Acute coronary syndrome in patients younger than 30 years--aetiologies, baseline characteristics and long-term clinical outcome.

Coronary atherosclerosis begins early in life, but acute coronary syndromes in adults aged <30 years are exceptional. We aimed to investigate the rate of occurrence, clinical and angiographic characteristics, and long-term clinical outcome of acute coronary syndrome (ACS) in young patients who were referred to two Swiss hospitals. From 1994 to 2010, data on all patients with ACS aged <30 years were retrospectively retrieved from our database and the patients were contacted by phone or physician's visit. Baseline, lesion and procedural characteristics, and clinical outcome were compared between patients in whom an underlying atypical aetiology was found (non-ATS group; ATS: atherosclerosis) and patients in whom no such aetiology was detected (ATS group). The clinical endpoint was freedom from any major adverse cardiac event (MACE) during follow-up. A total of 27 young patients with ACS aged <30 years were admitted during the study period. They accounted for 0.05% of all coronary angiograms performed. Mean patient age was 26.8 ± 3.5 years and 22 patients (81%) were men. Current smoking (81%) and dyslipidaemia (59%) were the most frequent risk factors. Typical chest pain (n = 23; 85%) and ST-segment elevation myocardial infarction (STEMI; n = 18 [67%]) were most often found. The ATS group consisted of 17 patients (63%) and the non-ATS group of 10 patients (37%). Hereditary thrombophilia was the most frequently encountered atypical aetiology (n = 4; 15%). At 5 years, mortality and MACE rate were 7% and 19%, respectively. ACS in young patients is an uncommon condition with a variety of possible aetiologies and distinct risk factors. In-hospital and 5-year clinical outcome is satisfactory

Clinical outcomes of patients with low-flow, low-gradient, severe aortic stenosis and either preserved or reduced ejection fraction undergoing transcatheter aortic valve implantation

Aims Our aim was to evaluate the invasive haemodynamic indices of high-risk symptomatic patients presenting with ‘paradoxical' low-flow, low-gradient, severe aortic stenosis (AS) (PLF-LG) and low-flow, low-gradient severe AS (LEF-LG) and to compare clinical outcomes following transcatheter aortic valve implantation (TAVI) among these challenging AS subgroups. Methods and results Of 534 symptomatic patients undergoing TAVI, 385 had a full pre-procedural right and left heart catheterization. A total of 208 patients had high-gradient severe AS [HGAS; mean gradient (MG) ≥40 mmHg], 85 had PLF-LG [MG ≤ 40 mmHg, indexed aortic valve area [iAVA] ≤0.6 cm2 m−2, stroke volume index ≤35 mL/m2, ejection fraction (EF) ≥50%], and 61 had LEF-LG (MG ≤ 40 mmHg, iAVA ≤0.6 cm2 m−2, EF ≤40%). Compared with HGAS, PLF-LG and LEF-LG had higher systemic vascular resistances (HGAS: 1912 ± 654 vs. PLF-LG: 2006 ± 586 vs. LEF-LG: 2216 ± 765 dyne s m−5, P = 0.007) but lower valvulo-arterial impedances (HGAS: 7.8 ± 2.7 vs. PLF-LG: 6.9 ± 1.9 vs. LEF-LG: 7.7 ± 2.5 mmHg mL−1 m−2, P = 0.027). At 30 days, no differences in cardiac death (6.5 vs. 4.9 vs. 6.6%, P = 0.90) or death (8.4 vs. 6.1 vs. 6.6%, P = 0.88) were observed among HGAS, PLF-LG, and LEF-LG groups, respectively. At 1 year, New York Heart Association functional improvement occurred in most surviving patients (HGAS: 69.2% vs. PLF-LG: 71.7% vs. LEF-LG: 89.3%, P = 0.09) and no significant differences in overall mortality were observed (17.6 vs. 20.5 vs. 24.5%, P = 0.67). Compared with HGAS, LEF-LG had a higher 1 year cardiac mortality (adjusted hazard ratio 2.45, 95% confidence interval 1.04-5.75, P = 0.04). Conclusion TAVI in PLF-LG or LEF-LG patients is associated with overall mortality rates comparable with HGAS patients and all groups profit symptomatically to a similar exten

Prospective Assessment of Sex-Related Differences in Symptom Status and Health Perception Among Patients With Atrial Fibrillation.

We prospectively assessed sex-specific differences in health perception, overall symptom status, and specific symptoms in a large cohort of patients with atrial fibrillation. We performed a prospective multicenter observational cohort study of 1553 patients with atrial fibrillation. Patients completed questionnaires about personal characteristics, comorbidities, and symptoms on a yearly basis. Mean age was 70±11 years among women and 67±12 years among men. Health perception on a visual analogue scale ranging from 0 to 100 (with higher scores indicating better health perception) was significantly lower in women than in men (70 [interquartile range: 50-80] versus 75 [interquartile range: 60-85]; javax.xml.bind.JAXBElement@29592a5d <0.0001). More women than men had any symptoms (85.0% versus 68.3%; javax.xml.bind.JAXBElement@7ac0b4e4 <0.0001), palpitations (65.2% versus 44.4%; javax.xml.bind.JAXBElement@41229466 <0.0001), dizziness (25.6% versus 13.5%; javax.xml.bind.JAXBElement@61871784 <0.0001), dyspnea (35.7% versus 21.8%; javax.xml.bind.JAXBElement@16cc22b <0.0001), and fatigue (25.3% versus 19.1%; javax.xml.bind.JAXBElement@7ef43176 =0.006). At 1-year follow-up, symptoms decreased in both sexes but remained more frequent in women (49.1% versus 32.6%, javax.xml.bind.JAXBElement@2b200b6a <0.0001). In multivariable adjusted longitudinal regression models, female sex remained an independent predictor for lower health perception (ß=-4.8; 95% CI, -6.5 to -3.1; javax.xml.bind.JAXBElement@72c212bd <0.0001), any symptoms (odds ratio [OR]: 2.6; 95% CI, 2.1-3.4; javax.xml.bind.JAXBElement@15d8fb54 <0.0001), palpitations (OR: 2.6; 95% CI, 2.1-3.2; javax.xml.bind.JAXBElement@4af80718 <0.0001), dizziness (OR: 2.9; 95% CI, 2.1-3.9; javax.xml.bind.JAXBElement@61282e76 <0.0001), dyspnea (OR: 2.1; 95% CI, 1.6-2.8; javax.xml.bind.JAXBElement@31d9f14 <0.0001), fatigue (OR: 1.6; 95% CI, 1.2-2.2; javax.xml.bind.JAXBElement@51cdd678 =0.0008), and chest pain (OR: 1.8; 95% CI, 1.3-2.6; javax.xml.bind.JAXBElement@5b87db9e =0.001). Women with atrial fibrillation have a substantially higher symptom burden and lower health perception than men. These relationships persisted after multivariable adjustment and during prospective follow-up

Incidence, Predictors, and Clinical Impact of Early Prasugrel Cessation in Patients With ST-Elevation Myocardial Infarction.

BACKGROUND: Early withdrawal of recommended antiplatelet treatment with clopidogrel adversely affects prognosis following percutaneous coronary interventions. Optimal antiplatelet treatment is essential following ST-segment elevation myocardial infarction (STEMI) given the increased risk of thrombotic complications. This study assessed the frequency, predictors, and clinical impact of early prasugrel cessation in patients with STEMI undergoing primary percutaneous coronary interventions. METHODS AND RESULTS: We pooled patients with STEMI discharged on prasugrel in 2 prospective registries (Bern PCI Registry [NCT02241291] and SPUM-ACS (Inflammation and Acute Coronary Syndromes) [NCT01000701]) and 1 STEMI trial (COMFORTABLE-AMI (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction) [NCT00962416]). Prasugrel treatment status at 1 year was categorized as no cessation; crossover to another P2Y12-inhibitor; physician-recommended discontinuation; and disruption because of bleeding, side effects, or patient noncompliance. In time-dependent analyses, we assessed the impact of prasugrel cessation on the primary end point, a composite of cardiac death, myocardial infarction, and stroke. Of all 1830 included patients (17% women, mean age 59 years), 83% were treated with new-generation drug-eluting stents. At 1 year, any prasugrel cessation had occurred in 13.8% of patients including crossover (7.2%), discontinuation (3.7%), and disruption (2.9%). Independent predictors of any prasugrel cessation included female sex, age, and history of cerebrovascular event. The primary end point occurred in 5.2% of patients and was more frequent following disruption (hazard ratio 3.04, 95% confidence interval,1.34-6.91; P=0.008), without significant impact of crossover or discontinuation. Consistent findings were observed for all-cause death, myocardial infarction, and stent thrombosis following prasugrel disruption. CONCLUSIONS: In this contemporary study of patients with STEMI, early prasugrel cessation was not uncommon and primarily involved change to another P2Y12-inhibitor. Disruption was the only type of early prasugrel cessation associated with statistically significant excess in ischemic risk within 1 year following primary percutaneous coronary interventions

Design of the Swiss Atrial Fibrillation Cohort Study (Swiss-AF): structural brain damage and cognitive decline among patients with atrial fibrillation.

Several studies found that patients with atrial fibrillation (AF) have an increased risk of cognitive decline and dementia over time. However, the magnitude of the problem, associated risk factors and underlying mechanisms remain unclear. This article describes the design and methodology of the Swiss Atrial Fibrillation (Swiss-AF) Cohort Study, a prospective multicentre national cohort study of 2400 patients across 13 sites in Switzerland. Eligible patients must have documented AF. Main exclusion criteria are the inability to provide informed consent and the presence of exclusively short episodes of reversible forms of AF. All patients undergo extensive phenotyping and genotyping, including repeated assessment of cognitive functions, quality of life, disability, electrocardiography and cerebral magnetic resonance imaging. We also collect information on health related costs, and we assemble a large biobank. Key clinical outcomes in Swiss-AF are death, stroke, systemic embolism, bleeding, hospitalisation for heart failure and myocardial infarction. Information on outcomes and updates on other characteristics are being collected during yearly follow-up visits. Up to 7 April 2017, we have enrolled 2133 patients into Swiss-AF. With the current recruitment rate of 15 to 20 patients per week, we expect that the target sample size of 2400 patients will be reached by summer 2017. Swiss-AF is a large national prospective cohort of patients with AF in Switzerland. This study will provide important new information on structural and functional brain damage in patients with AF and on other AF related complications, using a large variety of genetic, phenotypic and health economic parameters

Renal Function and Body Mass Index Contribute to Serum Neurofilament Light Chain Levels in Elderly Patients With Atrial Fibrillation.

Objective: Serum neurofilament light chain (sNfL) is increasingly used as a neuroaxonal injury biomarker in the elderly. Besides age, little is known about how other physiological factors like renal function and body mass index (BMI) alter its levels. Here, we investigated the association of estimated glomerular filtration rate (eGFR) and BMI with sNfL in a large sample of elderly patients with atrial fibrillation (AF). Methods: This is a cross-sectional analysis from the Swiss-AF Cohort (NCT02105844). We measured sNfL using an ultrasensitive single-molecule array assay. We calculated eGFR using the chronic kidney disease epidemiology collaboration (CKD-EPI) creatinine (eGFRcrea) and creatinine–cystatin C (eGFRcrea–cys) formulas, and BMI from weight and height measurements. We evaluated the role of eGFR and BMI as determinants of sNfL levels using multivariable linear regression and the adjusted R2 (R2adj). Results: Among 2,277 Swiss-AF participants (mean age 73.3 years), eGFRcrea showed an inverse curvilinear association with sNfL after adjustment for age and cardiovascular comorbidities. BMI also showed an independent, inverse linear association with sNfL. The R2adj of models with age, eGFRcrea, and BMI alone was 0.26, 0.35, and 0.02, respectively. A model with age and eGFRcrea combined explained 45% of the sNfL variance. Sensitivity analyses (i) further adjusting for vascular brain lesions (N = 1,402 participants with MRI) and (ii) using eGFRcrea–cys yielded consistent results. Interpretation: In an elderly AF cohort, both renal function and BMI were associated with sNfL, but only renal function explained a substantial proportion of the sNfL variance. This should be taken into account when using sNfL in elderly patients or patients with cardiovascular disease

Biomarker, Imaging, and Clinical Factors Associated With Overt and Covert Stroke in Patients With Atrial Fibrillation.

BACKGROUND Atrial fibrillation is a major risk factor for stroke and silent brain infarcts. We studied whether a multimodal approach offers additional insights to the CHA2DS2-VASc score in predicting stroke or new brain infarcts on magnetic resonance imaging (MRI) over a 2-year follow-up. METHODS Swiss-AF is a prospective, multicenter cohort study of patients with known atrial fibrillation. We included patients with available brain MRI both at enrollment and 2 years later. The dates of the baseline and follow-up visits ranged from March 2014 to November 2020. The primary outcome was assessed 2 years after baseline and was defined as a composite of clinically identified stroke or any new brain infarct on the 2-year MRI. We compared a multivariable logistic regression model including prespecified clinical, biomarker, and baseline MRI variables to the CHA2DS2-VASc score. RESULTS We included 1232 patients, 89.8% of them taking oral anticoagulants. The primary outcome occurred in 78 patients (6.3%). The following baseline variables were included in the final multivariate model and were significantly associated with the primary outcome: white matter lesion volume in milliliters (adjusted odds ratio [aOR], 1.91 [95% CI, 1.45-2.56]), NT-proBNP (N-terminal pro-B-type natriuretic peptide; aOR, 1.75 [95% CI, 1.20-2.63]), GDF-15 (growth differentiation factor-15; aOR, 1.68 [95% CI, 1.11-2.53]), serum creatinine (aOR, 1.50 [95% CI, 1.02-2.22]), IL (interleukin)-6 (aOR, 1.37 [95% CI, 1.00-1.86]), and hFABP (heart-type fatty acid-binding protein; aOR, 0.48 [95% CI, 0.31-0.73]). Overall performance and discrimination of the new model was superior to that of the CHA2DS2-VASc score (C statistic, 0.82 [95% CI, 0.77-0.87] versus 0.64 [95% CI, 0.58-0.70]). CONCLUSIONS In patients with atrial fibrillation, a model incorporating white matter lesion volume on baseline MRI and selected blood markers yielded new insights on residual stroke risk despite a high proportion of patients on oral anticoagulants. This may be relevant to develop further preventive measures

Serum neurofilament light in atrial fibrillation: clinical, neuroimaging and cognitive correlates

Emerging evidence suggests that atrial fibrillation is associated with cognitive dysfunction independently of stroke, but the underlying mechanisms remain unclear. In this cross-sectional analysis from the Swiss-atrial fibrillation Study (NCT02105844), we investigated the association of serum neurofilament light protein, a neuronal injury biomarker, with (i) the CHA; 2; DS; 2; -VASc score (congestive heart failure, hypertension, age 65-74 or >75 years, diabetes mellitus, stroke or transient ischaemic attack, vascular disease, sex), clinical and neuroimaging parameters and (ii) cognitive measures in atrial fibrillation patients. We measured neurofilament light in serum using an ultrasensitive single-molecule array assay in a sample of 1379 atrial fibrillation patients (mean age, 72 years; female, 27%). Ischaemic infarcts, small vessel disease markers and normalized brain volume were assessed on brain MRI. Cognitive testing included the Montreal cognitive assessment, trail-making test, semantic verbal fluency and digit symbol substitution test, which were summarized using principal component analysis. Results were analysed using univariable and multivariable linear regression. Neurofilament light was associated with the CHA; 2; DS; 2; -VASc score, with an average 19.2% [95% confidence interval (17.2%, 21.3%)] higher neurofilament per unit CHA; 2; DS; 2; -VASc increase. This association persisted after adjustment for age and MRI characteristics. In multivariable analyses, clinical parameters associated with neurofilament light were higher age [32.5% (27.2%, 38%) neurofilament increase per 10 years], diabetes mellitus, heart failure and peripheral artery disease [26.8% (16.8%, 37.6%), 15.7% (8.1%, 23.9%) and 19.5% (6.8%, 33.7%) higher neurofilament, respectively]. Mean arterial pressure showed a curvilinear association with neurofilament, with evidence for both an inverse linear and a U-shaped association. MRI characteristics associated with neurofilament were white matter lesion volume and volume of large non-cortical or cortical infarcts [4.3% (1.8%, 6.8%) and 5.5% (2.5%, 8.7%) neurofilament increase per unit increase in log-volume of the respective lesion], as well as normalized brain volume [4.9% (1.7%, 8.1%) higher neurofilament per 100 cm; 3; smaller brain volume]. Neurofilament light was inversely associated with all cognitive measures in univariable analyses. The effect sizes diminished after adjusting for clinical and MRI variables, but the association with the first principal component was still evident. Our results suggest that in atrial fibrillation patients, neuronal loss measured by serum neurofilament light is associated with age, diabetes mellitus, heart failure, blood pressure and vascular brain lesions, and inversely correlates with normalized brain volume and cognitive function

Patient clusters and cost trajectories in the Swiss Atrial Fibrillation cohort

Objective: Evidence on long-term costs of atrial fibrillation (AF) and associated factors is scarce. As part of the Swiss-AF prospective cohort study, we aimed to characterise AF costs and their development over time, and to assess specific patient clusters and their cost trajectories. Methods: Swiss-AF enrolled 2415 patients with variable duration of AF between 2014 and 2017. Patient clusters were identified using hierarchical cluster analysis of baseline characteristics. Ongoing yearly follow-ups include health insurance clinical and claims data. An algorithm was developed to adjudicate costs to AF and related complications. Results: A subpopulation of 1024 Swiss-AF patients with available claims data was followed up for a median (IQR) of 3.24 (1.09) years. Average yearly AF-adjudicated costs amounted to SFr5679 (€5163), remaining stable across the observation period. AF-adjudicated costs consisted mainly of inpatient and outpatient AF treatment costs (SFr4078; €3707), followed by costs of bleeding (SFr696; €633) and heart failure (SFr494; €449). Hierarchical analysis identified three patient clusters: cardiovascular (CV; N=253 with claims), isolated-symptomatic (IS; N=586) and severely morbid without cardiovascular disease (SM; N=185). The CV cluster and SM cluster depicted similarly high costs across all cost outcomes; IS patients accrued the lowest costs. Conclusion: Our results highlight three well-defined patient clusters with specific costs that could be used for stratification in both clinical and economic studies. Patient characteristics associated with adjudicated costs as well as cost trajectories may enable an early understanding of the magnitude of upcoming AF-related healthcare costs. Keywords: Atrial Fibrillation; Health Care Economics and Organization