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.

Association of chocolate consumption with neurological and cardiovascular outcomes in atrial fibrillation: data from two Swiss atrial fibrillation cohort studies (Swiss-AF and BEAT-AF).

AIM: To assess the associations of chocolate consumption with neurocognitive function, brain lesions on magnetic resonance imaging (MRI), and cardiovascular outcome in patients with atrial fibrillation (AF). METHODS: We analysed data from patients of two prospective multicentre Swiss atrial fibrillation cohort studies (Swiss-AF) and (BEAT-AF). Assessments of MRI findings and neurocognitive function were performed only in the Swiss-AF population (in 1727 of 2415 patients [71.5%] with a complete data set), as patients enrolled in BEAT-AF were not systematically evaluated for these outcomes. Otherwise, the two cohorts had an equivalent set of clinical assessments. Clinical outcome analysis was performed in 3931 patients of both cohorts. Chocolate consumption was assessed by questionnaire. Patients were categorised as no/low chocolate consumption (No/Low-Ch) ≤1 servings/week, moderate chocolate consumption (Mod-Ch) >1-6 servings/week, and high chocolate consumption (High-Ch) >6 servings/week, respectively. Brain lesions were evaluated by MRI. Assessment of cognitive function was performed by neurocognitive functional testing and included global cognition measurement with a cognitive construct score. Cerebral MRI and cognition were evaluated at baseline. Cross-sectional associations between chocolate consumption and MRI findings were analysed by multivariate logistic regression models and associations with neurocognitive function by multivariate linear regression models. Clinical outcome events during follow-up were recorded and assessed by a clinical event committee. The associations between chocolate consumption and clinical outcomes were evaluated by Cox regression models. The median follow-up time was 6 years. RESULTS: Chocolate consumption was not associated with prevalence or volume of vascular brain lesions on MRI, nor major adverse cardiac events (ischaemic stroke, myocardial infarction, cardiovascular death). However, No/Low-Ch was independently associated with a lower cognitive construct score compared to Mod-Ch (No/Low-Ch vs. Mod-Ch: coeff. -0.05, 95% CI -0.10-0), whereas other neurocognitive function tests were not independently associated with chocolate consumption categories. In addition, there was a higher risk of heart failure hospitalisation (No/Low-Ch vs. Mod-Ch: HR 1.24, 95% CI 1.01-1.52) and of all-cause mortality (No/Low-Ch vs. Mod-Ch: HR 1.29, 95% CI 1.06-1.58) in No/Low-Ch compared to Mod-Ch. No significant associations with the evaluated outcomes were observed when High-Ch was compared to Mod-Ch. CONCLUSION: While chocolate consumption was not associated with MRI findings and major adverse cardiac events in an atrial fibrillation population, No/Low-Ch was associated with a lower cognitive construct score, higher risk of heart failure hospitalisation and increased all-cause mortality compared to Mod-Ch. CLINICALTRIALS: gov Identifier: NCT02105844.

Role of genetic testing in young patients with idiopathic atrioventricular conduction disease.

AIMS: To investigate the role of genetic testing in patients with idiopathic atrioventricular conduction disease requiring pacemaker (PM) implantation before the age of 50 years. METHODS AND RESULTS: All consecutive PM implantations in Southern Switzerland between 2010 and 2019 were evaluated. Inclusion criteria were: (i) age at the time of PM implantation: < 50 years; (ii) atrioventricular block (AVB) of unknown aetiology. Study population was investigated by ajmaline challenge and echocardiographic assessment over time. Genetic testing was performed using next-generation sequencing panel, containing 174 genes associated to inherited cardiac diseases, and Sanger sequencing confirmation of suspected variants with clinical implication. Of 2510 patients who underwent PM implantation, 15 (0.6%) were young adults (median age: 44 years, male predominance) presenting with advanced AVB of unknown origin. The average incidence of idiopathic AVB computed over the 2010-2019 time window was 0.7 per 100 000 persons per year (95% CI 0.4-1.2). Most of patients (67%) presented with specific genetic findings (pathogenic variant) or variants of uncertain significance (VUS). A pathogenic variant of PKP2 gene was found in one patient (6.7%) with no overt structural cardiac abnormalities. A VUS of TRPM4, MYBPC3, SCN5A, KCNE1, LMNA, GJA5 genes was found in other nine cases (60%). Of these, three unrelated patients (20%) presented the same heterozygous missense variant c.2531G > A p.(Gly844Asp) in TRPM4 gene. Diagnostic re-assessment over time led to a diagnosis of Brugada syndrome and long-QT syndrome in two patients (13%). No cardiac events occurred during a median follow-up of 72 months. CONCLUSION: Idiopathic AVB in adults younger than 50 years is a very rare condition with an incidence of 0.7 per 100 000 persons/year. Systematic investigations, including genetic testing and ajmaline challenge, can lead to the achievement of a specific diagnosis in up to 20% of patients. Heterozygous missense variant c.2531G > A p.(Gly844Asp) in TRPM4 gene was found in an additional 20% of unrelated patients, suggesting possible association of the variant with the disease.

Physical activity and brain health in patients with atrial fibrillation.

BACKGROUND AND PURPOSE: Vascular brain lesions, such as ischemic infarcts, are common among patients with atrial fibrillation (AF) and are associated with impaired cognitive function. The role of physical activity (PA) in the prevalence of brain lesions and cognition in AF has not been investigated. METHODS: Patients from the multicenter Swiss-AF cohort study were included in this cross-sectional analysis. We assessed regular exercise (RE; at least once weekly) and minutes of weekly PA using a validated questionnaire. We studied associations with ischemic infarcts, white matter hyperintensities, cerebral microbleeds, and brain volume on brain magnetic resonance imaging and with global cognition measured with a cognitive construct (CoCo) score. RESULTS: Among 1490 participants (mean age = 72 ± 9 years), 730 (49%) engaged in RE. In adjusted regression analyses, RE was associated with a lower prevalence of ischemic infarcts (odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.63-0.98, p = 0.03) and of moderate to severe white matter hyperintensities (OR = 0.78, 95% CI = 0.62-0.99, p = 0.04), higher brain volume (ß-coefficient = 10.73, 95% CI = 2.37-19.09, p = 0.01), and higher CoCo score (ß-coefficient = 0.08, 95% CI = 0.03-0.12, p < 0.001). Increasing weekly PA was associated with higher brain volume (ß-coefficient = 1.40, 95% CI = 0.65-2.15, p < 0.001). CONCLUSIONS: In AF patients, RE was associated with a lower prevalence of ischemic infarcts and of moderate to severe white matter disease, with larger brain volume, and with better cognitive performance. Prospective studies are needed to investigate whether these associations are causal. Until then, our findings suggest that patients with AF should be encouraged to remain physically active.

Silent brain infarcts impact on cognitive function in atrial fibrillation.

AIMS: We aimed to investigate the association of clinically overt and silent brain lesions with cognitive function in atrial fibrillation (AF) patients. METHODS AND RESULTS: We enrolled 1227 AF patients in a prospective, multicentre cohort study (Swiss-AF). Patients underwent standardized brain magnetic resonance imaging (MRI) at baseline and after 2 years. We quantified new small non-cortical infarcts (SNCIs) and large non-cortical or cortical infarcts (LNCCIs), white matter lesions (WML), and microbleeds (Mb). Clinically, silent infarcts were defined as new SNCI/LNCCI on follow-up MRI in patients without a clinical stroke or transient ischaemic attack (TIA) during follow-up. Cognition was assessed using validated tests. The mean age was 71 years, 26.1% were females, and 89.9% were anticoagulated. Twenty-eight patients (2.3%) experienced a stroke/TIA during 2 years of follow-up. Of the 68 (5.5%) patients with ≥1 SNCI/LNCCI, 60 (88.2%) were anticoagulated at baseline and 58 (85.3%) had a silent infarct. Patients with brain infarcts had a larger decline in cognition [median (interquartile range)] changes in Cognitive Construct score [-0.12 (-0.22; -0.07)] than patients without new brain infarcts [0.07 (-0.09; 0.25)]. New WML or Mb were not associated with cognitive decline. CONCLUSION: In a contemporary cohort of AF patients, 5.5% had a new brain infarct on MRI after 2 years. The majority of these infarcts was clinically silent and occurred in anticoagulated patients. Clinically, overt and silent brain infarcts had a similar impact on cognitive decline. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02105844, https://clinicaltrials.gov/ct2/show/NCT02105844.

Long-term risk of adverse outcomes according to atrial fibrillation type.

Sustained forms of atrial fibrillation (AF) may be associated with a higher risk of adverse outcomes, but few if any long-term studies took into account changes of AF type and co-morbidities over time. We prospectively followed 3843 AF patients and collected information on AF type and co-morbidities during yearly follow-ups. The primary outcome was a composite of stroke or systemic embolism (SE). Secondary outcomes included myocardial infarction, hospitalization for congestive heart failure (CHF), bleeding and all-cause mortality. Multivariable adjusted Cox proportional hazards models with time-varying covariates were used to compare hazard ratios (HR) according to AF type. At baseline 1895 (49%), 1046 (27%) and 902 (24%) patients had paroxysmal, persistent and permanent AF and 3234 (84%) were anticoagulated. After a median (IQR) follow-up of 3.0 (1.9; 4.2) years, the incidence of stroke/SE was 1.0 per 100 patient-years. The incidence of myocardial infarction, CHF, bleeding and all-cause mortality was 0.7, 3.0, 2.9 and 2.7 per 100 patient-years, respectively. The multivariable adjusted (a) HRs (95% confidence interval) for stroke/SE were 1.13 (0.69; 1.85) and 1.27 (0.83; 1.95) for time-updated persistent and permanent AF, respectively. The corresponding aHRs were 1.23 (0.89, 1.69) and 1.45 (1.12; 1.87) for all-cause mortality, 1.34 (1.00; 1.80) and 1.30 (1.01; 1.67) for CHF, 0.91 (0.48; 1.72) and 0.95 (0.56; 1.59) for myocardial infarction, and 0.89 (0.70; 1.14) and 1.00 (0.81; 1.24) for bleeding. In this large prospective cohort of AF patients, time-updated AF type was not associated with incident stroke/SE.

Management of hemodynamically stable wide QRS complex tachycardia in patients with implantable cardioverter defibrillators.

Management of hemodynamically stable, incessant wide QRS complex tachycardia (WCT) in patients who already have an implantable cardioverter defibrillator (ICD) is challenging. First-line treatment is performed by medical staff who have no knowledge on programmed ICD therapy settings and there is always some concern for unexpected ICD shock. In these patients, a structured approach is necessary from presentation to therapy. The present review provides a systematic approach in four distinct phases to guide any physician involved in the management of these patients: PHASE I: assessment of hemodynamic status and use of the magnet to temporarily suspend ICD therapies, especially shocks; identification of possible arrhythmia triggers; risk stratification in case of electrical storm (ES). PHASE II: The preparation phase includes reversal of potential arrhythmia "triggers", mild patient sedation, and patient monitoring for therapy delivery. Based on resource availability and competences, the most adequate therapeutic approach is chosen. This choice depends on whether a device specialist is readily available or not. In the case of ES in a "high-risk" patient an accelerated patient management protocol is advocated, which considers urgent ventricular tachycardia transcatheter ablation with or without mechanical cardiocirculatory support. PHASE III: Therapeutic phase is based on the use of intravenous anti-arrhythmic drugs mostly indicated in this clinical context are presented. Device interrogation is very important in this phase when sustained monomorphic VT diagnosis is confirmed, then ICD ATP algorithms, based on underlying VT cycle length, are proposed. In high-risk patients with intractable ES, intensive patient management considers MCS and transcatheter ablation. PHASE IV: The patient is hospitalized for further diagnostics and management aimed at preventing arrhythmia recurrences.

Biomarkers of Inflammation and Risk of Hospitalization for Heart Failure in Patients With Atrial Fibrillation.

Background Hospitalization for heart failure (HF) is very common in patients with atrial fibrillation (AF). We hypothesized that biomarkers of inflammation can identify patients with AF at increased risk of this important complication. Methods and Results Patients with established AF were prospectively enrolled. Levels of hs-CRP (high-sensitivity C-reactive protein) and interleukin-6 were measured from plasma samples obtained at baseline. We calculated an inflammation score ranging from 0 to 4 (1 point for each biomarker between the 50th and 75th percentile, 2 points for each biomarker above the 75th percentile). Individual associations of biomarkers and the inflammation score with HF hospitalization were obtained from multivariable Cox proportional hazards models. A total of 3784 patients with AF (median age 72 years, 24% prior HF) were followed for a median of 4.0 years. The median (interquartile range) plasma levels of hs-CRP and interleukin-6 were 1.64 (0.81-3.69) mg/L and 3.42 (2.14-5.60) pg/mL, respectively. The overall incidence of HF hospitalization was 3.04 per 100 person-years and increased from 1.34 to 7.31 per 100 person-years across inflammation score categories. After multivariable adjustment, both biomarkers were significantly associated with the risk of HF hospitalization (per increase in 1 SD, adjusted hazard ratio [HR], 1.22; 95% CI, 1.11-1.34 for log-transformed hs-CRP; adjusted HR, 1.48; 95% CI, 1.35-1.62 for log-transformed interleukin-6). Similar results were obtained for the inflammation score (highest versus lowest score, adjusted HR, 2.43; 95% CI, 1.80-3.30; P value for trend <0.001). Conclusions Biomarkers of inflammation strongly predicted HF hospitalization in a large, contemporary sample of patients with AF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02105844.

Heart rate and adverse outcomes in patients with prevalent atrial fibrillation.

OBJECTIVE: The optimal target heart rate in patients with prevalent atrial fibrillation (AF) is not well defined. The aim of this study was to analyse the associations between heart rate and adverse outcomes in a large contemporary cohort of patients with prevalent AF. METHODS: From two prospective cohort studies, we included stable AF outpatients who were in AF on the baseline ECG. The main outcome events assessed during prospective follow-up were heart failure hospitalisation, stroke or systemic embolism and death. The associations between heart rate and adverse outcomes were evaluated using multivariable Cox regression models. RESULTS: The study population consisted of 1679 patients who had prevalent AF at baseline. Mean age was 74 years, and 24.6% were women. The mean heart rate on the baseline ECG was 78 (±19) beats per minute (bpm). The median follow-up was 3.9 years (IQR 2.2-5.0). Heart rate was not significantly associated with heart failure hospitalisation (adjusted HR (aHR) per 10 bpm increase, 1.00, 95% CI 0.94 to 1.07, p=0.95), stroke or systemic embolism (aHR 0.95, 95% CI 0.84 to 1.07, p=0.38) or death (aHR 1.02, 95% CI 0.95 to 1.09, p=0.66). There was no evidence of a threshold effect for heart rates <60 bpm or >100 bpm. CONCLUSIONS: In this large contemporary cohort of outpatients with prevalent AF, we found no association between heart rate and adverse outcome events. These data are in line with recommendations that strict heart rate control is not needed in otherwise stable outpatients with AF.

Alcohol consumption and risk of cardiovascular outcomes and bleeding in patients with established atrial fibrillation.

BACKGROUND: Little is known about the association between alcohol consumption and risk of cardiovascular events in patients with established atrial fibrillation (AF). The main aim of the current study was to investigate the associations of regular alcohol intake with incident stroke or systemic embolism in patients with established AF. METHODS: To assess the association between alcohol consumption and cardiovascular events in patients with established AF, we combined data from 2 comparable prospective cohort studies that followed 3852 patients with AF for a median of 3.0 years. Patients were grouped into 4 categories of daily alcohol intake (none, > 0 to < 1, 1 to < 2 and ≥ 2 drinks/d). The primary outcome was a composite of stroke and systemic embolism. Secondary outcomes were all-cause mortality, myocardial infarction, hospital admission for acute heart failure, and a composite of major and clinically relevant nonmajor bleeding. Associations were assessed using time-updated, multivariable-adjusted Cox proportional hazards models. RESULTS: Mean age (± standard deviation) was 71 ± 10 years (28% were women and 84% were on oral anticoagulants). We observed 136 confirmed strokes or systemic emboli. Compared with nondrinkers, adjusted hazard ratios for the primary outcome event were 0.87, 95% confidence interval (CI) 0.55-1.37 for > 0 to < 1 drinks/d; 0.70, 95% CI 0.39-1.25 for 1 to < 2 drinks/d; and 0.96, 95% CI 0.56-1.67 for ≥ 2 drinks/d (p for linear [quadratic] trend 0.71 [0.22]). There was no significant association between alcohol consumption and bleeding, but there was a nonlinear association with heart failure (p for quadratic trend 0.01) and myocardial infarction (p for quadratic trend 0.007). INTERPRETATION: In patients with AF, we did not find a significant association between low to moderate alcohol intake and risk of stroke or other cardiovascular events. Our findings do not support special recommendations for patients with established AF with regard to alcohol consumption. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT02105844.

Association of psychosocial factors with all-cause hospitalizations in patients with atrial fibrillation.

BACKGROUND: A high burden of cardiovascular comorbidities puts patients with atrial fibrillation (AF) at high risk for hospitalizations, but the role of other factors is less clear. HYPOTHESIS: To determine the relationship between psychosocial factors and the risk of unplanned hospitalizations in AF patients. METHODS: Prospective observational cohort study of 2378 patients aged 65 or older with previously diagnosed AF across 14 centers in Switzerland. Marital status and education level were defined as social factors, depression and health perception were psychological components. The pre-defined outcome was unplanned all-cause hospitalization. RESULTS: During a median follow-up of 2.0 years, a total of 1713 hospitalizations occurred in 37% of patients. Compared to patients who were married, adjusted rate ratios (aRR) for all-cause hospitalizations were 1.28 (95% confidence interval [CI], 0.97-1.69) for singles, 1.31 (95%CI, 1.06-1.62) for divorced patients, and 1.02 (95%CI, 0.82-1.25) for widowed patients. The aRRs for all-cause hospitalizations across increasing quartiles of health perception were 1.0 (highest health perception), 1.15 (95%CI, 0.84-1.59), 1.25 (95%CI, 1.03-1.53), and 1.66 (95%CI, 1.34-2.07). No different hospitalization rates were observed in patients with a secondary or primary or less education as compared to patients with a college degree (aRR, 1.06; 95%CI, 0.91-1.23 and 1.05; 95%CI, 0.83-1.33, respectively). Presence of depression was not associated with higher hospitalization rates (aRR, 0.94; 95%CI, 0.68-1.29). CONCLUSIONS: The findings suggest that psychosocial factors, including marital status and health perception, are strongly associated with the occurrence of hospitalizations in AF patients. Targeted psychosocial support interventions may help to avoid unnecessary hospitalizations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02105844.

Heart Rate Variability Triangular Index as a Predictor of Cardiovascular Mortality in Patients With Atrial Fibrillation.

Background Impaired heart rate variability (HRV) is associated with increased mortality in sinus rhythm. However, HRV has not been systematically assessed in patients with atrial fibrillation (AF). We hypothesized that parameters of HRV may be predictive of cardiovascular death in patients with AF. Methods and Results From the multicenter prospective Swiss-AF (Swiss Atrial Fibrillation) Cohort Study, we enrolled 1922 patients who were in sinus rhythm or AF. Resting ECG recordings of 5-minute duration were obtained at baseline. Standard parameters of HRV (HRV triangular index, SD of the normal-to-normal intervals, square root of the mean squared differences of successive normal-to-normal intervals and mean heart rate) were calculated. During follow-up, an end point committee adjudicated each cause of death. During a mean follow-up time of 2.6±1.0 years, 143 (7.4%) patients died; 92 deaths were attributable to cardiovascular reasons. In a Cox regression model including multiple covariates (age, sex, body mass index, smoking status, history of diabetes mellitus, history of hypertension, history of stroke/transient ischemic attack, history of myocardial infarction, antiarrhythmic drugs including ß blockers, oral anticoagulation), a decreased HRV index ≤ median (14.29), but not other HRV parameters, was associated with an increase in the risk of cardiovascular death (hazard ratio, 1.7; 95% CI, 1.1-2.6; P=0.01) and all-cause death (hazard ratio, 1.42; 95% CI, 1.02-1.98; P=0.04). Conclusions The HRV index measured in a single 5-minute ECG recording in a cohort of patients with AF is an independent predictor of cardiovascular mortality. HRV analysis in patients with AF might be a valuable tool for further risk stratification to guide patient management. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02105844.

Association of the CHA2D(S2)-VASc Score and Its Components With Overt and Silent Ischemic Brain Lesions in Patients With Atrial Fibrillation.

Background: Silent and overt ischemic brain lesions are common and associated with adverse outcome. Whether the CHA2DS2-VASc score and its components predict magnetic resonance imaging (MRI)-detected ischemic silent and overt brain lesions in patients with atrial fibrillation (AF) is unclear. Methods: In this cross-sectional analysis, patients with AF were enrolled in a multicenter cohort study in Switzerland. Outcomes were clinically overt, silent [in the absence of a history of stroke/transient ischemic attack (TIA)] and any MRI-detected ischemic brain lesions. Logistic regression analyses were performed to assess the relationship of the CHA2DS2-VASc score and its components with ischemic brain lesions. An adapted CHA2D-VASc score (excluding history of stroke/TIA) for the analyses of clinically overt and silent ischemic brain lesions was used. Results: Overall, 1,741 patients were included in the analysis (age 73 ± 8 years, 27.4% female). At least one ischemic brain lesion was observed in 36.8% (clinically overt: 10.5%; silent: 22.9%; transient ischemic attack: 3.4%). The CHA2D-VASc score was strongly associated with clinically overt and silent ischemic brain lesions {odds ratio (OR) [95% confidence interval (CI)] 1.32 (1.17-1.49), p < 0.001 and 1.20 (1.10-1.30), p < 0.001, respectively}. Age 65-74 years (OR 2.58; 95%CI 1.29-5.90; p = 0.013), age ≥75 years (4.13; 2.07-9.43; p < 0.001), hypertension (1.90; 1.28-2.88; p = 0.002) and diabetes (1.48; 1.00-2.18; p = 0.047) were associated with clinically overt brain lesions, whereas age 65-74 years (1.95; 1.26-3.10; p = 0.004), age ≥75 years (3.06; 1.98-4.89; p < 0.001) and vascular disease (1.39; 1.07-1.79; p = 0.012) were associated with silent ischemic brain lesions. Conclusions: A higher CHA2D-VASc score was associated with a higher risk of both overt and silent ischemic brain lesions. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02105844.

Incidence and Predictors of Atrial Fibrillation Progression.

Background The incidence and predictors of atrial fibrillation (AF) progression are currently not well defined, and clinical AF progression partly overlaps with rhythm control interventions (RCIs). Methods and Results We assessed AF type and intercurrent RCIs during yearly follow-ups in 2869 prospectively followed patients with paroxysmal or persistent AF. Clinical AF progression was defined as progression from paroxysmal to nonparoxysmal or from persistent to permanent AF. An RCI was defined as pulmonary vein isolation, electrical cardioversion, or new treatment with amiodarone. During a median follow-up of 3 years, the incidence of clinical AF progression was 5.2 per 100 patient-years, and 10.9 per 100 patient-years for any RCI. Significant predictors for AF progression were body mass index (hazard ratio [HR], 1.03; 95% CI, 1.01-1.05), heart rate (HR per 5 beats/min increase, 1.05; 95% CI, 1.02-1.08), age (HR per 5-year increase 1.19; 95% CI, 1.13-1.27), systolic blood pressure (HR per 5 mm Hg increase, 1.03; 95% CI, 1.00-1.05), history of hyperthyroidism (HR, 1.71; 95% CI, 1.16-2.52), stroke (HR, 1.50; 95% CI, 1.19-1.88), and heart failure (HR, 1.69; 95% CI, 1.34-2.13). Regular physical activity (HR, 0.80; 95% CI, 0.66-0.98) and previous pulmonary vein isolation (HR, 0.69; 95% CI, 0.53-0.90) showed an inverse association. Significant predictive factors for RCIs were physical activity (HR, 1.42; 95% CI, 1.20-1.68), AF-related symptoms (HR, 1.84; 95% CI, 1.47-2.30), age (HR per 5-year increase, 0.88; 95% CI, 0.85-0.92), and paroxysmal AF (HR, 0.61; 95% CI, 0.51-0.73). Conclusions Cardiovascular risk factors and comorbidities were key predictors of clinical AF progression. A healthy lifestyle may therefore reduce the risk of AF progression.

[One Case for Two]. / Ein Fall für zwei.

One Case for Two Abstract. We report on a 59-year-old patient with a rash, hypotension and chest pain after eating tuna fish. A diagnosis of scombroid fish poisoning was made. It is a syndrome resembling an allergic reaction that occurs after eating fish of the Scombridae family contaminated with high levels of histamine. The authorities responsible for food safety should be immediately informed in order to investigate the event from their perspective, i.e. inspect selling premises, sample and test implicated food, as well as to take appropriate measures. Anaphylaxis rarely manifests as a vasospastic acute coronary syndrome, called Kounis syndrome.

Relationships of Overt and Silent Brain Lesions With Cognitive Function in Patients With Atrial Fibrillation.

BACKGROUND: Patients with atrial fibrillation (AF) have an increased risk of cognitive decline, potentially resulting from clinically unrecognized vascular brain lesions. OBJECTIVES: This study sought to assess the relationships between cognitive function and vascular brain lesions in patients with AF. METHODS: Patients with known AF were enrolled in a multicenter study in Switzerland. Brain magnetic resonance imaging (MRI) and cognitive testing using the Montreal Cognitive Assessment (MoCA) were performed in all participants. Large noncortical or cortical infarcts (LNCCIs), small noncortical infarcts (SNCIs), microbleeds, and white matter lesions were quantified by a central core laboratory. Clinically silent infarcts were defined as infarcts on brain MRI in patients without a clinical history of stroke or transient ischemic attack. RESULTS: The study included 1,737 patients with a mean age of 73 ± 8 years (28% women, 90% taking oral anticoagulant agents). On MRI, LNCCIs were found in 387 patients (22%), SNCIs in 368 (21%), microbleeds in 372 (22%), and white matter lesions in 1715 (99%). Clinically silent infarcts among the 1,390 patients without a history of stroke or transient ischemic attack were found in 201 patients with LNCCIs (15%) and 245 patients with SNCIs (18%). The MoCA score was 24.7 ± 3.3 in patients with and 25.8 ± 2.9 in those without LNCCIs on brain MRI (p < 0.001). The difference in MoCA score remained similar when only clinically silent LNCCIs were considered (24.9 ± 3.1 vs. 25.8 ± 2.9; p < 0.001). In a multivariable regression model including all vascular brain lesion parameters, LNCCI volume was the strongest predictor of a reduced MoCA (ß = -0.26; 95% confidence interval: -0.40 to -0.13; p < 0.001). CONCLUSIONS: Patients with AF have a high burden of LNCCIs and other brain lesions on systematic brain MRI screening, and most of these lesions are clinically silent. LNCCIs were associated with worse cognitive function, even among patients with clinically silent infarcts. Our findings raise the question of MRI screening in patients with AF.