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AimsAlthough highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS.Methods and resultsA genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10-8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2-SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26-1.35; P = 2.7 × 10-51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08-1.37; P = 1.4 × 10-3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90-5.12; P = 2.1 × 10-20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17-1.23; P = 4.8 × 10-73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05-1.9; P = 1.9 × 10-12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS.ConclusionDyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies.

OBJECTIVES Previous reports suggest that betablockers appear non-beneficial after surgical aortic valve replacement (SAVR). This study aims to clarify the associations between betablockers and long-term outcome after SAVR. METHODS All patients with isolated SAVR due to aortic stenosis in Sweden between 2006 and 2020, alive at 6 months after surgery, were included. Patients were identified in the SWEDEHEART registry, and records were merged with data from 3 other mandatory national registries. Association between dispensed betablockers and major adverse cardiovascular events (MACE) (all-cause mortality, myocardial infarction and stroke) was analyzed using Cox proportional hazards models, with time-updated data on medication and adjusted for age, sex and comorbidities at baseline. RESULTS In total, 11 849 patients were included [median follow-up 5.4 years (range 0–13.5)]. Betablockers were prescribed to 79.7% of patients at baseline, decreasing to 62.2% after 5 years. Continuing treatment was associated with higher risk of MACE [adjusted hazard ratio 1.14 (95% confidence interval, CI 1.05–1.23)]. The association was consistent over subgroups based on age, sex and comorbidities except atrial fibrillation [hazard ratio (HR) 1.05 (95% CI 0.93–1.19)]. A sensitivity analysis including time-updated data on comorbidites attenuated the difference between the groups [HR 1.04 (95% CI 0.95–1.14, P  = 0.33)]. CONCLUSIONS Treatment with betablockers did not appear to be associated with inferior long-term outcome after SAVR, when adjusting for new concomitant diseases. Thus, it is likely that it is the underlying cardiac diseases that are associated with MACE rather than betablocker treatment. [ABSTRACT FROM AUTHOR]

It is unclear whether genetic markers interact with risk factors to influence atrial fibrillation (AF) risk. We performed genome-wide interaction analyses between genetic variants and age, sex, hypertension, and body mass index in the AFGen Consortium. Study-specific results were combined using meta-analysis (88,383 individuals of European descent, including 7,292 with AF). Variants with nominal interaction associations in the discovery analysis were tested for association in four independent studies (131,441 individuals, including 5,722 with AF). In the discovery analysis, the AF risk associated with the minor rs6817105 allele (at the PITX2 locus) was greater among subjects ≤ 65 years of age than among those > 65 years (interaction p-value = 4.0 × 10-5). The interaction p-value exceeded genome-wide significance in combined discovery and replication analyses (interaction p-value = 1.7 × 10-8). We observed one genome-wide significant interaction with body mass index and several suggestive interactions with age, sex, and body mass index in the discovery analysis. However, none was replicated in the independent sample. Our findings suggest that the pathogenesis of AF may differ according to age in individuals of European descent, but we did not observe evidence of statistically significant genetic interactions with sex, body mass index, or hypertension on AF risk.

The article discusses the benefits of early aortic valve replacement in asymptomatic severe aortic stenosis patients, as shown in the AVATAR trial. The study found that early surgery significantly improved outcomes compared to watchful waiting, with a lower risk of mortality and other adverse events. However, the study's limitations, such as a small sample size and specific patient characteristics, suggest caution in generalizing the results to all aortic stenosis patients. The findings highlight the need for more nuanced approaches to managing asymptomatic severe aortic stenosis, potentially incorporating exercise testing for better risk assessment. [Extracted from the article]

Background: Cardiopulmonary bypass (CPB) ensures tissue oxygenation during cardiac surgery. New technology allows continuous registration of CPB variables during the operation. The aim of the present investigation was to study the association between CPB management and the risk of postoperative acute kidney injury (AKI). Methods: This observational study based on prospectively registered data included 2661 coronary artery bypass grafting and/or valve patients operated during 2016–2020. Individual patient characteristics and postoperative outcomes collected from the SWEDEHEART registry were merged with CPB variables automatically registered every 20 s during CPB. Associations between CPB variables and AKI were analyzed with multivariable logistic regression models adjusted for patient characteristics. Results: In total, 387 patients (14.5%) developed postoperative AKI. After adjustments, longer time on CPB and aortic cross‐clamp, periods of compromised blood flow during aortic cross‐clamp time, and lower nadir hematocrit were associated with the risk of AKI, while mean blood flow, bladder temperature, central venous pressure, and mixed venous oxygen saturation were not. Patient characteristics independently associated with AKI were advanced age, higher body mass index, hypertension, diabetes mellitus, atrial fibrillation, lower left ventricular ejection fraction, estimated glomerular filtration rate <60 or >90 mL/min/m2, and preoperative hemoglobin concentration below or above the normal sex‐specific range. Conclusions: To reduce the risk of AKI after cardiac surgery, aortic clamp time and CPB time should be kept short, and low hematocrit and periods of compromised blood flow during aortic cross‐clamp time should be avoided if possible. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES The aim of this study was to evaluate the association between statin use after surgical aortic valve replacement for aortic stenosis and long-term risk for major adverse cardiovascular events (MACEs) in a large population-based, nationwide cohort. METHODS All patients who underwent isolated surgical aortic valve replacement due to aortic stenosis in Sweden 2006–2020 and survived 6 months after discharge were included. Individual patient data from 5 nationwide registries were merged. Primary outcome is MACE (defined as all-cause mortality, myocardial infarction or stroke). Multivariable Cox regression model adjusted for age, sex, comorbidities, valve type, operation year and secondary prevention medications is used to evaluate the association between time-updated dispense of statins and long-term outcome in the entire study population and in subgroups based on age, sex and comorbidities. RESULTS A total of 11 894 patients were included. Statins were dispensed to 49.8% (5918/11894) of patients at baseline, and 51.0% (874/1713) after 10 years. At baseline, 3.6% of patients were dispensed low dose, 69.4% medium dose and 27.0% high-dose statins. After adjustments, ongoing statin treatment was associated with a reduced risk for MACE [adjusted hazard ratio 0.77 (95% confidence interval 0.71–0.83). P  < 0.001], mainly driven by a reduction in all-cause mortality [adjusted hazard ratio, 0.70 (0.64–0.76)], P  < 0.001. The results were consistent in all subgroups. CONCLUSIONS The results suggest that statin therapy might be beneficial for patients undergoing surgical aortic valve replacement for aortic stenosis. Randomized controlled trials are warranted to establish causality between statin treatment and improved outcome. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Using existing transthoracic echocardiographic indices to quantify left ventricular wall motion abnormalities (WMAs) can be difficult due to the variations in the location of the abnormalities within the left ventricle, the quality of examinations, and the inter‐/intra‐observer variability of available indices. This study aimed to evaluate a new approach for measuring the extent of WMA by calculating the percentage of abnormal wall motion and comparing it to the wall motion score index (WMSI). The study also sought to assess inter‐ and intra‐observer variability. Methods: The study included 140 echocardiograms from 54 patients presenting with ST‐elevation myocardial infarction or Takotsubo syndrome. All patients underwent an echocardiographic examination according to a standard protocol and the images were used to measure the extent of akinesia (proportion akinesia, PrA), akinesia and hypokinesia (proportion akinesia/hypokinesia, PrAH), and WMSI. The inter‐observer variability between the two operators was analyzed. The intra‐observer analysis was performed by one observer using the same images at least 1 month after the first measurement. The agreement was analyzed using the Pearson correlation coefficient and Bland‐Altman plots. Results: Inter‐ and intra‐observer variability for PrA and PrAH were low and comparable to those for WMSI. Conclusion: PrA and PrAH are reliable and reproducible echocardiographic methods for the evaluation of left ventricular wall motion. [ABSTRACT FROM AUTHOR]