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BackgroundTraditional prognostic models for ST-segment elevation myocardial infarction (STEMI) have limitations in statistical methods and usability.ObjectiveWe aimed to develop a machine-learning (ML) based risk score to predict in-hospital mortality, intensive care unit (ICU) admission, and left ventricular ejection fraction less than 40% (LVEF

Coronary artery blood flow is influenced by various factors including vessel geometry, hemodynamic conditions, timing in the cardiac cycle, and rheological conditions. Multiple patterns of disturbed coronary flow may occur when blood flow separates from the laminar plane, associated with inefficient blood transit, and pathological processes modulated by the vascular endothelium in response to abnormal wall shear stress. Current simulation techniques, including computational fluid dynamics and fluid–structure interaction, can provide substantial detail on disturbed coronary flow and have advanced the contemporary understanding of the natural history of coronary disease. However, the clinical application of these techniques has been limited to hemodynamic assessment of coronary disease severity, with the potential to refine the assessment and management of coronary disease. Improved computational efficiency and large clinical trials are required to provide an incremental clinical benefit of these techniques beyond existing tools. This contemporary review is a clinically relevant overview of the disturbed coronary flow and its associated pathological consequences. The contemporary methods to assess disturbed flow are reviewed, including clinical applications of these techniques. Current limitations and future opportunities in the field are also discussed.

Background: High-grade atrioventricular block (HGAVB) is common after transcatheter aortic valve implantation (TAVI), often necessitating permanent pacemaker (PPM) implantation. Delayed HGAVB has varying definitions but typically refers to onset 48 hours after TAVI or following discharge and may cause syncope and sudden cardiac death. This review estimates the incidence of delayed HGAVB and identifies limitations of current literature. Methods: A systematic review was performed of the following online databases: Medline, Cochrane, Web of Science, and Scopus. Studies that labelled the outcome of “delayed” or “late” atrioventricular block after TAVI were included; patients with previous PPM or aortic valve surgery were excluded. Initial search yielded 775 studies, which, after screening, was narrowed to 19 studies. Results: Nineteen studies with 14,898 patients were included. Mean age was 81.7 years, and 46.3% were male. Mean Society of Thoracic Surgeons (STS) score was 5.6%, and 31.3% of patients had known atrial fibrillation. The most common access site was transfemoral (84.8%), whereas balloon-expandable valves were used in 62.1%, self-expanding valves in 34.0%, and mechanically expanding valves in 3.9% of cases. The incidence of delayed HGAVB ranged from 1.7% to 14.6%, with significant methodologic heterogeneity noted among the included studies. Conclusions: Delayed HGAVB is a common and potentially serious complication of TAVI, with similar risk factors to acute HGAVB. With a move toward an early discharge strategy post-TAVI, further prospective study of delayed HGAVB is warranted to improve understanding of predisposing factors, incidence, timing, and implications. Résumé: Contexte: L’apparition d’un bloc atrioventriculaire de haut degré (BAVHD) est fréquente après l’implantation valvulaire aortique par cathéter (IVAC), ce qui nécessite souvent l’implantation d’un stimulateur cardiaque permanent. Les définitions d’un BAVHD tardif varient, mais elles font habituellement référence à l’apparition du bloc 48 heures après l’IVAC ou après le congé de l’hôpital. Le bloc peut alors provoquer une syncope et une mort subite d’origine cardiaque. Cette analyse vise à estimer l’incidence de la formation d’un BAVHD tardif et à définir les lacunes dans les publications actuelles. Méthodologie: Une analyse des études publiées dans les bases de données en ligne suivantes a été menée : Medline, Cochrane, Web of Science et Scopus. Les études dont le libellé comprenait l’issue du bloc atrioventriculaire tardif ou éloigné (« delayed » ou « late ») ont été retenues. Les patients qui avaient antérieurement reçu un stimulateur cardiaque permanent ou subi une intervention chirurgicale de la valve aortique ont été exclus. La recherche initiale a permis de recenser 775 études, nombre qui a été réduit à 19 après l’application des critères de sélection. Résultats: Dix-neuf études totalisant 14 898 patients ont été retenues. L’âge moyen était 81,7 ans, et 46,3 % des patients étaient des hommes. Le score STS (Society of Thoracic Surgeons) moyen était de 5,6 %, et 31,3 % des patients avaient une fibrillation auriculaire. Le point d’accès le plus fréquent était par l’artère fémorale (84,8 %). Des valves expansibles par ballonnet ont été utilisées dans 62,1 % des cas, des valves auto-expansibles dans 34,0 % des cas et des valves expansibles mécaniquement dans 3,9 % des cas. L’incidence du BAVHD tardif variait de 1,7 % à 14,6 %, mais la méthodologie était très hétérogène d’une étude à l’autre. Conclusions: Le BAVHD tardif est une complication fréquente et potentiellement grave de l’IVAC, et ses facteurs de risque sont comparables à ceux du BAVHD aigu. Étant donné la volonté d’adopter une stratégie de congé précoce après une IVAC, une autre étude prospective sur le BAVHD tardif s’impose pour mieux comprendre les facteurs prédisposants, l’incidence, la chronologie et les implications.

A hyperdominant left anterior descending coronary artery variation is a rare but important diagnosis because of the risk for large-territory ischemia. We describe a very rare presentation of spontaneous coronary artery dissection in the distal portion of a hyperdominant left anterior descending coronary artery. No similar cases have been described.

Background Large observational studies have demonstrated a clear inverse association between renal function and risk of aortic stenosis (AS). Whether this represents a causal, reverse causal or correlative relationship remains unclear. We investigated this using a bidirectional 2‐sample Mendelian randomization approach. Methods and Results We collected summary statistics for the primary analysis of chronic kidney disease (CKD) and AS from genome‐wide association study meta‐analyses including 480 698 and 653 867 participants, respectively. We collected further genome‐wide association study summary statistics from up to 1 004 040 participants for sensitivity analyses involving estimated glomerular filtration rate (eGFR) derived from creatinine, eGFR derived from cystatin C, and serum urea nitrogen. Inverse‐variance weighted was the primary analysis method, with weighted‐median, weighted‐mode, Mendelian randomization‐Egger, and Mendelian randomization‐Pleiotropy Residual Sum and Outlier as sensitivity analyses. We did not find evidence of a causal relationship between genetically predicted CKD liability as the exposure and AS as the outcome (odds ratio [OR], 0.94 per unit increase in log odds of genetic liability to CKD [95% CI, 0.85–1.04], P=0.26) nor robust evidence of AS liability as the exposure and CKD as the outcome (OR, 1.04 per unit increase in log odds of genetic liability to AS [95% CI, 0.97–1.12], P=0.30). The sensitivity analyses were neutral overall, as were the analyses using eGFR derived from creatinine, eGFR derived from cystatin C, and serum urea nitrogen. All positive controls demonstrated strong significant associations. Conclusions The present study did not find evidence of a substantial effect of genetically predicted renal impairment on risk of AS. This has important implications for research efforts that attempt to identify prevention and treatment targets for both CKD and AS.

Abstract There are currently no approved pharmacological treatment options for aortic stenosis (AS), and there are limited identified drug targets for this chronic condition. It remains unclear whether inflammation plays a role in AS pathogenesis and whether immunomodulation could become a therapeutic target. We evaluated the potentially causal association between inflammation and AS by investigating the genetically proxied effects of tocilizumab (IL6 receptor, IL6R, inhibitor), canakinumab (IL1β inhibitor) and colchicine (β-tubulin inhibitor) through a Mendelian randomisation (MR) approach. Genetic proxies for these drugs were identified as single nucleotide polymorphisms (SNPs) in the gene, enhancer or promoter regions of IL6R, IL1β or β-tubulin gene isoforms, respectively, that were significantly associated with serum C-reactive protein (CRP) in a large European genome-wide association study (GWAS; 575,531 participants). These were paired with summary statistics from a large GWAS of AS in European patients (653,867 participants) to then perform primary inverse-variance weighted random effect and sensitivity MR analyses for each exposure. This analysis showed that genetically proxied tocilizumab was associated with reduced risk of AS (OR 0.56, 95% CI 0.45–0.70 per unit decrease in genetically predicted log-transformed CRP). Genetically proxied canakinumab was not associated with risk of AS (OR 0.80, 95% CI 0.51–1.26), and only one suitable SNP was identified to proxy the effect of colchicine (OR 34.37, 95% CI 1.99–592.89). The finding that genetically proxied tocilizumab was associated with reduced risk of AS is concordant with an inflammatory hypothesis of AS pathogenesis. Inhibition of IL6R may be a promising therapeutic target for AS management.

Background: CT coronary angiography (CTCA) is a guideline-endorsed assessment for patients with stable angina and suspected coronary disease. Although associated with excellent negative predictive value in ruling out obstructive coronary disease, there are limitations in the ability of CTCA to predict hemodynamically significant coronary disease. The CAPTivAte study aims to assess the utility of Aggregated Plaque Burden (APB) in predicting ischemia based on Fractional Flow Reserve (FFR). Methods: In this retrospective study, patients who had a CTCA and invasive FFR of the LAD were included. The entire length of the LAD was analyzed using semi-automated software which characterized total plaque burden and plaque morphological subtype (including Low Attenuation Plaque (LAP), Non-calcific plaque (NCP) and Calcific Plaque (CP). Aggregated Plaque Burden (APB) was calculated. Univariate and multivariate analysis were performed to assess the association between these CT-derived parameters and invasive FFR. Results: There were 145 patients included in this study. 84.8 % of patients were referred with stable angina. There was a significant linear association between APB and FFR in both univariate and multivariate analysis (Adjusted R-squared = 0.0469; p = 0.035). Mean Agatston scores are higher in FFR positive vessels compared to FFR negative vessels (371.6 (±443.8) vs 251.9 (±283.5, p = 0.0493). Conclusion: CTCA-derived APB is a reliable predictor of ischemia assessed using invasive FFR and may aid clinicians in rationalizing invasive vs non-invasive management strategies. Vessel-specific Agatston scores are significantly higher in FFR-positive vessels than in FFR-negative vessels. Associations between HU-derived plaque subtype and invasive FFR were inconclusive in this study.

Abstract Background Fractional Flow Reserve (FFR) is a widely applied invasive physiological assessment, endorsed by major guidelines to aid in the decision to perform or defer revascularisation. While a threshold of > 0.8 has been applied universally, clinical outcomes may be affected by numerous factors, including the presence of diabetes. This meta-analysis aims to investigate the outcomes of diabetic versus non-diabetic patients in whom revascularisation was deferred based on negative FFR. Methods We performed a meta-analysis investigating the outcomes of diabetic and non-diabetic patients in whom revascularisation was deferred based on negative FFR. A search was performed on MEDLINE, PubMed and EMBASE, and peer-reviewed studies that reported MACE for diabetic and non-diabetic patients with deferred revascularisation based on FFR > 0.8 were included. The primary end point was MACE. Results The meta-analysis included 7 studies in which 4275 patients had revascularisation deferred based on FFR > 0.8 (1250 diabetic). Follow up occurred over a mean of 3.2 years. Diabetes was associated with a higher odds of MACE (OR = 1.66, 95% CI 1.35–2.04, p = 0.8, the presence of diabetes portends an increased long-term risk of MACE compared to non-diabetic patients. Trail registration URL: https://www.crd.york.ac.uk/PROSPERO/ ; Unique identifier: CRD42022367312.

BackgroundPre-existing cardiovascular disease and cardiovascular risk factors are common in patients with COVID-19 and there remain concerns for poorer in-hospital outcomes in this cohort. We aimed to analyse the relationship between pre-existing cardiovascular disease, mortality and cardiovascular outcomes in patients hospitalised with COVID-19 in a prospective, multicentre observational study.MethodThis prospective, multicentre observational study included consecutive patients of age ≥18 in their index hospitalisation with laboratory-proven COVID-19 in Australia. Patients with suspected but not laboratory-proven COVID-19 and patients with no available past medical history were excluded. The primary exposure was pre-existing cardiovascular disease, defined as a composite of coronary artery disease, heart failure or cardiomyopathy, atrial fibrillation or flutter, severe valvular disease, peripheral arterial disease and stroke or transient ischaemic attack. The primary outcome was in-hospital mortality. Secondary outcomes were clinical cardiovascular complications (new onset atrial fibrillation or flutter, high-grade atrioventricular block, sustained ventricular tachycardia, new heart failure or cardiomyopathy, pericarditis, myocarditis or myopericarditis, pulmonary embolism and cardiac arrest) and myocardial injury.Results1,567 patients (mean age 60.7 (±20.5) years and 837 (53.4%) male) were included. Overall, 398 (25.4%) patients had pre-existing cardiovascular disease, 176 patients (11.2%) died, 75 (5.7%) had clinical cardiovascular complications and 345 (37.8%) had myocardial injury. Patients with pre-existing cardiovascular disease had significantly increased in-hospital mortality (aOR: 1.76 95% CI: 1.21–2.55, p = 0.003) and myocardial injury (aOR: 3.27, 95% CI: 2.23–4.79, p

Introduction Aortic stenosis is the most common cardiac valve pathology worldwide and has a mortality rate of over 50% at 5 years if left untreated. Transcatheter aortic valve implantation (TAVI) is a minimally invasive and highly effective alternative treatment option to open-heart surgery. High-grade atrioventricular conduction block (HGAVB) is one of the most common complications after TAVI and requires a permanent pacemaker. Due to this, patients are typically monitored for 48 hours post TAVI, however up to 40% of HGAVB may delayed, and occur after discharge. Delayed HGAVB can cause syncope or sudden unexplained cardiac death in a vulnerable population, and no accurate methods currently exist to identify patients at risk.Methods and analysis The prospective observational study on the accuracy of predictors of high-grade atrioventricular conduction block after transcatheter aortic valve implantation (CONDUCT-TAVI) trial is an Australian-led, multicentre, prospective observational study, aiming to improve the prediction of HGAVB, after TAVI. The primary objective of the trial is to assess whether published and novel invasive electrophysiology predictors performed immediately before and after TAVI can help predict HGAVB after TAVI. The secondary objective aims to further evaluate the accuracy of previously published predictors of HGAVB after TAVI, including CT measurements, 12-lead ECG, valve characteristics, percentage oversizing and implantation depth. Follow-up will be for 2 years, and detailed continuous heart rhythm monitoring will be obtained by inserting an implantable loop recorder in all participants.Ethics and dissemination Ethics approval has been obtained for the two participating centres. Results of the study will be submitted for publication in a peer-reviewed journal.Trial registration number ACTRN12621001700820.

Background The pathophysiological mechanism behind adverse outcomes associated with ischemia‐inducing epicardial coronary stenoses and microcirculatory dysfunction remains unclear. Wall shear stress (WSS) plays an important role in atherosclerotic plaque progression and vulnerability. We aimed to evaluate the relationship between WSS, functionally significant epicardial coronary stenoses, and microcirculatory dysfunction. Methods and Results Patients undergoing invasive coronary physiology testing were included. Fractional flow reserve, instantaneous wave‐free ratio, and the index of microcirculatory resistance were measured. Quantitative coronary angiography was used to obtain the lesion percentage diameter stenosis. Computational fluid dynamics analysis was performed to calculate WSS parameters. Multiple regression analysis was performed to calculate the standardized regression coefficient (β) for the coronary physiology indices. A total of 107 vessels from 88 patients were included. Fractional flow reserve independently predicted the total area of low WSS (β=−0.44; 95% CI, −0.62 to −0.25; P