Antithrombotic Treatment After Transcatheter Valve Interventions: Current Status and Future Directions.

PURPOSE The optimal antithrombotic strategy after transcatheter valve interventions is a subject of ongoing debate. Although there is evidence from randomized trials in patients undergoing transcatheter aortic valve replacement (TAVR), current evidence on optimal antithrombotic management after transcatheter mitral or tricuspid valve interventions is sparse. This article appraises the current evidence on this topic. METHODS This narrative review presents key research findings and guideline recommendations, as well as highlights areas for future research. FINDINGS After TAVR, randomized trial evidence suggests that single antiplatelet therapy is reasonable for patients without pre-existing indications for oral anticoagulation (OAC). If there is a concurrent indication for OAC, the addition of antiplatelet therapy increases bleeding risk. Whether direct oral anticoagulants achieve better outcomes than vitamin K antagonists is uncertain in this setting. Although OAC has been shown to reduce subclinical leaflet thrombosis (which may progress to structural valve degeneration), bleeding events are unacceptably high. There is a lack of randomized trial data comparing antithrombotic strategies after transcatheter mitral or tricuspid valve replacement or after mitral or tricuspid transcatheter edge-to-edge repair. Single antiplatelet therapy after mitral or tricuspid transcatheter edge-to-edge repair may be appropriate, whereas at least 3 months of OAC is suggested after transcatheter mitral valve replacement or transcatheter tricuspid valve replacement. IMPLICATIONS Randomized studies are warranted to address the knowledge gaps in antithrombotic therapy after transcatheter valve interventions and to optimize outcomes

Bias in Zipf's Law Estimators

The prevailing maximum likelihood estimators for inferring power law models from rank-frequency data are biased. The source of this bias is an inappropriate likelihood function. The correct likelihood function is derived and shown to be computationally intractable. A more computationally efficient method of approximate Bayesian computation (ABC) is explored. This method is shown to have less bias for data generated from idealised rank-frequency Zipfian distributions. However, the existing estimators and the ABC estimator described here assume that words are drawn from a simple probability distribution, while language is a much more complex process. We show that this false assumption leads to continued biases when applying any of these methods to natural language to estimate Zipf exponents. We recommend that researchers be aware of these biases when investigating power laws in rank-frequency data.Comment: 15 pages, 11 figure

Transcatheter aortic valve implantation and bleeding: incidence, predictors and prognosis

Peri-procedural bleeding complications are feared adverse events in patients undergoing transcatheter aortic valve implantation (TAVI). Little is known about the implications of peri-procedural bleeding on clinical outcome. In a prospective single-center registry of consecutive patients undergoing TAVI, we investigated incidence, predictors and clinical consequences of life-threatening and major bleeding as defined by the Valve Academic Research Consortium. Among 389 consecutive patients undergoing TAVI by a transfemoral (79.2%), transapical (19.6%) or trans-subclavian (1.3%) approach between July 2007 and October 2011, life-threatening or major peri-procedural bleeding events occurred in 64 (16.4%) and 125 patients (32.1%), respectively. Patients with peri-procedural bleeding events had a higher logistic EuroSCORE, more advanced renal disease, and were more symptomatic as assessed by New York Heart Association functional class at baseline as compared to patients with no bleeding. Life-threatening bleeding was associated with a higher all-cause (17.2 vs 5.6 vs 3.0%, p<0.001) and cardiovascular mortality (10.9 vs 5.6 vs 2.5%, p=0.02) at 30days compared to patients with major bleeding or no bleeding. Multivariate analysis identified transapical access (OR 2.6, 95% CI 1.4-4.8; p=0.002), glomerular filtration rate <30ml/min (OR 2.3, 95% CI 1.1-4.7, p=0.031), and diabetes (OR 1.8, 95% CI 1.001-3.2, p=0.049) as independent predictors of life-threatening, peri-procedural bleeding. Life-threatening bleeding complications in patients undergoing TAVI are associated with increased mortality. Renal impairment, diabetes, and transapical approach were identified as independent risk factors for life-threatening bleeding event

Valve-in-valve TAVI and risk of coronary obstruction: Validation of the VIVID classification.

BACKGROUND The Valve-in-Valve International Data (VIVID) registry proposed a simplified classification to assess the risk of coronary obstruction during valve-in-valve transcatheter aortic valve implantation (ViV-TAVI) based on preprocedural multi-detector computed tomography (MDCT). We investigated the validity of the VIVID classification in patients undergoing ViV-TAVI for degenerated bioprostheses. METHODS Patients undergoing ViV-TAVI for degenerated bioprostheses were prospectively included in this study. The risk of coronary obstruction among patients treated with stented valves was retrospectively evaluated based on anatomical assessment on pre-procedural MDCT. RESULTS Among a total of 137 patients that underwent ViV-TAVI between August 2007 and June 2021, 109 patients had stented, sutureless, or transcatheter degenerated bioprosthesis of which 96 (88%) had adequate MDCT data for risk assessment. High-risk anatomy for coronary obstruction (VIVID type IIB, IIIB, or IIIC) in either the left or right coronary artery was observed in 30 patients (31.3%). Of the 30 patients with high-risk anatomy, coronary protection using wire protection or BASILICA (bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction) was performed in 3 patients (10.0%). Three patients treated with stentless valves and one patient treated with a stented valve with externally mounted leaflets had coronary obstruction. None of the patients with high risk anatomy according to MDCT had coronary obstruction even without coronary protection. CONCLUSIONS Coronary obstruction occurred in none of the patients classified as high-risk patients according to the VIVID classification despite the absence of coronary protection. Refined tools are required to assess the risk of coronary obstruction. CLINICAL TRIAL REGISTRATION https://www. CLINICALTRIALS gov. NCT01368250

Mortality, Stroke, and Hospitalization Associated With Deferred vs Expedited Aortic Valve Replacement in Patients Referred for Symptomatic Severe Aortic Stenosis During the COVID-19 Pandemic.

This cohort study evaluates the outcomes associated with deferred vs expedited aortic valve replacement in patients with severe aortic stenosis during the COVID-19 pandemic

Protocol for a population-based study of rheumatic heart disease prevalence and cardiovascular outcomes among schoolchildren in Nepal

Rheumatic heart disease (RHD) remains a major contributor to morbidity and mortality in developing countries. The reported prevalence rates of RHD are highly variable and mainly attributable to differences in the sensitivity of either clinical screening to detect advanced heart disease or echocardiographic evaluation where disease is diagnosed earlier across a continuous spectrum. The clinical significance of diagnosis of subclinical RHD by echocardiographic screening and early implementation of secondary prevention has not been clearly established. METHODS AND ANALYSIS: The authors designed a cross-sectional survey to determine the prevalence of RHD in children from private and public schools between the age of 5 and 15 years in urban and rural areas of Eastern Nepal using both cardiac auscultation and echocardiographic evaluation. Children with RHD will be treated with secondary prevention and enrolled in a prospective cohort study. The authors will compare the prevalence rates by cardiac auscultation and echocardiography, determine risk factors associated with diagnosis and progression of RHD, investigate social and economic barriers for receiving adequate cardiac care and assess clinical outcomes with regular medical surveillance as a function of stage of disease at the time of diagnosis. Prospective clinical studies investigating the impact of secondary prevention for subclinical RHD on long-term clinical outcome will be of central relevance for future health resource utilisation in developing countries. ETHICS AND DISSEMINATION: The study was considered ethically uncritical and was given an exempt status by the ethics committee at University of Bern, Switzerland. The study has been submitted to the National Nepal Health Research Council and was registered with http://www.ClinicalTrials.gov (NCT01550068). The study findings will be reported in peer-reviewed publications. CLINICALTRIALS.GOV IDENTIFIER: NCT01550068

SGLT2 inhibitor therapy for transthyretin amyloid cardiomyopathy: early tolerance and clinical response to dapagliflozin.

AIMS Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve clinical outcomes in heart failure patients with reduced and preserved left ventricular ejection fraction (LVEF), but have not yet been investigated in transthyretin amyloid cardiomyopathy (ATTR-CM). This study aimed to evaluate tolerability, clinical outcomes, and changes in NT-proBNP levels and glomerular filtration rate (GFR) in ATTR-CM patients treated with dapagliflozin. METHODS AND RESULTS Patients with stable, tafamidis-treated ATTR-CM were retrospectively evaluated at the initiation of dapagliflozin and 3 months thereafter. Tafamidis-treated ATTR-CM patients without SGLT2i served as a reference cohort. Overall, SLGT2i therapy was initiated in 34 patients. Seventeen patients with stable disease on tafamidis, who were subsequently started on dapagliflozin, were included in the analysis. Patients selected for SGLT2i presented with signs of advanced disease, evidenced by higher Gillmore disease stage (stage ≥2: 53% vs. 27.5%; P = 0.041), baseline median NT-proBNP [median (IQR) 2668 pg/mL (1314-3451) vs. 1424 (810-2059); P = 0.038] and loop diuretic demand (76.5% vs. 45% of patients; P = 0.044), and lower LVEF (46.6 ± 12.9 vs. 53.7 ± 8.7%; P = 0.019) and GFR (51.8 ± 16.5 vs. 68.5 ± 18.6 mL/min; P = 0.037) compared with the reference cohort. At 3-month follow-up, a numerical decrease in NT-proBNP levels was observed in 13/17 (76.5%) patients in the dapagliflozin (-190 pg/mL, IQR: -1,028-71, P = 0.557) and 27/40 (67.5%) of patients in the control cohort (-115 pg/mL, IQR: -357-105, P = 0.551). Other disease parameters remained stable and no adverse events occurred. CONCLUSIONS In tafamidis-treated ATTR-CM patients, initiation of dapagliflozin was well tolerated. The efficacy of SGLT2i therapy in patients with ATTR-CM needs to be studied in randomized controlled trials

Imaging-Based, Patient-Specific Three-Dimensional Printing to Plan, Train, and Guide Cardiovascular Interventions: A Systematic Review and Meta-Analysis.

BACKGROUND To tailor cardiovascular interventions, the use of three-dimensional (3D), patient-specific phantoms (3DPSP) encompasses patient education, training, simulation, procedure planning, and outcome-prediction. AIM This systematic review and meta-analysis aims to investigate the current and future perspective of 3D printing for cardiovascular interventions. METHODS We systematically screened articles on Medline and EMBASE reporting the prospective use of 3DPSP in cardiovascular interventions by using combined search terms. Studies that compared intervention time depending on 3DPSP utilisation were included into a meta-analysis. RESULTS We identified 107 studies that prospectively investigated a total of 814 3DPSP in cardiovascular interventions. Most common settings were congenital heart disease (CHD) (38 articles, 6 comparative studies), left atrial appendage (LAA) occlusion (11 articles, 5 comparative, 1 randomised controlled trial [RCT]), and aortic disease (10 articles). All authors described 3DPSP as helpful in assessing complex anatomic conditions, whereas poor tissue mimicry and the non-consideration of physiological properties were cited as limitations. Compared to controls, meta-analysis of six studies showed a significant reduction of intervention time in LAA occlusion (n=3 studies), and surgery due to CHD (n=3) if 3DPSPs were used (Cohen's d=0.54; 95% confidence interval, 0.13 to 0.95; p=0.001), however heterogeneity across studies should be taken into account. CONCLUSIONS 3DPSP are helpful to plan, train, and guide interventions in patients with complex cardiovascular anatomy. Benefits for patients include reduced intervention time with the potential for lower radiation exposure and shorter mechanical ventilation times. More evidence and RCTs including clinical endpoints are needed to warrant adoption of 3DPSP into routine clinical practice