Is electrical cardioversion independently associated with infarcts on brain magnetic resonance imaging or clinical outcomes in patients with atrial fibrillation?

BACKGROUND: Electrical cardioversion (ECV) is frequently performed in symptomatic atrial fibrillation. OBJECTIVE: This study aimed to assess the association of ECV with infarcts on brain magnetic resonance imaging (bMRI) and clinical outcomes. METHODS: The Swiss Atrial Fibrillation Cohort Study included 2386 patients; 1731 patients were evaluated by bMRI. ECVs were recorded by questionnaire. Patients were assigned to categories by number of ECVs performed before enrollment (0, 1, ≥2). A bMRI study was conducted at baseline and after 2 years (n = 1227) and analyzed for large noncortical or cortical infarcts and small noncortical infarcts. Clinical outcomes were recorded during follow-up. Associations of ECV and outcome measures were assessed by multivariate analyses. RESULTS: There was no independent association between the number of ECVs and infarct prevalence (large noncortical or cortical infarcts and small noncortical infarcts) on baseline bMRI (ECV 1 vs 0: odds ratio [OR], 0.95 [95% CI, 0.68-1.24]; ECV ≥2 vs 0: OR, 1.04 [0.72-1.44]) or between ECVs performed during follow-up and new infarcts on bMRI at 2 years (OR, 1.46 [0.54-3.31]). ECVs were not associated with overt stroke or transient ischemic attack (ECV 1 vs 0: hazard ratio [HR], 1.36 [0.88-2.10]; ECV ≥2 vs 0: HR, 1.53 [0.94-2.48]), hospitalization for heart failure (ECV 1 vs 0: HR, 1.06 [0.82-1.37]; ECV ≥2 vs 0: HR, 1.03 [0.77-1.38]), or death (ECV 1 vs 0: HR, 0.90 [0.70-1.15]; ECV ≥2 vs 0: HR, 0.91 [0.69-1.20]). CONCLUSION: There was no association between ECV performed before enrollment and cerebral infarcts on baseline bMRI or between ECV performed during follow-up and new infarcts at 2 years. Moreover, ECV was not associated with clinical events.

A Systematic Review of Ongoing Registered Research Studies on Post-Operative Atrial Fibrillation after Cardiac Surgery.

Background/Objectives: New-onset atrial fibrillation (AF) after cardiac surgery is associated with patient-important outcomes. Uncertainty persists regarding its prevention, detection, and management. This review seeks to identify, compile, and describe ongoing registered research studies involving patients with or at risk for post-operative AF (POAF) after cardiac surgery. Methods: We searched clinical trial registries in January 2023 for studies focusing on POAF prediction, prevention, detection, or management. We extracted data from each record and performed descriptive analyses. Results: In total, 121 studies met the eligibility criteria, including 82 randomized trials. Prevention studies are the most common (n = 77, 63.6%), followed by prediction (n = 21, 17.4%), management (n = 16, 13.2%), and detection studies (n = 7, 5.8%). POAF after cardiac surgery is an area of active research. Conclusions: There are many ongoing randomized prevention studies. However, two major clinical gaps persist; future randomized trials should compare rate and rhythm control in patients who develop POAF, and long-term follow-up studies should investigate strategies to monitor for AF recurrence in patients with POAF.

Sex-specific association of cardiovascular drug doses with adverse outcomes in atrial fibrillation.

OBJECTIVES: Sex differences occur in atrial fibrillation (AF), including age at first manifestation, pathophysiology, treatment allocation, complication rates and quality of life. However, optimal doses of cardiovascular pharmacotherapy used in women with AF with or without heart failure (HF) are unclear. We investigated sex-specific associations of beta-blocker and renin-angiotensin system (RAS) inhibitor doses with cardiovascular outcomes in patients with AF or AF with concomitant HF. METHODS: We used data from the prospective Basel Atrial Fibrillation and Swiss Atrial Fibrillation cohorts on patients with AF. The outcome was major adverse cardiovascular events (MACEs), including death, myocardial infarction, stroke, systemic embolisation and HF-related hospitalisation. Predictors of interest were spline (primary analysis) or quartiles (secondary analysis) of beta-blocker or RAS inhibitor dose in per cent of the maximum dose (reference), in interaction with sex. Cox models were adjusted for demographics, comorbidities and comedication. RESULTS: Among 3961 patients (28% women), MACEs occurred in 1113 (28%) patients over a 5-year median follow-up. Distributions of RAS inhibitor and beta-blocker doses were similar in women and men. Cox models revealed no association between beta-blocker dose or RAS inhibitor dose and MACE. In a subgroup of patients with AF and HF, the lowest hazard of MACE was observed in women prescribed 100% of the RAS inhibitor dose. However, there was no association between RAS dose quartiles and MACE. CONCLUSIONS: In this study of patients with AF, doses of beta-blockers and RAS inhibitors did not differ by sex and were not associated with MACE overall.

Associations of inflammatory biomarkers with morbidity and mortality after noncardiac surgery: A systematic review and meta-analysis.

BACKGROUND: Noncardiac surgery is associated with an inflammatory response. Whether increased inflammation in the perioperative period is associated with subsequent morbidity and mortality is unknown. METHODS: MEDLINE, EMBASE, and CENTRAL were systematically searched from date of inception until May 2023. Longitudinal studies were included if they reported multivariable adjusted associations of biomarkers measured preoperatively and/or within 10 days after surgery with at least one prespecified adverse outcome in noncardiac surgery patients. Data were extracted independently and in duplicate. Risk estimates were pooled using DerSimonian-Laird random-effects models and reported as summary odds ratios (ORs) with 95% CIs. The outcomes were all-cause mortality and major adverse cardiovascular events. RESULTS: Fifty-two studies with a total of 121,849 patients were included. The median follow-up was 56 [IQR, 28-63] months and the average age was 57 (±3) years. Elevated preoperative C-reactive protein (CRP) levels were associated with a higher risk of mortality (OR 1.57, 95% CI 1.29-1.90, I2 = 93%, 28 studies). This association was stronger in non-cancer surgery populations (OR 2.10, 95% CI 1.92-2.31, I2 = 0%, 4 studies) when compared to cancer surgery populations (OR 1.51, 95% CI 1.26-1.81, I2 = 83%, 24 studies) (p for subgroup difference = 0.001). Similarly, higher postoperative CRP levels were associated with all-cause mortality (OR 1.61, 95% CI 1.17-2.20, I2 = 90%, 7 studies). Higher preoperative CRP levels were associated with major cardiovascular events (OR 2.11, 95% CI 1.51-2.94, I2 = 0%, 2 studies). Other preoperatively measured biomarkers associated with all-cause mortality were fibrinogen (OR 1.48, 95% CI 1.05-2.09, I2 = 52%, 5 studies), interleukin-6 (OR 1.17, 95% CI 1.07-1.28, I2 = 27%, 3 studies), and tumour necrosis factor-alpha (OR 1.37, 95% CI 1.16-1.61, I2 = 0%, 2 studies). CONCLUSION AND RELEVANCE: Inflammatory biomarker levels in the perioperative period were associated with all-cause mortality and adverse cardiovascular events in patients undergoing noncardiac surgery.

Prevalence and outcomes of heart failure phenotypes in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is common in patients with heart failure (HF). Real-world data about long-term outcomes and rhythm control interventions use in AF patients with and without HF remain scarce. METHODS: AF patients from two prospective, multicentre studies were classified based on the HF status at baseline into: HF with preserved ejection fraction (HFpEF), HF with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF), and no HF. The prespecified primary outcome was risk of HF hospitalisation. Other outcomes of interest included mortality, cardiovascular events, AF progression, and quality of life. RESULTS: A total of 1265 patients with AF were analysed (mean age 69.6 years, women 27.4%) with a median follow-up of 5.98 years. Patients with HFpEF (n = 126) had a 2.69-fold and patients with HFrEF/HFmrEF (n = 308) had a 2.12-fold increased risk of HF hospitalisation compared to patients without HF (n = 831, p < 0.001). Similar results applied for all-cause and cardiovascular mortality. The risk for AF progression was higher for patients with HFpEF and HFrEF/HFmrEF (6.30 and 6.79 per 100 patient-years, respectively) compared to patients without HF (4.20). The use of rhythm control strategies during follow-up was least in the HFpEF population (4.56 per 100 patient-years) compared to 7.74 in HFrEF/HFmrEF and 8.03 in patients with no HF. With regards to quality of life over time, this was worst among HFpEF patients. CONCLUSIONS: The presence of HFpEF among patients with AF carried a high risk of HF hospitalisations and AF progression, and worse quality of life. Rhythm control interventions were rarely offered to HFpEF patients. These results uncover an unmet need for enhanced therapeutic interventions in patients with AF and HFpEF.

Sodium Intake and Incident Atrial Fibrillation in Individuals With Vascular Disease.

Importance: Numerous prospective cohort studies have reported a J-shaped association of urinary sodium excretion with cardiovascular events and mortality. Objective: To study the association between sodium intake and incident atrial fibrillation (AF). Design, Setting, and Participants: This cohort study included participants in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) and Telmisartan Randomised Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND) multicenter, randomized clinical trials comparing the effect of ramipril 10 mg daily with telmisartan 80 mg daily, or their combination (ONTARGET) or 80 mg telmisartan daily with placebo (TRANSCEND) for the outcome of death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure. ONTARGET and TRANSCEND included 31 546 participants with vascular disease or high-risk diabetes, and this study excluded participants without a urine sample for sodium measurement, missing data for key covariates, a history of AF, or AF detected in the first year after enrollment. Analyses were performed in July 2023 to May 2024. Exposure: Estimated sodium intake from a morning fasting urine sample (Kawasaki formula). Main Outcomes and Measures: The main outcome was incident AF. The association between estimated sodium intake and incident AF was modeled using multivariable adjusted Cox regression and cubic splines. Results: A total of 27 391 participants (mean [SD] age, 66.3 [7.2] years; 19 310 [70.5%] male) were included. Mean (SD) estimated sodium intake was 4.8 (1.6) g/d. During a mean (SD) follow-up of 4.6 (1.0) years, 1562 participants (5.7%) had incident AF. After multivariable adjustment, a J-shaped association between sodium intake and AF risk was observed (P for nonlinearity = .03). Sodium intake of 8 g/d or greater (3% of participants) was associated with incident AF (hazard ratio, 1.32; 95% CI, 1.01-1.74) compared with sodium intake of 4 to 5.99 g/d. Cubic splines showed that sodium intake greater than 6 g/d (19% of participants) was associated with a 10% increased AF risk per additional 1-g/d sodium intake (hazard ratio, 1.10; 95% CI, 1.03-1.18), but with no further lowering of AF risk at lower levels of sodium intake. Conclusions and Relevance: In this cohort study of sodium intake and AF risk, there was a J-shaped association between sodium intakes and AF risk in patients with cardiovascular disease or diabetes. Lowering sodium intake for AF prevention is best targeted at individuals who consume high sodium diets.

Risk Factors for Hospital Readmission Following Noncardiac Surgery: International Cohort Study.

Objective: To determine timing and risk factors associated with readmission within 30 days of discharge following noncardiac surgery. Background: Hospital readmission after noncardiac surgery is costly. Data on the drivers of readmission have largely been derived from single-center studies focused on a single surgical procedure with uncertainty regarding generalizability. Methods: We undertook an international (28 centers, 14 countries) prospective cohort study of a representative sample of adults ≥45 years of age who underwent noncardiac surgery. Risk factors for readmission were assessed using Cox regression (ClinicalTrials.gov, NCT00512109). Results: Of 36,657 eligible participants, 2744 (7.5%; 95% confidence interval [CI], 7.2-7.8) were readmitted within 30 days of discharge. Rates of readmission were highest in the first 7 days after discharge and declined over the follow-up period. Multivariable analyses demonstrated that 9 baseline characteristics (eg, cancer treatment in past 6 months; adjusted hazard ratio [HR], 1.44; 95% CI, 1.30-1.59), 5 baseline laboratory and physical measures (eg, estimated glomerular filtration rate or on dialysis; HR, 1.47; 95% CI, 1.24-1.75), 7 surgery types (eg, general surgery; HR, 1.86; 95% CI, 1.61-2.16), 5 index hospitalization events (eg, stroke; HR, 2.21; 95% CI, 1.24-3.94), and 3 other factors (eg, discharge to nursing home; HR, 1.61; 95% CI, 1.33-1.95) were associated with readmission. Conclusions: Readmission following noncardiac surgery is common (1 in 13 patients). We identified perioperative risk factors associated with 30-day readmission that can help frontline clinicians identify which patients are at the highest risk of readmission and target them for preventive measures.

Barriers and facilitators to perioperative smoking cessation: A scoping review.

OBJECTIVE: Smoking cessation interventions are underutilized in the surgical setting. We aimed to systematically identify the barriers and facilitators to smoking cessation in the surgical setting. METHODS: Following the Joanna Briggs Institute (JBI) framework for scoping reviews, we searched 5 databases (MEDLINE, Embase, Cochrane CENTRAL, CINAHL, and PsycINFO) for quantitative or qualitative studies published in English (since 2000) evaluating barriers and facilitators to perioperative smoking cessation interventions. Data were analyzed using thematic analysis and mapped to the theoretical domains framework (TDF). RESULTS: From 31 studies, we identified 23 unique barriers and 13 facilitators mapped to 11 of the 14 TDF domains. The barriers were within the domains of knowledge (e.g., inadequate knowledge of smoking cessation interventions) in 23 (74.2%) studies; environmental context and resources (e.g., lack of time to deliver smoking cessation interventions) in 19 (61.3%) studies; beliefs about capabilities (e.g., belief that patients are nervous about surgery/diagnosis) in 14 (45.2%) studies; and social/professional role and identity (e.g., surgeons do not believe it is their role to provide smoking cessation interventions) in 8 (25.8%) studies. Facilitators were mainly within the domains of environmental context and resources (e.g., provision of quit smoking advice as routine surgical care) in 15 (48.4%) studies, reinforcement (e.g., surgery itself as a motivator to kickstart quit attempts) in 8 (25.8%) studies, and skills (e.g., smoking cessation training and awareness of guidelines) in 5 (16.2%) studies. CONCLUSION: The identified barriers and facilitators are actionable targets for future studies aimed at translating evidence informed smoking cessation interventions into practice in perioperative settings. More research is needed to evaluate how targeting these barriers and facilitators will impact smoking outcomes.

Heart rate variability and stroke or systemic embolism in patients with atrial fibrillation.

BACKGROUND: Stroke remains one of the most serious complications in atrial fibrillation (AF) patients and has been linked to disturbances of the autonomic nervous system. OBJECTIVE: The purpose of this study was to test the hypothesis that impaired cardiac autonomic function might be associated with an enhanced stroke risk in AF patients. METHODS: A total of 1922 AF patients who were in either sinus rhythm (SR group; n = 1121) or AF (AF group; n = 801) on a 5-minute resting electrocardiographic (ECG) recording were enrolled in the study. Heart rate variability triangular index (HRVI), standard deviation of normal-to-normal intervals, root mean square root of successive differences of normal-to-normal intervals, mean heart rate, 5-minute total power, and power in the high-frequency, low-frequency, and very-low-frequency ranges were calculated. Cox regression models were constructed to examine the association of heart rate variability (HRV) parameters with the composite endpoint of stroke or systemic embolism. RESULTS: Mean age was 71 ± 8 years in the SR group and 75 ± 8 years in the AF group. Thirty-seven patients in the SR group (3.4%) and 60 patients in the AF group (8.0%) experienced a stroke or systemic embolism during follow-up of 5 years. In patients with SR, HRVI <15 was the strongest HRV parameter to be associated with stroke or systemic embolism (hazard ratio 3.04; 95% confidence interval 1.3-7.0; P = .009) after adjustment for multiple confounders. In the AF group, no HRV parameter was found to be associated with the composite endpoint. CONCLUSION: HRVI measured during SR on a single 5-minute ECG recording is independently associated with stroke or systemic embolism in AF patients. HRV analysis in SR may help to improve risk stratification in AF patients.

Incidence and Risk Factors of Chronic Postoperative Pain in Same-day Surgery: A Prospective Cohort Study.

BACKGROUND: The amount of same-day surgery has increased markedly worldwide in recent decades, but there remains limited evidence on chronic postsurgical pain in this setting. METHODS: This study assessed pain 90 days after ambulatory surgery in an international, multicenter prospective cohort study of patients at least 45 yr old with comorbidities or at least 65 yr old. Pain was assessed using the Brief Pain Inventory. Chronic postsurgical pain was defined as a change of more than 1 point in self-rated average pain at the surgical site between baseline and 90 days, and moderate to severe chronic postsurgical pain was defined as a score greater than 4 in self-rated average pain at the surgical site at 90 days. Risk factors for chronic postsurgical pain were identified using multivariable logistic regression. RESULTS: Between November 2021 and January 2023, a total of 2,054 participants were included, and chronic postsurgical pain occurred in 12% of participants, of whom 93.1% had new chronic pain at the surgical site (i.e., participants without pain before surgery). Moderate to severe chronic postsurgical pain occurred in 9% of overall participants. Factors associated with chronic postsurgical pain were active smoking (odds ratio, 1.82; 95% CI, 1.20 to 2.76), orthopedic surgery (odds ratio, 4.7; 95% CI, 2.24 to 9.7), plastic surgery (odds ratio, 4.3; 95% CI, 1.97 to 9.2), breast surgery (odds ratio, 2.74; 95% CI, 1.29 to 5.8), vascular surgery (odds ratio, 2.71; 95% CI, 1.09 to 6.7), and ethnicity (i.e., for Hispanic/Latino ethnicity, odds ratio, 3.41; 95% CI, 1.68 to 6.9 and for First Nations/native persons, odds ratio, 4.0; 95% CI, 1.05 to 15.4). CONCLUSIONS: Persistent postsurgical pain after same-day surgery is common, is usually moderate to severe in nature, and occurs mostly in patients without chronic pain before surgery.

Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits.

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10-8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10-126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10-44) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 × 10-34). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research.

Atrial Fibrillation Ablation in Heart Failure With Reduced vs Preserved Ejection Fraction: A Systematic Review and Meta-Analysis.

Importance: Catheter ablation is associated with reduced heart failure (HF) hospitalization and death in select patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF). However, the benefit in patients with HF with preserved ejection fraction (HFpEF) is uncertain. Objective: To investigate whether catheter ablation for AF is associated with reduced HF-related outcomes according to HF phenotype. Data Source: A systematic search of MEDLINE, Embase, and Cochrane Central was conducted among studies published from inception to September 2023. Study Selection: Parallel-group randomized clinical trials (RCTs) comparing catheter ablation with conventional rate or rhythm control therapies in patients with HF, New York Heart Association functional class II or greater, and a history of paroxysmal or persistent AF were included. Pairs of independent reviewers screened 7531 titles and abstracts, of which 12 RCTs and 4 substudies met selection criteria. Data Extraction and Synthesis: Data were abstracted in duplicate according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Pooled effect estimates were calculated using random-effects Mantel-Haenszel models. Interaction P values were used to test for subgroup differences. Main Outcomes and Measures: The primary outcome was HF events, defined as HF hospitalization, clinically significant worsening of HF, or unscheduled visits to a clinician for treatment intensification. Secondary outcomes included cardiovascular and all-cause mortality. Results: A total of 12 RCTs with 2465 participants (mean [SD] age, 65.3 [9.7] years; 658 females [26.7%]) were included; there were 1552 participants with HFrEF and 913 participants with HFpEF. Compared with conventional rate or rhythm control, catheter ablation was associated with reduced risk of HF events in HFrEF (risk ratio [RR], 0.59; 95% CI, 0.48-0.72), while there was no benefit in patients with HFpEF (RR, 0.93; 95% CI, 0.65-1.32) (P for interaction = .03). Catheter ablation was associated with reduced risk of cardiovascular death compared with conventional therapies in HFrEF (RR, 0.49; 95% CI, 0.34-0.70) but a differential association was not detected in HFpEF (RR, 0.91; 95% CI, 0.46-1.79) (P for interaction = .12). Similarly, no difference in the association of catheter ablation with all-cause mortality was found between HFrEF (RR vs conventional therapies, 0.63; 95% CI, 0.47-0.86) and HFpEF (RR vs conventional therapies, 0.95; 95% CI, 0.39-2.30) groups (P for interaction = .39). Conclusions and Relevance: This study found that catheter ablation for AF was associated with reduced risk of HF events in patients with HFrEF but had limited or no benefit in HFpEF. Results from ongoing trials may further elucidate the role of catheter ablation for AF in HFpEF.

Recurrence of new-onset post-operative AF after cardiac surgery: detected by implantable loop recorders: A systematic review and Meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is one of the most common complications after cardiac surgery. New-onset post-operative AF may signal an elevated risk of AF and associated outcomes in long-term follow-up. We aimed to estimate the rate of AF recurrence as detected by an implantable loop recorder (ILR) in patients experiencing post-operative AF within 30 days after cardiac surgery. METHODS: We searched MEDLINE, Embase and Cochrane CENTRAL to April 2023 for studies of adults who did not have known AF, experienced new-onset AF within 30 days of cardiac surgery and received an ILR. We pooled individual participant data on timing of AF recurrence using a random-effects model with a frailty model applied to a Cox proportional hazard analysis. RESULTS: From 8671 citations, 8 single-centre prospective cohort studies met eligibility criteria. Data were available from 185 participants in 7 studies, with a median follow-up of 1.7 (IQR: 1.3-2.8) years. All included studies were at a low risk of bias. Pooled AF recurrence rates following 30 post-operative days were 17.8% (95% CI 11.9%-23.2%) at 3 months, 24.4% (17.7%-30.6%) at 6 months, 30.1% (22.8%-36.7%) at 12 months and 35.3% (27.6%-42.2%) at 18 months. CONCLUSIONS: In patients who experience new-onset post-operative AF after cardiac surgery, AF recurrence lasting at least 30 s occurs in approximately 1 in 3 in the first year after surgery. The optimal frequency and modality to use for monitoring for AF recurrence in this population remain uncertain.

Sex-specific differences in physiological parameters related to SARS-CoV-2 infections among a national cohort (COVI-GAPP study).

Considering sex as a biological variable in modern digital health solutions, we investigated sex-specific differences in the trajectory of four physiological parameters across a COVID-19 infection. A wearable medical device measured breathing rate, heart rate, heart rate variability, and wrist skin temperature in 1163 participants (mean age = 44.1 years, standard deviation [SD] = 5.6; 667 [57%] females). Participants reported daily symptoms and confounders in a complementary app. A machine learning algorithm retrospectively ingested daily biophysical parameters to detect COVID-19 infections. COVID-19 serology samples were collected from all participants at baseline and follow-up. We analysed potential sex-specific differences in physiology and antibody titres using multilevel modelling and t-tests. Over 1.5 million hours of physiological data were recorded. During the symptomatic period of infection, men demonstrated larger increases in skin temperature, breathing rate, and heart rate as well as larger decreases in heart rate variability than women. The COVID-19 infection detection algorithm performed similarly well for men and women. Our study belongs to the first research to provide evidence for differential physiological responses to COVID-19 between females and males, highlighting the potential of wearable technology to inform future precision medicine approaches.

Patients on vitamin K treatment: is switching to direct-acting oral anticoagulation cost-effective? A target trial on a prospective cohort.

AIMS: Direct-acting oral anticoagulants (DOACs) have, to a substantial degree, replaced vitamin K antagonists (VKA) as treatments for stroke prevention in atrial fibrillation (AF) patients. However, evidence on the real-world causal effects of switching patients from VKA to DOAC is lacking. We aimed to assess the empirical incremental cost-effectiveness of switching patients to DOAC compared with maintaining VKA treatment. METHODS: The target trial approach was applied to the prospective observational Swiss-AF cohort, which enrolled 2415 AF patients from 2014 to 2017. Clinical data, healthcare resource utilisation and EQ-5D-based utilities representing quality of life were collected in yearly follow-ups. Health insurance claims were available for 1024 patients (42.4%). Overall survival, quality-of-life, costs from the Swiss statutory health insurance perspective and cost-effectiveness were estimated by emulating a target trial in which patients were randomly assigned to switch to DOAC or maintain VKA treatment. RESULTS: 228 patients switching from VKA to DOAC compared with 563 patients maintaining VKA treatment had no overall survival advantage over a 5-year observation period (HR 0.99, 95% CI 0.45, 1.55). The estimated gain in quality-adjusted life years (QALYs) was 0.003 over the 5-year period at an incremental costs of CHF 23 033 (€ 20 940). The estimated incremental cost-effectiveness ratio was CHF 425 852 (€ 387 138) per QALY gained. CONCLUSIONS: Applying a causal inference method to real-world data, we could not demonstrate switching to DOACs to be cost-effective for AF patients with at least 1 year of VKA treatment. Our estimates align with results from a previous randomised trial.

Mineralocorticoid receptor antagonists and atrial fibrillation: a meta-analysis of clinical trials.

BACKGROUND AND AIMS: Mineralocorticoid receptor antagonists (MRAs) improve cardiovascular outcomes in a variety of settings. This study aimed to assess whether cardioprotective effects of MRAs are modified by heart failure (HF) and atrial fibrillation (AF) status and to study their impact on AF events. METHODS: MEDLINE, Embase, and Cochrane Central databases were searched to 24 March 2023 for randomized controlled trials evaluating the efficacy of MRAs as compared with placebo or usual care in reducing cardiovascular outcomes and AF events in patients with or at risk for cardiovascular diseases. Random-effects models and interaction analyses were used to test for effect modification. RESULTS: Meta-analysis of seven trials (20 741 participants, mean age: 65.6 years, 32% women) showed that the efficacy of MRAs, as compared with placebo, in reducing a composite of cardiovascular death or HF hospitalization remains consistent across patients with HF [risk ratio = 0.81; 95% confidence interval (CI): 0.67-0.98] and without HF (risk ratio = 0.84; 95% CI: 0.75-0.93; interaction P = .77). Among patients with HF, MRAs reduced cardiovascular death or HF hospitalization in patients with AF (hazard ratio = 0.95; 95% CI: 0.54-1.66) to a similar extent as in those without AF (hazard ratio = 0.82; 95% CI: 0.63-1.07; interaction P = .65). Pooled data from 20 trials (21 791 participants, mean age: 65.2 years, 31.3% women) showed that MRAs reduce AF events (risk ratio = 0.76; 95% CI: 0.67-0.87) in both patients with and without prior AF. CONCLUSIONS: Mineralocorticoid receptor antagonists are similarly effective in preventing cardiovascular events in patients with and without HF and most likely retain their efficacy regardless of AF status. Mineralocorticoid receptor antagonists may also be moderately effective in preventing incident or recurrent AF events.

Omega-3 Fatty Acids and Markers of Thrombosis in Patients with Atrial Fibrillation.

Omega-3 fatty acids (n-3 FAs) are associated with a lower risk of ischemic stroke in patients with atrial fibrillation (AF). Antithrombotic mechanisms may in part explain this observation. Therefore, we examined the association of n-3 FAs with D-dimer and beta-thromboglobulin (BTG), markers for activated coagulation and platelets, respectively. The n-3 FAs eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and alpha-linolenic acid (ALA) were determined via gas chromatography in the whole blood of 2373 patients with AF from the Swiss Atrial Fibrillation cohort study (ClinicalTrials.gov Identifier: NCT02105844). In a cross-sectional analysis, we examined the association of total n-3 FAs (EPA + DHA + DPA + ALA) and the association of individual fatty acids with D-dimer in patients with detectable D-dimer values (n = 1096) as well as with BTG (n = 2371) using multiple linear regression models adjusted for confounders. Median D-dimer and BTG levels were 0.340 ug/mL and 448 ng/mL, respectively. Higher total n-3 FAs correlated with lower D-dimer levels (coefficient 0.94, 95% confidence interval (Cl) 0.90-0.98, p = 0.004) and lower BTG levels (coefficient 0.97, Cl 0.95-0.99, p = 0.003). Likewise, the individual n-3 FAs EPA, DHA, DPA and ALA showed an inverse association with D-dimer. Higher levels of DHA, DPA and ALA correlated with lower BTG levels, whereas EPA showed a positive association with BTG. In patients with AF, higher levels of n-3 FAs were associated with lower levels of D-dimer and BTG, markers for activated coagulation and platelets, respectively. These findings suggest that n-3 FAs may exert antithrombotic properties in patients with AF.