Mapping the interplay of atrial fibrillation, brain structure, and cognitive dysfunction.

INTRODUCTION: Atrial fibrillation (AF) is associated with an elevated risk of cognitive impairment and dementia. Understanding the cognitive sequelae and brain structural changes associated with AF is vital for addressing ensuing health care needs. METHODS AND RESULTS: We examined 1335 stroke-free individuals with AF and 2683 matched controls using neuropsychological assessments and multimodal neuroimaging. The analysis revealed that individuals with AF exhibited deficits in executive function, processing speed, and reasoning, accompanied by reduced cortical thickness, elevated extracellular free-water content, and widespread white matter abnormalities, indicative of small vessel pathology. Notably, brain structural differences statistically mediated the relationship between AF and cognitive performance. DISCUSSION: Integrating a comprehensive analysis approach with extensive clinical and magnetic resonance imaging data, our study highlights small vessel pathology as a possible unifying link among AF, cognitive decline, and abnormal brain structure. These insights can inform diagnostic approaches and motivate the ongoing implementation of effective therapeutic strategies. Highlights We investigated neuropsychological and multimodal neuroimaging data of 1335 individuals with atrial fibrillation (AF) and 2683 matched controls. Our analysis revealed AF-associated deficits in cognitive domains of attention, executive function, processing speed, and reasoning. Cognitive deficits in the AF group were accompanied by structural brain alterations including reduced cortical thickness and gray matter volume, alongside increased extracellular free-water content as well as widespread differences of white matter integrity. Structural brain changes statistically mediated the link between AF and cognitive performance, emphasizing the potential of structural imaging markers as a diagnostic tool in AF-related cognitive decline.

Oral anticoagulation in patients with left ventricular thrombus - a systematic review and meta-analysis.

AIMS: Direct oral anticoagulants (DOACs) are increasingly used off-label to treat patients with left ventricular thrombus (LVT). We analyzed available meta-data comparing DOACs and vitamin K antagonists (VKAs) for efficacy and safety. METHODS: We conducted a systematic search and meta-analysis of observational and randomized data comparing DOACs versus VKAs in patients with LVT. Endpoints of interest were stroke or systemic embolism, thrombus resolution, all-cause death, and a composite bleeding endpoint. Estimates were pooled using a random-effect model meta-analysis, and their robustness was investigated using sensitivity and influential analyses. RESULTS: We identified 22 articles (18 observational studies, 4 small randomized clinical trials) reporting on a total of 3,587 patients (2,489 VKA vs. 1,098 DOAC therapy). The pooled estimates for stroke or systemic embolism (OR 0.81; 95% CI [0.57, 1.15]) and thrombus resolution (OR 1.12; 95% CI [0.86; 1.46]) were comparable, and there was low heterogeneity overall across the included studies. DOAC use was associated with lower odds of all-cause death (OR 0.65; 95%CI [0.46; 0.92]) and a composite bleeding endpoint (OR 0.67; 95%CI [0.47; 0.97]). A risk of bias was evident particularly for observational reports, with some publication bias suggested in funnel plots. CONCLUSION: In this comprehensive analysis of mainly observational data, the use of DOACs was not associated with a significant difference in stroke or systemic embolism, or thrombus resolution compared to VKA therapy. The use of DOACs was associated with a lower rate of all-cause death and fewer bleeding events. Adequately sized randomized clinical trials are needed to confirm these findings, which could allow a wider adoption of DOACs in patients with LVT.

Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control: the EAST-AFNET 4 trial.

AIMS: Clinical concerns exist about the potential proarrhythmic effects of the sodium channel blockers (SCBs) flecainide and propafenone in patients with cardiovascular disease. Sodium channel blockers were used to deliver early rhythm control (ERC) therapy in EAST-AFNET 4. METHODS AND RESULTS: We analysed the primary safety outcome (death, stroke, or serious adverse events related to rhythm control therapy) and primary efficacy outcome (cardiovascular death, stroke, and hospitalization for worsening of heart failure (HF) or acute coronary syndrome) during SCB intake for patients with ERC (n = 1395) in EAST-AFNET 4. The protocol discouraged flecainide and propafenone in patients with reduced left ventricular ejection fraction and suggested stopping therapy upon QRS prolongation >25% on therapy. Flecainide or propafenone was given to 689 patients [age 69 (8) years; CHA2DS2-VASc 3.2 (1); 177 with HF; 41 with prior myocardial infarction, coronary artery bypass graft, or percutaneous coronary intervention; 26 with left ventricular hypertrophy >15 mm; median therapy duration 1153 [237, 1828] days]. The primary efficacy outcome occurred less often in patients treated with SCB [3/100 (99/3316) patient-years] than in patients who never received SCB [SCBnever 4.9/100 (150/3083) patient-years, P < 0.001]. There were numerically fewer primary safety outcomes in patients receiving SCB [2.9/100 (96/3359) patient-years] than in SCBnever patients [4.2/100 (135/3220) patient-years, adjusted P = 0.015]. Sinus rhythm at 2 years was similar between groups [SCB 537/610 (88); SCBnever 472/579 (82)]. CONCLUSION: Long-term therapy with flecainide or propafenone appeared to be safe in the EAST-AFNET 4 trial to deliver effective ERC therapy, including in selected patients with stable cardiovascular disease such as coronary artery disease and stable HF. Clinical Trial Registration ISRCTN04708680, NCT01288352, EudraCT2010-021258-20, www.easttrial.org.

Blood-based cardiometabolic phenotypes in atrial fibrillation and their associated risk: EAST-AFNET 4 biomolecule study.

BACKGROUND: Atrial fibrillation (AF) and concomitant cardiometabolic disease processes interact and combine to lead to adverse events such as stroke, heart failure, myocardial infarction, and cardiovascular death. Circulating biomolecules provide quantifiable proxies for cardiometabolic disease processes. Their role in defining subphenotypes of AF is not known. METHODS AND RESULTS: This prespecified analysis of the EAST-AFNET4 biomolecule study assigned patients to clusters using polytomous variable latent class analysis (poLCA) based on baseline concentrations of thirteen precisely-quantified biomolecules potentially reflecting ageing, cardiac fibrosis, metabolic dysfunction, oxidative stress, cardiac load, endothelial dysfunction, and inflammation. In each cluster, rates of cardiovascular death, stroke, or hospitalization for heart failure or acute coronary syndrome, the primary outcome of EAST-AFNET 4, were calculated and compared between clusters over median 5.1 years follow-up. Findings were independently validated in a prospective cohort of 748 patients with AF (BBC-AF; median follow up 2.9 years).Unsupervised biomolecule analysis assigned 1586 patients (71 years old, 46% women) into four clusters. The highest-risk cluster was dominated by elevated BMP10, IGFBP7, NT-proBNP, ANGPT2 and GDF15. Patients in the lowest-risk cluster showed low concentrations of these biomolecules. Two intermediate-risk clusters differed by high or low concentrations of hsCRP, IL-6, and D-dimer. Patients in the highest-risk cluster had a 5-fold higher cardiovascular event rate than patients in the low-risk cluster. Early rhythm control was effective across clusters (pinteraction = 0.63). Sensitivity analyses and external validation in BBC-AF replicated clusters and risk gradients. CONCLUSIONS: Biomolecule concentrations identify cardiometabolic subphenotypes in patients with atrial fibrillation at high and low cardiovascular risk.

[Diagnosis of acute coronary syndrome]. / Diagnose des akuten Koronarsyndroms.

Acute coronary syndrome is one of the most important differential diagnostic considerations in emergency medicine. It describes the constellation of newly occurring clinical symptoms, often accompanied by typical 12-lead ECG changes and the release of cardiac troponins. The spectrum includes unstable angina pectoris, non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI). It is important to consistently carry out the diagnostic steps that are crucial for further therapeutic procedures to avoid delaying life-saving invasive coronary diagnostics, without losing sight of the diverse, sometimes time-critical differential diagnoses. Anamnesis and clinical examination form the basis of the further procedure. Further developments of biomarker assays with personalized limit values, new imaging modalities with ever higher resolution and faster imaging methods as well as advances in automated ECG analysis with integration of all findings through artificial intelligence will continue to offer many optimization options in the future diagnosis of acute coronary syndrome.

Embolic strokes of undetermined source: a clinical consensus statement of the ESC Council on Stroke, the European Association of Cardiovascular Imaging and the European Heart Rhythm Association of the ESC.

One in six ischaemic stroke patients has an embolic stroke of undetermined source (ESUS), defined as a stroke with unclear aetiology despite recommended diagnostic evaluation. The overall cardiovascular risk of ESUS is high and it is important to optimize strategies to prevent recurrent stroke and other cardiovascular events. The aim of clinicians when confronted with a patient not only with ESUS but also with any other medical condition of unclear aetiology is to identify the actual cause amongst a list of potential differential diagnoses, in order to optimize secondary prevention. However, specifically in ESUS, this may be challenging as multiple potential thromboembolic sources frequently coexist. Also, it can be delusively reassuring because despite the implementation of specific treatments for the individual pathology presumed to be the actual thromboembolic source, patients can still be vulnerable to stroke and other cardiovascular events caused by other pathologies already identified during the index diagnostic evaluation but whose thromboembolic potential was underestimated. Therefore, rather than trying to presume which particular mechanism is the actual embolic source in an ESUS patient, it is important to assess the overall thromboembolic risk of the patient through synthesis of the individual risks linked to all pathologies present, regardless if presumed causally associated or not. In this paper, a multi-disciplinary panel of clinicians/researchers from various backgrounds of expertise and specialties (cardiology, internal medicine, neurology, radiology and vascular surgery) proposes a comprehensive multi-dimensional assessment of the overall thromboembolic risk in ESUS patients through the composition of individual risks associated with all prevalent pathologies.

Longer and better lives for patients with atrial fibrillation: the 9th AFNET/EHRA consensus conference.

AIMS: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). METHODS AND RESULTS: Eighty-three international experts met in Münster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF. CONCLUSIONS: Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF.

New race-free creatinine- and cystatin C-based equations for the estimation of glomerular filtration rate and association with cardiovascular mortality in the AtheroGene study.

Renal function is associated with cardiovascular outcomes and mortality. Among equations used to eGFR, CKD-EPI equations show more accurate association with cardiovascular risk and mortality than MDRD. Recently, new CKD-EPI equations were proposed which do not include race and would be considered sufficiently accurate to estimate eGFR in clinical practice. It is unknown if these new race-free equations are comparably well associated with cardiovascular outcomes in high-risk individuals. The analysis was performed in the AtheroGene Study cohort including patients at high cardiovascular risk. eGFR was determined using the established as well as the recently developed formulas which are calculated without the otherwise existing coefficient for black race. The outcome was cardiovascular death. Analyses included Cox-proportional hazard regression and area-under-the-curve calculation. The analysis included 2089 patients followed up for a median of 3.8 years with a maximum of 6.9 years, corresponding to an overall period of 7701 patient-years. Cardiovascular death occurred in 93 (4.45%), corresponding to an annualized rate of 1.2/100 person-years. In all Cox regression analyses, the estimated adjusted GFR was an independent predictor of cardiovascular death. The equations which included cystatin C showed higher C-index compared to those which did not include cystatin C (0.75-0.76 vs. 0.71, respectively). The equations for the estimation of eGFR which include cystatin C are better associated with cardiovascular death compared to the race-free equations which include only creatinine. This finding adds on the related literature which supports the elimination of race in GFR-estimating equations, and promotion of the use of cystatin C.

C-reactive protein modifies lipoprotein(a)-related risk for coronary heart disease: the BiomarCaRE project.

BACKGROUND AND AIMS: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population. METHODS: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (<2 and ≥2 mg/L). RESULTS: Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23-1.72) and 1.48 (1.23-1.78) for a hsCRP group of <2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥ 2 mg/L [1.34 (1.03-1.76)], whereas among participants with a hsCRP concentration <2 mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98-1.71)] (highest vs. lowest fifth, fully adjusted models; Pinteraction = 0.024). CONCLUSIONS: While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds.

Practical guide on left atrial appendage closure for the non-implanting physician: an international consensus paper.

A significant proportion of patients who suffer from atrial fibrillation (AF) and are in need of thromboembolic protection are not treated with oral anticoagulation or discontinue this treatment shortly after its initiation. This undertreatment has not improved sufficiently despite the availability of direct oral anticoagulants which are associated with less major bleeding than vitamin K antagonists. Multiple reasons account for this, including bleeding events or ischaemic strokes whilst on anticoagulation, a serious risk of bleeding events, poor treatment compliance despite best educational attempts, or aversion to drug therapy. An alternative interventional therapy, which is not associated with long-term bleeding and is as effective as vitamin K anticoagulation, was introduced over 20 years ago. Because of significant improvements in procedural safety over the years, left atrial appendage closure, predominantly achieved using a catheter-based, device implantation approach, is increasingly favoured for the prevention of thromboembolic events in patients who cannot achieve effective anticoagulation. This management strategy is well known to the interventional cardiologist/electrophysiologist but is not more widely appreciated within cardiology or internal medicine. This article introduces the devices and briefly explains the implantation technique. The indications and device follow-up are more comprehensively described. Almost all physicians who care for adult patients will have many with AF. This practical guide, written within guideline/guidance boundaries, is aimed at those non-implanting physicians who may need to refer patients for consideration of this new therapy, which is becoming increasingly popular.

Disturbed atrial metabolism, shear stress, and cardiac load contribute to atrial fibrillation after ablation: AXAFA biomolecule study.

AIMS: Different disease processes can combine to cause atrial fibrillation (AF). Their contribution to recurrent AF after ablation in patients is not known. Cardiovascular processes associated with recurrent AF after AF ablation were determined by quantifying biomolecules related to inflammation, metabolism, proliferation, fibrosis, shear stress, atrial pressure, and others in the AXAFA biomolecule study. METHODS AND RESULTS: Twelve circulating cardiovascular biomolecules (ANGPT2, BMP10, CA125, hsCRP, ESM1, FABP3, FGF23, GDF15, IGFBP7, IL6, NT-proBNP, and hsTnT) were quantified in plasma samples obtained prior to a first AF ablation using high-throughput, high-precision assays. Cox regression was used to identify biomolecules associated with recurrent AF during the first 3 months after AF ablation. In 433 patients (64 years [58, 70]; 33% women), baseline concentrations of ANGPT2, BMP10, hsCRP, FGF23, FABP3, GDF15, and NT-proBNP were elevated in patients with recurrent AF (120/433; 28%). After adjustment for 11 clinical features and randomized treatment, elevated NT-proBNP [hazard ratio (HR) 1.58, 95% confidence interval (1.29, 1.94)], ANGPT2 [HR 1.37, (1.12, 1.67)], and BMP10 [HR 1.24 (1.02, 1.51)] remained associated with recurrent AF. Concentrations of ANGPT2, BMP10, and NT-proBNP decreased in patients who remained arrhythmia free, but not in patients with recurrent AF, highlighting their connection to AF. The other eight biomarkers showed unchanged concentrations. CONCLUSION: Elevated concentrations of ANGPT2, BMP10, and NT-proBNP are associated with recurrent AF after a first AF ablation, suggesting that processes linked to disturbed cardiomyocyte metabolism, altered atrial shear stress, and increased load contribute to AF after AF ablation in patients.

Anticoagulation with edoxaban in patients with long atrial high-rate episodes ≥24†h.

BACKGROUND AND AIMS: Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients. METHODS: This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation. RESULTS: Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE ≥24 h were present at baseline in 259/2389 patients (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE ≥24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P-interaction = .65) or safety (P-interaction = .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P < .001). CONCLUSIONS: This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.

Increased risk of dementia differs across cardiovascular diseases and types of dementia - Data from a nationwide study.

AIMS: Dementia is a major health problem. Cardiovascular diseases (CVD) and risk factors are associated with incident dementia. However, whether there is an association among CVD, Alzheimer's disease (AD) and vascular dementia (VD) at the population level remains unclear. METHODS: We analysed the association between CVD (heart failure [HF], atrial fibrillation [AF], myocardial infarction [MI], peripheral arterial disease, stroke and transient ischemic attack) and the incidence of dementia using nationwide FinnGen data of 218,192 individuals. The last follow-up information on dementia was available from October 2021. RESULTS: The age at the end of the follow-up was 61.7 ± 17.1 years, and 53% were women. Overall, we observed 9701 (4.4%) dementia, 6323 (2.9%) AD and 1918 (0.7%) VD cases. Individuals with CVD had a higher risk of developing dementia than unexposed individuals. In the multivariable-adjusted Cox models, stroke was most strongly associated with dementia (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.6-1.8). CVD was more strongly associated with VD than with AD. Individuals with HF and MI had an increased risk of AD (HF: HR 1.11, 95% CI 1.04-1.19; MI: HR 1.10, 95% CI 1.02-1.18). AF was associated with VD (HR 1.58, 95% CI 1.42-1.77), but not with AD (HR 1.03, 95% CI 0.97-1.09). Clinical characteristics, such as diabetes, smoking and alcohol abuse, were associated with both types of dementia. CONCLUSION: All major CVDs were associated with an increased risk of developing dementia, particularly VD. Therefore, CVD onset should prompt an assessment of cognitive decline and possible preventive measures.

[Genetic basis of atrial fibrillation-on the road to precision medicine]. / Die Genetik von Vorhofflimmern ­ auf dem Weg in die Präzisionsmedizin.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and has complex genetic underpinnings. Despite advancements in treatment, mortality of AF patients remains high. This review discusses the genetic basis of AF and its implications for diagnosis and therapy. Although AF pathology has long been known to include a hereditary component, the first genes associated with AF were not identified until the early 2000s. Subsequent research with genome-wide association studies (GWAS) has implicated other genes and numerous genetic variants in AF. These studies have revealed nearly 140 different regions in the DNA with genome-wide significance associated with AF. In addition to common variants, rare variants with large effects have also been identified. The integration of these genetic findings into clinical practice holds promise for improving AF diagnosis and treatment, moving us closer to precision medicine. However, challenges remain, including the need for more diverse genetic data of non-European ancestry and improved genetic analyses of responses to AF therapy.

Towards a new classification of atrial fibrillation detected after a stroke or a transient ischaemic attack.

Globally, up to 1·5 million individuals with ischaemic stroke or transient ischaemic attack can be newly diagnosed with atrial fibrillation per year. In the past decade, evidence has accumulated supporting the notion that atrial fibrillation first detected after a stroke or transient ischaemic attack differs from atrial fibrillation known before the occurrence of as stroke. Atrial fibrillation detected after stroke is associated with a lower prevalence of risk factors, cardiovascular comorbidities, and atrial cardiomyopathy than atrial fibrillation known before stroke occurrence. These differences might explain why it is associated with a lower risk of recurrence of ischaemic stroke than known atrial fibrillation. Patients with ischaemic stroke or transient ischaemic attack can be classified in three categories: no atrial fibrillation, known atrial fibrillation before stroke occurrence, and atrial fibrillation detected after stroke. This classification could harmonise future research in the field and help to understand the role of prolonged cardiac monitoring for secondary stroke prevention with application of a personalised risk-based approach to the selection of patients for anticoagulation.

Deep learning-based NT-proBNP prediction from the ECG for risk assessment in the community.

OBJECTIVES: The biomarker N-terminal pro B-type natriuretic peptide (NT-proBNP) has predictive value for identifying individuals at risk for cardiovascular disease (CVD). However, it is not widely used for screening in the general population, potentially due to financial and operational reasons. This study aims to develop a deep-learning model as an efficient means to reliably identify individuals at risk for CVD by predicting serum levels of NT-proBNP from the ECG. METHODS: A deep convolutional neural network was developed using the population-based cohort study Hamburg City Health Study (HCHS, n=8,253, 50.9 % women). External validation was performed in two independent population-based cohorts (SHIP-START, n=3,002, 52.1 % women, and SHIP-TREND, n=3,819, 51.2 % women). Assessment of model performance was conducted using Pearson correlation (R) and area under the receiver operating characteristics curve (AUROC). RESULTS: NT-proBNP was predictable from the ECG (R, 0.566 [HCHS], 0.642 [SHIP-START-0], 0.655 [SHIP-TREND-0]). Across cohorts, predicted NT-proBNP (pNT-proBNP) showed good discriminatory ability for prevalent and incident heart failure (HF) (baseline: AUROC 0.795 [HCHS], 0.816 [SHIP-START-0], 0.783 [SHIP-TREND-0]; first follow-up: 0.669 [SHIP-START-1, 5 years], 0.689 [SHIP-TREND-1, 7.3 years]), comparable to the discriminatory value of measured NT-proBNP. pNT-proBNP also demonstrated comparable results for other incident CVD, including atrial fibrillation, stroke, myocardial infarction, and cardiovascular death. CONCLUSIONS: Deep learning ECG algorithms can predict NT-proBNP concentrations with high diagnostic and predictive value for HF and other major CVD and may be used in the community to identify individuals at risk. Long-standing experience with NT-proBNP can increase acceptance of such deep learning models in clinical practice.

Correlation of systolic and diastolic blood pressure with echocardiographic phenotypes of cardiac structure and function from three German population-based studies.

Arterial hypertension is considered a risk factor for the development of heart failure. Here we investigate cross-sectional associations of systolic and diastolic blood pressure with subtle functional and morphological changes of left ventricular echocardiographic parameters representing early dysfunction in three representative German population-based studies. We assessed 26,719 individuals without symptomatic heart failure from the Hamburg City Health Study (HCHS, n = 7396, derivation cohort), the Gutenberg Health Study (GHS, 14,715, validation cohort) and the Study of Health in Pomerania (SHIP, 4608, validation cohort). Multivariable linear regression analyses with systolic and diastolic blood pressure as continuous exposure variables were adjusted for common cardiovascular risk factors and antihypertensive medication. Both systolic and diastolic blood pressure were consistently associated with measures of left ventricular hypertrophy (ß per standard deviation (SD) for LV mass (g) and systolic blood pressure: 5.09 (p < 0.001); diastolic blood pressure: 2.29 (p < 0.001) in HCHS). Systolic blood pressure correlated with declining diastolic function (ß per SD for E/e': 0.29, p < 0.001 in HCHS) and diastolic blood pressure with declining systolic function (ß per SD for LVEF, in %: - 0.15; p = 0.041 in HCHS) in all cohorts. Pending further validation, our results from three independent German population samples suggest differential effects of systolic versus diastolic blood pressure on left ventricular structure and function.

Outcomes of patients with atrial fibrillation on oral anticoagulation with and without heart failure: the ETNA-AF-Europe registry.

AIMS: Heart failure (HF) is a risk factor for major adverse events in atrial fibrillation (AF). Whether this risk persists on non-vitamin K antagonist oral anticoagulants (NOACs) and varies according to left ventricular ejection fraction (LVEF) is debated. METHODS AND RESULTS: We investigated the relation of HF in the ETNA-AF-Europe registry, a prospective, multicentre, observational study with an overall 4-year follow-up of edoxaban-treated AF patients. We report 2-year follow-up for ischaemic stroke/transient ischaemic attack (TIA)/systemic embolic events (SEE), major bleeding, and mortality. Of the 13 133 patients, 1854 (14.1%) had HF. Left ventricular ejection fraction was available for 82.4% of HF patients and was <40% in 671 (43.9%) and ≥40% in 857 (56.1%). Patients with HF were older, more often men, and had more comorbidities. Annualized event rates (AnERs) of any stroke/SEE were 0.86%/year and 0.67%/year in patients with and without HF. Compared with patients without HF, those with HF also had higher AnERs for major bleeding (1.73%/year vs. 0.86%/year) and all-cause death (8.30%/year vs. 3.17%/year). Multivariate Cox proportional models confirmed HF as a significant predictor of major bleeding [hazard ratio (HR) 1.65, 95% confidence interval (CI): 1.20-2.26] and all-cause death [HF with LVEF <40% (HR 2.42, 95% CI: 1.95-3.00) and HF with LVEF ≥40% (HR 1.80, 95% CI: 1.45-2.23)] but not of ischaemic stroke/TIA/SEE. CONCLUSION: Anticoagulated patients with HF at baseline featured higher rates of major bleeding and all-cause death, requiring optimized management and novel preventive strategies. NOAC treatment was similarly effective in reducing risk of ischaemic events in patients with or without concomitant HF.

An arrhythmogenic metabolite in atrial fibrillation.

BACKGROUND: Long-chain acyl-carnitines (ACs) are potential arrhythmogenic metabolites. Their role in atrial fibrillation (AF) remains incompletely understood. Using a systems medicine approach, we assessed the contribution of C18:1AC to AF by analysing its in vitro effects on cardiac electrophysiology and metabolism, and translated our findings into the human setting. METHODS AND RESULTS: Human iPSC-derived engineered heart tissue was exposed to C18:1AC. A biphasic effect on contractile force was observed: short exposure enhanced contractile force, but elicited spontaneous contractions and impaired Ca2+ handling. Continuous exposure provoked an impairment of contractile force. In human atrial mitochondria from AF individuals, C18:1AC inhibited respiration. In a population-based cohort as well as a cohort of patients, high C18:1AC serum concentrations were associated with the incidence and prevalence of AF. CONCLUSION: Our data provide evidence for an arrhythmogenic potential of the metabolite C18:1AC. The metabolite interferes with mitochondrial metabolism, thereby contributing to contractile dysfunction and shows predictive potential as novel circulating biomarker for risk of AF.