 1·335, 95% CI 1·223-1·457), hydroxychloroquine with a macrolide (23·8%; 1·447, 1·368-1·531), chloroquine (16·4%; 1·365, 1·218-1·531), and chloroquine with a macrolide (22·2%; 1·368, 1·273-1·469) were each independently associated with an increased risk of in-hospital mortality. Compared with the control group (0·3%), hydroxychloroquine (6·1%; 2·369, 1·935-2·900), hydroxychloroquine with a macrolide (8·1%; 5·106, 4·106-5·983), chloroquine (4·3%; 3·561, 2·760-4·596), and chloroquine with a macrolide (6·5%; 4·011, 3·344-4·812) were independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalisation.
Interpretation
We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19.
Funding
William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women\'s Hospital.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Lancet: 21 May 2020; epub ahead of print
Mehra MR, Desai SS, Ruschitzka F, Patel AN
Lancet: 21 May 2020; epub ahead of print | PMID: 32450107
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Abstract

Impact of Left Atrial Appendage Exclusion on Short Term Outcomes In Isolated Coronary Artery Bypass Graft Surgery.

Mahmood E, Matyal R, Mahmood F, Xu X, ... Karani S, Khabbaz KR

The objective of this study was to evaluate the impact of LAA exclusion on short term outcomes in patients with atrial fibrillation undergoing isolated coronary artery bypass graft (CABG) surgery.We queried the 2010-2014 National Readmissions Database (NRD) for patients who underwent coronary artery bypass graft repair with and without left atrial appendage ligation using ICD-9 procedure codes (ICD-9: 36.1xx). Only patients with a history of atrial fibrillation were included in our analysis. The primary outcome of our study was 30-day readmissions following discharge. Secondary outcomes were in hospital mortality and stroke. To assess the postoperative outcomes, we utilized multivariate logistic regression models to adjust for clinical and demographic covariates.In total we analyzed 253,287 CABG patients, 7.0% of whom received LAA closure. LAA exclusion was associated with a greater risk of postoperative respiratory failure (8.2% vs. 6.2%, p <.0001), acute kidney injury (21.8% vs. 18.5%, p <.0001), but did not significantly change the rate of blood transfusions or occurrence of cardiac tamponade. LAA exclusion was associated with a non-significant reduction in stroke (7.9% vs. 8.6%, p = .12), no difference in in-hospital mortality (2.2% vs. 2.2% p = .99), and a greater risk of 30-day readmission (16.0% vs. 9.6%, p < .0001) After covariate adjustment, LAA ligation remained a significant predictor of 30-day readmission (OR: 1.640, 95% CI: 1.603 - 1.677, p <.0001).LAA exclusion during isolated CABG in patients with AF is associated with a higher rate of 30-day readmission. Post-operative measures to mitigate the loss of the hormonal and hemodynamic effects of the LAA may increase the therapeutic benefit of this procedure.



Circulation: 02 Jun 2020; epub ahead of print
Mahmood E, Matyal R, Mahmood F, Xu X, ... Karani S, Khabbaz KR
Circulation: 02 Jun 2020; epub ahead of print | PMID: 32489114
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Impact:
Abstract

Advancing Research on the Complex Interrelations Between Atrial Fibrillation and Heart Failure: A Report From a US National Heart, Lung, and Blood Institute Virtual Workshop.

Al-Khatib SM, Benjamin EJ, Albert CM, Alonso A, ... Cooper LS, Go AS

The interrelationships between atrial fibrillation (AF) and heart failure (HF) are complex and poorly understood, yet the number of patients with AF and HF continues to increase worldwide. Thus, there is a need for initiatives that prioritize research on the intersection between AF and HF. This article summarizes the proceedings of a virtual workshop convened by the US National Heart, Lung, and Blood Institute to identify important research opportunities in AF and HF. Key knowledge gaps were reviewed and research priorities were proposed for characterizing the pathophysiological overlap and deleterious interactions between AF and HF; preventing HF in people with AF; preventing AF in individuals with HF; and addressing symptom burden and health status outcomes in AF and HF. These research priorities will hopefully help inform, encourage, and stimulate innovative, cost-efficient, and transformative studies to enhance the outcomes of patients with AF and HF.



Circulation: 08 Jun 2020; 141:1915-1926
Al-Khatib SM, Benjamin EJ, Albert CM, Alonso A, ... Cooper LS, Go AS
Circulation: 08 Jun 2020; 141:1915-1926 | PMID: 32511001
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Impact:
Abstract

Prognosis of unrecognised myocardial infarction determined by electrocardiography or cardiac magnetic resonance imaging: systematic review and meta-analysis.

Yang Y, Li W, Zhu H, Pan XF, ... Cai X, Huang Y
Objective
To evaluate the prognosis of unrecognised myocardial infarction determined by electrocardiography (UMI-ECG) or cardiac magnetic resonance imaging (UMI-CMR).
Design
Systematic review and meta-analysis of prospective studies.
Data sources
Electronic databases, including PubMed, Embase, and Google Scholar.
Study selection
Prospective cohort studies were included if they reported adjusted relative risks, odds ratios, or hazard ratios and 95% confidence intervals for all cause mortality or cardiovascular outcomes in participants with unrecognised myocardial infarction compared with those without myocardial infarction.
Data extraction and synthesis
The primary outcomes were composite major adverse cardiac events, all cause mortality, and cardiovascular mortality associated with UMI-ECG and UMI-CMR. The secondary outcomes were the risks of recurrent coronary heart disease or myocardial infarction, stroke, heart failure, and atrial fibrillation. Pooled hazard ratios and 95% confidence intervals were reported. The heterogeneity of outcomes was compared in clinically recognised and unrecognised myocardial infarction.
Results
The meta-analysis included 30 studies with 253 425 participants and 1 621 920 person years of follow-up. UMI-ECG was associated with increased risks of all cause mortality (hazard ratio 1.50, 95% confidence interval 1.30 to 1.73), cardiovascular mortality (2.33, 1.66 to 3.27), and major adverse cardiac events (1.61, 1.38 to 1.89) compared with the absence of myocardial infarction. UMI-CMR was also associated with increased risks of all cause mortality (3.21, 1.43 to 7.23), cardiovascular mortality (10.79, 4.09 to 28.42), and major adverse cardiac events (3.23, 2.10 to 4.95). No major heterogeneity was observed for any primary outcomes between recognised myocardial infarction and UMI-ECG or UMI-CMR. The absolute risk differences were 7.50 (95% confidence interval 4.50 to 10.95) per 1000 person years for all cause mortality, 11.04 (5.48 to 18.84) for cardiovascular mortality, and 27.45 (17.1 to 40.05) for major adverse cardiac events in participants with UMI-ECG compared with those without myocardial infarction. The corresponding data for UMI-CMR were 32.49 (6.32 to 91.58), 37.2 (11.7 to 104.20), and 51.96 (25.63 to 92.04), respectively.
Conclusions
UMI-ECG or UMI-CMR is associated with an adverse long term prognosis similar to that of recognised myocardial infarction. Screening for unrecognised myocardial infarction could be useful for risk stratification among patients with a high risk of cardiovascular disease.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

BMJ: 06 May 2020; 369:m1184
Yang Y, Li W, Zhu H, Pan XF, ... Cai X, Huang Y
BMJ: 06 May 2020; 369:m1184 | PMID: 32381490
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Impact:
Abstract

Left Atrial Appendage Closure Versus Direct Oral Anticoagulants in High-Risk Patients With Atrial Fibrillation.

Osmancik P, Herman D, Neuzil P, Hala P, ... Reddy VY,
Background
Percutaneous left atrial appendage closure (LAAC) is noninferior to vitamin K antagonists (VKAs) for preventing atrial fibrillation (AF)-related stroke. However, direct oral anticoagulants (DOACs) have an improved safety profile over VKAs, and their effect on cardiovascular and neurological outcomes relative to LAAC is unknown.
Objectives
This study sought to compare DOACs with LAAC in high-risk patients with AF.
Methods
Left Atrial Appendage Closure vs. Novel Anticoagulation Agents in Atrial Fibrillation (PRAGUE-17) was a multicenter, randomized, noninferiority trial comparing LAAC with DOACs. Patients were eligible to be enrolled if they had nonvalvular AF; were indicated for oral anticoagulation (OAC); and had a history of bleeding requiring intervention or hospitalization, a history of a cardioembolic event while taking an OAC, and/or a CHADS-VASc of ≥3 and HAS-BLED of >2. Patients were randomized to receive LAAC or DOAC. The primary composite outcome was stroke, transient ischemic attack, systemic embolism, cardiovascular death, major or nonmajor clinically relevant bleeding, or procedure-/device-related complications. The primary analysis was by modified intention to treat.
Results
A high-risk patient cohort (CHADS-VASc: 4.7 ± 1.5) was randomized to receive LAAC (n = 201) or DOAC (n = 201). LAAC was successful in 181 of 201 (90.0%) patients. In the DOAC group, apixaban was most frequently used (192 of 201; 95.5%). At a median 19.9 months of follow-up, the annual rates of the primary outcome were 10.99% with LAAC and 13.42% with DOAC (subdistribution hazard ratio [sHR]: 0.84; 95% confidence interval [CI]: 0.53 to 1.31; p = 0.44; p = 0.004 for noninferiority). There were no differences between groups for the components of the composite endpoint: all-stroke/TIA (sHR: 1.00; 95% CI: 0.40 to 2.51), clinically significant bleeding (sHR: 0.81; 95% CI: 0.44 to 1.52), and cardiovascular death (sHR: 0.75; 95% CI: 0.34 to 1.62). Major LAAC-related complications occurred in 9 (4.5%) patients.
Conclusions
Among patients at high risk for stroke and increased risk of bleeding, LAAC was noninferior to DOAC in preventing major AF-related cardiovascular, neurological, and bleeding events. (Left Atrial Appendage Closure vs. Novel Anticoagulation Agents in Atrial Fibrillation [PRAGUE-17]; NCT02426944).

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

J Am Coll Cardiol: 29 Jun 2020; 75:3122-3135
Osmancik P, Herman D, Neuzil P, Hala P, ... Reddy VY,
J Am Coll Cardiol: 29 Jun 2020; 75:3122-3135 | PMID: 32586585
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Abstract

Recurrence of Atrial Fibrillation After Catheter Ablation or Antiarrhythmic Drug Therapy in the CABANA Trial.

Poole JE, Bahnson TD, Monahan KH, Johnson G, ... Packer DL,
Background
The CABANA (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) trial randomized 2,204 patients with atrial fibrillation (AF) to catheter ablation or drug therapy. Analysis by intention-to-treat showed a nonsignificant 14% relative reduction in the primary outcome of death, disabling stroke, serious bleeding, or cardiac arrest.
Objectives
The purpose of this study was to assess recurrence of AF in the CABANA trial.
Methods
The authors prospectively studied CABANA patients using a proprietary electrocardiogram recording monitor for symptom-activated and 24-h AF auto detection. The AF recurrence endpoint was any post-90-day blanking atrial tachyarrhythmias lasting 30 s or longer. Biannual 96-h Holter monitoring was used to assess AF burden. Patients who used the CABANA monitors and provided 90-day post-blanking recordings qualified for this analysis (n = 1,240; 56% of CABANA population). Treatment comparisons were performed using a modified intention-to-treat approach.
Results
Median age of the 1,240 patients was 68 years, 34.4% were women, and AF was paroxysmal in 43.0%. Over 60 months of follow-up, first recurrence of any symptomatic or asymptomatic AF (hazard ratio: 0.52; 95% confidence interval: 0.45 to 0.60; p < 0.001) or first symptomatic-only AF (hazard ratio: 0.49; 95% confidence interval: 0.39 to 0.61; p < 0.001) were both significantly reduced in the catheter ablation group. Baseline Holter AF burden in both treatment groups was 48%. At 12 months, AF burden in ablation patients averaged 6.3%, and in drug-therapy patients, 14.4%. AF burden was significantly less in catheter ablation compared with drug-therapy patients across the 5-year follow-up (p < 0.001). These findings were not sensitive to the baseline pattern of AF.
Conclusions
Catheter ablation was effective in reducing recurrence of any AF by 48% and symptomatic AF by 51% compared with drug therapy over 5 years of follow-up. Furthermore, AF burden was also significantly reduced in catheter ablation patients, regardless of their baseline AF type. (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial [CABANA]; NCT00911508).

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

J Am Coll Cardiol: 29 Jun 2020; 75:3105-3118
Poole JE, Bahnson TD, Monahan KH, Johnson G, ... Packer DL,
J Am Coll Cardiol: 29 Jun 2020; 75:3105-3118 | PMID: 32586583
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Impact:
Abstract

Incidence and Implications of Atrial Fibrillation/Flutter in Hypertension: Insights From the SPRINT Trial.

Parcha V, Patel N, Kalra R, Kim J, ... Arora G, Arora P

We evaluated the impact of intensive blood pressure control on the incidence of new-onset atrial fibrillation/flutter (AF) and the prognostic implications of preexisting and new-onset AF in SPRINT (Systolic Blood Pressure Intervention Trial) participants. New-onset AF was defined as occurrence of AF in 12-lead electrocardiograms after randomization in participants free of AF at baseline. Poisson regression modeling was used to calculate incident rates of new-onset AF. Multivariable-adjusted Cox proportional hazard models were used to evaluate the risk of adverse cardiovascular events (composite of myocardial infarction, non-myocardial infarction acute coronary syndrome, stroke, heart failure, or cardiovascular death). In 9327 participants, 8.45% had preexisting AF, and 1.65% had new-onset AF. The incidence of new-onset AF was 4.53 per 1000-person years, with similar rates in the standard and intensive treatment arms (4.95 versus 4.11 per 1000-person years; adjusted =0.14). Participants with preexisting AF (adjusted hazard ratio, 1.83 [95% CI, 1.46-2.31]; <0.001) and new-onset AF (adjusted hazard ratio, 2.45 [95% CI, 1.58-3.80]; <0.001) had a greater risk for development of adverse cardiovascular events compared with those with no AF. Participants with preexisting AF who achieved blood pressure <120/80 mm Hg at 3 months continued have a poor prognosis (adjusted hazard ratio, 1.88 [95% CI, 1.32-2.70]; =0.001) compared with those with no AF. Intensive blood pressure control does not diminish the incidence of new-onset AF in an older, high-risk, nondiabetic population. Both preexisting and new-onset AF have adverse prognostic implications. In participants with preexisting AF, residual cardiovascular risk is evident even with on-treatment blood pressure <120/80 mm Hg. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.



Hypertension: 03 May 2020:HYPERTENSIONAHA12014690; epub ahead of print
Parcha V, Patel N, Kalra R, Kim J, ... Arora G, Arora P
Hypertension: 03 May 2020:HYPERTENSIONAHA12014690; epub ahead of print | PMID: 32362231
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Impact:
Abstract

Multisystem Inflammatory Syndrome in Children in New York State.

Dufort EM, Koumans EH, Chow EJ, Rosenthal EM, ... Zucker H,
Background
A multisystem inflammatory syndrome in children (MIS-C) is associated with coronavirus disease 2019. The New York State Department of Health (NYSDOH) established active, statewide surveillance to describe hospitalized patients with the syndrome.
Methods
Hospitals in New York State reported cases of Kawasaki\'s disease, toxic shock syndrome, myocarditis, and potential MIS-C in hospitalized patients younger than 21 years of age and sent medical records to the NYSDOH. We carried out descriptive analyses that summarized the clinical presentation, complications, and outcomes of patients who met the NYSDOH case definition for MIS-C between March 1 and May 10, 2020.
Results
As of May 10, 2020, a total of 191 potential cases were reported to the NYSDOH. Of 95 patients with confirmed MIS-C (laboratory-confirmed acute or recent severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection) and 4 with suspected MIS-C (met clinical and epidemiologic criteria), 53 (54%) were male; 31 of 78 (40%) were black, and 31 of 85 (36%) were Hispanic. A total of 31 patients (31%) were 0 to 5 years of age, 42 (42%) were 6 to 12 years of age, and 26 (26%) were 13 to 20 years of age. All presented with subjective fever or chills; 97% had tachycardia, 80% had gastrointestinal symptoms, 60% had rash, 56% had conjunctival injection, and 27% had mucosal changes. Elevated levels of C-reactive protein, d-dimer, and troponin were found in 100%, 91%, and 71% of the patients, respectively; 62% received vasopressor support, 53% had evidence of myocarditis, 80% were admitted to an intensive care unit, and 2 died. The median length of hospital stay was 6 days.
Conclusions
The emergence of multisystem inflammatory syndrome in children in New York State coincided with widespread SARS-CoV-2 transmission; this hyperinflammatory syndrome with dermatologic, mucocutaneous, and gastrointestinal manifestations was associated with cardiac dysfunction.

Copyright © 2020 Massachusetts Medical Society.

N Engl J Med: 28 Jun 2020; epub ahead of print
Dufort EM, Koumans EH, Chow EJ, Rosenthal EM, ... Zucker H,
N Engl J Med: 28 Jun 2020; epub ahead of print | PMID: 32598830
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Impact:
Abstract

Smartphone Activation of Citizen Responders to Facilitate Defibrillation in Out-of-Hospital Cardiac Arrest.

Andelius L, Malta Hansen C, Lippert FK, Karlsson L, ... Gislason GH, Folke F
Background
Dispatching citizen responders through a smartphone application (app) holds the potential to increase bystander cardiopulmonary resuscitation (CPR) and defibrillation in out-of-hospital cardiac arrest (OHCA).
Objectives
This study investigated arrival at the OHCA location of app-dispatched citizen responders before the Emergency Medical Services (EMS) and the association with bystander CPR and bystander defibrillation.
Methods
Suspected OHCAs with alerted citizen responders from September 1, 2017, to August 31, 2018, were included. Citizen responders located 1.8 km (1.1 miles) from the OHCA were dispatched to start CPR or retrieve an automated external defibrillator. OHCAs where at least 1 citizen responder arrived before EMS were compared with OHCAs where EMS arrived first. In both groups, random bystanders could be present before the arrival of citizen responders and the EMS. Primary outcomes were bystander CPR and bystander defibrillation, which included CPR and defibrillation by citizen responders and random bystanders.
Results
Citizen responders were alerted in 819 suspected OHCAs, of which 438 (53.5%) were confirmed cardiac arrests eligible for inclusion. At least 1 citizen responder arrived before EMS in 42.0% (n = 184) of all included OHCAs. When citizen responders arrived before EMS, the odds for bystander CPR increased (odds ratio: 1.76; 95% confidence interval: 1.07 to 2.91; p = 0.027) and the odds for bystander defibrillation more than tripled (odds ratio: 3.73; 95% confidence interval: 2.04 to 6.84; p < 0.001) compared with OHCAs in which citizen responders arrived after EMS.
Conclusions
Arrival of app-dispatched citizen responders before EMS was associated with increased odds for bystander CPR and a more than 3-fold increase in odds for bystander defibrillation. (The HeartRunner Trial; NCT03835403).

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 06 Jul 2020; 76:43-53
Andelius L, Malta Hansen C, Lippert FK, Karlsson L, ... Gislason GH, Folke F
J Am Coll Cardiol: 06 Jul 2020; 76:43-53 | PMID: 32616162
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Impact:
Abstract

Effect of Intensive Blood Pressure Lowering on the Risk of Atrial Fibrillation.

Soliman EZ, Rahman AF, Zhang ZM, Rodriguez CJ, ... Ambrosius WT, Lewis CE

It remains uncertain whether intensive control of blood pressure (BP) results in a lower risk of atrial fibrillation (AF) in patients with hypertension. Using data from SPRINT (Systolic Blood Pressure Intervention Trial), which enrolled participants with hypertension at increased risk of cardiovascular disease, we examined whether intensive BP lowering (target systolic BP [SBP] <120 mm Hg), compared with standard BP lowering (target SBP<140 mm Hg), results in a lower risk of AF. This analysis included 8022 participants (4003 randomized to the intensive arm and 4019 to standard BP arm) who were free of AF at the time of enrollment and with available baseline and follow-up electrocardiographic data. AF was ascertained from standard 12-lead electrocardiograms recorded at biannual study examinations and an exit visit. During up to 5.2 years of follow-up and a total of 28 322 person-years, 206 incident AF cases occurred; 88 in the intensive BP-lowering arm and 118 in the standard BP-lowering arm. Intensive BP lowering was associated with a 26% lower risk of developing new AF (hazard ratio, 0.74 [95% CI, 0.56-0.98]; =0.037). This effect was consistent among prespecified subgroups of SPRINT participants stratified by age, sex, race, SBP tertiles, prior cardiovascular disease, and prior chronic kidney disease when interactions between treatment effect and these subgroups were assessed using Hommel adjustedvalues. In conclusion, intensive treatment to a target of SBP <120 mm Hg in patients with hypertension at high risk of cardiovascular disease has the potential to reduce the risk of AF. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.



Hypertension: 03 May 2020:HYPERTENSIONAHA12014766; epub ahead of print
Soliman EZ, Rahman AF, Zhang ZM, Rodriguez CJ, ... Ambrosius WT, Lewis CE
Hypertension: 03 May 2020:HYPERTENSIONAHA12014766; epub ahead of print | PMID: 32362229
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Impact:
Abstract

Brain control of humoral immune responses amenable to behavioural modulation.

Zhang X, Lei B, Yuan Y, Zhang L, ... Hu J, Qi H

It has been speculated that brain activities might directly control adaptive immune responses in lymphoid organs, although there is little evidence for this. Here we show that splenic denervation in mice specifically compromises the formation of plasma cells during a T cell-dependent but not T cell-independent immune response. Splenic nerve activity enhances plasma cell production in a manner that requires B-cell responsiveness to acetylcholine mediated by the α9 nicotinic receptor, and T cells that express choline acetyl transferase probably act as a relay between the noradrenergic nerve and acetylcholine-responding B cells. We show that neurons in the central nucleus of the amygdala (CeA) and the paraventricular nucleus (PVN) that express corticotropin-releasing hormone (CRH) are connected to the splenic nerve; ablation or pharmacogenetic inhibition of these neurons reduces plasma cell formation, whereas pharmacogenetic activation of these neurons increases plasma cell abundance after immunization. In a newly developed behaviour regimen, mice are made to stand on an elevated platform, leading to activation of CeA and PVN CRH neurons and increased plasma cell formation. In immunized mice, the elevated platform regimen induces an increase in antigen-specific IgG antibodies in a manner that depends on CRH neurons in the CeA and PVN, an intact splenic nerve, and B cell expression of the α9 acetylcholine receptor. By identifying a specific brain-spleen neural connection that autonomically enhances humoral responses and demonstrating immune stimulation by a bodily behaviour, our study reveals brain control of adaptive immunity and suggests the possibility to enhance immunocompetency by behavioural intervention.



Nature: 29 Apr 2020; 581:204-208
Zhang X, Lei B, Yuan Y, Zhang L, ... Hu J, Qi H
Nature: 29 Apr 2020; 581:204-208 | PMID: 32405000
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Impact:
Abstract

Retinal innervation tunes circuits that drive nonphotic entrainment to food.

Fernandez DC, Komal R, Langel J, Ma J, ... Zhao H, Hattar S

Daily changes in light and food availability are major time cues that influence circadian timing. However, little is known about the circuits that integrate these time cues to drive a coherent circadian output. Here we investigate whether retinal inputs modulate entrainment to nonphotic cues such as time-restricted feeding. Photic information is relayed to the suprachiasmatic nucleus (SCN)-the central circadian pacemaker-and the intergeniculate leaflet (IGL) through intrinsically photosensitive retinal ganglion cells (ipRGCs). We show that adult mice that lack ipRGCs from the early postnatal stages have impaired entrainment to time-restricted feeding, whereas ablation of ipRGCs at later stages had no effect. Innervation of ipRGCs at early postnatal stages influences IGL neurons that express neuropeptide Y (NPY) (hereafter, IGL neurons), guiding the assembly of a functional IGL-SCN circuit. Moreover, silencing IGL neurons in adult mice mimicked the deficits that were induced by ablation of ipRGCs in the early postnatal stages, and acute inhibition of IGL terminals in the SCN decreased food-anticipatory activity. Thus, innervation of ipRGCs in the early postnatal period tunes the IGL-SCN circuit to allow entrainment to time-restricted feeding.



Nature: 29 Apr 2020; 581:194-198
Fernandez DC, Komal R, Langel J, Ma J, ... Zhao H, Hattar S
Nature: 29 Apr 2020; 581:194-198 | PMID: 32404998
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Impact:
Abstract

Association Between Treatment With Apixaban, Dabigatran, Rivaroxaban, or Warfarin and Risk for Osteoporotic Fractures Among Patients With Atrial Fibrillation.

Lau WCY, Cheung CL, Man KKC, Chan EW, ... Lee ACH, Wong ICK
Background
It is unclear whether anticoagulant type is associated with the risk for osteoporotic fracture, a deleterious complication of anticoagulants among patients with atrial fibrillation (AF).
Objective
To compare the risk for osteoporotic fracture between anticoagulants.
Design
Population-based cohort study.
Setting
Territory-wide electronic health record database of the Hong Kong Hospital Authority.
Participants
Patients newly diagnosed with AF between 2010 and 2017 who received a new prescription for warfarin or a direct oral anticoagulant (DOAC) (apixaban, dabigatran, or rivaroxaban). Follow-up ended on 31 December 2018.
Measurements
Osteoporotic hip and vertebral fractures in anticoagulant users were compared using propensity score-weighted cumulative incidence differences (CIDs).
Results
There were 23 515 patients identified (3241 apixaban users, 6867 dabigatran users, 3866 rivaroxaban users, and 9541 warfarin users). Overall mean age was 74.4 years (SD, 10.8), ranging from 73.1 years (warfarin) to 77.9 years (apixaban). Over a median follow-up of 423 days, 401 fractures were identified (crude event number [weighted rate per 100 patient-years]: apixaban, 53 [0.82]; dabigatran, 95 [0.76]; rivaroxaban, 57 [0.67]; and warfarin, 196 [1.11]). After 24-month follow-up, DOAC use was associated with a lower risk for fracture than warfarin use (apixaban CID, -0.88% [95% CI, -1.66% to -0.21%]; dabigatran CID, -0.81% [CI, -1.34% to -0.23%]; and rivaroxaban CID, -1.13% [CI, -1.67% to -0.53%]). No differences were seen in all head-to-head comparisons between DOACs at 24 months (apixaban vs. dabigatran CID, -0.06% [CI, -0.69% to 0.49%]; rivaroxaban vs. dabigatran CID, -0.32% [CI, -0.84% to 0.18%]; and rivaroxaban vs. apixaban CID, -0.25% [CI, -0.86% to 0.40%]).
Limitation
Residual confounding is possible.
Conclusion
Among patients with AF, DOAC use may result in a lower risk for osteoporotic fracture compared with warfarin use. Fracture risk does not seem to be altered by the choice of DOAC. These findings may help inform the benefit-risk assessment when choosing between anticoagulants.
Primary funding source
The University of Hong Kong and University College London Strategic Partnership Fund.



Ann Intern Med: 18 May 2020; epub ahead of print
Lau WCY, Cheung CL, Man KKC, Chan EW, ... Lee ACH, Wong ICK
Ann Intern Med: 18 May 2020; epub ahead of print | PMID: 32423351
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Abstract

A lower X-gate in TASK channels traps inhibitors within the vestibule.

Rödström KEJ, Kiper AK, Zhang W, Rinné S, ... Decher N, Carpenter EP

TWIK-related acid-sensitive potassium (TASK) channels-members of the two pore domain potassium (K) channel family-are found in neurons, cardiomyocytes and vascular smooth muscle cells, where they are involved in the regulation of heart rate, pulmonary artery tone, sleep/wake cycles and responses to volatile anaesthetics. K channels regulate the resting membrane potential, providing background K currents controlled by numerous physiological stimuli. Unlike other K channels, TASK channels are able to bind inhibitors with high affinity, exceptional selectivity and very slow compound washout rates. As such, these channels are attractive drug targets, and TASK-1 inhibitors are currently in clinical trials for obstructive sleep apnoea and atrial fibrillation. In general, potassium channels have an intramembrane vestibule with a selectivity filter situated above and a gate with four parallel helices located below; however, the K channels studied so far all lack a lower gate. Here we present the X-ray crystal structure of TASK-1, and show that it contains a lower gate-which we designate as an \'X-gate\'-created by interaction of the two crossed C-terminal M4 transmembrane helices at the vestibule entrance. This structure is formed by six residues (VLRFMT) that are essential for responses to volatile anaesthetics, neurotransmitters and G-protein-coupled receptors. Mutations within the X-gate and the surrounding regions markedly affect both the channel-open probability and the activation of the channel by anaesthetics. Structures of TASK-1 bound to two high-affinity inhibitors show that both compounds bind below the selectivity filter and are trapped in the vestibule by the X-gate, which explains their exceptionally low washout rates. The presence of the X-gate in TASK channels explains many aspects of their physiological and pharmacological behaviour, which will be beneficial for the future development and optimization of TASK modulators for the treatment of heart, lung and sleep disorders.



Nature: 28 Apr 2020; epub ahead of print
Rödström KEJ, Kiper AK, Zhang W, Rinné S, ... Decher N, Carpenter EP
Nature: 28 Apr 2020; epub ahead of print | PMID: 32499642
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Abstract

Increased Susceptibility of Mice Lacking Renin-b to Angiotensin II-Induced Organ Damage.

Nakagawa P, Nair AR, Agbor LN, Gomez J, ... Grobe JL, Sigmund CD

Several cardiac and renal diseases are attributed to a dysregulation of the renin-angiotensin system. Renin, the rate-limiting enzyme of the renin-angiotensin system, has 2 isoforms. The classical renin isoform (renin-a) encoding preprorenin is mainly confined to the juxtaglomerular cells and released into the circulation upon stimulation. Alternatively, renin-b is predicted to remain intracellular and is expressed in the brain, heart, and adrenal gland. In the brain, ablation of renin-b (Ren-b mice) results in increased brain renin-angiotensin system activity. However, the consequences of renin-b ablation in tissues outside the brain remain unknown. Therefore, we hypothesized that renin-b protects from hypertensive cardiac and renal end-organ damage in mice. Ren-b mice exhibited normal blood pressure at baseline. Thus, we induced hypertension by using a slow pressor dose of Ang II (angiotensin II). Ang II increased blood pressure in both wild type and Ren-b to the same degree. Although the blood pressure between Ren-b and wild-type mice was elevated equally, 4-week infusion of Ang II resulted in exacerbated cardiac remodeling in Ren-b mice compared with wild type. Ren-b mice also exhibited a modest increase in renal glomerular matrix deposition, elevated plasma aldosterone, and a modestly enhanced dipsogenic response to Ang II. Interestingly, ablation of renin-b strongly suppressed plasma renin, but renal cortical renin mRNA was preserved. Altogether, these data indicate that renin-b might play a protective role in the heart, and thus renin-b could be a potential target to treat hypertensive heart disease.



Hypertension: 07 Jun 2020:HYPERTENSIONAHA12014972; epub ahead of print
Nakagawa P, Nair AR, Agbor LN, Gomez J, ... Grobe JL, Sigmund CD
Hypertension: 07 Jun 2020:HYPERTENSIONAHA12014972; epub ahead of print | PMID: 32507043
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Abstract

Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State.

Rosenberg ES, Dufort EM, Udo T, Wilberschied LA, ... Holtgrave DR, Zucker HA
Importance
Hydroxychloroquine, with or without azithromycin, has been considered as a possible therapeutic agent for patients with coronavirus disease 2019 (COVID-19). However, there are limited data on efficacy and associated adverse events.
Objective
To describe the association between use of hydroxychloroquine, with or without azithromycin, and clinical outcomes among hospital inpatients diagnosed with COVID-19.
Design, setting, and participants
Retrospective multicenter cohort study of patients from a random sample of all admitted patients with laboratory-confirmed COVID-19 in 25 hospitals, representing 88.2% of patients with COVID-19 in the New York metropolitan region. Eligible patients were admitted for at least 24 hours between March 15 and 28, 2020. Medications, preexisting conditions, clinical measures on admission, outcomes, and adverse events were abstracted from medical records. The date of final follow-up was April 24, 2020.
Exposures
Receipt of both hydroxychloroquine and azithromycin, hydroxychloroquine alone, azithromycin alone, or neither.
Main outcomes and measures
Primary outcome was in-hospital mortality. Secondary outcomes were cardiac arrest and abnormal electrocardiogram findings (arrhythmia or QT prolongation).
Results
Among 1438 hospitalized patients with a diagnosis of COVID-19 (858 [59.7%] male, median age, 63 years), those receiving hydroxychloroquine, azithromycin, or both were more likely than those not receiving either drug to have diabetes, respiratory rate >22/min, abnormal chest imaging findings, O2 saturation lower than 90%, and aspartate aminotransferase greater than 40 U/L. Overall in-hospital mortality was 20.3% (95% CI, 18.2%-22.4%). The probability of death for patients receiving hydroxychloroquine + azithromycin was 189/735 (25.7% [95% CI, 22.3%-28.9%]), hydroxychloroquine alone, 54/271 (19.9% [95% CI, 15.2%-24.7%]), azithromycin alone, 21/211 (10.0% [95% CI, 5.9%-14.0%]), and neither drug, 28/221 (12.7% [95% CI, 8.3%-17.1%]). In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in mortality for patients receiving hydroxychloroquine + azithromycin (HR, 1.35 [95% CI, 0.76-2.40]), hydroxychloroquine alone (HR, 1.08 [95% CI, 0.63-1.85]), or azithromycin alone (HR, 0.56 [95% CI, 0.26-1.21]). In logistic models, compared with patients receiving neither drug cardiac arrest was significantly more likely in patients receiving hydroxychloroquine + azithromycin (adjusted OR, 2.13 [95% CI, 1.12-4.05]), but not hydroxychloroquine alone (adjusted OR, 1.91 [95% CI, 0.96-3.81]) or azithromycin alone (adjusted OR, 0.64 [95% CI, 0.27-1.56]), . In adjusted logistic regression models, there were no significant differences in the relative likelihood of abnormal electrocardiogram findings.
Conclusions and relevance
Among patients hospitalized in metropolitan New York with COVID-19, treatment with hydroxychloroquine, azithromycin, or both, compared with neither treatment, was not significantly associated with differences in in-hospital mortality. However, the interpretation of these findings may be limited by the observational design.



JAMA: 10 May 2020; epub ahead of print
Rosenberg ES, Dufort EM, Udo T, Wilberschied LA, ... Holtgrave DR, Zucker HA
JAMA: 10 May 2020; epub ahead of print | PMID: 32392282
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Abstract

Association Between Atrial Fibrillation and Cognitive Impairment in Individuals With Prior Stroke: A Meta-Analysis and Meta-Regression Analysis.

Kokkinidis DG, Zareifopoulos N, Theochari CA, Arfaras-Melainis A, ... Kalogeropoulos AP, Fontes JDT

Background and Purpose- Atrial fibrillation (AF) is the most common chronic arrhythmia. Dementia and cognitive impairment (CI) are major burdens to public health. The prevalence of all 3 entities is projected to increase due to population aging. Previous reports have linked AF with a higher risk of CI and dementia in patients without prior stroke. Stroke is known to increase the risk for dementia and CI. It is unclear if AF in patients with history of stroke can further increase the risk for dementia or CI. Our purpose was to evaluate the impact of AF on risk for dementia or CI among patients with history of stroke. Methods- Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed. Pubmed, Scopus, and Cochrane central were searched. The outcomes of interest were dementia, CI, and the composite end point of dementia or CI. A random-effect model meta-analysis was performed. Meta-regression analysis was also performed. Publication bias was assessed with the Egger test and with funnel plots. Results- Fourteen studies and 14 360 patients (1363 with AF) were included in the meta-analysis. In the meta-analysis of adjusted odds ratio, AF was associated with increased risk of CI (odds ratio, 1.60 [95% CI, 1.20-2.14]), dementia (odds ratio, 3.11 [95% CI, 2.05-4.73]), and the composite end point of CI or dementia (odds ratio, 2.26 [95% CI, 1.61-3.19]). The heterogeneity for the composite end point of dementia or CI was moderate (adjusted analysis). The heterogeneity for the analysis of the end point of CI only was substantial in the unadjusted analysis and moderate in the adjusted analysis. The heterogeneity for the end point of dementia only was moderate in the unadjusted analysis and zero in the adjusted analysis. Conclusions- Our results indicate that an association between AF and CI or dementia is patients with prior strokes is possible given the persistent positive associations we noticed in the unadjusted and adjusted analyses. The heterogeneity levels limit the certainty of our findings.



Stroke: 20 Apr 2020:STROKEAHA119027815; epub ahead of print
Kokkinidis DG, Zareifopoulos N, Theochari CA, Arfaras-Melainis A, ... Kalogeropoulos AP, Fontes JDT
Stroke: 20 Apr 2020:STROKEAHA119027815; epub ahead of print | PMID: 32312222
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Abstract

Abnormalities in Sodium Current and Calcium Homeostasis as Drivers of Arrhythmogenesis in Hypertrophic Cardiomyopathy.

Coppini R, Santini L, Olivotto I, Ackerman MJ, Cerbai E

Hypertrophic cardiomyopathy (HCM) is a common inherited monogenic disease with a prevalence of 1/500 in the general population, representing an important cause of arrhythmic sudden cardiac death (SCD), heart failure, and atrial fibrillation in the young. HCM is a global condition, diagnosed in more than 50 countries and in all continents, HCM affects people of both sexes and various ethnic and racial origins, with similar clinical course and phenotypic expression. The most unpredictable and devastating consequence of HCM is represented by arrhythmic SCD, most commonly caused by sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Indeed, HCM represents one of the main causes of arrhythmic SCD in the young, with a marked preference for children and adults <30 years. SCD is most prevalent in patients with pediatric onset of HCM but may occur at any age. However, risk is substantially lower after 60 years, suggesting that the potential for ventricular tachyarrhythmias is mitigated by ageing. SCD had been linked originally to sports and vigorous activity in HCM patients. However, it is increasingly clear that the majority of events occur at rest or during routine daily occupations, suggesting that triggers are far from consistent. In general, the pathophysiology of SCD in HCM remains unresolved. While the pathologic and physiologic substrates abound and have been described in detail, specific factors precipitating ventricular tachyarrhythmias are still unknown. SCD is a rare phenomenon in HCM cohorts (<1%/year) and attempts to identify patients at risk, while generating clinically useful algorithms for primary prevention, remain very inaccurate on an individual basis. One of the reasons for our limited understanding of these phenomena is that limited translational research exists in the field, while most efforts have focused on clinical markers of risk derived from pathology, instrumental patient evaluation and imaging. Specifically, few studies conducted in animal models and human samples have focused on targeting the cellular mechanisms of arrhythmogenesis in HCM, despite potential implications for therapeutic innovation and SCD prevention. These studies found that altered intracellular Ca2+ homeostasis and increased late Na+ current, leading to an increased likelihood of early and delayed after-depolarizations, contribute to generate arrhythmic events in diseased cardiomyocytes. As an array of novel experimental opportunities have emerged to investigate these mechanisms, including novel \"disease-in-the-dish\" cellular models with patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), important gaps in knowledge remain. Accordingly, the aim of the present review is to provide a contemporary reappraisal of the cellular basis of SCD-predisposing arrhythmias in patients with HCM and discuss the implications for risk stratification and management.

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

Cardiovasc Res: 03 May 2020; epub ahead of print
Coppini R, Santini L, Olivotto I, Ackerman MJ, Cerbai E
Cardiovasc Res: 03 May 2020; epub ahead of print | PMID: 32365196
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Abstract

Impact of atrial fibrillation in patients with heart failure and reduced, mid-range or preserved ejection fraction.

Son MK, Park JJ, Lim NK, Kim WH, Choi DJ
Objective
To determine the prognostic value of atrial fibrillation (AF) in patients with heart failure (HF) and preserved, mid-range or reduced ejection fraction (EF).
Methods
Patients hospitalised for acute HF were enrolled in the Korean Acute Heart Failure registry, a prospective, observational, multicentre cohort study, between March 2011 and February 2014. HF types were defined as reduced EF (HFrEF, LVEF <40%), mid-range EF (HFmrEF, LVEF 40%-49%) or preserved EF (HFpEF, LVEF ≥50%).
Results
Of 5414 patients enrolled, HFrEF, HFmrEF and HFpEF were seen in 3182 (58.8%), 875 (16.2%) and 1357 (25.1%) patients, respectively. The prevalence of AF significantly increased with increasing EF (HFrEF 28.9%, HFmrEF 39.8%, HFpEF 45.2%; p for trend <0.001). During follow-up (median, 4.03 years; IQR, 1.39-5.58 years), 2806 (51.8%) patients died. The adjusted HR of AF for all-cause death was 1.06 (0.93-1.21) in the HFrEF, 1.10 (0.87-1.39) in the HFmrEF and 1.22 (1.02-1.46) in the HFpEF groups. The HR for the composite of all-cause death or readmission was 0.97 (0.87-1.07), 1.14 (0.93-1.38) and 1.03 (0.88-1.19) in the HFrEF, HFmrEF and HFpEF groups, respectively, and the HR for stroke was 1.53 (1.03-2.29), 1.04 (0.57-1.91) and 1.90 (1.13-3.20), respectively. Similar results were observed after propensity score matching analysis.
Conclusions
AF was more common with increasing EF. AF was seen to be associated with increased mortality only in patients with HFpEF and was associated with an increased risk of stroke in patients with HFrEF or HFpEF.
Trial registration number
NCT01389843.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 26 Apr 2020; epub ahead of print
Son MK, Park JJ, Lim NK, Kim WH, Choi DJ
Heart: 26 Apr 2020; epub ahead of print | PMID: 32341140
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Impact:
Abstract

Cardiovascular manifestations and treatment considerations in covid-19.

Kang Y, Chen T, Mui D, Ferrari V, ... Chen Y, Han Y

Since its recognition in December 2019, covid-19 has rapidly spread globally causing a pandemic. Pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease are associated with a greater severity and higher fatality rate of covid-19. Furthermore, covid-19 contributes to cardiovascular complications, including acute myocardial injury as a result of acute coronary syndrome, myocarditis, stress-cardiomyopathy, arrhythmias, cardiogenic shock, and cardiac arrest. The cardiovascular interactions of covid-19 have similarities to that of severe acute respiratory syndrome, Middle East respiratory syndrome and influenza. Specific cardiovascular considerations are also necessary in supportive treatment with anticoagulation, the continued use of renin-angiotensin-aldosterone system inhibitors, arrhythmia monitoring, immunosuppression or modulation, and mechanical circulatory support.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Apr 2020; epub ahead of print
Kang Y, Chen T, Mui D, Ferrari V, ... Chen Y, Han Y
Heart: 29 Apr 2020; epub ahead of print | PMID: 32354800
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Impact:
Abstract

Gene Therapy for Inherited Arrhythmias.

Bezzerides VJ, Prondzynski M, Carrier L, Pu WT

Inherited arrhythmias are disorders caused by one or more genetic mutations that increase the risk of arrhythmia, which result in life-long risk of sudden death. These mutations either primarily perturb electrophysiological homeostasis (e.g., long QT syndrome and catecholaminergic polymorphic ventricular tachycardia), cause structural disease that is closely associated with severe arrhythmias (e.g., hypertrophic cardiomyopathy), or cause a high propensity for arrhythmia in combination with altered myocardial structure and function (e.g., arrhythmogenic cardiomyopathy). Currently available therapies offer incomplete protection from arrhythmia and fail to alter disease progression. Recent studies suggest that gene therapies may provide potent, molecularly targeted options for at least a subset of inherited arrhythmias. Here we provide an overview of gene therapy strategies, and review recent studies on gene therapies for catecholaminergic polymorphic ventricular tachycardia and hypertrophic cardiomyopathy caused by MYBPC3 mutations.

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

Cardiovasc Res: 21 Apr 2020; epub ahead of print
Bezzerides VJ, Prondzynski M, Carrier L, Pu WT
Cardiovasc Res: 21 Apr 2020; epub ahead of print | PMID: 32321160
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Abstract

Comprehensive review of evaluation and management of cardiac paragangliomas.

Tella SH, Jha A, Taïeb D, Horvath KA, Pacak K

Cardiac paraganglioma (PGL) is a rare neuroendocrine tumour causing significant morbidity primarily due to norepinephrine secretion potentially causing severe hypertension, palpitations, lethal tachyarrhythmias, stroke and syncope. Cardiologists are faced with two clinical scenarios. The first is the elevated norepinephrine, whose actions must be properly counteracted by adrenoceptor blockade to avoid catastrophic consequences. The second is to evaluate the precise location of a cardiac PGL and its spread since compression of cardiovascular structures may result in ischaemia, angina, non-noradrenergic-induced arrhythmia, cardiac dysfunction or failure. Thus, appropriate assessment of elevated norepinephrine by its metabolite normetanephrine is a gold biochemical standard at present. Furthermore, dedicated cardiac CT, MRI and transthoracic echocardiogram are necessary for the precise anatomic information of cardiac PGL. Moreover, a cardiologist needs to be aware of advanced functional imaging using Ga-DOTA(0)-Tyr(3)-octreotide positron emission tomography/CT, which offers the best cardiac PGL-specific diagnostic accuracy and helps to stage and rule out metastasis, determining the next therapeutic strategies. Patients should also undergo genetic testing, especially for mutations in genes encoding succinate dehydrogenase enzyme subunits that are most commonly present as a genetic cause of these tumours. Curative surgical resection after appropriate α-adrenoceptor and β-adrenoceptor blockade in norepinephrine-secreting tumours is the primary therapeutic strategy. Therefore, appropriate and up-to-date knowledge about early diagnosis and management of cardiac PGLs is paramount for optimal outcomes in patients where a cardiologist is an essential team member of a multidisciplinary team in its management.

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

Heart: 21 May 2020; epub ahead of print
Tella SH, Jha A, Taïeb D, Horvath KA, Pacak K
Heart: 21 May 2020; epub ahead of print | PMID: 32444502
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Abstract

Exclusion versus preservation of the left atrial appendage in rheumatic mitral valve surgery.

Kim WK, Kim HJ, Kim JB, Jung SH, ... Chung CH, Lee JW
Objectives
This study aimed to evaluate the impact of left atrial appendage exclusion on clinical outcomes in patients with atrial fibrillation (AF) undergoing rheumatic mitral surgery.
Methods
We retrospectively reviewed 1226 consecutive patients with AF (54.5±11.6 years; 68.2% females) who underwent rheumatic mitral valve (MV) surgery from 1997 to 2016. The left atrial appendage was preserved in 836 (68.2%) and excluded in 390 (31.8%) patients. Surgical AF ablation was performed in 506 (60.5%) and 304 (77.9%) patients with preserved and excluded left atrial appendage, respectively. For baseline adjustment, propensity matching was used.
Results
During a median follow-up of 63.4 months (IQRs, 20-111 months), there were no significant intergroup differences in the risks of mortality (2.77% vs 3.03%/patient-years) and thromboembolic events (0.91% vs 1.02%/patient-years). In the 258 pairs of propensity-score matched patients, death (2.77% vs 3.03%/patient-years) and thromboembolism (1.36% vs 0.82%/patient-years) outcomes were comparable for both groups. In a subgroup undergoing ablation (n=810), there were no significant differences in the adjusted risks of death (HR, 0.67; 95% CI, 0.34 to 1.32) and thromboembolism (HR, 0.47; 95% CI, 0.18 to 1.26). In a subgroup not undergoing ablation (n=416), however, left atrial appendage preservation tended to have higher adjusted risks for death (HR, 2.24; 95% CI, 0.98 to 5.13) and thromboembolism (HR, 4.41; 95% CI, 0.97 to 20.1).
Conclusions
Left atrial appendage preservation did not seem to have greater risks of adverse clinical events in patients with AF undergoing rheumatic MV surgery particularly when ablation procedure is combined.

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

Heart: 05 May 2020; epub ahead of print
Kim WK, Kim HJ, Kim JB, Jung SH, ... Chung CH, Lee JW
Heart: 05 May 2020; epub ahead of print | PMID: 32376607
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Abstract

Catheter-based renal denervation as adjunct to pulmonary vein isolation for treatment of atrial fibrillation: a systematic review and meta-analysis.

Ukena C, Becker N, Pavlicek V, Millenaar D, ... Böhm M, Mahfoud F
Objective
Renal denervation (RDN) can reduce sympathetic activity and blood pressure (BP) in hypertensive patients, which both have an impact on atrial fibrillation. We performed a systematic meta-analysis on the effects of renal denervation (RDN) in addition to pulmonary vein isolation (PVI) in patients with atrial fibrillation.
Methods
All published randomized controlled trials investigating the effects of RDN as adjunctive treatment to PVI for rhythm control of atrial fibrillation were included. Primary endpoint was recurrence of atrial fibrillation after 12 months on average.
Results
A total of six randomized controlled studies including 689 patients with hypertension and symptomatic atrial fibrillation were included. In five studies, patients had uncontrolled BP despite prescription of an average of three antihypertensive agents. PVI was performed with irrigated radio-frequency catheters in 387 patients, and in 302 with cryoballoon. Cardiac ablation catheters were used for RDN in 78% of all cases. In the remaining 22%, RDN was performed using a designated, nonirrigated radio-frequency catheter system. After 12 months, the mean odds ratio for recurrence of atrial fibrillation for PVI with RDN compared with PVI alone was 0.43 (95% confidence interval 0.32-0.59). After RDN, BP was reduced significantly whereas no changes were reported in the PVI-only groups. No relevant complications associated to RDN were documented.
Conclusion
This meta-analysis supports the concept of RDN as an adjunctive treatment for atrial fibrillation. Further studies with standardized PVI and RDN procedures are needed.



J Hypertens: 29 Apr 2020; 38:783-790
Ukena C, Becker N, Pavlicek V, Millenaar D, ... Böhm M, Mahfoud F
J Hypertens: 29 Apr 2020; 38:783-790 | PMID: 32238783
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Abstract

Ischemic Stroke in Patients With Sinus Node Disease, Atrial Fibrillation, and Other Cardiac Conditions.

Bodin A, Bisson A, Gaborit C, Herbert J, ... Lip GYH, Fauchier L

Background and Purpose- Atrial fibrillation (AF) is known to increase risk of ischemic stroke (IS), but the risk of IS in isolated sinus node disease (SND) is unclear. We compared the incidence of IS in patients with SND, patients with AF, and in a control population with other cardiac diseases (disease of the circulatory system using the ). Methods- This French longitudinal cohort study was based on the national database covering hospital care for the entire population from 2008 to 2015. Results- Of 1 692 157 patients included in the cohort, 100 366 had isolated SND, 1 564 270 had isolated AF, and 27 521 had AF associated with SND. Incidence of IS during follow-up was higher in isolated patients with AF than in AF associated with SND (yearly rate 2.22% versus 2.06%) and in isolated patients with AF than in isolated patients with SND (yearly rate 2.22% versus 1.59%). The incidence of IS was lower in a control population with other cardiac conditions (n=479 108) compared with SND and patients with AF (0.96%/y, 1.59%/y, and 2.22%/y, respectively). After 1:1 propensity score matching, SND was associated with lower incidence of IS compared to AF (hazard ratio, 0.77 [95% CI, 0.73-0.82]) but higher incidence of IS compared to control population (hazard ratio, 1.27 [95%CI, 1.19-1.35]). Conclusions- Patients with SND had a lower risk of thromboembolic events than patients with AF but a higher risk than a control population with other cardiac diseases. Randomized clinical trial in a selected SND population, with, for example, a high CHADS-VASc score, would be required to determine the value of IS prevention by anticoagulation.



Stroke: 10 May 2020:STROKEAHA120029048; epub ahead of print
Bodin A, Bisson A, Gaborit C, Herbert J, ... Lip GYH, Fauchier L
Stroke: 10 May 2020:STROKEAHA120029048; epub ahead of print | PMID: 32390547
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Impact:
Abstract

Adherence to Anticoagulant Guideline for Atrial Fibrillation Improves Outcomes in Asian Population: The COOL-AF Registry.

Krittayaphong R, Winijkul A, Kunjara-Na-Ayudhya R, Apiyasawat S, ... Lip GYH,

Background and Purpose- Guideline adherent oral anticoagulant (OAC) management of patients with nonvalvular atrial fibrillation has been associated with improved outcomes, but limited data are available from Asia. We aimed to investigate outcomes in patients who received guideline compliant management compared with those who were OAC undertreated or overtreated, in a large nationwide multicenter cohort of patients with nonvalvular atrial fibrillation in Thailand. Methods- Patients with nonvalvular atrial fibrillation were prospectively enrolled from 27 hospitals-all of which are data contributors to the COOL-AF Registry (Cohort of Antithrombotic Use and Optimal INR Level in Patients With Non-Valvular Atrial Fibrillation in Thailand). Patients were categorized as follows: (1) guideline adherence group when OAC was given in high-risk or intermediate-risk, but not in low-risk patients; (2) undertreatment group when OAC was not given in the high-risk or intermediate-risk groups; and (3) overtreatment group when OAC was given in the low-risk group or when OAC was given in combination with antiplatelets without indication. Results- A total of 3327 patients who had follow-up clinical outcome data were included. The mean age of patients was 67.4 years and 58.1% were male. The numbers of patients in the guideline adherence group, undertreatment group, and overtreatment group were 2267 (68.1%), 624 (18.8%), and 436 (13.1%) patients, respectively. The overall rate of ischemic stroke, major bleeding, all bleeding, and death was 3.0%, 4.4%, 15.1%, and 7.8%, respectively. Undertreated patients had a higher risk of ischemic stroke and death compared with guideline adherent patients, and overtreated patients had a higher risk of bleeding and death compared with OAC guideline-managed patients. Conclusions- Adherence to OAC management guidelines is associated with improved clinical outcomes in Asian nonvalvular atrial fibrillation patients. Undertreatment or overtreatment was found to be associated with increased risk of adverse outcomes compared with guideline-adherent management.



Stroke: 10 May 2020:STROKEAHA120029295; epub ahead of print
Krittayaphong R, Winijkul A, Kunjara-Na-Ayudhya R, Apiyasawat S, ... Lip GYH,
Stroke: 10 May 2020:STROKEAHA120029295; epub ahead of print | PMID: 32390554
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Impact:
Abstract

Diagnostic accuracy of handheld electrocardiogram devices in detecting atrial fibrillation in adults in community versus hospital settings: a systematic review and meta-analysis.

Wong KC, Klimis H, Lowres N, von Huben A, Marschner S, Chow CK

With increasing use of handheld ECG devices for atrial fibrillation (AF) screening, it is important to understand their accuracy in community and hospital settings and how it differs among settings and other factors. A systematic review of eligible studies from community or hospital settings reporting the diagnostic accuracy of handheld ECG devices (ie, devices producing a rhythm strip) in detecting AF in adults, compared with a gold standard 12-lead ECG or Holter monitor, was performed. Bivariate hierarchical random-effects meta-analysis and meta-regression were performed using R V.3.6.0. The search identified 858 articles, of which 14 were included. Six studies recruited from community (n=6064 ECGs) and eight studies from hospital (n=2116 ECGs) settings. The pooled sensitivity was 89% (95% CI 81% to 94%) in the community and 92% (95% CI 83% to 97%) in the hospital. The pooled specificity was 99% (95% CI 98% to 99%) in the community and 95% (95% CI 90% to 98%) in the hospital. Accuracy of ECG devices varied: sensitivity ranged from 54.5% to 100% and specificity ranged from 61.9% to 100%. Meta-regression showed that setting (p=0.032) and ECG device type (p=0.022) significantly contributed to variations in sensitivity and specificity. The pooled sensitivity and specificity of single-lead handheld ECG devices were high. Setting and handheld ECG device type were significant factors of variation in sensitivity and specificity. These findings suggest that the setting including user training and handheld ECG device type should be carefully reviewed.

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

Heart: 10 May 2020; epub ahead of print
Wong KC, Klimis H, Lowres N, von Huben A, Marschner S, Chow CK
Heart: 10 May 2020; epub ahead of print | PMID: 32393588
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Abstract

Genome-wide association studies of cardiac electrical phenotypes.

Glinge C, Lahrouchi N, Jabbari R, Tfelt-Hansen J, Bezzina CR

The genetic basis of cardiac electrical phenotypes has in the last twenty-five years been the subject of intense investigation. While in the first years, such efforts were dominated by the study of familial arrhythmia syndromes, in recent years large consortia of investigators have successfully pursued genome-wide association studies (GWAS) for the identification of single nucleotide polymorphisms that govern interindividual variability in electrocardiographic parameters in the general population. We here provide a review of GWAS conducted on cardiac electrical phenotypes in the last 14 years and discuss the implications of these discoveries for our understanding of the genetic basis of disease susceptibility and variability in disease severity. Furthermore, we review functional follow-up studies that have been conducted on GWAS loci associated with cardiac electrical phenotypes and highlight the challenges and opportunities offered by such studies.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Cardiovasc Res: 18 May 2020; epub ahead of print
Glinge C, Lahrouchi N, Jabbari R, Tfelt-Hansen J, Bezzina CR
Cardiovasc Res: 18 May 2020; epub ahead of print | PMID: 32428210
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Abstract

Periprocedural Bridging Anticoagulation in Patients with Venous Thromboembolism: A Registry-based Cohort Study.

Barnes GD, Li Y, Gu X, Haymart B, ... Froehlich JB, Kaatz S
Background
Use of bridging anticoagulation increases a patient\'s bleeding risk without clear evidence of thrombotic prevention among warfarin-treated patients with atrial fibrillation. Contemporary use of bridging anticoagulation among warfarin-treated patients with venous thromboembolism (VTE) have not been studied.
Methods
We identified warfarin-treated patients with VTE who temporarily stopped warfarin for a surgical procedure between 2010 and 2018 at six health systems. Using the 2012 American College of Chest Physicians (ACCP) guideline, we assessed use of periprocedural bridging anticoagulation based on recurrent VTE risk. Recurrent VTE risk and 30-day outcomes (bleeding, thromboembolism, emergency department visit) were each assessed using logistic regression adjusted for multiple procedures per patient.
Results
During the study period, 789 warfarin-treated patients with VTE underwent 1529 procedures (median 2, IQR 1-4). Unadjusted use of bridging anticoagulation was more common in patients at high-risk for VTE recurrence (99/171, 57.9%) than for patients at moderate (515/1078, 47.8%) or low risk of recurrence (134/280, 47.86%). Bridging anticoagulation use was higher in high-risk patients compared to low- or moderate-risk patients in both unadjusted (p=0.013) and patient-level cluster-adjusted analyses (p=0.031). Adherence to ACCP guidelines in high- and low-risk patients did not change during the study period (OR 0.98 per year, 95% CI 0.91-1.05). Adverse events were rare and not statistically different between the two treatment groups.
Conclusions
Bridging anticoagulation was commonly overused among low-risk patients and underused among high-risk patients treated with warfarin for VTE. Adverse events were rare and not different between the two treatment groups.

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J Thromb Haemost: 18 May 2020; epub ahead of print
Barnes GD, Li Y, Gu X, Haymart B, ... Froehlich JB, Kaatz S
J Thromb Haemost: 18 May 2020; epub ahead of print | PMID: 32428998
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Abstract

Ventricular fibrillation mechanism and global fibrillatory organisation are determined by gap junction coupling and fibrosis pattern.

Handa BS, Li X, Baxan N, Roney C, ... Peters NS, Ng FS
Aims
Conflicting data exist supporting differing mechanisms for sustaining ventricular fibrillation (VF), ranging from disorganised multiple-wavelet activation to organised rotational activities (RAs). Abnormal gap junction (GJ) coupling and fibrosis are important in initiation and maintenance of VF. We investigated whether differing ventricular fibrosis patterns and the degree of GJ coupling affected the underlying VF mechanism.
Methods and results
Optical mapping of 65 Langendorff-perfused rat hearts was performed to study VF mechanisms in control hearts with acute GJ modulation, and separately in three differing chronic ventricular fibrosis models; compact (CF), diffuse (DiF) and patchy (PF). VF dynamics were quantified with phase mapping and frequency dominance index (FDI) analysis, a power ratio of the highest amplitude dominant frequency in the cardiac frequency spectrum.Enhanced GJ coupling with rotigaptide (n = 10) progressively organised fibrillation in a concentration-dependent manner; increasing FDI (0nM: 0.53±0.04, 80nM: 0.78±0.03, p < 0.001), increasing RA sustained VF time (0nM:44±6%, 80nM: 94±2%, p < 0.001) and stabilised RAs (maximum rotations for a RA; 0nM:5.4±0.5, 80nM: 48.2±12.3, p < 0.001). GJ uncoupling with carbenoxolone progressively disorganised VF; the FDI decreased (0µM: 0.60±0.05, 50µM: 0.17±0.03, p < 0.001) and RA-sustained VF time decreased (0µM: 61±9%, 50µM: 3±2%, p < 0.001).In CF, VF activity was disorganised and the RA-sustained VF time was the lowest (CF: 27±7% versus PF: 75±5%, p < 0.001). Global fibrillatory organisation measured by FDI was highest in PF (PF: 0.67±0.05 versus CF: 0.33±0.03, p < 0.001). PF harboured the longest duration and most spatially stable RAs (patchy: 1411±266ms versus compact: 354±38ms, p < 0.001). DiF (n = 11) exhibited an intermediately organised VF pattern, sustained by a combination of multiple-wavelets and short-lived RAs.
Conclusion
The degree of GJ coupling and pattern of fibrosis influences the mechanism sustaining VF. There is a continuous spectrum of organisation in VF, ranging between globally organised fibrillation sustained by stable RAs and disorganised, possibly multiple-wavelet driven fibrillation with no RAs.
Translational perspective
Multiple competing mechanisms have been proposed for sustaining VF. We reframed conflicting mechanisms reported in sustaining fibrillation and defined them as part of a continuum of varying global organisation, with some sustained by stable rotationalactivities. The underlying cardiac electroarchitecture, namely gap junction coupling and fibrosis, were important determinants of the VF mechanism. Characterising the VF mechanism and its relationship to the cardiac electroarchitecture may facilitate a patient-tailored treatment approach towards VF prevention in VF survivors. Organised fibrillation sustained by stable rotational activities could be considered for targeted ablation. Disorganised fibrillation dynamics may be better suited for conventional pharmacotherapy.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Cardiovasc Res: 12 May 2020; epub ahead of print
Handa BS, Li X, Baxan N, Roney C, ... Peters NS, Ng FS
Cardiovasc Res: 12 May 2020; epub ahead of print | PMID: 32402067
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Abstract

Mutations in cause an autosomal-recessive form of hypertrophic cardiomyopathy.

Salazar-Mendiguchía J, Ochoa JP, Palomino-Doza J, Domínguez F, ... Monserrat L,
Objective
Up to 50% of patients with hypertrophic cardiomyopathy (HCM) show no disease-causing variants in genetic studies.has been suggested as a candidate gene for the development of cardiomyopathies, although evidence for a causative role in HCM is limited. We sought to investigate the relationship between rare variants inand the development of HCM.
Methods
was sequenced by next generation sequencing in 4867 index cases with a clinical diagnosis of HCM and in 3628 probands with other cardiomyopathies. Additionally, 3136 index cases with familial cardiovascular diseases other than cardiomyopathy (mainly channelopathies and aortic diseases) were used as controls.
Results
Sixteen index cases with rare homozygous or compound heterozygous variants in(15 HCM and one restrictive cardiomyopathy) were included. No homozygous or compound heterozygous were identified in the control population. Familial evaluation showed that only homozygous and compound heterozygous had signs of disease, whereas all heterozygous family members were healthy. The mean age at diagnosis was 35 years (range 15-69). Fifty per cent of patients had concentric left ventricular hypertrophy (LVH) and 45% were asymptomatic at the moment of the first examination. Significant degrees of late gadolinium enhancement were detected in 80% of affected individuals, and 20% of patients had left ventricular (LV) systolic dysfunction. Fifty per cent had non-sustained ventricular tachycardia. Twenty per cent of patients suffered an adverse cerebrovascular event (20%).
Conclusion
appears to be an uncommon cause of HCM inherited in an autosomal-recessive manner and associated with concentric LVH and a high rate of LV dysfunction.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 24 May 2020; epub ahead of print
Salazar-Mendiguchía J, Ochoa JP, Palomino-Doza J, Domínguez F, ... Monserrat L,
Heart: 24 May 2020; epub ahead of print | PMID: 32451364
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Abstract

Altered Atrial Cytosolic Calcium Handling Contributes to the Development of Postoperative Atrial Fibrillation.

Fakuade FE, Steckmeister V, Seibertz F, Gronwald J, ... Mason FE, Voigt N
Aims
Atrial fibrillation is a commonly occurring arrhythmia after cardiac surgery (postoperative AF, poAF) and is associated with poorer outcomes. Considering that reduced atrial contractile function is a predictor of poAF and that Ca2+ plays an important role in both excitation-contraction coupling and atrial arrhythmogenesis, this study aims to test whether alterations of intracellular Ca2+ handling contribute to impaired atrial contractility and to the arrhythmogenic substrate predisposing patients to poAF.
Methods and results
Right atrial appendages were obtained from patients in sinus rhythm undergoing open-heart surgery. Cardiomyocytes were investigated by simultaneous measurement of [Ca2+]i and action potentials (AP, patch-clamp). Patients were followed-up for 6 days to identify those with and without poAF. Speckle-tracking analysis of preoperative echocardiography revealed reduced left atrial contraction strain in poAF patients. At the time of surgery, cellular Ca2+ transients (CaT) and the sarcoplasmic reticulum (SR) Ca2+ content were smaller in the poAF group. CaT decay was slower in poAF, but the decay of caffeine-induced Ca2+ transients was unaltered, suggesting preserved NCX function. In agreement, western blots revealed reduced SERCA2a expression in poAF patients but unaltered phospholamban expression/phosphorylation. Computational modeling indicated that reduced SERCA activity promotes occurrence of CaT- and AP-alternans. Indeed, alternans of CaT and AP occurred more often and at lower stimulation frequencies in atrial myocytes from poAF patients. Resting membrane potential and AP duration were comparable between both groups at various pacing frequencies (0.25-8 Hz).
Conclusions
Biochemical, functional and modeling data implicate reduced SERCA-mediated Ca2+ reuptake into the SR as a major contributor to impaired preoperative atrial contractile function and to the pre-existing arrhythmogenic substrate in patients developing poAF.
Translational perspective
Development of atrial fibrillation (AF) within the immediate postoperative period (poAF), represents one of the most frequent complications after cardiac surgery and is associated with poorer outcomes. Our results suggest that reduced Ca2+ uptake into the sarcoplasmic reticulum (SR), associated with increased cellular susceptibility to Ca2+-transient (CaT)- and action potential (AP)-alternans, contributes to the arrhythmogenic substrate predisposing patients to the development of poAF. Therefore, modulation of SERCA activity may represent a novel mechanistic target to prevent development of poAF.Furthermore, we show that the impaired SR Ca2+ uptake contributes to reduced systolic Ca2+ release and impaired atrial contractility in poAF patients. Atrial contractility may therefore represent an important factor for identification of patients at risk for poAF development.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Cardiovasc Res: 09 Jun 2020; epub ahead of print
Fakuade FE, Steckmeister V, Seibertz F, Gronwald J, ... Mason FE, Voigt N
Cardiovasc Res: 09 Jun 2020; epub ahead of print | PMID: 32520995
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Abstract

Association of arterial stiffness with left atrial structure and phasic function: a community-based cohort study.

Yoshida Y, Nakanishi K, Daimon M, Ishiwata J, ... Homma S, Komuro I
Objectives
Increased arterial stiffness is currently recognized as an independent risk factor for atrial fibrillation, although the pathophysiological mechanisms remain unclear. This study aimed to investigate the association of arterial stiffness with left atrial (LA) volume and phasic function in a community-based cohort.
Methods
We included 1156 participants without overt cardiovascular disease who underwent extensive cardiovascular examination. Arterial stiffness was evaluated by cardio-ankle vascular index (CAVI). Speckle-tracking echocardiography was employed to evaluate LA phasic function including reservoir, conduit, and pump strain as well as left ventricular global longitudinal strain (LVGLS).
Results
CAVI was negatively correlated with reservoir and conduit strain (r = -0.37 and -0.45, both P < 0.001), whereas weakly, but positively correlated with LA volume index and pump strain (r = 0.12 and 0.09, both P < 0.01). In multivariable analysis, CAVI was significantly associated with reservoir and conduit strain independent of traditional cardiovascular risk factors and LV morphology and function including LVGLS (standardized β = -0.22 and -0.27, respectively, both P < 0.001), whereas there was no independent association with LA volume index and pump strain. In the categorical analysis, the abnormal CAVI (≥9.0) carried the significant risk of impaired reservoir and conduit strain (adjusted odds ratio = 2.61 and 3.73 vs. normal CAVI, both P < 0.01) in a fully adjusted model including laboratory and echocardiographic parameters.
Conclusion
Arterial stiffness was independently associated with LA phasic function, even in the absence of overt cardiovascular disease, which may explain the higher incidence of atrial fibrillation in individuals with increased arterial stiffness.



J Hypertens: 30 May 2020; 38:1140-1148
Yoshida Y, Nakanishi K, Daimon M, Ishiwata J, ... Homma S, Komuro I
J Hypertens: 30 May 2020; 38:1140-1148 | PMID: 32371804
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Abstract

Chemokine Receptor CXCR-2 Initiates Atrial Fibrillation by Triggering Monocyte Mobilization in Mice.

Zhang YL, Cao HJ, Han X, Teng F, ... Guo SB, Li HH

Atrial fibrillation (AF) is frequently associated with increased inflammatory response characterized by infiltration of monocytes/macrophages. The chemokine receptor CXCR-2 is a critical regulator of monocyte mobilization in hypertension and cardiac remodeling, but it is not known whether CXCR-2 is involved in the development of hypertensive AF. AF was induced by infusion of Ang II (angiotensin II; 2000 ng/kg per minute) for 3 weeks in male C57BL/6 wild-type mice, CXCR-2 knockout mice, bone marrow-reconstituted chimeric mice, and mice treated with the CXCR-2 inhibitor SB225002. Microarray analysis revealed that 4 chemokine ligands of CXCR-2 were significantly upregulated in the atria during 3 weeks of Ang II infusion. CXCR-2 expression and the number of CXCR2 immune cells markedly increased in Ang II-infused atria in a time-dependent manner. Moreover, Ang II-infused wild-type mice had increased blood pressure, AF inducibility, atrial diameter, fibrosis, infiltration of macrophages, and superoxide production compared with saline-treated wild-type mice, whereas these effects were significantly attenuated in CXCR-2 knockout mice and wild-type mice transplanted with CXCR-2-deficient bone marrow cells or treated with SB225002. Moreover, circulating blood CXCL-1 levels and CXCR2 monocyte counts were higher and associated with AF in human patients (n=31) compared with sinus rhythm controls (n=31). In summary, this study identified a novel role for CXCR-2 in driving monocyte infiltration of the atria, which accelerates atrial remodeling and AF after hypertension. Blocking CXCR-2 activation may serve as a new therapeutic strategy for AF.



Hypertension: 30 Jul 2020; 76:381-392
Zhang YL, Cao HJ, Han X, Teng F, ... Guo SB, Li HH
Hypertension: 30 Jul 2020; 76:381-392 | PMID: 32639881
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Abstract

Favorable effect of catheter ablation on nocturnal hypertension in patients with paroxysmal atrial fibrillation.

Wada T, Sakuragi S, Saito T, Kawaguchi T, ... Katayama Y, Ito H
Objectives
The current study was performed to determine whether pulmonary vein isolation (PVI) improves nocturnal hypertension in patients with paroxysmal atrial fibrillation (PAF).
Background
Abnormal night-time blood pressure (BP) fluctuation is a risk factor for atrial fibrillation. Imbalance of autonomic nervous function is a risk factor common to both of these abnormalities. PVI can reportedly modify the autonomic nervous function balance in patients with atrial fibrillation.
Methods
The study population comprised 50 consecutive patients (mean age, 69.8 ± 7.5 years; 35.0% male) with PAF scheduled for PVI. Both 24-h ambulatory BP monitoring and heart rate variability analysis were performed before and at 3 months after PVI.
Results
Patients were classified into two groups according to the presence of nocturnal BP dipping before PVI: the normal dipping group (n = 27) and the nondipping group (n = 23). The low-frequency spectrum power and the ratio of low-frequency spectrum power to high-frequency spectrum power (low-frequency spectrum/high-frequency spectrum) were higher in the nondipping than the normal dipping group (low-frequency spectrum: 219.9 ± 210.2 vs. 92.7 ± 50.5 ms, respectively, P = 0.03; low-frequency spectrum/high-frequency spectrum: 1.8 ± 1.9 vs. 0.9 ± 0.8, respectively, P = 0.05). In the nondipping group, the elevated night-time BP disappeared in eight (35%) patients at 3 months after PVI, which was associated with an increase in high-frequency spectrum power. These patients did not develop atrial fibrillation recurrence during follow-up (mean, 568 ± 218 days).
Conclusion
Among patients with PAF, the nondipping group showed greater sympathetic activity (higher low-frequency spectrum power and low-frequency spectrum/high-frequency spectrum) than the dipping group. Restoration of BP dipping after PVI is associated with increased parasympathetic activity (higher high-frequency spectrum power) and reduced recurrence of arrhythmic events.



J Hypertens: 30 May 2020; 38:1174-1182
Wada T, Sakuragi S, Saito T, Kawaguchi T, ... Katayama Y, Ito H
J Hypertens: 30 May 2020; 38:1174-1182 | PMID: 32371808
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Abstract

Cost-Effectiveness of Extended Electrocardiogram Monitoring for Atrial Fibrillation After Stroke: A Systematic Review.

Chew DS, Rennert-May E, Spackman E, Mark DB, Exner DV
Background and purpose
Management of cryptogenic stroke involves the identification of modifiable risk factors, such as atrial fibrillation (AF). Extended rhythm monitoring increases AF detection rates but at an increased device cost compared with conventional Holter monitoring. The objective of the study was to identify and synthesize the existing literature on the cost-effectiveness of prolonged rhythm monitoring devices for AF detection in cryptogenic stroke.
Methods
We conducted a systematic review of available economic evaluations of prolonged ECG monitoring for AF detection following cryptogenic stroke compared with standard care.
Results
Of the 530 unique citations, 8 studies assessed the cost-utility of prolonged ECG monitoring compared with standard care following cryptogenic stroke. The prolonged ECG monitoring strategies included 7-day ambulatory monitoring, 30-day external loop recorders or intermittent ECG monitoring, and implantable loop recorders. The majority of cost-utility analyses reported incremental cost-effectiveness ratios below $50 000 per QALY gained; and two studies reported a cost-savings.
Conclusions
There is limited economic literature on the cost-effectiveness of extended ECG monitoring devices for detection of atrial fibrillation in cryptogenic stroke. In patients with cryptogenic stroke, extended ECG monitoring for AF detection may be economically attractive when traditional willingness-to-pay thresholds are adopted. However, there was substantial variation in the reported ICERs. The direct comparison of cost-effectiveness across technologies is limited by heterogeneity in modeling assumptions.



Stroke: 04 Jun 2020:STROKEAHA120029340; epub ahead of print
Chew DS, Rennert-May E, Spackman E, Mark DB, Exner DV
Stroke: 04 Jun 2020:STROKEAHA120029340; epub ahead of print | PMID: 32498661
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Abstract

Comparative Effectiveness of Rivaroxaban, Apixaban, and Warfarin in Atrial Fibrillation Patients With Polypharmacy.

Mentias A, Heller E, Vaughan Sarrazin M
Background and purpose
Comparative effectiveness and safety of oral anticoagulants in patients with atrial fibrillation and high polypharmacy are unknown.
Methods
We used Medicare administrative data to evaluate patients with new atrial fibrillation diagnosis from 2015 to 2017, who initiated an oral anticoagulant within 90 days of diagnosis. Patients taking ≤3, 4 to 8, or ≥9 other prescription medications were categorized as having low, moderate, or high polypharmacy, respectively. Within polypharmacy categories, patients receiving apixaban 5 mg twice daily, rivaroxaban 20 mg once daily, or warfarin were matched using a 3-way propensity score matching. Study outcomes included ischemic stroke, bleeding, and all-cause mortality.
Results
The study cohort included 6985 patients using apixaban, 3838 using rivaroxaban, and 6639 using warfarin. In the propensity-matched cohorts there was no difference in risk of ischemic stroke between the 3 drugs in patients with low and moderate polypharmacy. However, among patients with high polypharmacy, the risk of ischemic stroke was higher with apixaban compared with warfarin (adjusted hazard ratio 2.34 [95% CI, 1.01-5.42]; =0.05) and similar to rivaroxaban (adjusted hazard ratio, 1.38 [95% CI, 0.67-2.84]; =0.4). There was no difference in risk of death between the 3 drugs in patients with low and moderate polypharmacy, but apixaban was associated with a higher risk of death compared with rivaroxaban (adjusted hazard ratio, 2.03 [95% CI, 1.01-4.08]; =0.05) in the high polypharmacy group. Apixaban had lower bleeding risk compared with warfarin in the low polypharmacy group (adjusted hazard ratio, 0.54 [95% CI, 0.32-0.90]; =0.02), but there was no difference in bleeding between the 3 drugs in the moderate and high polypharmacy groups.
Conclusions
Our study suggests that among patients with significant polypharmacy (>8 drugs), there may be a higher stroke and mortality risk with apixaban compared with warfarin and rivaroxaban. However, differences were of borderline significance.



Stroke: 09 Jun 2020:STROKEAHA120029541; epub ahead of print
Mentias A, Heller E, Vaughan Sarrazin M
Stroke: 09 Jun 2020:STROKEAHA120029541; epub ahead of print | PMID: 32517580
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Abstract

Serial measurement of interleukin-6 and risk of mortality in anticoagulated patients with atrial fibrillation: Insights from ARISTOTLE and RE-LY trials.

Aulin J, Hijazi Z, Siegbahn A, Andersson U, ... Wallentin L, Oldgren J
Background
The inflammatory biomarker interleukin-6 (IL-6) is associated with mortality in atrial fibrillation (AF).
Objective
To investigate if repeated IL-6 measurements improve the prognostication for stroke or systemic embolism, major bleeding, and mortality in anticoagulated patients with AF.
Methods
IL-6 levels by ELISA were measured at study entry and at 2 months in 4,830 patients in the ARISTOTLE trial with 1.8 years median follow-up. In the RE-LY trial IL-6 were measured at study entry, 3, 6, and 12 months in 2,559 patients with 2.0 years median follow-up. Associations between a second IL-6 measurement and outcomes, adjusted for baseline IL-6, clinical variables, and other cardiovascular biomarkers, were analyzed by Cox-regression.
Results
Median IL-6 levels were 2.0 ng/L (interquartile range [IQR] 1.30-3.20) and 2.10 ng/L (IQR 1.40-3.40) at the two time-points in ARISTOTLE, and, in RE-LY, 2.5 ng/L (IQR 1.6-4.3), 2.5 ng/L (IQR 1.6-4.2), 2.4 ng/L (IQR 1.6, 3.9),and 2.4 ng/L (IQR 1.5, 3.9), respectively. IL-6 was associated with mortality; hazard ratios per 50% higher IL-6 at 2 or 3 months, respectively, were 1.32 (95% CI 1.23-1.41, p<0.0001) in ARISTOTLE, and 1.11 (1.01-1.22, p=0.0290) in RE-LY; with improved C index from 0.74 to 0.76 in ARISTOTLE, but not in the smaller RE-LY cohort. There were no consistent associations with second IL-6 and stroke or systemic embolism, or major bleeding.
Conclusions
Persistent systemic inflammatory activity, assessed by repeated IL-6 measurements, is associated with mortality independent of established clinical risk factors and other strong cardiovascular biomarkers in anticoagulated patients with AF.

This article is protected by copyright. All rights reserved.

J Thromb Haemost: 07 Jun 2020; epub ahead of print
Aulin J, Hijazi Z, Siegbahn A, Andersson U, ... Wallentin L, Oldgren J
J Thromb Haemost: 07 Jun 2020; epub ahead of print | PMID: 32510737
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Abstract

Comparative Safety and Effectiveness of Oral Anticoagulants in Nonvalvular Atrial Fibrillation: The NAXOS Study.

Van Ganse E, Danchin N, Mahé I, Hanon O, ... Belhassen M, Steg PG
Background and purpose
The effects of direct oral anticoagulants in nonvalvular atrial fibrillation should be assessed in actual conditions of use. France has near-universal healthcare coverage with a unified healthcare information system, allowing large population-based analyses. NAXOS (Evaluation of Apixaban in Stroke and Systemic Embolism Prevention in Patients With Nonvalvular Atrial Fibrillation) aimed to compare the safety, effectiveness, and mortality of apixaban with vitamin K antagonists (VKAs), rivaroxaban, and dabigatran, in oral anticoagulant-naive patients with nonvalvular atrial fibrillation.
Methods
This was an observational study using French National Health System claims data and including all adults with nonvalvular atrial fibrillation who initiated oral anticoagulant between 2014 and 2016. Outcomes of interest were major bleeding events leading to hospitalization (safety), stroke and systemic thromboembolic events (effectiveness), and all-cause mortality. Four approaches were used for comparative analyses: matching on propensity score (PS; 1:n); as a sensitivity analysis, matching on high-dimensional PS; adjustment on PS; and adjustment on known confounders. For each outcome, cumulative incidence rates accounting for competing risks of death were estimated.
Results
Overall, 321 501 patients were analyzed, of whom 35.0%, 27.2%, 31.1%, and 6.6% initiated VKAs, apixaban, rivaroxaban, and dabigatran, respectively. Apixaban was associated with a lower PS-matched risk of major bleeding compared with VKAs (hazard ratio [HR], 0.43 [95% CI, 0.40-0.46]) and rivaroxaban (HR, 0.67 [95% CI, 0.63-0.72]), but not dabigatran (HR, 0.93 [95% CI, 0.81-1.08]). Apixaban was associated with a lower risk of stroke and systemic thromboembolic event compared with VKAs (HR, 0.60 [95% CI, 0.56-0.65]), but not rivaroxaban (HR, 1.05 [95% CI, 0.97-1.15]) or dabigatran (HR, 0.93 [95% CI, 0.78-1.11]). All-cause mortality was lower with apixaban than with VKAs, but not lower than with rivaroxaban or dabigatran.
Conclusions
Apixaban was associated with superior safety, effectiveness, and lower mortality than VKAs; with superior safety than rivaroxaban and similar safety to dabigatran; and with similar effectiveness when compared with rivaroxaban or dabigatran. These observational data suggest potentially important differences in outcomes between direct oral anticoagulants, which should be explored in randomized trials.



Stroke: 15 Jun 2020:STROKEAHA120028825; epub ahead of print
Van Ganse E, Danchin N, Mahé I, Hanon O, ... Belhassen M, Steg PG
Stroke: 15 Jun 2020:STROKEAHA120028825; epub ahead of print | PMID: 32539675
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Abstract

Thrombolysis Outcomes in Acute Ischemic Stroke by Fluid-Attenuated Inversion Recovery Hyperintense Arteries.

Zhou Z, Yoshimura S, Delcourt C, Lindley RI, ... Xu J, Anderson CS
Background and purpose
To determine factors associated with fluid-attenuated inversion recovery (FLAIR) hyperintense arteries (FLAIR-HAs) on magnetic resonance imaging and their prognostic significance in thrombolysis-treated patients with acute ischemic stroke from the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) trial alteplase-dose arm.
Methods
Patients with acute ischemic stroke (N=293) with brain magnetic resonance imaging (FLAIR and diffusion-weighted imaging sequences) scanned <4.5 hours of symptom onset were assessed for location and extent (score) of FLAIR-HAs, infarct volume, large vessel occlusion (LVO), and other ischemic signs. Logistic regression models were used to determine predictors of FLAIR-HAs and the association of FLAIR-HAs with 90-day outcomes: favorable functional outcome (primary; modified Rankin Scale scores, 0-1), other modified Rankin Scale scores, and intracerebral hemorrhage.
Results
Prior atrial fibrillation, LVO, large infarct volume, and anterior circulation infarction were independently associated with FLAIR-HAs. The rate of modified Rankin Scale scores 0 to 1 was numerically lower in patients with FLAIR-HAs versus without (69/152 [45.4%] versus 75/131 [57.3%]), as was the subset of LVO (37/93 [39.8%] versus 9/16 [56.3%]), but not in those without LVO (25/36 [69.4%] versus 60/106 [56.6%]). After adjustment for covariables, FLAIR-HAs were independently associated with increased primary outcome (adjusted odds ratio [95% CI]: overall 4.14 [1.63-10.50]; with LVO 4.92 [0.87-27.86]; no LVO 6.16 [1.57-24.14]) despite an increased risk of hemorrhagic infarct (4.77 [1.12-20.26]).
Conclusions
FLAIR-HAs are more frequent in acute ischemic stroke with cardioembolic features and indicate potential for a favorable prognosis in thrombolysis-treated patients possibly mediated by LVO. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01422616.



Stroke: 29 Jun 2020; 51:2240-2243
Zhou Z, Yoshimura S, Delcourt C, Lindley RI, ... Xu J, Anderson CS
Stroke: 29 Jun 2020; 51:2240-2243 | PMID: 32568636
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Abstract

Heterogeneity in Conduction Underlies Obesity Related Atrial Fibrillation Vulnerability.

Schram-Serban C, Heida A, Roos-Serote MC, Knops P, ... Bogers AJJC, de Groot NMS

- Obese patients are more vulnerable to development of atrial fibrillation (AF) but pathophysiology underlying this relation is only partly understood. The aim of this study is to compare the severity and extensiveness of conduction disorders between obese patients and non-obese patients measured at a high-resolution scale.- Patients (N=212) undergoing cardiac surgery (male:161, 63±11years) underwent epicardial mapping of the right atrium (RA), Bachmann\'s bundle (BB) and left atrium (LA) during sinus rhythm. Conduction delay (CD) was defined as inter-electrode conduction time (CT) of 7-11ms and conduction block (CB) as CT ≥12ms. Prevalence of CD/CB, continuous CDCB (cCDCB), length of CD/CB/cCDCB lines, and severity of CB were analyzed.- In obese patients, the overall incidence of CD (3.1% versus 2.6%, p=0.002), CB (1.8% versus 1.2%, p<0.001) and cCDCB (2.6% versus 1.9%, p<0.001) was higher and CD (p=0.012) and cCDCB (p<0.001) lines are longer. There were more conduction disorders at BB and this area has a higher incidence of CD (4.4% versus 3.3%, p=0.002), CB (3.1% versus 1.6%, p<0.001), cCDCB (4.6% versus 2.7%, p<0.001) and longer CD (p<0.001) or cCDCB (p=0.017) lines. The severity of CB is also higher, particularly in the BB (p=0.008) and PV (p=0.020) areas. In addition, obese patients have a higher incidence of early de-novo post-operative AF (PoAF) (p=0.003). BMI (p=0.037) and the overall amount of CB (p=0.012) were independent predictors for incidence of early PoAF.- Compared to non-obese patients, obese patients have higher incidences of conduction disorders which are also more extensive and more severe. These differences in heterogeneity in conduction are already present during SR and may explain the higher vulnerability to AF of obese patients.



Circ Arrhythm Electrophysiol: 16 Apr 2020; epub ahead of print
Schram-Serban C, Heida A, Roos-Serote MC, Knops P, ... Bogers AJJC, de Groot NMS
Circ Arrhythm Electrophysiol: 16 Apr 2020; epub ahead of print | PMID: 32301327
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Abstract

Ablation of Supraventricular Tachycardias From Concealed Left-sided Nodoventricular And Nodofascicular Accessory Pathways.

Cardona-Guarache R, Han FT, Nguyen DT, Chicos AB, ... Heaven D, Scheinman MM

- Nodoventricular (NV) and nodofascicular (NF) accessory pathways (AP) are uncommon connections between the AV node and the fascicles or ventricles.- Five patients with NF or NV tachycardia were studied.- We identified 5 patients with concealed, left-sided NV (n=4) and NF (n=1) AP. We proved the participation of AP in tachycardia by delivering His-synchronous PVCs that either delayed the subsequent atrial electrogram or terminated the tachycardia (n=3), and by observing an increase in VA interval coincident with left bundle branch block (LBBB) (n=2). The APs were not atrioventricular pathways because the septal VA interval during tachycardia was <70ms in 3, 1 had spontaneous AV dissociation, and in 1 the atria were dissociated from the circuit with atrial overdrive pacing. Entrainment from the right ventricle showed ventricular fusion in 4 out of 5 cases. A left-sided origin of the AP was suspected after failed ablation of the right inferior extension of AV node in 3 cases and by observing a VA increase with LBBB in 2 cases. The NF and 3 of the NV AP were successfully ablated from within the proximal coronary sinus (CS) guided by recorded potentials at the roof of the CS, and 1 NV AP was ablated via a transseptal approach near the CS os.- Left-sided NF and NV AP appear to connect the ventricles with the CS musculature in the region of the CS os. Mapping and successful ablation sites can be guided by recording potentials within or near the CS os.



Circ Arrhythm Electrophysiol: 13 Apr 2020; epub ahead of print
Cardona-Guarache R, Han FT, Nguyen DT, Chicos AB, ... Heaven D, Scheinman MM
Circ Arrhythm Electrophysiol: 13 Apr 2020; epub ahead of print | PMID: 32286853
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Abstract

Patterns of oral anticoagulation use with cardioversion in clinical practice.

Geurink K, Holmes D, Ezekowitz MD, Pieper K, ... Peterson ED, Pokorney SD
Background
Cardioversion is common among patients with atrial fibrillation (AF). We hypothesised that novel oral anticoagulants (NOAC) used in clinical practice resulted in similar rates of stroke compared with vitamin K antagonists (VKA) for cardioversion.
Methods
Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II, patients with AF who had a cardioversion, follow-up data and an AF diagnosis within 6 months of enrolment were identified retrospectively. Clinical outcomes were compared for patients receiving a NOAC or VKA for 1 year following cardioversion.
Results
Among 13 004 patients with AF, 2260 (17%) underwent cardioversion. 1613 met the inclusion criteria for this analysis. At the time of cardioversion, 283 (17.5%) were receiving a VKA and 1330 (82.5%) a NOAC. A transoesophageal echocardiogram (TOE) was performed in 403 (25%) cardioversions. The incidence of stroke/transient ischaemic attack (TIA) at 30 days was the same for patients having (3.04 per 100 patient-years) or not having (3.04 per 100 patient-years) a TOE (p=0.99). There were no differences in the incidence of death (HR 1.19, 95% CI 0.62 to 2.28, p=0.61), cardiovascular hospitalisation (HR 1.02, 95% CI 0.76 to 1.35, p=0.91), stroke/TIA (HR 1.18, 95% CI 0.30 to 4.74, p=0.81) or bleeding-related hospitalisation (HR 1.29, 95% CI 0.66 to 2.52, p=0.45) at 1 year for patients treated with either a NOAC or VKA.
Conclusions
Cardioversion was a low-risk procedure for patients treated with NOAC, and there were statistically similar rates of stroke/TIA 30 days after cardioversion as for patients treated with VKA. There were no statically significant differences in death, stroke/TIA or major bleeding at 1 year among patients treated with NOAC compared with VKA after cardioversion.

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

Heart: 25 Jun 2020; epub ahead of print
Geurink K, Holmes D, Ezekowitz MD, Pieper K, ... Peterson ED, Pokorney SD
Heart: 25 Jun 2020; epub ahead of print | PMID: 32591363
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Abstract

Community pharmacy-based study of adherence to non-vitamin K antagonist oral anticoagulants.

Capiau A, Mehuys E, Van Tongelen I, Christiaens T, ... de Backer TLM, Boussery K
Objective
This study aimed to assess implementation adherence (how well the patient\'s actual intake matches the prescribed dosing regimen) to non-vitamin K antagonist oral anticoagulants (NOACs) and to explore experiences with and beliefs about NOACs in a real-world sample of long-term NOAC users.
Methods
A cross-sectional observational study was conducted in home-dwelling adults who started taking a NOAC at least 1 year prior to inclusion. Pharmacy dispensing data were used to calculate the Medication Possession Ratio (MPR). Patients were recruited in 158 community pharmacies in Flanders, Belgium. They completed a questionnaire collecting basic characteristics and exploring self-reported adherence to NOACs (using the Medication Adherence Report Scale, MARS) and experiences with and beliefs about NOACs (using the Beliefs about Medicines Questionnaire, BMQ).
Results
A total of 766 patients (mean age 76.2±8.8 years, median CHADS-VASc score 4 (IQR=3-4)) were included. The majority (93.5%) used NOAC for stroke prevention in atrial fibrillation. The median MPR was 95.2% (IQR=87.8-99.7) which corresponds with half of the study population not taking their NOAC on at least 17 cumulative days per year. Almost 21% of participants reported non-adherence on the MARS (score <25), with unintentional non-adherence (forgetfulness) most frequently reported (15.4%). Although two-thirds of NOAC users indicated to experience adverse drug reactions, the BMQ demonstrated a positive attitude towards NOAC therapy, where necessity beliefs outweigh the concerns.
Conclusions
Our data indicate that long-term NOAC users have high implementation adherence and a positive attitude towards NOAC therapy. However, taking into account patients\' thromboembolic risk and NOACs\' short half-lives, further optimisation of NOAC use seems warranted in this population.

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

Heart: 22 Jun 2020; epub ahead of print
Capiau A, Mehuys E, Van Tongelen I, Christiaens T, ... de Backer TLM, Boussery K
Heart: 22 Jun 2020; epub ahead of print | PMID: 32576607
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Impact:
Abstract

Factors Associated with Large Improvements in Health-Related Quality of Life in Patients with Atrial Fibrillation: Results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF).

Steinberg BA, Holmes DN, Pieper K, Allen LA, ... Peterson ED, Piccini JP

- Atrial fibrillation (AF) adversely impacts health-related quality of life (hrQoL). While some patients demonstrate improvements in hrQoL, the factors associated with large improvements in hrQoL are not well described.- We assessed factors associated with a 1-year increase in AFEQT of 1 standard deviation (≥18 points; 3x clinically important difference), among outpatients in the ORBIT-AF I registry.- Overall, 28% (181/636) of patients had such a hrQoL improvement. Compared with patients not showing large hrQoL improvement, they were of similar age (median 73 vs. 74, p=0.3), equally likely to be female (44% vs. 48%, p=0.3), but more likely to have newly-diagnosed AF at baseline (18% vs. 8%; p=0.0004), prior antiarrhythmic drug use (52% vs. 40%, 0.005), baseline antiarrhythmic drug use (34.8% vs, 26.8%, p=0.045), and more likely to undergo AF-related procedures during follow-up (AF ablation: 6.6% vs. 2.0%, p=0.003; cardioversion:12.2% vs. 5.9% p=0.008). In multivariable analysis, a history of alcohol abuse (adjusted OR 2.41, p=0.01) and increased baseline diastolic BP (adjusted OR 1.23 per 10-point increase and >65 mm Hg, p=0.04) were associated with large improvements in hrQoL at 1 year, whereas patients with prior stroke/TIA, COPD, and PAD were less likely to improve (p<0.05 for each).- In this national registry of AF patients, potentially treatable AF risk factors are associated with large hrQoL improvement, whereas less reversible conditions appeared negatively associated with hrQoL improvement. Understanding which patients are most likely to have large hrQoL improvement may facilitate targeting interventions for high-value care that optimizes patient reported outcomes in AF.- clinicaltrials.gov.; Unique Identifier: NCT01165710.



Circ Arrhythm Electrophysiol: 15 Apr 2020; epub ahead of print
Steinberg BA, Holmes DN, Pieper K, Allen LA, ... Peterson ED, Piccini JP
Circ Arrhythm Electrophysiol: 15 Apr 2020; epub ahead of print | PMID: 32298144
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Abstract

Irrigated Microwave Catheter Ablation Can Create Deep Ventricular Lesions Through Epicardial Fat with Relative Sparing of Adjacent Coronary Arteries.

Qian PC, Barry MA, Tran VT, Lu J, ... Thiagalingam A, Thomas SP

- Radiofrequency ablation depth can be inadequate to reach intramural or epicardial substrate, and energy delivery in the pericardium is limited by penetration through epicardial fat and coronary anatomy. We hypothesized that open irrigated microwave catheter ablation can create deep myocardial lesions endocardially and epicardially though fat while acutely sparing nearby the coronary arteries.- In-house designed and constructed irrigated microwave catheters were tested in in-vitro phantom models and in 15 sheep. Endocardial ablations were performed at 140-180W for 4min; epicardial ablations via subxiphoid access were performed at 90-100W for 4min at sites near coronary arteries.- Epicardial ablations at 90-100W produced mean lesion depth of 10±4mm, width 18±10mm, and length 29±8mm through median epicardial fat thickness of 1.2mm. Endocardial ablations at 180W reached depths of 10.7±3.3mm, width of 16.6±5mm, and length of 20±5mm. Acute coronary occlusion or spasm was not observed at a median separation distance of 2.7mm (IQR 1.2-3.4mm). Saline electrodes recorded unipolar and bipolar electrograms; microwave ablation caused reductions in voltage and changes in electrogram morphology with loss of pace-capture. In-vitro models demonstrated the heat sink effect of coronary flow, as well as preferential microwave coupling to myocardium and blood as opposed to lung and epicardial fat phantoms.- Irrigated microwave catheter ablation may be an effective ablation modality for deep ventricular lesion creation with capacity for fat penetration and sparing of nearby coronary arteries due to cooling endoluminal flow. Clinical translation could improve the treatment of ventricular tachycardia arising from mid myocardial or epicardial substrates.



Circ Arrhythm Electrophysiol: 15 Apr 2020; epub ahead of print
Qian PC, Barry MA, Tran VT, Lu J, ... Thiagalingam A, Thomas SP
Circ Arrhythm Electrophysiol: 15 Apr 2020; epub ahead of print | PMID: 32299229
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Abstract

Interleukin-13 drives metabolic conditioning of muscle to endurance exercise.

Knudsen NH, Stanya KJ, Hyde AL, Chalom MM, ... Cooper JA, Lee CH

Repeated bouts of exercise condition muscle mitochondria to meet increased energy demand-an adaptive response associated with improved metabolic fitness. We found that the type 2 cytokine interleukin-13 (IL-13) is induced in exercising muscle, where it orchestrates metabolic reprogramming that preserves glycogen in favor of fatty acid oxidation and mitochondrial respiration. Exercise training-mediated mitochondrial biogenesis, running endurance, and beneficial glycemic effects were lost inmice. By contrast, enhanced muscle IL-13 signaling was sufficient to increase running distance, glucose tolerance, and mitochondrial activity similar to the effects of exercise training. In muscle, IL-13 acts through both its receptor IL-13Rα1 and the transcription factor Stat3. The genetic ablation of either of these downstream effectors reduced running capacity in mice. Thus, coordinated immunological and physiological responses mediate exercise-elicited metabolic adaptations that maximize muscle fuel economy.

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Science: 30 Apr 2020; 368
Knudsen NH, Stanya KJ, Hyde AL, Chalom MM, ... Cooper JA, Lee CH
Science: 30 Apr 2020; 368 | PMID: 32355002
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Abstract

Integrating the STOP-BANG score and clinical data to predict cardiovascular events after infarction: A machine learning study.

Calvillo-Argüelles O, Sierra-Fernández CR, Padilla-Ibarra J, Rodriguez-Zanella H, ... van der Harst P, Juarez-Orozco LE
Background
Obstructive sleep apnea (OSA) conveys worse clinical outcomes in coronary artery disease patients. The STOP-BANG score is a simple tool that evaluates the risk of OSA and can be added to the large number of clinical variables and scores obtained during the management of myocardial infarction (MI) patients. Currently, machine learning (ML) is able to select and integrate numerous variables to optimize prediction tasks.
Research question
Can the integration of STOP-BANG score with clinical data and scores through ML better identify patients who suffered an in-hospital cardiovascular event after acute MI?
Study design and methods
This is a prospective observational cohort study of 124 acute MI patients in which the STOP-BANG score classified 34 low-(27.4%), 30 intermediate-(24.2%), and 60 high-(48.4%) OSA-risk patients who were followed during hospitalization. ML implemented feature selection and integration across 47 variables (including STOP-BANG score, Killip-class, GRACE score and LVEF) to identify those patients who developed an in-hospital cardiovascular event (i.e. death, ventricular arrhythmias, atrial fibrillation, recurrent angina, re-infarction, stroke, worsening heart failure or cardiogenic shock) after definitive MI treatment. ROC curves were used to compare ML performance against STOP-BANG, Killip-class, GRACE and LVEF, independently.
Results
There was an increasing proportion of cardiovascular events across the low-, intermediate- and high-OSA-risk groups (p=0.005). ML selected 7 accessible variables (i.e. Killip-class, leukocytes, GRACE score, CRP, oxygen saturation, STOP-BANG score and NT-proBNP) and their integration outperformed all comparators (AUC=0.83 [0.74, 0.90], p<0.01).
Interpretation
The integration of the STOP-BANG score into clinical evaluation (considering Killip-class, GRACE score and simple laboratory values) of subjects admitted for an acute MI through ML can significantly optimize the identification of patients who will present an in-hospital cardiovascular event.

Copyright © 2020. Published by Elsevier Inc.

Chest: 24 Apr 2020; epub ahead of print
Calvillo-Argüelles O, Sierra-Fernández CR, Padilla-Ibarra J, Rodriguez-Zanella H, ... van der Harst P, Juarez-Orozco LE
Chest: 24 Apr 2020; epub ahead of print | PMID: 32343966
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Abstract

Ablation at Right Coronary Cusp as an Alternative and Favorable Approach to Eliminate Premature Ventricular Complexes Originating from the Proximal Left Anterior Fascicle.

Chen S, Lu X, Peng S, Xue Y, ... Ouyang F, Liu S

- Premature ventricular complexes (PVC) with narrow QRS duration originating from proximal left anterior fascicle (LAF) is challenging for ablation. This study was performed to evaluate the safety and feasibility of ablation from right coronary sinus (RCC) for proximal LAF-PVC and to investigate this PVC\'s characteristics.- Mapping at RCC and left ventricle and electrocardiogram analysis were performed in 20 patients with LAF-PVC.- The earliest activation site (EAS), with Purkinje-potential during both PVC and sinus rhythm (SR), was localized at proximal LAF in 8 patients (proximal-group) and at non-proximal LAF in 12 patients (non-proximal-group). The Purkinje-potentials preceding PVC-QRS at the EAS in proximal-group (32.6±2.5ms) was significantly earlier than that in non-proximal-group (28.3±4.5ms, P=0.025). Similar difference in the Purkinje-potentials preceding SR-QRS at the EAS was also observed between proximal and non-proximal-group (35.1±4.7ms vs. 25.2±5.0ms, P<0.001). In proximal-group, the distance between the EAS to left His-bundle and to RCC were shorter than that of non-proximal-group (12.3±2.8mm vs. 19.7±5.0mm, P=0.002; and 3.9±0.8mm vs. 15.7±7.8, P<0.001, respectively). No difference in the distance from RCC to proximal LAF was identified between the two groups. PVCs were successfully eliminated from RCC for all proximal-group but at left ventricular EAS for non-proximal-group. The radiofrequency application times, ablation time and procedure time of non-proximal-group were longer than that of proximal-group. Electrocardiographic analysis showed that, when compared to non-proximal-group, the PVCs of proximal-group had narrower QRS duration; smaller S-wave in lead I, V5 and V6; lower R-wave in lead I, aVR, aVL, V1, V2 and V4; and smaller q-wave in lead III and aVF. The QRS duration difference (PVC-QRS and SR-QRS) <15ms predicted the proximal LAF origin with high sensitivity and specificity.- PVCs originating from proximal LAF, with unique electrocardiographic characteristics, could be eliminated safely from RCC.



Circ Arrhythm Electrophysiol: 16 Apr 2020; epub ahead of print
Chen S, Lu X, Peng S, Xue Y, ... Ouyang F, Liu S
Circ Arrhythm Electrophysiol: 16 Apr 2020; epub ahead of print | PMID: 32302210
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Impact:
Abstract

The prognostic importance of right ventricular remodeling and the circadian blood pressure pattern on the long-term cardiovascular outcome.

Tadic M, Cuspidi C, Celic V, Petrovic O, ... Grassi G, Ivanovic B
Objective
We sought to investigate the predictive value of right ventricular (RV) remodeling and 24-h blood pressure (BP) patterns on long-term cardiovascular prognosis in the initially untreated hypertensive patients.
Methods
The current study included 505 initially untreated hypertensive patients who were consequently included in this study from 2007 to 2012. All the patients underwent laboratory analysis, 24-h BP monitoring and echocardiographic examination at baseline. The patients were followed for a median period of 9 years. The adverse outcome was defined as the hospitalization due to cardiovascular events (atrial fibrillation, myocardial infarction, myocardial revascularization, heart failure, stroke, or cardiovascular death).
Results
During the 9-year follow-up period adverse cardiovascular events occurred in 82 hypertensive patients. Night-time SBP, the nondipping BP pattern, left ventricle hypertrophy, RV hypertrophy, right atrial enlargement, RV diastolic dysfunction, and RV systolic dysfunction were associated with adverse cardiovascular events. Nevertheless, night-time SBP, the nondipping BP pattern, mitral E/e\', left ventricle hypertrophy, and RV hypertrophy were the only independent predictors of cardiovascular events. When all four BP patterns were included in the model, only the reverse dipping BP pattern was an independent predictor of cardiovascular events.
Conclusion
The present investigation showed that RV hypertrophy and the reverse dipping BP pattern were independent long-term predictors of the cardiovascular outcome. Detailed echocardiographic evaluation and 24-h ambulatory blood pressure monitoring should be performed even in low-risk hypertensive patients.



J Hypertens: 03 May 2020; epub ahead of print
Tadic M, Cuspidi C, Celic V, Petrovic O, ... Grassi G, Ivanovic B
J Hypertens: 03 May 2020; epub ahead of print | PMID: 32371765
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Impact:
Abstract

The Year in Review in Cardiac Electrophysiology.

Kapa S, Chung MK, Gopinathannair R, Noseworthy PA, ... Wan E, Wang PJ

In the past year there have been numerous advances in our understanding of arrhythmia mechanisms, diagnosis, and new therapies. We have seen advances in basic cardiac electrophysiology with data suggesting that secretoneurin may be a biomarker for patients at risk of ventricular arrhythmias and we have learned of the potential role of a natriuretic peptide receptor-C in atrial fibrosis and the role of an atrial specific two-pore potassium channel TASK-1 as a therapeutic target for atrial fibrillation. We have seen studies demonstrating role of sensory neurons in sleep apnea-related atrial fibrillation and the association between bariatric surgery and atrial fibrillation ablation outcomes. Artificial intelligence applied to electrocardiography has yielded estimates of age, gender, and overall health. We have seen new tools for collection of patient-centered outcomes following catheter ablation. There have been significant advances in the ability to identify ventricular tachycardia termination sites through high-density mapping of deceleration zones. We have learned that right ventricular dysfunction may be a predictor of survival benefit after ICD implantation in non-ischemic cardiomyopathy patients. We have seen further insights into the role of His bundle pacing on improving outcomes. As our understanding of cardiac laminopathies advance, we may have new tools to predict arrhythmic event rates in gene carriers. Finally, we have seen numerous advances in the treatment of arrhythmias in patients with congenital heart disease.



Circ Arrhythm Electrophysiol: 17 May 2020; epub ahead of print
Kapa S, Chung MK, Gopinathannair R, Noseworthy PA, ... Wan E, Wang PJ
Circ Arrhythm Electrophysiol: 17 May 2020; epub ahead of print | PMID: 32423252
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Impact:
Abstract

Pulsed-Field Ablation Using a Lattice Electrode for Focal Energy Delivery: Biophysical Characterization, Lesion Durability and Safety Evaluation.

Yavin H, Shapira-Daniels A, Barkagan M, Sroubek J, ... Melidone R, Anter E

- Pulsed field ablation (PFA) is a nonthermal energy that may provide safety advantages over radiofrequency ablation (RFA). One-shot PFA catheters have been developed for pulmonary vein isolation, but they do not permit flexible lesion sets. This study investigated a novel lattice-tip catheter designed for focal RFA or PFA ablation.- The effects of PFA (biphasic, 24 amperes) were investigated in 25 swine using a lattice-tip catheter and system (Affera Inc). Step 1 (n=14) examined the feasibility to create atrial line of block and described its acute effects on the phrenic nerve and esophagus. Step 2 (n=7) examined the subacute effects of PFA on block durability, phrenic nerve and esophagus ≥2 weeks. Step 3 compared the effects of PFA and RFA on the esophagus using a mechanical deviation model approximating the esophagus to the right atrium (n=4) and by direct ablation within its lumen (n=4). The effects of endocardial PFA and RFA on the phrenic nerve were also compared (n=10). Histological analysis was performed.- PFA produced acute block in 100% of lines, achieved with 2.1 (1.3-3.2) applications/cm-line. Histological analysis following [35 (18-37)] days showed 100% transmurality (thickness range 0.4-3.4 mm) with a lesion width of 19.4 (10.9-27.4 mm). PFA selectively affected cardiomyocytes but spared blood vessels and nervous tissue. PFA applied from the posterior atria [23 (21-25) applications] to the approximated esophagus [6 (4.5-14) mm] produced transmural lesions without esophageal injury. PFA [16.5 (15-18) applications)] applied inside the esophageal lumen produced mild edema compared to RFA [13 (12-14) applications] which produced epithelial ulcerations. PFA resulted in no or transient stunning of the phrenic nerve (<5min) without histological changes while RFA produced paralysis.- PFA using a lattice-tip ablation catheter for focal ablation produced durable atrial lesions and showed lower vulnerability to esophageal or phrenic nerve damage compared to RFA.



Circ Arrhythm Electrophysiol: 05 May 2020; epub ahead of print
Yavin H, Shapira-Daniels A, Barkagan M, Sroubek J, ... Melidone R, Anter E
Circ Arrhythm Electrophysiol: 05 May 2020; epub ahead of print | PMID: 32372696
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Impact:
Abstract

Continuous electrocardiography for detecting atrial fibrillation beyond 1 year after stroke in primary care.

Lyckhage LF, Hansen ML, Toft JC, Larsen SL, ... Ali AM, Wienecke T
Background and purpose
The diagnostic benefit of using continuous ECG (cECG) for poststroke atrial fibrillation (AF) screening in a primary care setting is unclear. We aimed to assess the diagnostic yield from screening patients who previously had a stroke with a 7-day Holter monitor.
Methods
Patients older than 49 years, naive to AF, with an ischaemic stroke over 1 year before enrolment were included. In a primary care setting, all patients were screened for AF using pulse palpation, 12-lead ECG and 7-day Holter monitoring. Further, NT-proBNP was determined at baseline.
Results
7-day Holter monitoring uncovered AF in 17 of 366 patients (4.6% (95% CI 2.7 to 7.3)). The number needed to screen was 22 patients (14-37). 12-lead ECG uncovered AF in 3 patients (0.82% (95% CI 0.17 to 2.4)), and 122 patients had irregular pulse during pulse palpation (33.5% (95% CI 28.7 to 38.2)). When using 7-day Holter monitoring as reference standard, the sensitivity of pulse palpation and 12-lead ECG was 47% (95% CI 23% to 72%) and 18% (95% CI 4% to 43%). High levels (≥400 pg/mL) of NT-proBNP versus low levels (≤200 pg/mL) were not associated with AF in the univariate analysis nor when adjusted for age (OR 2.4 (95% CI 0.5 to 8.4) and 1.6 (95% CI 0.3 to 6.0)).
Conclusions
A relevant proportion of patients with stroke more than 1 year before inclusion were diagnosed with AF through 7-day Holter monitoring. Given the low sensitivities of pulse palpation and 12-lead ECG, additional cECG may be considered during poststroke primary care follow-up.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 02 Jul 2020; epub ahead of print
Lyckhage LF, Hansen ML, Toft JC, Larsen SL, ... Ali AM, Wienecke T
Heart: 02 Jul 2020; epub ahead of print | PMID: 32620555
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Impact:
Abstract

Remote Management of Pacemaker Patients with Biennial In-clinic Evaluation: Continuous Home Monitoring in the Japanese At Home Study - A Randomized Clinical Trial.

Watanabe E, Yamazaki F, Goto T, Asai T, ... Varma N, Ando K

- Current expert consensus recommends remote monitoring (RM) for cardiac implantable electronic devices, with at least annual in-office follow-up. We studied safety and resource consumption of exclusive remote follow-up (RFU) in pacemaker patients for two years.- In Japan, consecutive pacemaker patients committed to RM were randomized to either RFU or conventional in-office follow-up (CFU) at twice-yearly intervals. RFU patients were only seen if indicated by remote monitoring. All returned to hospital after two years. The primary endpoint was a composite of death, stroke, or cardiovascular events requiring surgery, and the primary hypothesis was non-inferiority with 5% margin.- Of 1274 randomized patients (50.4% female, age 77±10 years), 558 (RFU) and 550 (CFU) patients reached either the primary endpoint or 24 months follow-up. The primary endpoint occurred in 10.9% and 11.8%, resp. (P=0.0012 for non-inferiority). The median (IQR) number of in-office follow-ups was 0.50 (0.50 - 0.63) in RFU and 2.01 (1.93 - 2.05) in CFU per patient-year (P<0.001). Insurance claims for follow-ups and directly related diagnostic procedures were 18,800 Yen (16,500 - 20,700 Yen) in RFU and 21,400 Yen (16,700 - 25,900 Yen) in CFU (P<0.001). Only 1.4% of remote follow-ups triggered an unscheduled in-office follow-up, and only 1.5% of scheduled in-office follow-ups were considered actionable.- Replacing periodic in-office follow-ups with remote follow-ups for 2 years in pacemaker patients committed to RM does not increase the occurrence of major cardiovascular events and reduces resource consumption.- The trial was registered at https://clinicaltrials.gov; Unique Identifier: NCT01523704.



Circ Arrhythm Electrophysiol: 27 Apr 2020; epub ahead of print
Watanabe E, Yamazaki F, Goto T, Asai T, ... Varma N, Ando K
Circ Arrhythm Electrophysiol: 27 Apr 2020; epub ahead of print | PMID: 32342703
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Abstract

The Effect of Chloroquine, Hydroxychloroquine and Azithromycin on the Corrected QT Interval in Patients with SARS-CoV-2 Infection.

Saleh M, Gabriels J, Chang D, Kim BS, ... Mountantonakis S, Epstein LM

- The novel SARs-CoV-2 coronavirus is responsible for the global COVID-19 pandemic. Small studies have shown a potential benefit of chloroquine/hydroxychloroquine ± azithromycin for the treatment of COVID-19. Use of these medications alone, or in combination, can lead to a prolongation of the QT interval, possibly increasing the risk of Torsade de pointes (TdP) and sudden cardiac death.- Hospitalized patients treated with chloroquine/hydroxychloroquine ± azithromycin from March 1st through the 23rd at three hospitals within the Northwell Health system were included in this prospective, observational study. Serial assessments of the QT interval were performed. The primary outcome was QT prolongation resulting in TdP. Secondary outcomes included QT prolongation, the need to prematurely discontinue any of the medications due to QT prolongation and arrhythmogenic death.- Two hundred one patients were treated for COVID-19 with chloroquine/hydroxychloroquine. Ten patients (5.0%) received chloroquine, 191 (95.0%) received hydroxychloroquine and 119 (59.2%) also received azithromycin. The primary outcome of TdP was not observed in the entire population. Baseline QTc intervals did not differ between patients treated with chloroquine/hydroxychloroquine (monotherapy group) vs. those treated with combination group (chloroquine/hydroxychloroquine and azithromycin) (440.6 ± 24.9 ms vs. 439.9 ± 24.7 ms, p =0.834). The maximum QTc during treatment was significantly longer in the combination group vs the monotherapy group (470.4 ± 45.0 ms vs. 453.3 ± 37.0 ms, p = 0.004). Seven patients (3.5%) required discontinuation of these medications due to QTc prolongation. No arrhythmogenic deaths were reported.- In the largest reported cohort of COVID-19 patients to date treated with chloroquine/hydroxychloroquine {plus minus} azithromycin, no instances of TdP or arrhythmogenic death were reported. Although use of these medications resulted in QT prolongation, clinicians seldomly needed to discontinue therapy. Further study of the need for QT interval monitoring is needed before final recommendations can be made.



Circ Arrhythm Electrophysiol: 28 Apr 2020; epub ahead of print
Saleh M, Gabriels J, Chang D, Kim BS, ... Mountantonakis S, Epstein LM
Circ Arrhythm Electrophysiol: 28 Apr 2020; epub ahead of print | PMID: 32347743
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Abstract

Focal Pulsed Field Ablation for Pulmonary Vein Isolation and Linear Atrial Lesions: A Preclinical Assessment of Safety and Durability.

Koruth J, Kuroki K, Kawamura I, Stoffregen WC, ... Neuzil P, Reddy VY

- A novel ablation and mapping system can toggle between delivering biphasic pulsed field (PF) and radiofrequency (RF) energy from a 9mm lattice-tip catheter. We assessed the preclinical feasibility and safety of: i) focal PF-based thoracic vein (TV) isolation and linear ablation, ii) combined PF and RF focal ablation, and iii) PF delivered directly atop the esophagus.- Two cohorts of 6 swine were treated with pulsed fields at low-dose (PF) and high-dose (PF) and followed for 4 and 2 weeks, respectively, to isolate 25 TVs and create 5 right atrial (PF), 6 mitral (PF) and 6 roof lines (RF+PF). Baseline and follow-up voltage mapping, venous potentials, ostial diameters and phrenic nerve viability were assessed. PF and RF lesions were delivered in 4 and 1 swine from the inferior vena cava onto a forcefully deviated esophagus. All tissues were submitted for histopathology.- 100% of TVs (25/25) were successfully isolated with 12.4±3.6 applications/vein with mean PF times of <90 seconds/vein. Durable isolation improved from 61.5 % PF to 100 % with PF (p=0.04), and all linear lesions were successfully completed without incurring venous stenoses or phrenic injury. PF sections had higher transmurality rates than PF (98.3 vs 88.1%; p=0.03) despite greater mean thickness (2.51.3 mm; p<0.001). PF lesions demonstrated homogenous fibrosis without epicardial fat, nerve or vessel involvement. In comparison, RF+PF sections revealed similar transmurality, but expectedly more necrosis, inflammation and epicardial fat, nerve and vessel involvement. Significant ablation-related esophageal necrosis, inflammation and fibrosis were seen in all RF sections, as compared to no PF sections.- The lattice-tip catheter can deliver focal PF to durably isolate veins and create linear lesions with excellent transmurality and without complications. The PF lesions did not damage the phrenic nerve, vessels and the esophagus.



Circ Arrhythm Electrophysiol: 05 May 2020; epub ahead of print
Koruth J, Kuroki K, Kawamura I, Stoffregen WC, ... Neuzil P, Reddy VY
Circ Arrhythm Electrophysiol: 05 May 2020; epub ahead of print | PMID: 32370542
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Abstract

Prediction of mortality from 12-lead electrocardiogram voltage data using a deep neural network.

Raghunath S, Ulloa Cerna AE, Jing L, vanMaanen DP, ... Haggerty CM, Fornwalt BK

The electrocardiogram (ECG) is a widely used medical test, consisting of voltage versus time traces collected from surface recordings over the heart. Here we hypothesized that a deep neural network (DNN) can predict an important future clinical event, 1-year all-cause mortality, from ECG voltage-time traces. By using ECGs collected over a 34-year period in a large regional health system, we trained a DNN with 1,169,662 12-lead resting ECGs obtained from 253,397 patients, in which 99,371 events occurred. The model achieved an area under the curve (AUC) of 0.88 on a held-out test set of 168,914 patients, in which 14,207 events occurred. Even within the large subset of patients (n = 45,285) with ECGs interpreted as \'normal\' by a physician, the performance of the model in predicting 1-year mortality remained high (AUC = 0.85). A blinded survey of cardiologists demonstrated that many of the discriminating features of these normal ECGs were not apparent to expert reviewers. Finally, a Cox proportional-hazard model revealed a hazard ratio of 9.5 (P < 0.005) for the two predicted groups (dead versus alive 1 year after ECG) over a 25-year follow-up period. These results show that deep learning can add substantial prognostic information to the interpretation of 12-lead resting ECGs, even in cases that are interpreted as normal by physicians.



Nat Med: 10 May 2020; epub ahead of print
Raghunath S, Ulloa Cerna AE, Jing L, vanMaanen DP, ... Haggerty CM, Fornwalt BK
Nat Med: 10 May 2020; epub ahead of print | PMID: 32393799
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Abstract

Prevalence of primary aldosteronism and association with cardiovascular complications in patients with resistant and refractory hypertension.

Parasiliti-Caprino M, Lopez C, Prencipe N, Lucatello B, ... Benso A, Maccario M
Objectives
To assess the prevalence of primary aldosteronism and its association with cardiometabolic complications in patients with resistant and refractory hypertension.
Methods
One hundred and ten consecutive patients with true resistant hypertension [insufficient blood pressure control despite appropriate lifestyle measures and treatment with at least three classes of antihypertensive medication, including a diuretic] and without previous cardiovascular events were screened for secondary hypertension. Refractory hypertension was diagnosed in case of uncontrolled blood pressure despite the use of at least five antihypertensive drugs.
Results
Primary aldosteronism was diagnosed in 32 cases (29.1%). The multivariate analysis showed that primary aldosteronism is a strong factor positively associated with left ventricular hypertrophy [odds ratio (OR) = 12.98, 95% confidence interval (CI) 3.82-60.88; P < 0.001], microalbuminuria (OR = 3.67, 95% CI 1.44-9.78; P = 0.007), carotid intima-media thickness at least 0.9 mm (OR = 2.69, 95% CI 1.02-7.82; P = 0.037), aortic ectasia (OR = 4.08, 95% CI 1,18-15.04; P = 0.027) and atrial fibrillation (OR 8.80, 95% CI 1.53-73.98; P = 0.022). Moreover, primary aldosteronism was independently associated with the presence of at least one (OR = 8.60, 95% CI 1.73-69.88; P = 0.018) and at least two types of organ damage (OR = 3.08, 95% CI 1.19-8.24; P = 0.022). Thirteen patients (11.8%) were affected by refractory hypertension. This group was characterized by significantly higher values of carotid intima-media thickness, higher rate of aldosterone-producing adenoma and atrial fibrillation, compared with the other individuals with resistant hypertension.
Conclusion
The current study indicates that primary aldosteronism is a frequent cause of secondary hypertension and cardiovascular complications among patients with resistant and refractory hypertension, suggesting a crucial role of aldosterone in the pathogenesis of severe hypertensive phenotypes and cardiovascular disease.



J Hypertens: 06 May 2020; epub ahead of print
Parasiliti-Caprino M, Lopez C, Prencipe N, Lucatello B, ... Benso A, Maccario M
J Hypertens: 06 May 2020; epub ahead of print | PMID: 32384388
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Abstract

Ablation of Reentry-Vulnerable-Zones Determined by Left Ventricular Activation from Multiple Directions: A Novel Approach for Ventricular Tachycardia Ablation: A Multicenter Study (PHYSIO-VT).

Anter E, Neuzil P, Reddy VY, Petru J, ... Shen C, Wit AL

- The optimal method to identify the arrhythmogenic substrate of scar-related VT is unknown. Sites of activation slowing during sinus rhythm (SR) often co-localize with the VT circuit. However, the utility and limitations of such approach for guiding ablation is unknown.- We conducted a multicenter study in patients with infarct-related VT. The LV was mapped during activation from 3 directions: SR (or atrial pacing), right ventricular (RV) and left ventricular (LV) pacing at 600 msec. Ablation was applied selectively to the cumulative area of slow activation, defined as the sum of all regions with activation times of ≥40 msec per 10mm. Hemodynamically tolerated VTs were mapped with activation or entrainment. The primary outcome was a composite of appropriate ICD therapies and cardiovascular death.- In 85 patients, the LV was mapped during activation from 2.4±0.6 directions. The direction of LV activation influenced the location and magnitude of activation slowing. The spatial overlap of activation slowing between SR and RV pacing was 84.2%±7.1%, between SR and LV pacing was 61.4%±8.8%, and between RV and LV pacing was 71.3%±9.6% (P<0.05 between all comparisons). Mapping during SR identified only 66.2%±8.2% of the entire area of activation slowing and 58% critical isthmus sites. Activation from other directions by RV and LV stimulation unmasked an additional 33% of slowly conducting zones and 25% critical isthmus sites. The area of maximal activation slowing often corresponded to the site where the wavefront first interacted with the infarct. During a follow-up period of 3.6 years, the primary endpoint occurred in 14/85 (16.5%) patients.- The spatial distribution of activation slowing is dependent on the direction of LV activation with the area of maximal slowing corresponding to the site where the wavefront first interacts with the infarct. This data may have implications for VT substrate mapping strategies.



Circ Arrhythm Electrophysiol: 05 May 2020; epub ahead of print
Anter E, Neuzil P, Reddy VY, Petru J, ... Shen C, Wit AL
Circ Arrhythm Electrophysiol: 05 May 2020; epub ahead of print | PMID: 32372657
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Abstract

Direct-Acting Oral Anticoagulants Versus Warfarin in Medicare Patients With Chronic Kidney Disease and Atrial Fibrillation.

Wetmore JB, Roetker NS, Yan H, Reyes JL, Herzog CA
Background and purpose
The comparative effectiveness of direct-acting oral anticoagulants, compared with warfarin, for risks of stroke/systemic embolism, major bleeding, or death have not been studied in Medicare beneficiaries with atrial fibrillation and nondialysis-dependent chronic kidney disease.
Methods
Medicare data from 2011 to 2017 were used to identify patients with stages 3, 4, or 5 chronic kidney disease and new atrial fibrillation who received a new prescription for warfarin, apixaban, rivaroxaban, or dabigatran. We estimated marginal hazard ratios with 95% CIs for the association of each direct-acting oral anticoagulant, compared with warfarin, for the outcomes of interest using inverse-probability-of-treatment weighted Cox proportional hazards models in as-treated and intention-to-treat analyses.
Results
A total of 22 739 individuals met criteria (46.3% warfarin, 29.6% apixaban, 17.2% rivaroxaban, 6.9% dabigatran). Across the groups of anticoagulant users, mean age was 78.4 to 79.0 years; 50.3% to 51.4% were women, and 80.3% to 82.8% had stage 3 chronic kidney disease. In the as-treated analysis, for stroke/systemic embolism, hazard ratios, all compared with warfarin, were 0.70 (0.51-0.96) for apixaban, 0.80 (0.54-1.17) for rivaroxaban, and 1.15 (0.69-1.94) for dabigatran. For major bleeding, analogous hazard ratios were 0.47 (0.37-0.59) for apixaban, 1.05 (0.85-1.30) for rivaroxaban, and 0.95 (0.70-1.31) for dabigatran. There was no difference in the risk of all-cause mortality between the direct-acting oral anticoagulants and warfarin. Results of the intention-to-treat analysis were similar.
Conclusions
Apixaban, compared with warfarin, was associated with decreased risk of stroke/systemic embolism and major bleeding; risks for both outcomes with rivaroxaban and dabigatran did not differ from risks with warfarin.



Stroke: 08 Jul 2020:STROKEAHA120028934; epub ahead of print
Wetmore JB, Roetker NS, Yan H, Reyes JL, Herzog CA
Stroke: 08 Jul 2020:STROKEAHA120028934; epub ahead of print | PMID: 32640949
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Abstract

Prevalence and Outcome of Potential Candidates for Left Atrial Appendage Closure After Stroke With Atrial Fibrillation: WATCH-AF Registry.

Ong E, Meseguer E, Guidoux C, Lavallée PC, ... Nighoghossian N, Amarenco P
Background and purpose
As a result of contraindications (eg, frailty, cognitive impairment, comorbidities) or patient refusal, many patients with stroke and atrial fibrillation cannot be discharged on oral anticoagulant. Among them, the proportion of potential candidates for left atrial appendage closure (LAAC) and their 12-month outcome is not well known.
Methods
The prospective WATCH-AF registry (Warfarin Aspirin Ten-A Inhibitors and Cerebral Infarction and Hemorrhage and Atrial Fibrillation) enrolled consecutive patients admitted within 72 hours of an acute stroke associated with atrial fibrillation in 2 stroke centers. Scales to evaluate stroke severity, disability, functional independence, risk of fall, cognition, ischemic and hemorrhagic risk-stratification, and comorbidities were systematically collected at admission, discharge, 3, 12 months poststroke. The 2 main end points were death or dependency (modified Rankin Scale score >3) and recurrent stroke (brain infarction and brain hemorrhage).
Results
Among 400 enrolled patients (370 with brain infarction, 30 with brain hemorrhage), 31 died before discharge and 57 (14.3%) were possible European Heart Rhythm Association/European Society of Cardiology and American Heart Association/American College of Cardiology/Heart Rhythm Society candidates for LAAC. At 12 months, the rate of death or dependency was 17.9%, and the rate of stroke recurrence was 9.8% in the 274/400 (68.5%) patients discharged on a long-term oral anticoagulant strategy, as compared with 17.5% and 24.7%, respectively, in 57 patients candidate for LAAC. As compared with patients on a long-term oral anticoagulant strategy, there was a 2-fold increase in the risk of stroke recurrence in the group with an indication for LAAC (adjusted hazard ratio, 2.58 [95% CI, 1.40-4.76]; P=0.002).
Conclusions
Fourteen percent of patients with stroke associated with atrial fibrillation were potential candidates for LAAC. The 12-month stroke risk of these candidates was 3-fold the risk of anticoagulated patients.



Stroke: 08 Jul 2020:STROKEAHA120029267; epub ahead of print
Ong E, Meseguer E, Guidoux C, Lavallée PC, ... Nighoghossian N, Amarenco P
Stroke: 08 Jul 2020:STROKEAHA120029267; epub ahead of print | PMID: 32640939
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Abstract

A Lattice-Tip Focal Ablation Catheter that Toggles Between Radiofrequency and Pulsed Field Energy to Treat Atrial Fibrillation: A First-in-Human Trial.

Reddy VY, Anter E, Rackauskas G, Peichl P, ... Kautzner J, Neuzil P

- The tissue selectivity of pulsed field ablation (PFA) provides safety advantages over radiofrequency ablation (RFA) in treating atrial fibrillation (AF). \"One-shot\" PFA catheters have been shown capable of performing pulmonary vein isolation (PVI), but not flexible lesion sets such as linear lesions. A novel lattice-tip ablation catheter with a compressible 9-mm nitinol tip is able to deliver either focal RFA or PFA lesions, each in 2-5 seconds.- In a 3-center, single-arm, first-in-human trial, the 7.5-French lattice catheter was used with a custom mapping system to treat paroxysmal or persistent AF. Toggling between energy sources, point-by-point PV encirclement was performed using biphasic PFA posteriorly, and either temperature-controlled irrigated RFA or PFA anteriorly (RF/PF or PF/PF, respectively). Linear lesions were created using either PFA or RFA.- The 76-patient cohort included 55 paroxysmal and 21 persistent AF patients undergoing either RF/PF (40 patients) or PF/PF (36 patients) ablation. The PVI therapy duration time (transpiring from first to last lesion) was 22.6±8.3 min/patient, with a mean of 50.1 RF/PF lesions/patient. Linear lesions included 14 mitral (4 RF / 2 RF+PF / 8 PF), 34 LA roof (12 RF / 22 PF) and 44 CTI (36 RF / 8 PF) lines, with therapy duration times of 5.1±3.5, 1.8±2.3 and 2.4±2.1 min/patient, respectively. All lesion sets were acutely successful, using 4.7±3.5 min of fluoroscopy. There were no device-related complications, including no strokes. Post-procedure esophagogastroduodenoscopy revealed minor mucosal thermal injury in 2 of 36 RF/PF and 0 of 24 PF/PF patients. Post-procedure brain MRI revealed DWI+/FLAIR- and DWI+/FLAIR+ asymptomatic lesions in 5 and 3 of 51 patients, respectively.- A novel lattice-tip catheter could safely and rapidly ablate AF using either a combined RF/PF approach (capitalizing on the safety of PFA and the years of experience with radiofrequency energy) or an entirely PF approach.



Circ Arrhythm Electrophysiol: 07 May 2020; epub ahead of print
Reddy VY, Anter E, Rackauskas G, Peichl P, ... Kautzner J, Neuzil P
Circ Arrhythm Electrophysiol: 07 May 2020; epub ahead of print | PMID: 32383391
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Abstract

Triggered Ca2+ Waves Induce Depolarization of Maximum Diastolic Potential and Action Potential Prolongation in Dog Atrial Myocytes.

Gussak G, Marszalec W, Yoo S, Modi R, ... Burrell AR, Wasserstrom JA

- We have identified a novel form of abnormal Ca2+ wave activity in normal and failing dog atrial myocytes which occurs during the action potential (AP) and is absent during diastole. The goal of this study was to determine if triggered Ca2+ waves affect cellular electrophysiological properties.- Simultaneous recordings of intracellular Ca2+ and APs allowed measurements of maximum diastolic potential (MDP) and AP duration (APD) during TCWs in isolated dog atrial myocytes. Computer simulations then explored electrophysiological behavior arising from TCWs at the tissue scale.- At 3.3-5hz, TCWs occurred during the AP and often outlasted several AP cycles. MDP was reduced and APD was significantly prolonged during TCWs. All electrophysiological responses to TCWs were abolished by SEA0400 and ORM10103, indicating that Na-Ca exchange current caused depolarization. The time constant of recovery from inactivation of Ca2+ current was 40-70ms in atrial myocytes (depending on holding potential) so this current could be responsible for AP activation during depolarization induced by TCWs. Modeling studies demonstrated that the characteristic properties of TCWs are potentially arrhythmogenic by promoting both conduction block and reentry arising from the depolarization induced by TCWs.- Triggered Ca2+ waves activate inward NCX and dramatically reduce atrial MDP and prolong APD, establishing the substrate for reentry which could contribute to the initiation and/or maintenance of atrial arrhythmias.



Circ Arrhythm Electrophysiol: 19 May 2020; epub ahead of print
Gussak G, Marszalec W, Yoo S, Modi R, ... Burrell AR, Wasserstrom JA
Circ Arrhythm Electrophysiol: 19 May 2020; epub ahead of print | PMID: 32433891
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