Impact of disease stage on the performance of strain markers in the prediction of atrial fibrillation.

BACKGROUND: Assessing atrial fibrillation (AF) risk may be useful in primary prevention (PP; people with risk factors) and secondary prevention (SP; eg. embolic stroke of unknown source). We sought whether disease stage influenced the prediction of AF by echocardiography. METHODS: We compared a PP cohort (351 community-based participants ≥65 years with ≥1 risk factor for AF) and a SP cohort (453 patients after transient ischemic attack or stroke). LV global longitudinal strain (GLS) and left atrial reservoir strain (LARS) were measured from DICOM images. AF was diagnosed by 12 lead ECG, Holter or by single lead monitor over median follow-up of 22 months (PP) and 35 months (SP). The clinical and echocardiographic characteristics of those with AF were compared to those in sinus rhythm. Nested Cox-regression models assessed for independent and incremental predictive value of LARS and GLS in both cohorts. RESULTS: AF developed in 42 PP (12%) and 60 SP (13%), and was associated with age, higher CHARGE-AF score, increased LA volume and LV mass (p < 0.05). Patients developing AF had reduced GLS (17 ± 3.5% vs. 20 ± 3%, p < 0.001) and LARS (28 ± 11% vs. 35 ± 8%, p < 0.001). However, the predictive value of both GLS (area under the ROC curve 0.83 vs 0.56, p < 0.001) and LARS (0.83 vs 0.57, p < 0.001) was greater in SP than PP. LARS was independently associated with AF in both cohorts (p < 0.05), but GLS was only independently associated in the SP cohort. CONCLUSION: AF risk assessment with LARS is suitable for different risk cohorts, but GLS is more useful in SP.

Potentially actionable FGFR2 high-level amplification in thymic sebaceous carcinoma.

Our aim was to investigate sebaceous differentiation in thymus tumours and to identify new actionable genomic alterations. To this end we screened 35 normal and 23 hyperplastic thymuses, 127 thymomas and 41 thymic carcinomas for the presence of sebaceous differentiation as defined by morphology and expression of adipophilin and androgen receptor (AR). One primary thymic carcinoma showed morphology of sebaceous carcinomas (keratinizing and foam cells, calcifications, giant cells), a strong expression of adipophilin and AR together with squamous markers. NGS revealed high-level amplification of fibroblast growth factor receptor 2 (FGFR2). In thymuses and thymomas, no cells with sebaceous morphology were present. Occasionally, macrophages or epithelial cells showed adipophilin-positivity, however, without co-expression of AR. Thymic sebaceous carcinoma should be considered if a thymic carcinoma shows clear or foamy features. Testing for FGFR2 amplification might be warranted when searching for actionable genomic alterations in sebaceous carcinomas in the mediastinum and in other locations.

Patient Risk Factors for Bioprosthetic Aortic Valve Degeneration: A Systematic Review and Meta-Analysis.

The choice of valve type for aortic valve replacement surgery is sometimes challenging. The main risk for bioprostheses is structural valve degeneration (SVD); however, little is known about what the most important risk factors are. We conducted a systematic review and meta-analysis to identify the risk factors and estimate their pooled effect sizes to aid the prosthesis choice for replacement. We followed PRISMA guidelines and systematically searched three electronic databases (PubMed, Scopus, and Web of Science) using appropriate key terms: 'aortic valve', 'bioprosthesis', 'degeneration', 'durability', 'prosthesis failure', etc. Hazard ratio (HR) and odds ratio (OR) and associated 95% confidence intervals (CI) were extracted. Pooled risk estimates were calculated using a random-effects model. Twenty-nine (29) observational studies were included with a total of 25,490 patients, 981 of whom developed SVD over a mean follow-up time of 18.5 years. Four (4) factors influencing bioprosthetic SVD were identified: increasing age was a protective factor (per 1-yr increase, HR: 0.91 [95% CI 0.89, 0.94], p<0.0001), whereas increased body surface area (HR 1.77 [1.04, 3.01], p=0.034), patient-prosthesis mismatch (HR 1.95 [1.56, 2.43], p<0.001), and smoking (HR 2.28 [1.37, 3.79], p=0.0015) were risk factors for SVD. We found younger age, patient-prosthesis mismatch, body surface area, and smoking, as risk factors for aortic SVD, which should be considered for valve selection. This study generates a further hypothesis that accelerated flow across the valve is a shared key component in the pathophysiology of SVD, thus future research should consider other high cardiac output states.

Echocardiographic Risk Assessment to Guide Screening for Atrial Fibrillation.

BACKGROUND: Although atrial fibrillation (AF) is a significant population health burden, and an avoidable cause of stroke, AF screening remains controversial. The aim of this study was to investigate whether coincidental echocardiography could provide information about patients at risk for AF. METHODS: Asymptomatic participants ≥65 years of age with more than one AF risk factor (N = 445) undergoing echocardiography for risk evaluation were followed over a median of 15 months for incident AF. Left atrial volume index (LAVi), left ventricular (LV) global longitudinal strain (GLS; absolute value), left atrial (LA) strain, and LV mass were measured. During the follow-up period, AF was diagnosed clinically by primary care physicians or by using a single-lead portable electrocardiographic monitoring device (five 60-sec recordings performed by participants over 1 week). RESULTS: AF was diagnosed in 45 patients (10%; mean age, 70.5 ± 4.2 years; 55% women). AF detection was higher in those with LV hypertrophy, GLS < 16%, LAVi > 34 mL/m2, and LA reservoir strain < 34%. GLS, LAVi, and LA reservoir strain were independently associated with AF (P < .05). Those with AF had reduced GLS, higher LAVi, and higher LV mass (P < .05), but LA strain was similar in both groups (P > .05). GLS and LAVi were the strongest predictors, and cut points of 14.3% for GLS and 39 mL/m2 were associated with increased risk for developing AF. Those with all four risk parameters (LV hypertrophy, GLS < 16%, LA reservoir strain < 34%, and LAVi > 34 mL/m2) had a 60% AF detection rate, compared with 7% without these features (P = .004). CONCLUSION: Echocardiography is widely used in patients at risk for AF, and simple LV and LA measurements may be used to enrich the process of AF screening.

Association between socioeconomic status and incident atrial fibrillation.

BACKGROUND: Low socioeconomic status is associated with cardiovascular diseases, and an association with atrial fibrillation (AF) could guide screening. AIM: To investigate if indices of advantage/disadvantage (IAD), index of education/occupation (IEO) and index of economic resources were associated with incident AF, independent of risk factors and cardiac function. METHODS: We studied community-based participants aged ≥65 years with AF risk factors (n = 379, age 70 ± 4 years, 45% men). The CHARGE-AF score (a well validated AF risk score) was used to assess 5-year risk of developing AF. Participants also had baseline echocardiograms. IAD, IEO and index of economic resources were obtained from the 2011 Socio-Economic Indexes for Areas score, in which higher decile ranks indicate more advantaged areas. Patients were followed up for incident AF (median 21 (range 5-31) months), with AF diagnosed by clinical review, including 12-lead electrocardiogram (ECG), as well as single-lead portable ECG monitoring used to record 60 s ECG tracings five times/day for 1 week. Cox proportional hazards models were used to assess the association between socioeconomic status and incident AF. RESULTS: Subjects with AF (n = 50, 13%) were more likely to be male (64 vs 42%, P = 0.003) and had higher CHARGE-AF score (median 7.1% (5.2-12.8%) vs 5.3% (3.3-8.6%), P < 0.001). Areas with lower socioeconomic status (IAD and IEO) had a higher risk of incident AF independent of LV function and CHARGE-AF score (hazard ratio for IAD 1.16, 95% confidence interval 1.05-1.29, P = 0.005 and hazard ratio for IEO 1.18, 95% confidence interval 1.07-1.30, P = 0.001). CONCLUSION: Regional socioeconomic status is associated with risk of incident AF, independent of LV function and clinical risk. This association might permit better regional targeting of prevention.