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Background: Neuropsychiatric side effects of cardiac drugs such as nervousness, mood swings and agitation may be misinterpreted as symptoms of anxiety. Anxiety in cardiac patients is highly prevalent and associated with poor outcomes, thus an accurate identification is essential. The objectives were to: (I) describe the possible neuropsychiatric side effects of common cardiac drug therapies, (II) describe the use of cardiac drug therapy in cardiac patients with self-reported symptoms of anxiety compared to those with no symptoms of anxiety, and (III) investigate the association between the use of cardiac drug therapy and self-reported symptoms of anxiety., Methods: DenHeart is a large national cross-sectional survey combined with national register data. Symptoms of anxiety were measured by the Hospital Anxiety and Depression Scale (HADS-A) on patients with ischemic heart disease, arrhythmia, heart failure and heart valve disease. Side effects were obtained from 'product summaries', and data on redeemed prescriptions obtained from the Danish National Prescription Registry. Multivariate logistic regression analyses explored the association between cardiac drug therapies and symptoms of anxiety (HADS-A ≥ 8)., Results: Among 8998 respondents 2891 (32%) reported symptoms of anxiety (HADS-A ≥ 8). Neuropsychiatric side effects were reported from digoxin, antiarrhythmics, beta-blockers, ACE-inhibitors and angiotensin receptor antagonists. Statistically significant higher odds of reporting HADS ≥ 8 was found in users of diuretics, lipid-lowering agents, nitrates, antiarrhythmics and beta-blockers compared to patients with no prescription., Conclusion: Some cardiac drugs were associated with self-reported symptoms of anxiety among patients with cardiac disease. Of these drugs neuropsychiatric side effects were only reported for antiarrhythmics and beta-blockers. Increased awareness about the possible adverse effects from these drugs are important., (© 2022. The Author(s).)

Ventricular arrhythmia (VA) is a leading cause of sudden death and health deterioration. Recent advances in predictive analytics and wearable technology for behavior assessment show promise but require further investigation. Yet, previous studies have only assessed other health outcomes and monitored patients for short durations (7−14 days). This study explores how behaviors reported by a consumer wearable can assist VA risk prediction. An exploratory observational study was conducted with participants who had an implantable cardioverter-defibrillator (ICD) and wore a Fitbit Alta HR consumer wearable. Fitbit reported behavioral markers for physical activity (light, fair, vigorous), sleep, and heart rate. A case-crossover analysis using conditional logistic regression assessed the effects of time-adjusted behaviors over 1−8 weeks on VA incidence. Twenty-seven patients (25 males, median age 59 years) were included. Among the participants, ICDs recorded 262 VA events during 8093 days monitored by Fitbit (median follow-up period 960 days). Longer light to fair activity durations and a higher heart rate increased the odds of a VA event (p < 0.001). In contrast, lengthier fair to vigorous activity and sleep durations decreased the odds of a VA event (p < 0.001). Future studies using consumer wearables in a larger population should prioritize these outcomes to further assess VA risk.

As pulmonary arterial hypertension (PAH) progress, arrhythmias are becoming an increasingly prominent phenomenon. Supraventricular tachycardias have been shown to have an incidence of up to 35% in pulmonary hypertension.Continuous cardiac monitoring was deployed in a patient with severe PAH 100 days before bilateral lung transplantation (BLTX). Despite being graded as WHO functional class IV, no arrhythmias were observed before BLTX. Furthermore, the case describes clinical improvement, along with a significant increase in heart rate variability (HRV) and decrease in night-time heart rate in the post-transplantation period.No arrhythmias were observed preoperatively during continuous monitoring in a 100-day period despite the patient's intrinsically high risk for arrhythmias. Increasing HRV and lower resting heart rate were observed after BLTX. Since these parameters correlate with the clinical condition, they might be valuable in risk assessment in patients with pulmonary hypertension., Competing Interests: Competing interests: SD is a part-time employee of Vital Beats, not related to this work. JHS is a member of an advisory board for Medtronic, has received research grant and speaker fee from Medtronic unrelated to this study and has received research grant from Gilead unrelated to this research project. JC is a member of an advisory board for Janssen, and the institution has received research grants and speaker fees. In the same way for United Therapeutics for clinical trials and Astra Zeneca and Ferrer for speaker fees., (© BMJ Publishing Group Limited 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Elderly individuals occupy an increasing part of the general population. Conventional and speckle-tracking transthoracic echocardiography may help guide risk stratification in these individuals. The purpose of this study was to evaluate the potential utility of conventional and speckle-tracking echocardiography in the screening of cardiac abnormalities in the elderly population., Methods: Two cohorts of elderly individuals (sample size: 1441 and 944) were analyzed, who were part of a randomized controlled clinical trial (LOOP study) and of an observational study (Copenhagen City Heart Study), recruiting participants from the general population >70 years of age with cardiovascular risk factors (arterial hypertension, diabetes mellitus, heart failure, or prior stroke) and sinus rhythm. Participants underwent a comprehensive transthoracic echocardiographic examination, including myocardial speckle tracking. Cardiac abnormalities were defined according to the ASE/EACVI guidelines., Results: Structural cardiac abnormalities such as left ventricular (LV) remodeling, mitral annular calcification (MAC), and aortic valve sclerosis (with or without stenosis) were highly prevalent in the LOOP study (40%, 39%, and 27%, respectively). Moreover, a high prevalence of functional cardiac alterations such as LV diastolic dysfunction (LVDD), abnormal LV longitudinal systolic strain (GLS), and abnormal left atrial (LA) reservoir strain was present in the LOOP study (27%, 18%, and 9%, respectively). Likewise, the rate of LVDD, abnormal GLS, and abnormal LA reservoir strain was comparable in the validation sample from the Copenhagen City Heart Study. In line with these findings, subjects with LV remodeling, MAC, and aortic valve changes had a higher prevalence of LVDD, abnormal GLS, and abnormal LA reservoir strain than those without structural cardiac alterations., Conclusion: The findings of this study highlight the potential clinical utility of conventional and speckle-tracking echocardiography in the screening of structural and functional cardiac abnormalities in the elderly population. Further studies are warranted to determine the prognostic relevance of these findings., Competing Interests: Dr. Jørgensen: Speaker Honoraria from Novo Nordisk and Astra Zeneca. Dr. Køber: Speaker honoraria from Novo, Novartis, AstraZeneca and Boehringer. Dr. Diederichsen: Advisor for Vital Beats. Dr. Haugan: travel and educational grants from Medtronic, Abbott, and BIOTRONIK. Speaker honoraria from Boehringer-Ingelheim not related to this work. Dr. Brandes: Research grant from the Region of Southern Denmark, the Region of Zealand, Canadian Institutes of Health Research, and Theravance. Speaker honoraria from Bayer, Boehringer Ingelheim, and Bristol-Myers Squibb. Travel grant from Biotronik. Dr. Biering-Sørensen: Steering Committee member of the Amgen financed GALACTIC-HF trial and Steering Committee of the Boston Scientific financed LUX-Dx TRENDS trial. Advisory Board for Sanofi Pasteur and Amgen. Speaker Honoraria from Novartis and Sanofi Pasteur. Research grants from GE Healthcare and Sanofi Pasteur. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Four-dimensional (4D) echocardiography may provide more accurate estimations of left atrial (LA) volumes than 2-dimensional (2D) measures. We sought to compare the concordance of a novel 4D LA quantification software versus 2D echocardiography against cardiac magnetic resonance (CMR). This was a multimodality imaging substudy of a randomized clinical trial (the LOOP study). Elderly participants with stroke risk factors were included. A subgroup of this study population underwent transthoracic echocardiography (n = 1441) and a subset underwent CMR within two weeks (n = 73). The mean age of the echocardiographic study population was 74 years and 54% were men. The maximal LA volume (LAVmax) was 47 mL by 2D, 52 mL by 4D, and 104 mL by CMR. While 2D echocardiography showed a moderate correlation with 4D (R 2  = 0.51) it yielded significantly lower values for LAVmax with a mean difference of 4.5 ± 11.9 mL, p < 0.001. 4D echocardiography correlated strongly with CMR measurements (R 2  = 0.70), whereas 2D echocardiography showed a moderate correlation (R 2  = 0.53). However, both modalities systematically underestimated LAVmax largely compared to CMR (2D vs. CMR: - 54.9 ± 21.3 mL; 4D vs. CMR: - 49.7 ± 18.6 mL). Similar observations were made for minimal LA volume and LA volume before atrial contraction. Analyses time by 4D was shorter than for 2D (90 ± 11 vs. 118 ± 16 s, p < 0.001). Intra- and interobserver variability was lower for 4D than 2D. Four-dimensional echocardiography is faster, more reproducible, and correlates more closely to CMR than 2D echocardiography. Both 4D and 2D echocardiography systematically underestimates LA volumes compared to CMR, emphasizing that values of LA volumes are not interchangeable between echocardiography and CMR., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Pressure-strain loop analyses is a noninvasive technique capable of evaluating myocardial work. Reference values are needed to benchmark these myocardial work indices for clinical practice., Methods: Healthy participants from a general population study were used to establish reference values for global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) measured by pressure-strain loop analyses. The relation to age and sex was examined. We furthermore examined the proportion of abnormal work indices according to low, intermediate, and high cardiovascular risk by the Framingham risk score., Results: The healthy sample consisted of 1827 participants (median age, 45 years; 39% men). Lower reference values were GWI, 1576 mm Hg%; GCW, 1708 mm Hg%; and GWE, 93.0% and upper reference value for GWW was 159 mm Hg%. Women exhibited significantly higher GWI, GCW, and GWW and lower GWE. Sex significantly modified the association between all indices and age ( P for interaction: 0.001 for GWI, 0.009 for GCW, 0.003 for GWW, and 0.009 for GWE). For men, only GCW increased with age, whereas the other indices did not change with age. For women, GCW increased linearly with increasing age, whereas GWI, GWW, and GWE changed in a curvilinear fashion with age such that GWI increased in younger participants, GWW increased in elderly, and GWE declined concordantly. Abnormalities in myocardial work indices became more frequent with increasing Framingham risk score category (abnormal GWI: 2% versus 4% versus 5%, P =0.001; abnormal GCW: 2% versus 3% versus 4%, P =0.006; abnormal GWW: 3% versus 6% versus 11%, P <0.001; abnormal GWE: 3% versus 4% versus 11%, P <0.001)., Conclusions: Myocardial work indices differ between sexes and change with age in a sex-dependent manner. Accordingly, we established age- and sex-specific reference values from a general population sample. Abnormal work indices become more frequent with higher clinical risk., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02993172.

Background: Infections of cardiac implantable devices (CIEDI) have poor outcomes despite improvement in lead extraction (TLE) procedures. Methods: To explore the influence of CIEDI on the outcomes of TLE and the differences between patients with systemic (Sy) vs. local (Lo) CIEDI, we performed a sub-analysis of the EORP ELECTRa (European Lead Extraction ConTRolled) Registry. Results: Among 3555 patients enrolled by 73 centers in 19 Countries, the indication for TLE was CIEDI in 1850: 1170 with Lo-CIEDI and 680 with Sy-CIEDI. Patients with CIEDI had a worse in-hospital prognosis in terms of major complications (3.57% vs. 1.71%; p = 0.0007) and mortality (2.27% vs. 0.49%; p < 0.0001). Sy-CIEDI was an independent predictor of in-hospital death (H.R. 2.14; 95%CI 1.06−4.33. p = 0.0345). Patients with Sy-CIEDI more frequently had an initial CIED implant and a higher prevalence of comorbidities, while subjects with Lo-CIEDI had a higher prevalence of previous CIED procedures. Time from signs of CIEDI and TLE was longer for Lo-CIEDI despite a shorter pre-TLE antibiotic treatment. Conclusions: Patients with CIEDI have a worse in-hospital prognosis after TLE, especially for patients with Sy-CIEDI. These results raise the suspicion that in a relevant group of patients CIEDI can be systemic from the beginning without progression from Lo-CIEDI. Future research is needed to characterize this subgroup of patients.

Aims: Prophylactic implantable cardioverter-defibrillators (ICD) reduce mortality in patients with ischaemic heart failure (HF), whereas the effect of ICD in patients with non-ischaemic HF is less clear. We aimed to investigate the association between concomitant coronary atherosclerosis and mortality in patients with non-ischaemic HF and the effect of ICD implantation in these patients., Methods and Results: Patients were included from DANISH (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-Ischaemic Systolic Heart Failure on Mortality), randomizing patients to ICD or control. Study inclusion criteria for HF were left ventricular ejection fraction ≤ 35% and increased levels (>200 pg/mL) of N-terminal pro-brain natriuretic peptide. Of the 1116 patients from DANISH, 838 (75%) patients had available data from coronary angiogram and were included in this subgroup analysis. We used Cox regression to assess the relationship between coronary atherosclerosis and mortality and the effect of ICD implantation. Of the included patients, 266 (32%) had coronary atherosclerosis. Of these, 216 (81%) had atherosclerosis without significant stenoses, and 50 (19%) had significant stenosis. Patients with atherosclerosis were significantly older {67 [interquartile range (IQR) 61-73] vs. 61 [IQR 54-68] years; P < 0.0001}, and more were men (77% vs. 70%; P = 0.03). During a median follow-up of 64.3 months (IQR 47-82), 174 (21%) of the patients died. The effect of ICD on all-cause mortality was not modified by coronary atherosclerosis [hazard ratio (HR) 0.94; 0.58-1.52; P = 0.79 vs. HR 0.82; 0.56-1.20; P = 0.30], P for interaction = 0.67. In univariable analysis, coronary atherosclerosis was a significant predictor of all-cause mortality [HR, 1.41; 95% confidence interval (CI), 1.04-1.91; P = 0.03]. However, this association disappeared when adjusting for cardiovascular risk factors (age, gender, diabetes, hypertension, smoking, and estimated glomerular filtration rate) (HR 1.05, 0.76-1.45, P = 0.76)., Conclusions: In patients with non-ischaemic systolic heart failure, ICD implantation did not reduce all-cause mortality in patients either with or without concomitant coronary atherosclerosis. The concomitant presence of coronary atherosclerosis was associated with increased mortality. However, this association was explained by other risk factors., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: We investigated the mortality risk associated with the initiation of antipsychotic treatment among patients with dementia and whether comorbidities related to the cardiovascular system and diabetes interact with antipsychotic treatment to increase the mortality risk beyond the risk of death independently associated with antipsychotics and comorbidity alone., Methods: We designed a matched cohort study using nationwide registry data. All Danish residents aged 65-95 years diagnosed with dementia between 2009 and 2014 were included. Dementia was assessed as a first-time registered dementia diagnosis in the Danish National Patient Register or the Danish Psychiatric Central Research Register and/or a first-time prescription for antidementia medication. Patients exposed to antipsychotics were matched with up to three unexposed patients. Cox proportional hazards models were used to compare rates of death within 180 days after the initiation of antipsychotic treatment. The models were adjusted for potential confounders. Analyses were stratified for diabetes, heart disease, and cerebrovascular disease, and we calculated the relative excess risk due to interaction (RERI)., Results: The study cohort included 8244 exposed patients and 24,730 unexposed patients. A total of 5938 patients died during the first 180 days of follow-up. Patients exposed to antipsychotics had a significantly higher adjusted risk of death (hazard ratio: 1.35, 95% confidence interval: 1.27-1.43) than unexposed patients. Crude mortality rates were higher among patients with heart disease and diabetes when antipsychotic treatment was initiated compared with patients without comorbidities. Relative risk estimates did not differ between patients with and without heart disease, cerebrovascular disease, and diabetes, and RERI suggested no positive additive interaction. Risk analysis suggested higher mortality in patients without cerebrovascular disease who initiated antipsychotics., Conclusion: This nationwide study adds to the evidence that antipsychotic treatment is associated with increased mortality and suggests that attention should be paid to all initiators of antipsychotics irrespective of cardiovascular disease and diabetes., (© 2022 The American Geriatrics Society.)

Background: Identification of patients with nonischemic cardiomyopathy who may benefit from prophylactic implantation of a cardioverter-defibrillator. We hypothesized that periodic repolarization dynamics (PRD), a marker of repolarization instability associated with sympathetic activity, could be used to identify patients who will benefit from prophylactic implantable cardioverter defibrillator (ICD) implantation., Methods: We performed a post hoc analysis of DANISH (Danish ICD Study in Patients With Dilated Cardiomyopathy), in which patients with nonischemic cardiomyopathy, left ventricular ejection fraction (LVEF) ≤35%, and elevated NT-proBNP (N-terminal probrain natriuretic peptides) were randomized to ICD implantation or control group. Patients were included in the PRD substudy if they had a 24-hour Holter monitor recording at baseline with technically acceptable ECG signals during the night hours (00:00-06:00). PRD was assessed using wavelet analysis according to previously validated methods. The primary end point was all-cause mortality. Cox regression models were adjusted for age, sex, NT-proBNP, estimated glomerular filtration rate, LVEF, atrial fibrillation, ventricular pacing, diabetes, cardiac resynchronization therapy, and mean heart rate. We proposed PRD ≥10 deg 2 as an exploratory cut-off value for ICD implantation., Results: A total of 748 of the 1116 patients in DANISH qualified for the PRD substudy. During a mean follow-up period of 5.1±2.0 years, 82 of 385 patients died in the ICD group and 85 of 363 patients died in the control group ( P =0.40). In Cox regression analysis, PRD was independently associated with mortality (hazard ratio [HR], 1.28 [95% CI, 1.09-1.50] per SD increase; P =0.003). PRD was significantly associated with mortality in the control group (HR, 1.51 [95% CI, 1.25-1.81]; P <0.001) but not in the ICD group (HR, 1.04 [95% CI, 0.83-1.54]; P =0.71). There was a significant interaction between PRD and the effect of ICD implantation on mortality ( P =0.008), with patients with higher PRD having greater benefit in terms of mortality reduction. ICD implantation was associated with an absolute mortality reduction of 17.5% in the 280 patients with PRD ≥10 deg 2 (HR, 0.54 [95% CI, 0.34-0.84]; P =0.006; number needed to treat=6), but not in the 468 patients with PRD <10 deg 2 (HR, 1.17 [95% CI, 0.77-1.78]; P =0.46; P for interaction=0.01)., Conclusions: Increased PRD identified patients with nonischemic cardiomyopathy in whom prophylactic ICD implantation led to significant mortality reduction.

Objectives: In this extended follow-up study of the DANISH (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart Failure on Mortality) trial, adding 4 years of additional follow-up, we examined the effect of implantable cardioverter-defibrillator (ICD) implantation according to baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) level., Background: In the DANISH trial, NT-proBNP level at baseline appeared to modify the response to ICD implantation., Methods: In the DANISH trial, 1,116 patients with nonischemic systolic HF were randomized to receive an ICD (N = 556) or usual clinical care (N = 550). Outcomes were analyzed according to NT-proBNP levels (below/above median) at baseline. The primary outcome was death from any cause., Results: All 1,116 patients in the DANISH trial had an available NT-proBNP measurement at baseline (median: 1,177 pg/mL; range: 200-22,918 pg/mL). There was a trend toward a reduction in all-cause death with ICD implantation, compared with usual clinical care, in patients with NT-proBNP levels lower than the median (HR: 0.75 [95% CI: 0.55-1.03]), but not in those with higher NT-proBNP levels (HR: 0.95 [95% CI: 0.74-1.21]) (P interaction  = 0.28). Similarly, ICD implantation significantly reduced the rate of cardiovascular (CV) and sudden cardiovascular death (SCD) in patients with NT-proBNP levels lower than the median (CV death, HR: 0.69 [95% CI: 0.47-1.00]; SCD, HR: 0.37 [95% CI: 0.19-0.75]), but not in those with higher levels (CV death, HR: 0.94 [95% CI: 0.70-1.25]; SCD, HR: 0.86 [95% CI: 0.49-1.51]) (P interaction  = 0.20 and 0.08 for CV death and SCD, respectively)., Conclusions: Lower baseline NT-proBNP levels could identify patients with nonischemic systolic HF who may derive benefit from ICD implantation. (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart Failure on Mortality [DANISH]; NCT00542945)., Competing Interests: Funding Support and Author Disclosures Dr Butt has received advisory board honoraria from Bayer, outside the submitted work. Dr Nielsen is supported by a grant from the Novo Nordisk Foundation (NNF16OC0018658) outside this work. Dr Bruun has received funding from the Novo Nordisk Foundation, the Augustinus Foundation, the Kaj Hansen Foundation, and from Health Insurance Denmark outside this work. Dr Brandes has received a research grant from Theravance and the Regions of Southern Denmark and Zealand; has received speaker honoraria from Bayer, Boehringer Ingelheim, and Bristol-Myers Squibb; and has received a travel grant from Biotronik outside this work. Dr Gustafsson has received speaker honorarium from Orion, Novartis, and Vifor Pharma; and has received advisory board honorarium from Abott, Bayer, Alnylam, Ionis, Pfizer, Corvia, and Pharmacosmos. Dr Hassager has received speaker honorarium from Abiomed. Dr Svendsen has received speaker honorarium from Medtronic. Dr Pehrson has received lecture fees from Abbott, Bristol Myers Squibb, and AstraZeneca. Dr Køber has received speaker honorarium from Novartis, AstraZeneca, Boehringer, and Novo Nordisk. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Left atrial enlargement predicts incident atrial fibrillation (AF). However, the prognostic value of peak atrial longitudinal strain (PALS) for predicting incident AF in participants from the general population is currently unknown. Our aim was to investigate if PALS can be used to predict AF and ischaemic stroke in the general population., Methods and Results: A total of 400 participants from the general population underwent a health examination, including two-dimensional speckle tracking echocardiography of the left atrium. The primary endpoint was incident AF at follow-up. All participants with known AF and prior stroke at baseline were excluded (n = 54). The secondary endpoint consisted of the composite of AF and ischaemic stroke. During a median follow-up of 16 years, 36 participants (9%) were diagnosed with incident AF and 30 (7%) experienced an ischaemic stroke, resulting in 66 (16%) experiencing the composite outcome. PALS was a univariable predictor of AF [per 5% decrease: hazard ratio (HR) 1.42; 95% confidence interval (CI) (1.19-1.69), P < 0.001]. However, the prognostic value of PALS was modified by age (P = 0.002 for interaction). After multivariable adjustment PALS predicted AF in participants aged <65 years [per 5% decrease: HR 1.46; 95% CI (1.06-2.02), P = 0.021]. In contrast, PALS did not predict AF in participants aged ≥65 years after multivariable adjustment [per 5% decrease: HR 1.05; 95% CI (0.81-1.35), P = 0.72]. PALS also predicted the secondary endpoint in participants aged <65 years and the association remained significant after multivariable adjustment., Conclusion: In a low-risk general population, PALS provides novel prognostic information on the long-term risk of AF and ischaemic stroke in participants aged <65 years., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: DANISH (The Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators [ICDs] in Patients With Nonischemic Systolic Heart Failure on Mortality) found that primary-prevention ICD implantation was not associated with an overall survival benefit in patients with nonischemic systolic heart failure during a median follow-up of 5.6 years, although there was a beneficial effect on all-cause mortality in patients ≤70 years. This study presents an additional 4 years of follow-up data from DANISH., Methods: In DANISH, 556 patients with nonischemic systolic heart failure were randomized to receive an ICD and 560 to receive usual clinical care and followed until June 30, 2016. In this long-term follow-up study, patients were followed until May 18, 2020. Analyses were conducted for the overall population and according to age (≤70 and >70 years)., Results: During a median follow-up of 9.5 years (25th-75th percentile, 7.9-10.9 years), 208/556 patients (37%) in the ICD group and 226/560 patients (40%) in the control group died. Compared with the control group, the ICD group did not have significantly lower all-cause mortality (hazard ratio [HR] 0.89, [95% CI, 0.74-1.08]; P = 0.24). In patients ≤70 years (n = 829), all-cause mortality was lower in the ICD group than the control group (117/389 [30%] versus 158/440 [36%]; HR, 0.78 [95% CI, 0.61-0.99]; P = 0.04), whereas in patients >70 years (n = 287), all-cause mortality was not significantly different between the ICD and control group (91/167 [54%] versus 68/120 [57%]; HR, 0.92 [95% CI, 0.67-1.28]; P = 0.75). Cardiovascular death showed similar trends (overall, 147/556 [26%] versus 164/560 [29%]; HR, 0.87 [95% CI, 0.70-1.09]; P = 0.20; ≤70 years, 87/389 [22%] versus 122/440 [28%]; HR, 0.75 [95% CI, 0.57-0.98]; P = 0.04; >70 years, 60/167 [36%] versus 42/120 [35%]; HR, 0.97 [95% CI, 0.65-1.45]; P = 0.91). The ICD group had a significantly lower incidence of sudden cardiovascular death in the overall population (35/556 [6%] versus 57/560 [10%]; HR, 0.60 [95% CI, 0.40-0.92]; P = 0.02) and in patients ≤70 years (19/389 [5%] versus 49/440 [11%]; HR, 0.42 [95% CI, 0.24-0.71]; P = 0.0008), but not in patients >70 years (16/167 [10%] versus 8/120 [7%]; HR, 1.34 [95% CI, 0.56-3.19]; P = 0.39)., Conclusions: During a median follow-up of 9.5 years, ICD implantation did not provide an overall survival benefit in patients with nonischemic systolic heart failure. In patients ≤70 years, ICD implantation was associated with a lower incidence of all-cause mortality, cardiovascular death, and sudden cardiovascular death. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00542945.

Aims: Treatment with implantable cardioverter-defibrillators (ICD) is a cornerstone for prevention of sudden cardiac death in arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed at describing the complications associated with ICD treatment in a multinational cohort with long-term follow-up., Methods and Results: The Nordic ARVC registry was established in 2010 and encompasses a large multinational cohort of ARVC patients, including their clinical characteristics, treatment, and events during follow-up. We included 299 patients (66% males, median age 41 years). During a median follow-up of 10.6 years, 124 (41%) patients experienced appropriate ICD shock therapy, 28 (9%) experienced inappropriate shocks, 82 (27%) had a complication requiring surgery (mainly lead-related, n = 75), and 99 (33%) patients experienced the combined endpoint of either an inappropriate shock or a surgical complication. The crude rate of first inappropriate shock was 3.4% during the first year after implantation but decreased after the first year and plateaued over time. Contrary, the risk of a complication requiring surgery was 5.5% the first year and remained high throughout the study period. The combined risk of any complication was 7.9% the first year. In multivariate cox regression, presence of atrial fibrillation/flutter was a risk factor for inappropriate shock (P < 0.05), whereas sex, age at implant, and device type were not (all P > 0.05)., Conclusion: Forty-one percent of ARVC patients treated with ICD experienced potentially life-saving ICD therapy during long-term follow-up. A third of the patients experienced a complication during follow-up with lead-related complications constituting the vast majority., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: Fascicular heart blocks can progress to complete heart blocks, but this risk has not been evaluated in a large general population., Objective: The purpose of this study was to investigate the association between various types of fascicular blocks diagnosed by electrocardiographic (ECG) readings and the risk of incident higher degree atrioventricular block (AVB), syncope, pacemaker implantation, and death., Methods: We studied primary care patients referred for ECG recording between 2001 and 2015. Cox regression models were used to estimate hazard ratios (HRs) as well as absolute risks of cardiovascular outcomes., Results: Of 358,958 primary care patients (median age 54 years; 55% women), 13,636 (3.8%) had any type of fascicular block. Patients were followed up to 15.9 years. We found increasing HRs of incident syncope, pacemaker implantation, and third-degree AVB with increasing complexity of fascicular block. Compared with no block, isolated left anterior fascicular block (LAFB) was associated with 0%-2% increased 10-year risk of developing third-degree AVB (HR 1.6; 95% confidence interval [CI] 1.25-2.05), whereas right bundle branch block combined with LAFB and first-degree AVB was associated with up to 23% increased 10-year risk (HR 11.0; 95% CI 7.7-15.7), depending on age and sex group. Except for left posterior fascicular block (HR 2.09; 95% CI 1.87-2.32), we did not find any relevant associations between fascicular block and death., Conclusion: We found that higher degrees of fascicular blocks were associated with increasing risk of syncope, pacemaker implantation, and complete heart block, but the association with death was negligible., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: There are limited data on the association of membranous septum (MS) morphology and transcatheter heart valve (THV) implantation depth, and the development of new conduction abnormalities (CA) after transcatheter aortic valve implantation (TAVI)., Aims: The aim of this study was to describe the morphology of the MS and predict the risk of new CA after TAVI based on the MS morphology and THV implantation depth., Methods: Based on preprocedural CT scans, the MS depth was measured for every 25% of the entire MS width in 272 TAVI patients without preprocedural bundle branch block (BBB) or pacemaker. Post-procedural CT scans for THV implantation depth assessment were available in 130 of these patients., Results: The MS depth was a median of 2.5 mm (IQR 1.4-3.8) deeper at the posterior edge when compared to the anterior edge of the MS. New CA developed in 7.1% of patients in whom the THV did not cross the lower MS border at its anterior edge (3.6% with new BBB and high degree CA, respectively), in 18.8% of patients (15.6% with new BBB and 3.1% with new high-degree CA) where the THV overlapped the lower MS border by <2.5 mm and in 47.1% of patients (24.3% with new BBB and 22.9% with new high-degree CA) with THV overlap of the lower MS border by ≥2.5 mm., Conclusions: The difference of the MS depth and THV implantation depth measured at the anterior edge of the MS predicted new CA after TAVI.

Background: Atrial Fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, responsible for considerable morbidity and mortality. The heterogenic and complex pathogenesis of AF remains poorly understood, which contributes to the current limitation in effective treatments. We aimed to identify rare genetic variants associated with AF in patients with familial AF. Methods and results: We performed whole exome sequencing in a large family with familial AF and identified a rare variant in the gene CACNA1A c.5053G > A which co-segregated with AF. The gene encodes for the protein variants Ca V 2.1-V1686M, and is important in neuronal function. Functional characterization of the CACNA1A, using patch-clamp recordings on transiently transfected mammalian cells, revealed a modest loss-of-function of Ca V 2.1-V1686M. Conclusion: We identified a rare loss-of-function variant associated with AF in a gene previously linked with neuronal function. The results allude to a novel link between dysfunction of an ion channel previously associated with neuronal functions and increased risk of developing AF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vad, Yan, Denti, Ahlberg, Refsgaard, Bomholtz, Santos, Rasmussen, Haunsø, Svendsen, Christophersen, Schmitt, Olesen and Bentzen.)

Background: Atrial remodeling is associated with future atrial fibrillation (AF) and stroke. AF has been associated with cognitive impairment and cerebral white matter lesions. We wished to investigate the possible direct association between atrial remodeling and cerebrovascular disease in patients with and without AF documented by implantable loop recorder (ILR)., Methods: Cardiac and cerebral magnetic resonance imaging were acquired in a cross-sectional study, including participants ≥70 years of age with stroke risk factors without known AF. Cerebrovascular disease was visually rated using the Fazekas scale and number of lacunar strokes. Left atrial (LA) and ventricular volumes and function were analyzed. Associations between atrial remodeling and cerebrovascular disease were assessed with logistic regression models. The analyses were stratified according to sinus rhythm or any AF during 3 months of continuous ILR monitoring to account for subclinical AF., Results: Of 200 participants investigated, 87% had a Fazekas score ≥1 and 45% had ≥1 lacunar infarct. Within 3 months of ILR monitoring, AF was detected in 28 (14%) participants. For participants with sinus rhythm (n = 172), lower LA passive emptying fraction was associated with Fazekas score after multivariable adjustment (OR [95% CI]: 0.51 [0.27; 0.86] p = 0.02), and increased LA maximum (OR [95% CI]: 1.38 [1.07; 1.82] p = 0.01) and minimum volumes (OR [95% CI]: 1.48 [1.03; 2.17] p = 0.04) were associated with lacunar infarcts. There were no significant associations in patients with AF., Conclusion: In AF-free patients, as documented by ILR monitoring, we found an independent association between LA passive emptying fraction and Fazekas score and between atrial volumes and lacunar infarcts., (© 2021 S. Karger AG, Basel.)

Cardiac rehabilitation (CR) is a multidisciplinary intervention including patient assessment and medical actions to promote stabilization, management of cardiovascular risk factors, vocational support, psychosocial management, physical activity counselling, and prescription of exercise training. Millions of people with cardiac implantable electronic devices live in Europe and their numbers are progressively increasing, therefore, large subsets of patients admitted in CR facilities have a cardiac implantable electronic device. Patients who are cardiac implantable electronic devices recipients are considered eligible for a CR programme. This is not only related to the underlying heart disease but also to specific issues, such as psychological adaptation to living with an implanted device and, in implantable cardioverter-defibrillator patients, the risk of arrhythmia, syncope, and sudden cardiac death. Therefore, these patients should receive special attention, as their needs may differ from other patients participating in CR. As evidence from studies of CR in patients with cardiac implantable electronic devices is sparse, detailed clinical practice guidelines are lacking. Here, we aim to provide practical recommendations for CR in cardiac implantable electronic devices recipients in order to increase CR implementation, efficacy, and safety in this subset of patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Introduction: Patients with cardiac disease often experience anxiety (prevalence about 20%-25%) and have a doubled mortality risk when suffering from anxiety compared with patients without anxiety. This calls for interventions aiming to reduce anxiety., Methods and Analysis: The Heart & Mind Trial consists of three parts: (1) screening of all hospitalised and outpatient cardiac patients with arrhythmia, heart failure or ischaemic heart disease at four university hospitals in Denmark using the Hospital Anxiety and Depression Scale-Anxiety subscale (HADS-A); Patients scoring ≥8 is invited to participate; (2) Assessment of the type of anxiety by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders and (3) Randomised clinical superiority trial with blinded outcome assessment, with 1:1 randomisation to cognitive-behavioural therapy (CBT) performed by a CBT-trained cardiac nurse plus usual care or, usual care alone. The primary outcome is anxiety measured with HADS-A at 5 months. Secondary outcomes include anxiety symptoms measured with Becks Anxiety Inventory and heart rate variability. Exploratory outcomes measured at 12 months include blood cortisol (stress response), blood C reactive protein (stress response), health-related quality of life, readmission, mortality and attributable direct costs. A total of 336 patients will be included. The primary analyses are based on the intention-to-treat principle. For the primary outcome, we will use a linear regression model. For the long-term outcomes, mixed regression models will be used including repeated measurements., Ethics and Dissemination: The trial is performed in accordance with the Declaration of Helsinki. All patients must give informed consent prior to participation and the trial is initiated after approval by the Danish Data Protection Agency (P-2020-894) and the National Committee on Health Research Ethics (H-20066739). Positive, neutral and negative results of the trial will be published., Trial Registration Number: NCT04582734., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To study the relationship between subclinical atrial fibrillation (AF) and changes in cognitive function in a large cohort of individuals with stroke risk factors., Methods: Individuals with no prior AF diagnosis but with risk factors for stroke were recruited to undergo annual cognitive assessment with the Montreal Cognitive Assessment (MoCA) along with implantable loop recorder (ILR) monitoring for AF for 3 years. If AF episodes lasting ≥6 minutes were detected, oral anticoagulation (OAC) treatment was initiated., Results: A total of 1194 participants (55.2 % men, mean age 74.5 (±3.9)) had a combined duration of heart rhythm monitoring of ≈1.3 million days. Among these, 339 participants (28.3%) had adjudicated AF, with a median AF burden of 0.072% (0.02, 0.39), and 324 (96%) initiated OAC. When stratifying the participants into AF burden groups (No AF, AF low (AF burden <0.25%), and AF high, (AF burden >0.25%)), only participants in the AF low group had a decrease in MoCA score over time (P = .03), although this was not significant after adjustment for stroke risk factors. A subgroup analysis of 175 participants (14.6%) with a MoCA <26 at 3 years found no association to AF diagnosis or burden., Conclusions: In a high-risk population, subclinical AF detected by continuous monitoring and subsequently treated with OAC was not associated with a significant change in MoCA score over a 3-year period., (Copyright © 2021. Published by Elsevier Inc.)

Background: Artificial intelligence (AI), such as machine learning (ML), shows great promise for improving clinical decision-making in cardiac diseases by outperforming statistical-based models. However, few AI-based tools have been implemented in cardiology clinics because of the sociotechnical challenges during transitioning from algorithm development to real-world implementation., Objective: This study explored how an ML-based tool for predicting ventricular tachycardia and ventricular fibrillation (VT/VF) could support clinical decision-making in the remote monitoring of patients with an implantable cardioverter defibrillator (ICD)., Methods: Seven experienced electrophysiologists participated in a near-live feasibility and qualitative study, which included walkthroughs of 5 blinded retrospective patient cases, use of the prediction tool, and questionnaires and interview questions. All sessions were video recorded, and sessions evaluating the prediction tool were transcribed verbatim. Data were analyzed through an inductive qualitative approach based on grounded theory., Results: The prediction tool was found to have potential for supporting decision-making in ICD remote monitoring by providing reassurance, increasing confidence, acting as a second opinion, reducing information search time, and enabling delegation of decisions to nurses and technicians. However, the prediction tool did not lead to changes in clinical action and was found less useful in cases where the quality of data was poor or when VT/VF predictions were found to be irrelevant for evaluating the patient., Conclusions: When transitioning from AI development to testing its feasibility for clinical implementation, we need to consider the following: expectations must be aligned with the intended use of AI; trust in the prediction tool is likely to emerge from real-world use; and AI accuracy is relational and dependent on available information and local workflows. Addressing the sociotechnical gap between the development and implementation of clinical decision-support tools based on ML in cardiac care is essential for succeeding with adoption. It is suggested to include clinical end-users, clinical contexts, and workflows throughout the overall iterative approach to design, development, and implementation., (©Stina Matthiesen, Søren Zöga Diederichsen, Mikkel Klitzing Hartmann Hansen, Christina Villumsen, Mats Christian Højbjerg Lassen, Peter Karl Jacobsen, Niels Risum, Bo Gregers Winkel, Berit T Philbert, Jesper Hastrup Svendsen, Tariq Osman Andersen. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 26.11.2021.)

Background: Current implantable cardioverter-defibrillator (ICD) devices are equipped with a device-embedded accelerometer capable of capturing physical activity (PA). In contrast, wearable accelerometer-based methods enable the measurement of physical behavior (PB) that encompasses not only PA but also sleep behavior, sedentary time, and rest-activity patterns., Objective: This systematic review evaluates accelerometer-based methods used in patients carrying an ICD or at high risk of sudden cardiac death., Methods: Papers were identified via the OVID MEDLINE and OVID EMBASE databases. PB could be assessed using a wearable accelerometer or an embedded accelerometer in the ICD., Results: A total of 52 papers were deemed appropriate for this review. Out of these studies, 30 examined device-embedded accelerometry (189,811 patients), 19 examined wearable accelerometry (1601 patients), and 3 validated wearable accelerometry against device-embedded accelerometry (106 patients). The main findings were that a low level of PA after implantation of the ICD and a decline in PA were both associated with an increased risk of mortality, heart failure hospitalization, and appropriate ICD shock. Second, PA was affected by cardiac factors (eg, onset of atrial fibrillation, ICD shocks) and noncardiac factors (eg, seasonal differences, societal factors)., Conclusion: This review demonstrated the potential of accelerometer-measured PA as a marker of clinical deterioration and ventricular arrhythmias. Notwithstanding that the evidence of PB assessed using wearable accelerometry was limited, there seems to be potential for accelerometers to improve early warning systems and facilitate preventative and proactive strategies., (© 2021 Heart Rhythm Society.)

Aims: Left atrial (LA) volume and function impose significant impact on cardiovascular pathogenesis if compromised. We aimed at investigating the genetic architecture of LA volume and function using cardiac magnetic resonance imaging data., Methods and Results: We used the UK Biobank, which is a large prospective population study with available phenotypic and genetic data. On a subset of 35 658 European individuals, we performed genome-wide association studies on five volumetric and functional LA variables, generated using a machine learning algorithm. In total, we identified 18 novel genetic loci, mapped to genes with known roles in cardiomyopathy (e.g. MYO18B, TTN, DSP, ANKRD1) and arrhythmia (e.g. TTN, CASQ2, MYO18B, C9orf3). We observed high genetic correlation between LA volume and function and stroke, which was most pronounced for LA passive emptying fraction (rg = 0.40, P = 4 × 10-6). To investigate whether the genetic risk of atrial fibrillation (AF) is associated with LA traits that precede overt AF, we produced a polygenetic risk score for AF. We found that polygenetic risk for AF is associated with increased LA volume and decreased LA function in participants without AF [LAmax 0.25 (mL/m2)/standard deviation (SD), 95% confidence interval (CI) (0.15; 0.36), P = 5.13 × 10-6; LAmin 0.21 (mL/m2)/SD, 95% CI (0.15; 0.28), P = 1.86 × 10-10; LA active emptying fraction -0.35%/SD, 95% CI (-0.43; -0.26), P = 3.14 × 10-14]., Conclusion: We report on 18 genetic loci associated with LA volume and function and show evidence for several plausible candidate genes important for LA structure., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: To determine the risk of major adverse cardiovascular events (MACE) and death, associated with an early large and rapid decline in glycated haemoglobin (HbA1C) following first time initiation of an oral antidiabetic drug (OAD)., Methods and Results: We included 10 518 primary care patients with type 2 diabetes, who initiated an OAD for the first time. For each individual, we measured a decline in HbA1C, as the difference between the pre-treatment HbA1C (within 3 months before OAD initiation) and the post-treatment HbA1C (within 1.5-4.5 months after OAD initiation), divided by the time between the two measurements. The decline was reported in mmol/mol change per 3 months in HbA1C and categorized by the median decline into levels of steep [≥9 mmol/mol (≥0.8%)] and flat decline [<9 mmol/mol per 3 months (<0.8%)]. Pre-treatment HbA1C was categorized by the median, into levels of low (48-62 mmol/mol) and high (>62 mmol/mol). Multiple Cox regression was used to study the effect of decline (steep vs. flat) on the outcome hazard rates separately for patients with low and high pre-treatment HbA1C. Analyses were adjusted for age, sex, traditional cardiovascular risk factors, severe comorbidities, and concomitant medication treatment. During a median follow-up time of 7.7 years, 1625 developed MACE and 2323 died. We found that a steep decline vs. a flat decline was significantly associated with a decreased hazard for MACE, both in individuals with high [hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.69-0.94; P = 0.005] and low pre-treatment HbA1C (HR 0.79; 95% CI 0.66-0.96; P = 0.015). The hazard of MACE was more pronounced on the short-term vs. long-term in individuals with high pre-treatment HbA1C. We found no significant association between combinations of pre-treatment HbA1C and decline categories and hazard of all-cause mortality. However, a combination of a low pre-treatment HbA1C and steep decline was associated with increased 1-year mortality (HR 1.52; 95% CI 1.00-2.29; P = 0.048) and hypoglycaemia (HR 1.82; 95% CI 1.11-2.98; P = 0.017)., Conclusion: A combination of a high pre-treatment HbA1C and a steep decline in HbA1C was associated with a decreased short-term risk of MACE. A low pre-treatment HbA1C and a steep decline was associated with a long-term reduced risk of MACE, but a short-term increased risk of death and hypoglycaemia., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Global longitudinal strain (GLS) is a sensitive marker of myocardial dysfunction and atrial reservoir function. We sought to evaluate its value for predicting atrial fibrillation (AF) in the general population., Methods: Participants from the Copenhagen City Heart Study examined with echocardiography, including speckle tracking analyses, were included. The endpoint was AF obtained through national registries. Proportional hazards Cox regression was applied, including multivariable adjustments made for CHADS 2 and CHARGE-AF risk factors. Abnormal GLS was defined as >-18%., Results: The data from 1,309 participants were analyzed. Of those, 153 (12%) developed AF during a median follow-up time of 15.9 years. The follow-up was 100%. The mean age was 57 years, 38% had hypertension, and GLS was  - 18%. In unadjusted analysis, GLS was a univariable predictor of outcome (1.08 (1.04-1.13), p < 0.001, per 1% absolute decrease), but did not remain an independent predictor after adjusting for neither CHADS 2 nor CHARGE-AF risk factors. However, hypertension modified the relationship between GLS and AF (p for interaction = 0.010), such that GLS only predicted AF in subjects without hypertension. In participants without hypertension, GLS remained an independent predictor of AF after adjusting for CHADS 2 and CHARGE-AF (HR = 1.11 (1.03-1.20) and HR = 1.09 (1.01-1.19), respectively). In these participants, an abnormal GLS was associated with a more than twofold increased risk of AF (HR = 2.16 (1.26-3.72). The incidence rate was 3.17 and 6.81 per 1000 person-years for normal vs. abnormal GLS, respectively., Conclusion: Global longitudinal strain predicts AF in individuals without hypertension from the general population, independently of common risk scores., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: This study sought to compare 2 ways of achieving cardiac resynchronization., Background: Cardiac resynchronization therapy (CRT) in patients with symptomatic heart failure and left bundle branch block (LBBB) can be achieved with His-bundle pacing correcting the bundle branch block (His-CRT). The present study is the largest randomized study comparing His-CRT and biventricular pacing (BiV-CRT) to date., Methods: Fifty patients with symptomatic heart failure, left ventricular ejection fraction (LVEF) ≤35% and LBBB according to electrocardiography were randomized 1:1 to His-CRT or BiV-CRT and followed for 6 months. At implantation, 7 patients crossed over from His-pacing to LV-pacing in the His-CRT group and 1 patient crossed over from LV-pacing to His-pacing in the BiV-CRT group., Results: His-corrective pacing was achieved in 72% of the patients in the His-CRT group. Intention-to-treat 6-month follow-up LVEF increased by 16 ± 7% in the His-CRT group compared with 13 ± 6% in the BiV-CRT group (nonsignificant) and improvements were seen in clinical and physical parameters in both treatment arms with no significant differences between the groups. Pacing thresholds were higher for His-CRT compared with BiV-CRT both at implantation (1.8 ± 1.2 V vs. 1.2 ± 0.8 V; p < 0.01) and at 6-month follow-up (2.3 ± 1.4 V vs. 1.4 ± 0.5 V; p < 0.01). The per-protocol LVEF was significantly higher at 6 months (48 ± 8% vs. 42 ± 8%; p < 0.05) and the end-systolic volume was lower (65 ± 22 ml vs. 83 ± 27 ml; p < 0.05) in His-CRT patients compared with BiV-CRT., Conclusions: In heart failure patients with LBBB, His-CRT provided similar clinical and physical improvement compared with BiV-CRT at the expense of higher pacing thresholds., Competing Interests: Funding Support and Author Disclosures This study was funded by a research grant from the Clinical Research Unit at the Heart Center, Rigshospitalet, Copenhagen, Denmark. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: It is unknown whether screening for atrial fibrillation and subsequent treatment with anticoagulants if atrial fibrillation is detected can prevent stroke. Continuous electrocardiographic monitoring using an implantable loop recorder (ILR) can facilitate detection of asymptomatic atrial fibrillation episodes. We aimed to investigate whether atrial fibrillation screening and use of anticoagulants can prevent stroke in individuals at high risk., Methods: We did a randomised controlled trial in four centres in Denmark. We included individuals without atrial fibrillation, aged 70-90 years, with at least one additional stroke risk factor (ie, hypertension, diabetes, previous stroke, or heart failure). Participants were randomly assigned in a 1:3 ratio to ILR monitoring or usual care (control) via an online system in permuted blocks with block sizes of four or eight participants stratified according to centre. In the ILR group, anticoagulation was recommended if atrial fibrillation episodes lasted 6 min or longer. The primary outcome was time to first stroke or systemic arterial embolism. This study is registered with ClinicalTrials.gov, NCT02036450., Findings: From Jan 31, 2014, to May 17, 2016, 6205 individuals were screened for inclusion, of whom 6004 were included and randomly assigned: 1501 (25·0%) to ILR monitoring and 4503 (75·0%) to usual care. Mean age was 74·7 years (SD 4·1), 2837 (47·3%) were women, and 5444 (90·7%) had hypertension. No participants were lost to follow-up. During a median follow-up of 64·5 months (IQR 59·3-69·8), atrial fibrillation was diagnosed in 1027 participants: 477 (31·8%) of 1501 in the ILR group versus 550 (12·2%) of 4503 in the control group (hazard ratio [HR] 3·17 [95% CI 2·81-3·59]; p<0·0001). Oral anticoagulation was initiated in 1036 participants: 445 (29·7%) in the ILR group versus 591 (13·1%) in the control group (HR 2·72 [95% CI 2·41-3·08]; p<0·0001), and the primary outcome occurred in 318 participants (315 stroke, three systemic arterial embolism): 67 (4·5%) in the ILR group versus 251 (5·6%) in the control group (HR 0·80 [95% CI 0·61-1·05]; p=0·11). Major bleeding occurred in 221 participants: 65 (4·3%) in the ILR group versus 156 (3·5%) in the control group (HR 1·26 [95% CI 0·95-1·69]; p=0·11)., Interpretation: In individuals with stroke risk factors, ILR screening resulted in a three-times increase in atrial fibrillation detection and anticoagulation initiation but no significant reduction in the risk of stroke or systemic arterial embolism. These findings might imply that not all atrial fibrillation is worth screening for, and not all screen-detected atrial fibrillation merits anticoagulation., Funding: Innovation Fund Denmark, The Research Foundation for the Capital Region of Denmark, The Danish Heart Foundation, Aalborg University Talent Management Program, Arvid Nilssons Fond, Skibsreder Per Henriksen, R og Hustrus Fond, The AFFECT-EU Consortium (EU Horizon 2020), Læge Sophus Carl Emil Friis og hustru Olga Doris Friis' Legat, and Medtronic., Competing Interests: Declaration of interests JHS is a member of Medtronic advisory boards and has received speaker honoraria and research grants from Medtronic in relation to this work and outside the submitted work. SZD is a part-time employee of Vital Beats outside the submitted work. DWK is a member of a Medtronic advisory board on stroke and has received speaker honoraria and travel grants from Medtronic, St Jude Medical, and Boehringer Ingelheim, outside the submitted work. AB reports research grants from The Region of Southern Denmark and The Region of Zealand, and Theravance; speaker honoraria from Bayer, Boehringer Ingelheim, and Bristol-Myers Squibb; and a travel grant from Biotronik, outside the submitted work. JBN is an employee of Regeneron Pharmaceuticals, outside the submitted work. AGH is an employee of Acesion Pharma, outside the submitted work. KJH reports travel and educational grants from Medtronic, Abbott, and BIOTRONIK; and speaker honoraria from Boehringer Ingelheim, outside the submitted work. LK reports speaker honoraria from Novo, AstraZeneca, Novartis, and Boehringer Ingelheim, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Patients with an implantable cardioverter-defibrillator (ICD) are at a high risk of malignant ventricular arrhythmias. The use of remote ICD monitoring, wearable devices, and patient-reported outcomes generate large volumes of potential valuable data. Artificial intelligence-based methods can be used to develop personalized prediction models and improve early-warning systems., Objective: The purpose of this study was to develop an integrated web-based personalized prediction engine for ICD therapy., Methods: This international, multicenter, prospective, observational study consists of 2 phases: (1) a development study and (2) a feasibility study. We plan to enroll 400 participants with an ICD (with or without cardiac resynchronization therapy) on remote monitoring: 300 participants in the development study and 100 in the feasibility study. During 12-month follow-up, electronic health record data, remote monitoring data, accelerometry-assessed physical behavior data, and patient-reported data are collected. By using machine- and deep-learning approaches, a prediction engine is developed to assess the risk probability of ICD therapy (shock and antitachycardia pacing). The feasibility of the prediction engine as a clinical tool, the SafeHeart Platform, is assessed during the feasibility study., Results: Development study recruitment commenced in 2021. The feasibility study starts in 2022., Conclusion: SafeHeart is the first study to prospectively collect a multimodal data set to construct a personalized prediction engine for ICD therapy. Moreover, SafeHeart explores the integration and added value of detailed objective accelerometer data in the prediction of clinical events. The translation of the SafeHeart Platform to clinical practice is examined during the feasibility study., (© 2021 Published by Elsevier Inc. on behalf of Heart Rhythm Society.)

Aims: The aim of this study was to investigate the association between within-individual changes in physical activity and onset of atrial fibrillation (AF)., Methods and Results: A total of 1410 participants from the general population (46.2% women, mean age 74.7 ± 4.1 years) with risk factors but with no prior AF diagnosis underwent continuous monitoring for AF episodes along with daily accelerometric assessment of physical activity using an implantable loop recorder during ≈3.5 years. The combined duration of monitoring was ≈1.6 million days, where 10 851 AF episodes lasting ≥60 min were detected in 361 participants (25.6%) with a median of 5 episodes (2, 25) each. The median daily physical activity was 112 (66, 168) min/day. A dynamic parameter describing within-individual changes in daily physical activity, i.e. average daily activity in the last week compared to the previous 100 days, was computed and used to model the onset of AF. A 1-h decrease in average daily physical activity was associated with AF onset the next day [odds ratio 1.24 (1.18-1.31)]. This effect was modified by overall level of activity (P < 0.001 for interaction), and the signal was strongest in the tertile of participants with lowest activity overall [low: 1.62 (1.41-1.86), mid: 1.27 (1.16-1.39), and high: 1.10 (1.01-1.19)]., Conclusions: Within-individual changes in physical activity are associated with the onset of AF episodes as detected by continuous monitoring in a high-risk population. For each person, a 1-h decrease in daily physical activity during the last week increased the odds of AF onset the next day by ≈25%, while the strongest association was seen in the group with the lowest activity overall., Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT02036450., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Cardiac arrhythmias are considered a prominent phenomenon in patients with pulmonary hypertension (PH). Older studies reported that 8% to 35% of patients with PH had supraventricular tachycardia (SVT), associated with adverse outcomes. Still, these arrhythmias have only been investigated via short-term monitoring or limited electrocardiogram recordings., Methods: Patients without previous arrhythmias diagnosed with PH at a tertiary facility received an insertable cardiac monitor as part of a prospective cohort study. Baseline assessments included World Health Organization functional class, six-minute walk test, echocardiography, and cardiac magnetic resonance imaging., Results: Thirty-four patients with PH were included. Twenty-four patients had pulmonary arterial hypertension (PAH) and 10 had chronic thromboembolic PH (CTEPH). During 46 patient-years of continuous monitoring (median: 594 (range: 334-654) days per patient), 70 arrhythmia episodes were recorded in 13 patients (38%), with a median of two (range: 1-3) episodes and an arrhythmic burden median of 1.6 (range: 0.1-228) minutes per patient. SVTs were the most common arrhythmias, with 16% of episodes being atrial fibrillation and 84% being other types of SVTs. Additionally, three patients experienced bradycardias, including one resulting in syncope and subsequent pacemaker implantation. None of the patients had sustained ventricular arrhythmias., Conclusions: Arrhythmias were seen in 38% of contemporary patients with PH during long-term continuous monitoring; however, the vast majority of episodes were short and self-limiting. Modern therapy may alleviate the development of arrhythmias in stable patients with PH. This study is the first study to deploy long-term continuous monitoring in patients with PH., Competing Interests: Declaration of Competing Interest Mads Ørbæk Andersen has nothing to declare. Søren Zöga Diederichsen is a part-time employee of Vital Beats, not related to this work. Jesper Hastrup Svendsen is a member of an advisory board for Medtronic, has received research grant and speaker fee from Medtronic unrelated to this study and har received research grant from Gilead unrelated to this research project. Jørn Carlsen is a member of an advisory board for Janssen Cilag, and the institution has received research grants and speaker fees. In the same way for United Therapeutics for clinical trials and Astra Zeneca and Ferrer for speaker fees., (Copyright © 2021. Published by Elsevier B.V.)

Cardiac resynchronization therapy (CRT) reduces the risk of ventricular arrhythmias (VA) in heart failure (HF) patients with left bundle branch block (LBBB) while the effect is less clear among non-LBBB patients. This study aimed to investigate if absence of LBBB features whether by echocardiography or strict ECG criteria would identify patients at risk of developing VA in a cohort with LBBB according to conventional ECG criteria. Two hundred six CRT candidates were prospectively included from 2 centers. Prior to CRT presence of a typical LBBB contraction pattern was identified using longitudinal strain in the apical 4-chamber view. All preimplantation ECGs were categorized as LBBB or non-LBBB according to Strauss´ strict criteria. Primary end-point was defined as any appropriate antitachycardia pacing (ATP) or shock therapy within 2 years after CRT implantation. A total of 129 (63%) patients had a typical LBBB contraction pattern, while 134 (66%) met the strict ECG criteria. Over 2 years, 45 patients (22%) experienced VA. Absence of a typical LBBB contraction pattern was independently associated with an increased risk of VA (hazard ratio ([HR] 1.89; 95% CI 1.04 to 3.44; p: 0.036). Strict LBBB was not independently associated with the occurrence of VA. Fulfilling neither strict ECG nor echocardiographic criteria for LBBB was associated with a 3.3-fold increase in risk of VA ([HR] 3.34; 95% CI 1.75 to 6.94; (p < 0.001). The risk of VA was almost 2-fold higher if a typical LBBB contraction pattern was absent prior to CRT.

EQ-5D is a generic instrument to measure health-related quality of life. In 2009, a new version, EQ-5D-5L, was introduced as an attempt to reduce ceiling effects and improve sensitivity to small changes over time. The objective of this study was to assess the measurement properties of the EQ-5D-5L instrument compared to the EQ-5D-3L instrument in an elderly general population with a moderate to a high degree of comorbidity. A subgroup of participants in a large clinical trial completed the EQ-5D-3L and the EQ-5D-5L questionnaires. Based on the collected data, we tested for feasibility and ceiling and floor effects. Furthermore, we assessed the redistribution properties of the responses and examined the level of inconsistency, informativity, and convergent validity. A total of 1002 persons diagnosed with hypertension, diabetes, heart failure, and/or previous stroke completed both the EQ-5D-3L and the EQ-5D-5L questionnaires. The overall ceiling effect decreased from 46% with the EQ-5D-3L to 30% with the EQ-5D-5L and absolute and relative informativity were higher for EQ-5D-5L, and there was a stronger correlation between EQ-5D-5L and EQ VAS. The EQ-5D-5L seemed to perform better than the EQ-5D-3L in terms of feasibility, ceiling effect, discriminatory power, and convergent validity. The overall ceiling effect was higher than that found in patient samples in previous studies but lower than the one found in population studies.

The World Heart Federation (WHF) commenced a Roadmap initiative in 2015 to reduce the global burden of cardiovascular disease and resultant burgeoning of healthcare costs. Roadmaps provide a blueprint for implementation of priority solutions for the principal cardiovascular diseases leading to death and disability. Atrial fibrillation (AF) is one of these conditions and is an increasing problem due to ageing of the world's population and an increase in cardiovascular risk factors that predispose to AF. The goal of the AF roadmap was to provide guidance on priority interventions that are feasible in multiple countries, and to identify roadblocks and potential strategies to overcome them. Since publication of the AF Roadmap in 2017, there have been many technological advances including devices and artificial intelligence for identification and prediction of unknown AF, better methods to achieve rhythm control, and widespread uptake of smartphones and apps that could facilitate new approaches to healthcare delivery and increasing community AF awareness. In addition, the World Health Organisation added the non-vitamin K antagonist oral anticoagulants (NOACs) to the Essential Medicines List, making it possible to increase advocacy for their widespread adoption as therapy to prevent stroke. These advances motivated the WHF to commission a 2020 AF Roadmap update. Three years after the original Roadmap publication, the identified barriers and solutions were judged still relevant, and progress has been slow. This 2020 Roadmap update reviews the significant changes since 2017 and identifies priority areas for achieving the goals of reducing death and disability related to AF, particularly targeted at low-middle income countries. These include advocacy to increase appreciation of the scope of the problem; plugging gaps in guideline management and prevention through physician education, increasing patient health literacy, and novel ways to increase access to integrated healthcare including mHealth and digital transformations; and greater emphasis on achieving practical solutions to national and regional entrenched barriers. Despite the advances reviewed in this update, the task will not be easy, but the health rewards of implementing solutions that are both innovative and practical will be great., Competing Interests: Ben Freedman reports prior fees and advisory board honoraria from Bayer Pharma AG, Boehringer Ingelheim, Daiichi-Sankyo, Omron and Pfizer/BMS, loan devices from Alivecor, and grants to the institution for investigator-initiated studies from BMS/Pfizer, unrelated to the current work. Jeff Healey has held research grants and received speaking fees from BMS/Pfizer, Bayer, Servier, Medtronic, Boston Scientific, Abbott, ARCA biopharma, Cipher pharma, and Myokardia. Lis Neubeck has received honoraria from Pfizer BMS and Daiichi Sankyo (<£2000). Renate Schnabel has received lecture fees from BMS/Pfizer outside this work. Jesper Hastrup Svendsen reports grants, personal fees, and other from Medtronic and grants from Gilead. Isabel Arbelo has received speaker fees from Biosense Webster. FD Richard Hobbs has received occasional fees and or travel expenses reimbursed in the past five years for consultancy, speaking, or advisory meetings from BI and Bayer. Janina Stepinska has received research grants from Bayer and Sanofi; consulting or lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Pfizer, Sanofi, and Servier. Antoni Martínez-Rubio has participated in scientific advisory boards or research projects financed by Bayer, Boehringer Ingelheim, Daichii-Sankyo, and Pfizer., (Copyright: © 2021 The Author(s).)

Aims: Improved risk stratification to identify non-ischaemic heart failure patients who will benefit from primary prophylactic implantable cardioverter-defibrillator (ICD) is needed. We examined the potential of ventricular arrhythmia to identify patients who could benefit from an ICD., Methods and Results: A total of 850 non-ischaemic systolic heart failure patients with left ventricle ≤35% and elevated N-terminal pro-brain natriuretic peptides had a 24-h Holter monitor recording performed. We examined present non-sustained ventricular tachycardia (NSVT), defined as ≥3 consecutive premature ventricular contractions (PVCs) with a rate of ≥100/min, and number of PVCs per hour stratified into low (<30) and high burden (≥30) groups. Outcome measures were overall mortality, sudden cardiac death (SCD), and cardiovascular death (CVD). In total, 193 patients died, 49 from SCD and 125 from CVD. Non-sustained ventricular tachycardia (365 patients) was significantly associated with increased all-cause mortality [hazard ratio (HR) 1.47; 95% confidence interval (CI) 1.07-2.03; P = 0.02] and to CVD (HR 1.89; CI 1.25-2.87; P = 0.003). High burden PVC (352 patients) was associated with increased all-cause mortality (HR1.38; CI 1.00-1.90; P = 0.046) and with CVD (HR 1.78; CI 1.19-2.66; P = 0.005). There was no statistically significant association with SCD for neither NSVT nor PVC. In interaction analyses, neither NSVT (P = 0.56) nor high burden of PVC (P = 0.97) was associated with survival benefit from ICD implantation., Conclusion: Ventricular arrhythmia in non-ischaemic heart failure patients was associated with a worse prognosis but could not be used to stratify patients to ICD implantation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) have increased prevalence of atrial arrhythmias indicating atrial involvement in the disease. We aimed to assess the long-term evolution of P-wave indices as electrocardiographic (ECG) markers of atrial substrate during ARVC progression., Methods and Results: We included 100 patients with a definite ARVC diagnosis according to 2010 Task Force criteria [34% females, median age 41 (inter-quartile range 30-55) years]. All available sinus rhythm ECGs (n = 1504) were extracted from the regional electronic ECG databases and automatically processed using Glasgow algorithm. P-wave duration, P-wave area, P-wave frontal axis, and prevalence of abnormal P terminal force in lead V1 (aPTF-V1) were assessed and compared at ARVC diagnosis, 10 years before and up to 15 years after diagnosis.Prior to ARVC diagnosis, none of the P-wave indices differed significantly from the data at ARVC diagnosis. After ascertainment of ARVC diagnosis, P-wave area in lead V1 decreased from -1 to -30 µV ms at 5 years (P = 0.002). P-wave area in lead V2 decreased from 82 µV ms at ARVC diagnosis to 42 µV ms 10 years after ARVC diagnosis (P = 0.006). The prevalence of aPTF-V1 increased from 5% at ARVC diagnosis to 18% by the 15th year of follow-up (P = 0.004). P-wave duration and frontal axis did not change during disease progression., Conclusion: Initial ARVC progression was associated with P-wave flattening in right precordial leads and in later disease stages an increased prevalence of aPTF-V1 was seen., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: Atrial fibrillation (AF) in heart failure (HF) patients has been associated with a worse outcome. Similarly, excessive supraventricular ectopic activity (ESVEA) has been linked to development of AF, stroke, and death. This study aimed to investigate AF and ESVEA's association with outcomes and effect of prophylactic implantable cardioverter defibrillator (ICD) implantation in nonischemic HF patients., Methods: A total of 850 patients with nonischemic HF, left ventricle ejection fraction ≤35%, and elevated N-terminal pro-brain natriuretic peptides underwent 24 hours Holter recording. The presence of AF (≥30 seconds) and ESVEA (≥30 supraventricular ectopic complexes (SVEC) per hour or run of SVEC ≥20 beats) were registered. Outcomes were all-cause mortality, cardiovascular death (CVD), and sudden cardiac death (SCD)., Results: AF was identified in 188 patients (22%) and ESVEA in 84 patients (10%). After 4 years and 11 months of follow-up, a total of 193 patients (23%) had died. AF was associated with all-cause mortality (hazard ratio [HR] 1.44; confidence interval [CI] 1.04-1.99; P = .03) and CVD (HR 1.59; CI 1.07-2.36; P = .02). ESVEA was associated with all-cause mortality (HR 1.73; CI 1.16-2.57; P = .0073) and CVD (HR 1.76; CI 1.06-2.92; P = .03). Neither AF nor ESVEA was associated with SCD. ICD implantation was not associated with an improved prognosis for neither AF (P value for interaction = .17), nor ESVEA (P value for interaction = .68)., Conclusions: Both AF and ESVEA were associated with worsened prognosis in nonischemic HF. However, ICD implantation was not associated with an improved prognosis for either group., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Whether detailed genetic information contributes to risk stratification of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains uncertain. Pathogenic genetic variants in some genes seem to carry a higher risk for arrhythmia and earlier disease onset than others, but comparisons between variants in the same gene have not been done. Combined Annotation Dependent Depletion (CADD) score is a bioinformatics tool that measures the pathogenicity of each genetic variant. We hypothesized that a higher CADD score is associated with arrhythmic events and earlier age at ARVC manifestations in individuals carrying pathogenic or likely pathogenic genetic variants in plakophilin-2 (PKP2)., Methods: CADD scores were calculated using the data from pooled Scandinavian and North American ARVC cohorts, and their association with cardiac events defined as ventricular tachycardia/ventricular fibrillation (VT/VF) or syncope and age at definite ARVC diagnosis were assessed., Results: In total, 33 unique genetic variants were reported in 179 patients (90 males, 71 probands, 96 with definite ARVC diagnosis at a median age of 35 years). Cardiac events were reported in 76 individuals (43%), of whom 53 had sustained VT/VF (35%). The CADD score was neither associated with age at cardiac events (HR 1.002, 95% CI: 0.953-1.054, p = 0.933) nor with age at definite ARVC diagnosis (HR 0.992, 95% CI: 0.947-1.039, p = 0.731)., Conclusion: No correlation was found between CADD scores and clinical manifestations of ARVC, indicating that the score has no additional risk stratification value among carriers of pathogenic or likely pathogenic PKP2 genetic variants., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Aims: Women with arrhythmogenic right ventricular cardiomyopathy (ARVC) are at relatively lower risk of ventricular arrhythmias (VAs) than men, but the physical burden associated with pregnancy on VA risk remains insufficiently studied. We aimed to assess the risk of VA in relation to pregnancies in women with ARVC., Methods and Results: We included 199 females with definite ARVC (n = 121) and mutation-positive family members without ascertained ARVC diagnosis (n = 78), of whom 120 had at least one childbirth. Ventricular arrhythmia-free survival after the latest childbirth was compared between women with one (n = 20), two (n = 67), and three or more (n = 37) childbirths. Cumulative probability of VA for each pregnancy (n = 261) was assessed from conception through 2 years after childbirth and compared between those pregnancies that occurred before (n = 191) or after (n = 19) ARVC diagnosis and in mutation-positive family members (n = 51). The nulliparous women had lower median age at ARVC diagnosis (38 vs. 42 years, P < 0.001) and first VA (22 vs. 41 years, P < 0.001). Ventricular arrhythmia-free survival after the latest childbirth was not related to the number of pregnancies. No pregnancy-related VA was reported among the family members. Women who gave birth after ARVC diagnosis had elevated risk of VA postpartum (hazard ratio 13.74, 95% confidence interval 2.9-63, P = 0.001), though only two events occurred during pregnancies., Conclusion: In women with ARVC, pregnancy was uneventful for the overwhelming majority and the number of prior completed pregnancies was not associated with VA risk. Pregnancy-related VA was primarily related to the phenotypical severity rather than pregnancy itself., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: Little is known about cardiac structure and function among atrial fibrillation (AF) subtypes; paroxysmal AF vs. persistent AF (PxAF), and across AF burden. We sought to assess differences in left atrial (LA) measures by AF subtype and burden., Methods and Results: This was a cross-sectional echocardiographic substudy of a randomized trial of AF patients scheduled for catheter ablation. Patients had an echocardiogram performed 0-90 days prior to study inclusion. We performed conventional echocardiographic measures, left ventricular (LV) and LA speckle tracking. Measures were compared between AF subtype and burden (0%, 0-99%, and 99-100%) determined by 72-h Holter monitoring. Of 212 patients, 107 had paroxysmal AF and 105 had PxAF. Those with PxAF had significantly reduced systolic function (LV ejection fraction: 48% vs. 53%; P < 0.001), larger end-systolic and end-diastolic LA volumes (LAVi and LAEDVi), reduced LA emptying fraction (LAEF: 29% vs. 36%, P < 0.001), and reduced LA strain (LAs) (LAs: 20% vs. 26%, P < 0.001). LA measures remained significantly lower in PxAF after multivariable adjustments. All LA measures and measures of systolic function were significantly impaired in patients with 99-100% AF burden, whereas all measures were similar between the other groups (LAVi: 40mL/m2 vs. 33mL/m2 vs. 34mL/m2; LAEDVi: 31mL/m2 vs. 21mL/m2 vs. 22mL/m2, LA emptying fraction: 23% vs. 35% vs. 36%, LAs: 16% vs. 25% vs. 25%, for 99-100%, 0-99%, and 0% AF, respectively, P < 0.001 for all). These differences were consistent after multivariable adjustments., Conclusion: LA mechanics differ between AF subtype and burden and these characteristics influence the clinical interpretation of these measures., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Objective: To assess outcomes at 12 and 24 months after participation in a multidisciplinary cardiac rehabilitation program plus usual care compared with usual care alone for patients treated for atrial fibrillation with catheter ablation., Design: Long-term follow-up on the randomized CopenHeart RFA trial., Setting: Patients were enrolled and outcome assessed at the hospital and the intervention were carried out at the hospital or at local rehabilitation centers., Participants: Patients (N=210) treated for atrial fibrillation with catheter ablation included in the CopenHeart RFA trial., Interventions: A 6-month cardiac rehabilitation program consisting of physical exercise and psychoeducational consultations plus usual care or usual care alone., Main Outcome Measures: Physical capacity was measured by peak oxygen uptake (Vo 2 peak) at 12 months, and patient-reported outcomes on perceived health, anxiety, and depression were collected by validated questionnaires at 12 and 24 months. Information on hospital admissions and mortality was collected through national registers up to 24 months., Results: Mean Vo 2 peak was higher at 12 months in the cardiac rehabilitation group (cardiac rehabilitation group: 25.82 mL/kg/min vs usual care group, 22.43 mL/kg/min, P=.003). A lower proportion of patients had high levels of anxiety at 24 months in the cardiac rehabilitation group compared to usual care (12% vs 24%, P=.004). There was no difference in mortality or hospital admissions at 24 months between groups., Conclusions: This long-term follow-up of a comprehensive multidisciplinary cardiac rehabilitation program for patients treated for atrial fibrillation with catheter ablation found sustained improvements with respect to physical capacity and anxiety compared to usual care but no difference on mortality or hospital admission., (Copyright © 2020 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Aims: In Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), electrophysiological pathology has been claimed to precede morphological and functional pathology. Accordingly, an ECG without ARVC markers should be rare in ARVC patients with pathology identified by cardiac imaging. We quantified the prevalence of ARVC patients with evidence of structural disease, yet without ECG Task Force Criteria (TFC)., Methods and Results: We included 182 probands and family members with ARVC-associated mutations (40 ± 17 years, 50% women, 73% PKP2 mutations) from the Nordic ARVC Registry in a cross-sectional analysis. For echocardiography and cardiac MR (CMR), we differentiated between "abnormalities" and TFC. "Abnormalities" were defined as RV functional or structural measures outside TFC reference values, without combinations required to fulfill TFC. ECG TFC were used as defined, as these are not composite parameters. We found that only 4% of patients with ARVC fulfilled echocardiographic TFC without any ECG TFC. However, importantly, 38% of patients had imaging abnormalities without any ECG TFC. These results were supported by CMR data from a subset of 51 patients: 16% fulfilled CMR TFC without fulfilling ECG TFC, while 24% had CMR abnormalities without any ECG TFC. In a multivariate analysis, echocardiographic TFC were associated with arrhythmic events., Conclusion: More than one third of ARVC genotype positive patients had subtle imaging abnormalities without fulfilling ECG TFC. Although most patients will have both imaging and ECG abnormalities, structural abnormalities in ARVC genotype positive patients cannot be ruled out by the absence of ECG TFC., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter-Defibrillators (EU-CERT-ICD), a prospective investigator-initiated, controlled cohort study, was conducted in 44 centres and 15 European countries. It aimed to assess current clinical effectiveness of primary prevention ICD therapy., Methods and Results: We recruited 2327 patients with ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and guideline indications for prophylactic ICD implantation. Primary endpoint was all-cause mortality. Clinical characteristics, medications, resting, and 12-lead Holter electrocardiograms (ECGs) were documented at enrolment baseline. Baseline and follow-up (FU) data from 2247 patients were analysable, 1516 patients before first ICD implantation (ICD group) and 731 patients without ICD serving as controls. Multivariable models and propensity scoring for adjustment were used to compare the two groups for mortality. During mean FU of 2.4 ± 1.1 years, 342 deaths occurred (6.3%/years annualized mortality, 5.6%/years in the ICD group vs. 9.2%/years in controls), favouring ICD treatment [unadjusted hazard ratio (HR) 0.682, 95% confidence interval (CI) 0.537-0.865, P = 0.0016]. Multivariable mortality predictors included age, left ventricular ejection fraction (LVEF), New York Heart Association class

The involvement of fibrosis as an underlying pathology in heart diseases is becoming increasingly clear. In recent years, fibrosis has been granted a causative role in heart diseases and is now emerging as a major contributor to Atrial Fibrillation (AF) pathogenesis. AF is the most common arrhythmia encountered in the clinic, but the substrate for AF is still being debated. Consensus in the field is a combination of cardiac tissue remodeling, inflammation and genetic predisposition. The extracellular matrix (ECM) is subject of growing investigation, since measuring circulatory biomarkers of ECM formation and degradation provides both diagnostic and prognostic information. However, fibrosis is not just fibrosis. Each specific collagen biomarker holds information on regulatory mechanisms, as well as information about which section of the ECM is being remodeled, providing a detailed description of cardiac tissue homeostasis. This review entails an overview of the implication of fibrosis in AF, the different collagens and their significance, and the potential of using biomarkers of ECM remodeling as tools for understanding AF pathogenesis and identifying patients at risk for further disease progression., Competing Interests: Declarations of Competing Interest AR, MK and FGE are full-time employees at Nordic Bioscience, Herlev, Denmark. Other authors have no competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)