Showing papers on "Atrial fibrillation published in 2022"

Epicardial adipose tissue in contemporary cardiology

Abstract: Interest in epicardial adipose tissue (EAT) is growing rapidly, and research in this area appeals to a broad, multidisciplinary audience. EAT is unique in its anatomy and unobstructed proximity to the heart and has a transcriptome and secretome very different from that of other fat depots. EAT has physiological and pathological properties that vary depending on its location. It can be highly protective for the adjacent myocardium through dynamic brown fat-like thermogenic function and harmful via paracrine or vasocrine secretion of pro-inflammatory and profibrotic cytokines. EAT is a modifiable risk factor that can be assessed with traditional and novel imaging techniques. Coronary and left atrial EAT are involved in the pathogenesis of coronary artery disease and atrial fibrillation, respectively, and it also contributes to the development and progression of heart failure. In addition, EAT might have a role in coronavirus disease 2019 (COVID-19)-related cardiac syndrome. EAT is a reliable potential therapeutic target for drugs with cardiovascular benefits such as glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter 2 inhibitors. This Review provides a comprehensive and up-to-date overview of the role of EAT in cardiovascular disease and highlights the translational nature of EAT research and its applications in contemporary cardiology.

Screening for Atrial Fibrillation: US Preventive Services Task Force Recommendation Statement.

Abstract: Importance Atrial fibrillation (AF) is the most common cardiac arrhythmia. The prevalence of AF increases with age, from less than 0.2% in adults younger than 55 years to about 10% in those 85 years or older, with a higher prevalence in men than in women. It is uncertain whether the prevalence of AF differs by race and ethnicity. Atrial fibrillation is a major risk factor for ischemic stroke and is associated with a substantial increase in the risk of stroke. Approximately 20% of patients who have a stroke associated with AF are first diagnosed with AF at the time of the stroke or shortly thereafter. Objective To update its 2018 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review on the benefits and harms of screening for AF in older adults, the accuracy of screening tests, the effectiveness of screening tests to detect previously undiagnosed AF compared with usual care, and the benefits and harms of anticoagulant therapy for the treatment of screen-detected AF in older adults. Population Adults 50 years or older without a diagnosis or symptoms of AF and without a history of transient ischemic attack or stroke. Evidence Assessment The USPSTF concludes that evidence is lacking, and the balance of benefits and harms of screening for AF in asymptomatic adults cannot be determined. Recommendation The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for AF. (I statement).

Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation: Patient-Level Network Meta-Analyses of Randomized Clinical Trials With Interaction Testing by Age and Sex

Abstract: Direct oral anticoagulants (DOACs) are preferred over warfarin for stroke prevention in atrial fibrillation. Meta-analyses using individual patient data offer substantial advantages over study-level data.We used individual patient data from the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database, which includes all patients randomized in the 4 pivotal trials of DOACs versus warfarin in atrial fibrillation (RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy], ROCKET AF [Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation], ARISTOTLE [Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation], and ENGAGE AF-TIMI 48 [Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48]), to perform network meta-analyses using a stratified Cox model with random effects comparing standard-dose DOAC, lower-dose DOAC, and warfarin. Hazard ratios (HRs [95% CIs]) were calculated for efficacy and safety outcomes. Covariate-by-treatment interaction was estimated for categorical covariates and for age as a continuous covariate, stratified by sex.A total of 71 683 patients were included (29 362 on standard-dose DOAC, 13 049 on lower-dose DOAC, and 29 272 on warfarin). Compared with warfarin, standard-dose DOACs were associated with a significantly lower hazard of stroke or systemic embolism (883/29 312 [3.01%] versus 1080/29 229 [3.69%]; HR, 0.81 [95% CI, 0.74-0.89]), death (2276/29 312 [7.76%] versus 2460/29 229 [8.42%]; HR, 0.92 [95% CI, 0.87-0.97]), and intracranial bleeding (184/29 270 [0.63%] versus 409/29 187 [1.40%]; HR, 0.45 [95% CI, 0.37-0.56]), but no statistically different hazard of major bleeding (1479/29 270 [5.05%] versus 1733/29 187 [5.94%]; HR, 0.86 [95% CI, 0.74-1.01]), whereas lower-dose DOACs were associated with no statistically different hazard of stroke or systemic embolism (531/13 049 [3.96%] versus 1080/29 229 [3.69%]; HR, 1.06 [95% CI, 0.95-1.19]) but a lower hazard of intracranial bleeding (55/12 985 [0.42%] versus 409/29 187 [1.40%]; HR, 0.28 [95% CI, 0.21-0.37]), death (1082/13 049 [8.29%] versus 2460/29 229 [8.42%]; HR, 0.90 [95% CI, 0.83-0.97]), and major bleeding (564/12 985 [4.34%] versus 1733/29 187 [5.94%]; HR, 0.63 [95% CI, 0.45-0.88]). Treatment effects for standard- and lower-dose DOACs versus warfarin were consistent across age and sex for stroke or systemic embolism and death, whereas standard-dose DOACs were favored in patients with no history of vitamin K antagonist use (P=0.01) and lower creatinine clearance (P=0.09). For major bleeding, standard-dose DOACs were favored in patients with lower body weight (P=0.02). In the continuous covariate analysis, younger patients derived greater benefits from standard-dose (interaction P=0.02) and lower-dose DOACs (interaction P=0.01) versus warfarin.Compared with warfarin, DOACs have more favorable efficacy and safety profiles among patients with atrial fibrillation.

Effect of MRI-Guided Fibrosis Ablation vs Conventional Catheter Ablation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation: The DECAAF II Randomized Clinical Trial.

Abstract: Importance Ablation of persistent atrial fibrillation (AF) remains a challenge. Left atrial fibrosis plays an important role in the pathophysiology of AF and has been associated with poor procedural outcomes. Objective To investigate the efficacy and adverse events of targeting atrial fibrosis detected on magnetic resonance imaging (MRI) in reducing atrial arrhythmia recurrence in persistent AF. Design, Setting, and Participants The Efficacy of Delayed Enhancement-MRI-Guided Fibrosis Ablation vs Conventional Catheter Ablation of Atrial Fibrillation trial was an investigator-initiated, multicenter, randomized clinical trial involving 44 academic and nonacademic centers in 10 countries. A total of 843 patients with symptomatic or asymptomatic persistent AF and undergoing AF ablation were enrolled from July 2016 to January 2020, with follow-up through February 19, 2021. Interventions Patients with persistent AF were randomly assigned to pulmonary vein isolation (PVI) plus MRI-guided atrial fibrosis ablation (421 patients) or PVI alone (422 patients). Delayed-enhancement MRI was performed in both groups before the ablation procedure to assess baseline atrial fibrosis and at 3 months postablation to assess for ablation scar. Main Outcomes and Measures The primary end point was time to first atrial arrhythmia recurrence after a 90-day blanking period postablation. The primary safety composite outcome was defined by the occurrence of 1 or more of the following events within 30 days postablation: stroke, PV stenosis, bleeding, heart failure, or death. Results Among 843 patients who were randomized (mean age 62.7 years; 178 [21.1%] women), 815 (96.9%) completed the 90-day blanking period and contributed to the efficacy analyses. There was no significant difference in atrial arrhythmia recurrence between groups (fibrosis-guided ablation plus PVI patients, 175 [43.0%] vs PVI-only patients, 188 [46.1%]; hazard ratio [HR], 0.95 [95% CI, 0.77-1.17]; P = .63). Patients in the fibrosis-guided ablation plus PVI group experienced a higher rate of safety outcomes (9 [2.2%] vs 0 in PVI group; P = .001). Six patients (1.5%) in the fibrosis-guided ablation plus PVI group had an ischemic stroke compared with none in PVI-only group. Two deaths occurred in the fibrosis-guided ablation plus PVI group, and the first one was possibly related to the procedure. Conclusions and Relevance Among patients with persistent AF, MRI-guided fibrosis ablation plus PVI, compared with PVI catheter ablation only, resulted in no significant difference in atrial arrhythmia recurrence. Findings do not support the use of MRI-guided fibrosis ablation for the treatment of persistent AF. Trial Registration ClinicalTrials.gov Identifier: NCT02529319.

Baseline Characteristics of Patients With HF With Mildly Reduced and Preserved Ejection Fraction: DELIVER Trial.

Abstract: This report describes the baseline clinical profiles and management of DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial participants and how these compare with those in other contemporary heart failure with preserved ejection fraction trials.The DELIVER trial was designed to evaluate the effects of the sodium-glucose cotransporter-2 inhibitor dapagliflozin on cardiovascular death, heart failure (HF) hospitalization, or urgent HF visits in patients with HF with mildly reduced and preserved left ventricular ejection fraction (LVEF).Adults with symptomatic HF and LVEF >40%, with or without type 2 diabetes mellitus, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and evidence of structural heart disease were randomized to dapagliflozin 10 mg once daily or matching placebo.A total of 6,263 patients were randomized (mean age: 72 ± 10 years; 44% women; 45% type 2 diabetes mellitus; 45% with body mass index ≥30 kg/m2; and 57% with history of atrial fibrillation or flutter). Most participants had New York Heart Association functional class II symptoms (75%). Baseline mean LVEF was 54.2 ± 8.8% and median NT-proBNP of 1,399 pg/mL (IQR: 962 to 2,210 pg/mL) for patients in atrial fibrillation/flutter compared with 716 pg/mL (IQR: 469 to 1,281 pg/mL) in those who were not. Patients in both hospitalized and ambulatory settings were enrolled, including 10% enrolled in-hospital or within 30 days of a hospitalization for HF. Eighteen percent of participants had HF with improved LVEF.DELIVER is the largest and broadest clinical trial of this population to date and enrolled high-risk, well-treated patients with HF with mildly reduced and preserved LVEF. (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [NCT03619213]).

2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19

Abstract: The International Initiative on Thrombosis and Cancer is an independent academic working group of experts aimed at establishing global consensus for the treatment and prophylaxis of cancer-associated thrombosis. The 2013, 2016, and 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines have been made available through a free, web-based mobile phone application. The 2022 clinical practice guidelines, which are based on a literature review up to Jan 1, 2022, include guidance for patients with cancer and with COVID-19. Key recommendations (grade 1A or 1B) include: (1) low-molecular-weight heparins (LMWHs) for the initial (first 10 days) treatment and maintenance treatment of cancer-associated thrombosis; (2) direct oral anticoagulants for the initial treatment and maintenance treatment of cancer-associated thrombosis in patients who are not at high risk of gastrointestinal or genitourinary bleeding, in the absence of strong drug-drug interactions or of gastrointestinal absorption impairment; (3) LMWHs or direct oral anticoagulants for a minimum of 6 months to treat cancer-associated thrombosis; (4) extended prophylaxis (4 weeks) with LMWHs to prevent postoperative venous thromboembolism after major abdominopelvic surgery in patients not at high risk of bleeding; and (5) primary prophylaxis of venous thromboembolism with LMWHs or direct oral anticoagulants (rivaroxaban or apixaban) in ambulatory patients with locally advanced or metastatic pancreatic cancer who are treated with anticancer therapy and have a low risk of bleeding.

ECG-Based Deep Learning and Clinical Risk Factors to Predict Atrial Fibrillation

Abstract: Background: Artificial intelligence (AI)–enabled analysis of 12-lead ECGs may facilitate efficient estimation of incident atrial fibrillation (AF) risk. However, it remains unclear whether AI provides meaningful and generalizable improvement in predictive accuracy beyond clinical risk factors for AF. Methods: We trained a convolutional neural network (ECG-AI) to infer 5-year incident AF risk using 12-lead ECGs in patients receiving longitudinal primary care at Massachusetts General Hospital (MGH). We then fit 3 Cox proportional hazards models, composed of ECG-AI 5-year AF probability, CHARGE-AF clinical risk score (Cohorts for Heart and Aging in Genomic Epidemiology–Atrial Fibrillation), and terms for both ECG-AI and CHARGE-AF (CH-AI), respectively. We assessed model performance by calculating discrimination (area under the receiver operating characteristic curve) and calibration in an internal test set and 2 external test sets (Brigham and Women’s Hospital [BWH] and UK Biobank). Models were recalibrated to estimate 2-year AF risk in the UK Biobank given limited available follow-up. We used saliency mapping to identify ECG features most influential on ECG-AI risk predictions and assessed correlation between ECG-AI and CHARGE-AF linear predictors. Results: The training set comprised 45 770 individuals (age 55±17 years, 53% women, 2171 AF events) and the test sets comprised 83 162 individuals (age 59±13 years, 56% women, 2424 AF events). Area under the receiver operating characteristic curve was comparable using CHARGE-AF (MGH, 0.802 [95% CI, 0.767–0.836]; BWH, 0.752 [95% CI, 0.741–0.763]; UK Biobank, 0.732 [95% CI, 0.704–0.759]) and ECG-AI (MGH, 0.823 [95% CI, 0.790–0.856]; BWH, 0.747 [95% CI, 0.736–0.759]; UK Biobank, 0.705 [95% CI, 0.673–0.737]). Area under the receiver operating characteristic curve was highest using CH-AI (MGH, 0.838 [95% CI, 0.807 to 0.869]; BWH, 0.777 [95% CI, 0.766 to 0.788]; UK Biobank, 0.746 [95% CI, 0.716 to 0.776]). Calibration error was low using ECG-AI (MGH, 0.0212; BWH, 0.0129; UK Biobank, 0.0035) and CH-AI (MGH, 0.012; BWH, 0.0108; UK Biobank, 0.0001). In saliency analyses, the ECG P-wave had the greatest influence on AI model predictions. ECG-AI and CHARGE-AF linear predictors were correlated (Pearson r : MGH, 0.61; BWH, 0.66; UK Biobank, 0.41). Conclusions: AI-based analysis of 12-lead ECGs has similar predictive usefulness to a clinical risk factor model for incident AF and the approaches are complementary. ECG-AI may enable efficient quantification of future AF risk.

Rivaroxaban in Rheumatic Heart Disease–Associated Atrial Fibrillation

Abstract: Testing of factor Xa inhibitors for the prevention of cardiovascular events in patients with rheumatic heart disease-associated atrial fibrillation has been limited.We enrolled patients with atrial fibrillation and echocardiographically documented rheumatic heart disease who had any of the following: a CHA2DS2VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating a higher risk of stroke), a mitral-valve area of no more than 2 cm2, left atrial spontaneous echo contrast, or left atrial thrombus. Patients were randomly assigned to receive standard doses of rivaroxaban or dose-adjusted vitamin K antagonist. The primary efficacy outcome was a composite of stroke, systemic embolism, myocardial infarction, or death from vascular (cardiac or noncardiac) or unknown causes. We hypothesized that rivaroxaban therapy would be noninferior to vitamin K antagonist therapy. The primary safety outcome was major bleeding according to the International Society of Thrombosis and Hemostasis.Of 4565 enrolled patients, 4531 were included in the final analysis. The mean age of the patients was 50.5 years, and 72.3% were women. Permanent discontinuation of trial medication was more common with rivaroxaban than with vitamin K antagonist therapy at all visits. In the intention-to-treat analysis, 560 patients in the rivaroxaban group and 446 in the vitamin K antagonist group had a primary-outcome event. Survival curves were nonproportional. The restricted mean survival time was 1599 days in the rivaroxaban group and 1675 days in the vitamin K antagonist group (difference, -76 days; 95% confidence interval [CI], -121 to -31; P<0.001). A higher incidence of death occurred in the rivaroxaban group than in the vitamin K antagonist group (restricted mean survival time, 1608 days vs. 1680 days; difference, -72 days; 95% CI, -117 to -28). No significant between-group difference in the rate of major bleeding was noted.Among patients with rheumatic heart disease-associated atrial fibrillation, vitamin K antagonist therapy led to a lower rate of a composite of cardiovascular events or death than rivaroxaban therapy, without a higher rate of bleeding. (Funded by Bayer; INVICTUS ClinicalTrials.gov number, NCT02832544.).

Atrial fibrillation

Abstract: Atrial fibrillation (AF) is the most common cardiac arrhythmia despite substantial efforts to understand the pathophysiology of the condition and develop improved treatments. Identifying the underlying causative mechanisms of AF in individual patients is difficult and the efficacy of current therapies is suboptimal. Consequently, the incidence of AF is steadily rising and there is a pressing need for novel therapies. Research has revealed that defects in specific molecular pathways underlie AF pathogenesis, resulting in electrical conduction disorders that drive AF. The severity of this so-called electropathology correlates with the stage of AF disease progression and determines the response to AF treatment. Therefore, unravelling the molecular mechanisms underlying electropathology is expected to fuel the development of innovative personalized diagnostic tools and mechanism-based therapies. Moreover, the co-creation of AF studies with patients to implement novel diagnostic tools and therapies is a prerequisite for successful personalized AF management. Currently, various treatment modalities targeting AF-related electropathology, including lifestyle changes, pharmaceutical and nutraceutical therapy, substrate-based ablative therapy, and neuromodulation, are available to maintain sinus rhythm and might offer a novel holistic strategy to treat AF. Atrial fibrillation (AF) is the most common cardiac arrhythmia and is increasing in prevalence as populations age. This Primer provides an overview of AF epidemiology, the mechanisms underlying electropathology in AF, and the diagnostic approaches and treatments, and highlights important directions to improve understanding and management of AF in co-creation with patients.

Bariatric surgery and cardiovascular disease: a systematic review and meta-analysis

Abstract: Abstract Aims Obesity is a global health problem, associated with significant morbidity and mortality, often due to cardiovascular (CV) diseases. While bariatric surgery is increasingly performed in patients with obesity and reduces CV risk factors, its effect on CV disease is not established. We conducted a systematic review and meta-analysis to evaluate the effect of bariatric surgery on CV outcomes, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Methods and results PubMed and Embase were searched for literature until August 2021 which compared bariatric surgery patients to non-surgical controls. Outcomes of interest were all-cause and CV mortality, atrial fibrillation (AF), heart failure (HF), myocardial infarction, and stroke. We included 39 studies, all prospective or retrospective cohort studies, but randomized outcome trials were not available. Bariatric surgery was associated with a beneficial effect on all-cause mortality [pooled hazard ratio (HR) of 0.55; 95% confidence interval (CI) 0.49–0.62, P < 0.001 vs. controls], and CV mortality (HR 0.59, 95% CI 0.47–0.73, P < 0.001). In addition, bariatric surgery was also associated with a reduced incidence of HF (HR 0.50, 95% CI 0.38–0.66, P < 0.001), myocardial infarction (HR 0.58, 95% CI 0.43–0.76, P < 0.001), and stroke (HR 0.64, 95% CI 0.53–0.77, P < 0.001), while its association with AF was not statistically significant (HR 0.82, 95% CI 0.64–1.06, P = 0.12). Conclusion The present systematic review and meta-analysis suggests that bariatric surgery is associated with reduced all-cause and CV mortality, and lowered incidence of several CV diseases in patients with obesity. Bariatric surgery should therefore be considered in these patients.

Multi-national survey on the methods, efficacy, and safety on the post-approval clinical use of pulsed field ablation (MANIFEST-PF)

Abstract: Abstract Aims Pulsed field ablation (PFA) is a novel atrial fibrillation (AF) ablation modality that has demonstrated preferential tissue ablation, including no oesophageal damage, in first-in-human clinical trials. In the MANIFEST-PF survey, we investigated the ‘real world’ performance of the only approved PFA catheter, including acute effectiveness and safety—in particular, rare oesophageal effects and other unforeseen PFA-related complications. Methods and results This retrospective survey included all 24 clinical centres using the pentaspline PFA catheter after regulatory approval. Institution-level data were obtained on patient characteristics, procedure parameters, acute efficacy, and adverse events. With an average of 73 patients treated per centre (range 7–291), full cohort included 1758 patients: mean age 61.6 years (range 19–92), female 34%, first-time ablation 94%, paroxysmal/persistent AF 58/35%. Most procedures employed deep sedation without intubation (82.1%), and 15.1% were discharged same day. Pulmonary vein isolation (PVI) was successful in 99.9% (range 98.9–100%). Procedure time was 65 min (38–215). There were no oesophageal complications or phrenic nerve injuries persisting past hospital discharge. Major complications (1.6%) were pericardial tamponade (0.97%) and stroke (0.4%); one stroke resulted in death (0.06%). Minor complications (3.9%) were primarily vascular (3.3%), but also included transient phrenic nerve paresis (0.46%), and TIA (0.11%). Rare complications included coronary artery spasm, haemoptysis, and dry cough persistent for 6 weeks (0.06% each). Conclusion In a large cohort of unselected patients, PFA was efficacious for PVI, and expressed a safety profile consistent with preferential tissue ablation. However, the frequency of ‘generic’ catheter complications (tamponade, stroke) underscores the need for improvement.

OUP accepted manuscript

Abstract: Obesity is a global health problem, associated with significant morbidity and mortality, often due to cardiovascular (CV) diseases. While bariatric surgery is increasingly performed in patients with obesity and reduces CV risk factors, its effect on CV disease is not established. We conducted a systematic review and meta-analysis to evaluate the effect of bariatric surgery on CV outcomes, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline.PubMed and Embase were searched for literature until August 2021 which compared bariatric surgery patients to non-surgical controls. Outcomes of interest were all-cause and CV mortality, atrial fibrillation (AF), heart failure (HF), myocardial infarction, and stroke. We included 39 studies, all prospective or retrospective cohort studies, but randomized outcome trials were not available. Bariatric surgery was associated with a beneficial effect on all-cause mortality [pooled hazard ratio (HR) of 0.55; 95% confidence interval (CI) 0.49-0.62, P < 0.001 vs. controls], and CV mortality (HR 0.59, 95% CI 0.47-0.73, P < 0.001). In addition, bariatric surgery was also associated with a reduced incidence of HF (HR 0.50, 95% CI 0.38-0.66, P < 0.001), myocardial infarction (HR 0.58, 95% CI 0.43-0.76, P < 0.001), and stroke (HR 0.64, 95% CI 0.53-0.77, P < 0.001), while its association with AF was not statistically significant (HR 0.82, 95% CI 0.64-1.06, P = 0.12).The present systematic review and meta-analysis suggests that bariatric surgery is associated with reduced all-cause and CV mortality, and lowered incidence of several CV diseases in patients with obesity. Bariatric surgery should therefore be considered in these patients.

OUP accepted manuscript

Abstract: Abstract Aims Pulsed field ablation (PFA) is a novel atrial fibrillation (AF) ablation modality that has demonstrated preferential tissue ablation, including no oesophageal damage, in first-in-human clinical trials. In the MANIFEST-PF survey, we investigated the ‘real world’ performance of the only approved PFA catheter, including acute effectiveness and safety—in particular, rare oesophageal effects and other unforeseen PFA-related complications. Methods and results This retrospective survey included all 24 clinical centres using the pentaspline PFA catheter after regulatory approval. Institution-level data were obtained on patient characteristics, procedure parameters, acute efficacy, and adverse events. With an average of 73 patients treated per centre (range 7–291), full cohort included 1758 patients: mean age 61.6 years (range 19–92), female 34%, first-time ablation 94%, paroxysmal/persistent AF 58/35%. Most procedures employed deep sedation without intubation (82.1%), and 15.1% were discharged same day. Pulmonary vein isolation (PVI) was successful in 99.9% (range 98.9–100%). Procedure time was 65 min (38–215). There were no oesophageal complications or phrenic nerve injuries persisting past hospital discharge. Major complications (1.6%) were pericardial tamponade (0.97%) and stroke (0.4%); one stroke resulted in death (0.06%). Minor complications (3.9%) were primarily vascular (3.3%), but also included transient phrenic nerve paresis (0.46%), and TIA (0.11%). Rare complications included coronary artery spasm, haemoptysis, and dry cough persistent for 6 weeks (0.06% each). Conclusion In a large cohort of unselected patients, PFA was efficacious for PVI, and expressed a safety profile consistent with preferential tissue ablation. However, the frequency of ‘generic’ catheter complications (tamponade, stroke) underscores the need for improvement.

Apixaban vs. standard of care after transcatheter aortic valve implantation: the ATLANTIS trial.

Abstract: AIMS The respective roles of oral anticoagulation or antiplatelet therapy following transcatheter aortic valve implantation (TAVI) remain debated. ATLANTIS is an international, randomized, open-label, superiority trial comparing apixaban to the standard of care. METHODS AND RESULTS After successful TAVI, 1500 patients were randomized (1:1) to receive apixaban 5 mg (2.5 mg if impaired renal function or concomitant antiplatelet therapy) (n = 749) twice daily, or standard of care (n = 751). Randomization was stratified by the need for chronic anticoagulation therapy. Standard-of-care patients received a vitamin K antagonist (VKA) (Stratum 1) or antiplatelet therapy (Stratum 2) if there was an indication for anticoagulation or not, respectively. The primary endpoint was the composite of death, myocardial infarction, stroke or transient ischaemic attack, systemic embolism, intracardiac or bioprosthesis thrombosis, deep vein thrombosis or pulmonary embolism, and life-threatening, disabling, or major bleeding over 1-year follow-up. The primary safety endpoint was major, disabling, or life-threatening bleeding. The primary outcome occurred in 138 (18.4%) and 151 (20.1%) patients receiving apixaban or standard of care, respectively [hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.73-1.16] and there was no evidence of interaction between treatment and stratum (Pinteraction = 0.57). The primary safety endpoint was similar in both groups (HR 1.02; 95% CI 0.72-1.44). In Stratum 1 (n = 451), an exploratory analysis showed no difference for all endpoints between apixaban and VKA. In Stratum 2 (n = 1049), the primary outcome and primary safety endpoint did not differ, but obstructive valve thrombosis was reduced with apixaban vs. antiplatelet therapy (HR 0.19; 95% CI 0.08-0.46), while a signal of higher non-cardiovascular mortality was observed with apixaban. CONCLUSION After TAVI, apixaban was not superior to the standard of care, irrespective of an indication for oral anticoagulation.

First-in-Human Experience and Acute Procedural Outcomes Using a Novel Pulsed Field Ablation System: The PULSED AF Pilot Trial

Abstract: Background: Pulsed field ablation (PFA) is a novel form of ablation using electrical fields to ablate cardiac tissue. There are only limited data assessing the feasibility and safety of this type of ablation in humans. Methods: PULSED AF (Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF; https://www.clinicaltrials.gov ; unique identifier: NCT04198701) is a nonrandomized, prospective, multicenter, global, premarket clinical study. The first-in-human pilot phase evaluated the feasibility and efficacy of pulmonary vein isolation using a novel PFA system delivering bipolar, biphasic electrical fields through a circular multielectrode array catheter (PulseSelect; Medtronic, Inc). Thirty-eight patients with paroxysmal or persistent atrial fibrillation were treated in 6 centers in Australia, Canada, the United States, and the Netherlands. The primary outcomes were ability to achieve acute pulmonary vein isolation intraprocedurally and safety at 30 days. Results: Acute electrical isolation was achieved in 100% of pulmonary veins (n=152) in the 38 patients. Skin-to-skin procedure time was 160±91 minutes, left atrial dwell time was 82±35 minutes, and fluoroscopy time was 28±9 minutes. No serious adverse events related to the PFA system occurred in the 30-day follow-up including phrenic nerve injury, esophageal injury, stroke, or death. Conclusions: In this first-in-human clinical study, 100% pulmonary vein isolation was achieved using only PFA with no PFA system–related serious adverse events. Graphic Abstract: A graphic abstract is available for this article.

Ambient air pollution and cardiovascular diseases: An umbrella review of systematic reviews and meta‐analyses

Abstract: The available evidence on the effects of ambient air pollution on cardiovascular diseases (CVDs) has increased substantially. In this umbrella review, we summarized the current epidemiological evidence from systematic reviews and meta-analyses linking ambient air pollution and CVDs, with a focus on geographical differences and vulnerable subpopulations. We performed a search strategy through multiple databases including articles between 2010 and 31 January 2021. We performed a quality assessment and evaluated the strength of evidence. Of the 56 included reviews, the most studied outcomes were stroke (22 reviews), all-cause CVD mortality, and morbidity (19). The strongest evidence was found between higher short- and long-term ambient air pollution exposure and all-cause CVD mortality and morbidity, stroke, blood pressure, and ischemic heart diseases (IHD). Short-term exposures to particulate matter <2.5 μm (PM2.5 ), <10 μm (PM10 ), and nitrogen oxides (NOx ) were consistently associated with increased risks of hypertension and triggering of myocardial infarction (MI), and stroke (fatal and nonfatal). Long-term exposures of PM2.5 were largely associated with increased risk of atherosclerosis, incident MI, hypertension, and incident stroke and stroke mortality. Few reviews evaluated other CVD outcomes including arrhythmias, atrial fibrillation, or heart failure but they generally reported positive statistical associations. Stronger associations were found in Asian countries and vulnerable subpopulations, especially among the elderly, cardiac patients, and people with higher weight status. Consistent with experimental data, this comprehensive umbrella review found strong evidence that higher levels of ambient air pollution increase the risk of CVDs, especially all-cause CVD mortality, stroke, and IHD. These results emphasize the importance of reducing the alarming levels of air pollution across the globe, especially in Asia, and among vulnerable subpopulations.

Clinical Importance of Left Atrial Infiltration in Cardiac Transthyretin Amyloidosis

Abstract: The aim of this study was to characterize left atrial (LA) pathology in explanted hearts with transthyretin amyloid cardiomyopathy (ATTR-CM); LA mechanics using echocardiographic speckle-tracking in a large cohort of patients with ATTR-CM; and to study the association with mortality. The clinical significance of LA involvement in ATTR-CM is of great clinical interest. Congo red staining and immunohistochemistry was performed to assess the presence, type, and extent of amyloid and associated changes in 5 explanted ATTR-CM atria. Echo speckle tracking was used to assess LA reservoir, conduit, contractile function, and stiffness in 906 patients with ATTR-CM (551 wild-type (wt)-ATTR-CM; 93 T60A-ATTR-CM; 241 V122I-ATTR-CM; 21 other). There was extensive ATTR amyloid infiltration in the 5 atria, with loss of normal architecture, vessels remodeling, capillary disruption, and subendocardial fibrosis. Echo speckle tracking in 906 patients with ATTR-CM demonstrated increased atrial stiffness (median [25th-75th quartile] 1.83 [1.15-2.92]) that remained independently associated with prognosis after adjusting for known predictors (lnLA stiff: HR: 1.23; 95% CI: 1.03-1.49; P = 0.029). There was substantial impairment of the 3 phasic functional atrial components (reservoir 8.86% [5.94%-12.97%]; conduit 6.5% [4.53%-9.28%]; contraction function 4.0% [2.29%-6.56%]). Atrial contraction was absent in 22.1% of patients whose electrocardiograms showed sinus rhythm (SR) “atrial electromechanical dissociation” (AEMD). AEMD was associated with poorer prognosis compared with patients with SR and effective mechanical contraction (P = 0.0018). AEMD conferred a similar prognosis to patients in atrial fibrillation. The phenotype of ATTR-CM includes significant infiltration of the atrial walls, with progressive loss of atrial function and increased stiffness, which is a strong independent predictor of mortality. AEMD emerged as a distinctive phenotype identifying patients in SR with poor prognosis.

Inappropriate sinus tachycardia in post-COVID-19 syndrome

Abstract: Inappropriate sinus tachycardia (IST) is a common observation in patients with post-COVID-19 syndrome (PCS) but has not yet been fully described to date. To investigate the prevalence and the mechanisms underlying IST in a prospective population of PCS patients. Consecutive patients admitted to the PCS Unit between June and December 2020 with a resting sinus rhythm rate ≥ 100 bpm were prospectively enrolled in this study and further examined by an orthostatic test, 2D echocardiography, 24-h ECG monitoring (heart rate variability was a surrogate for cardiac autonomic activity), quality-of-life and exercise capacity testing, and blood sampling. To assess cardiac autonomic function, a 2:1:1 comparative sub-analysis was conducted against both fully recovered patients with previous SARS-CoV-2 infection and individuals without prior SARS-CoV-2 infection. Among 200 PCS patients, 40 (20%) fulfilled the diagnostic criteria for IST (average age of 40.1 ± 10 years, 85% women, 83% mild COVID-19). No underlying structural heart disease, pro-inflammatory state, myocyte injury, or hypoxia were identified. IST was accompanied by a decrease in most heart rate variability parameters, especially those related to cardiovagal tone: pNN50 (cases 3.2 ± 3 vs. recovered 10.5 ± 8 vs. non-infected 17.3 ± 10; p < 0.001) and HF band (246 ± 179 vs. 463 ± 295 vs. 1048 ± 570, respectively; p < 0.001). IST is prevalent condition among PCS patients. Cardiac autonomic nervous system imbalance with decreased parasympathetic activity may explain this phenomenon.

Atrial Fibrillation Detection Using a Feedforward Neural Network

Abstract: In this study, we aimed to develop an automatic atrial fibrillation detection technique for the early prediction of atrial fibrillation, that can be used with wearable devices. An effective deep learning-based technology is proposed to automatically detect atrial fibrillation. First, novel preprocessing algorithms, wavelet transform and sliding window filtering, are introduced to reduce the noise and outliers, respectively, from ECG signals. Then, a robust R-wave detection algorithm is developed. In addition, we proposed a feedforward neural network to detect atrial fibrillation based on ECG records. Experiments verified using a tenfold cross-validation strategy showed that the proposed method achieves competitive detection performance, and can be applied to wearable detection devices. The proposed R-wave detection algorithm achieved a detection sensitivity of 99.22%, a positive recognition rate of 98.55%, and a deviance of 2.25% on the MIT-BIH arrhythmia database. The proposed atrial fibrillation detection model achieved an accuracy of 84.00%, a detection sensitivity of 84.26%, a specificity of 93.23%, and an area under the receiver operating curve of 89.40% on a mixed dataset composed of the Challenge2017 database and the MIT-BIH arrhythmia database. The analysis demonstrated that the proposed atrial fibrillation detection method could automatically detect atrial fibrillation with high accuracy and efficiency, could be applied to wearable devices, and has great value in the early detection of atrial fibrillation. We believe that our work will make a valuable contribution to the area of atrial fibrillation.

Cardiovascular disease and mortality sequelae of COVID-19 in the UK Biobank

Abstract: Objective To examine association of COVID-19 with incident cardiovascular events in 17 871 UK Biobank cases between March 2020 and 2021. Methods COVID-19 cases were defined using health record linkage. Each case was propensity score-matched to two uninfected controls on age, sex, deprivation, body mass index, ethnicity, diabetes, prevalent ischaemic heart disease (IHD), smoking, hypertension and high cholesterol. We included the following incident outcomes: myocardial infarction, stroke, heart failure, atrial fibrillation, venous thromboembolism (VTE), pericarditis, all-cause death, cardiovascular death, IHD death. Cox proportional hazards regression was used to estimate associations of COVID-19 with each outcome over an average of 141 days (range 32–395) of prospective follow-up. Results Non-hospitalised cases (n=14 304) had increased risk of incident VTE (HR 2.74 (95% CI 1.38 to 5.45), p=0.004) and death (HR 10.23 (95% CI 7.63 to 13.70), p<0.0001). Individuals with primary COVID-19 hospitalisation (n=2701) had increased risk of all outcomes considered. The largest effect sizes were with VTE (HR 27.6 (95% CI 14.5 to 52.3); p<0.0001), heart failure (HR 21.6 (95% CI 10.9 to 42.9); p<0.0001) and stroke (HR 17.5 (95% CI 5.26 to 57.9); p<0.0001). Those hospitalised with COVID-19 as a secondary diagnosis (n=866) had similarly increased cardiovascular risk. The associated risks were greatest in the first 30 days after infection but remained higher than controls even after this period. Conclusions Individuals hospitalised with COVID-19 have increased risk of incident cardiovascular events across a range of disease and mortality outcomes. The risk of most events is highest in the early postinfection period. Individuals not requiring hospitalisation have increased risk of VTE, but not of other cardiovascular-specific outcomes.

Latent Pulmonary Vascular Disease May Alter the Response to Therapeutic Atrial Shunt Device in Heart Failure

Abstract: In REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure), implantation of an atrial shunt device did not provide overall clinical benefit for patients with heart failure with preserved or mildly reduced ejection fraction. However, prespecified analyses identified differences in response in subgroups defined by pulmonary artery systolic pressure during submaximal exercise, right atrial volume, and sex. Shunt implantation reduces left atrial pressures but increases pulmonary blood flow, which may be poorly tolerated in patients with pulmonary vascular disease (PVD). On the basis of these results, we hypothesized that patients with latent PVD, defined as elevated pulmonary vascular resistance during exercise, might be harmed by shunt implantation, and conversely that patients without PVD might benefit.REDUCE LAP-HF II enrolled 626 patients with heart failure, ejection fraction ≥40%, exercise pulmonary capillary wedge pressure ≥25 mm Hg, and resting pulmonary vascular resistance <3.5 Wood units who were randomized 1:1 to atrial shunt device or sham control. The primary outcome-a hierarchical composite of cardiovascular death, nonfatal ischemic stroke, recurrent HF events, and change in health status-was analyzed using the win ratio. Latent PVD was defined as pulmonary vascular resistance ≥1.74 Wood units (highest tertile) at peak exercise, measured before randomization.Compared with patients without PVD (n=382), those with latent PVD (n=188) were older, had more atrial fibrillation and right heart dysfunction, and were more likely to have elevated left atrial pressure at rest. Shunt treatment was associated with worse outcomes in patients with PVD (win ratio, 0.60 [95% CI, 0.42, 0.86]; P=0.005) and signal of clinical benefit in patients without PVD (win ratio, 1.31 [95% CI, 1.02, 1.68]; P=0.038). Patients with larger right atrial volumes and men had worse outcomes with the device and both groups were more likely to have pacemakers, heart failure with mildly reduced ejection fraction, and increased left atrial volume. For patients without latent PVD or pacemaker (n=313; 50% of randomized patients), shunt treatment resulted in more robust signal of clinical benefit (win ratio, 1.51 [95% CI, 1.14, 2.00]; P=0.004).In patients with heart failure with preserved or mildly reduced ejection fraction, the presence of latent PVD uncovered by invasive hemodynamic exercise testing identifies patients who may worsen with atrial shunt therapy, whereas those without latent PVD may benefit.