Role of 18F-sodium fluoride positron emission tomography in imaging atherosclerosis.

Atherosclerosis involving vascular beds across the human body remains the leading cause of death worldwide. Coronary and peripheral artery disease, which are almost universally a result of atherosclerotic plaque, can manifest clinically as myocardial infarctions, ischemic stroke, or acute lower-limb ischemia. Beyond imaging myocardial perfusion and blood-flow, nuclear imaging has the potential to depict the activity of the processes that are directly implicated in the atherosclerotic plaque progression and rupture. Out of several tested tracers to date, the literature is most advanced for 18F-sodium fluoride positron emission tomography. In this review, we present the latest data in the field of atherosclerotic 18F-sodium fluoride positron emission tomography imaging, discuss the advantages and limitation of the techniques, and highlight the aspects that require further research in the future.

Analysis of complications in transfemoral transcatheter aortic valve implantation: a single-center study.

INTRODUCTION: Transfemoral access is the prevailing approach for transcatheter aortic valve implantation (TAVI) in contemporary practice, with a shift from surgical arteriotomy to a percutaneous arterial approach. OBJECTIVES: This study assesses long- and short-term mortality, along with Valve Academic Research Consortium 2 (VARC 2)-defined complications in percutaneous transfemoral approach (PTA) TAVI. Furthermore, it explores the impact of the learning curve on procedural outcomes. PATIENTS AND METHODS: The study includes 600 patients undergoing PTA TAVI at the National Institute of Cardiology, Warsaw, Poland (January 2009-September 2020). Retrospective data comparison involves two groups: early experience (first 200 patients) and late experience (next 400). RESULTS: The primary endpoint (composite of life-threatening bleeding, major vascular complication, or one-month death) occurred less in the late experience group (28.0% vs. 17.5%, P = 0.003). Late experience also showed fewer vascular complications (19.0% vs. 10.7%, P = 0.005) and major bleeding (17.5% vs. 8.5%, P = 0.001). Propensity matching yielded similar trends, including reduced pacemaker implantation (22.8% vs. 10.9%, P = 0.03) and shorter hospitalization (11 [8-18] vs. 7 [6-12] days, P <0.001). CONCLUSIONS: The late experience group in PTA TAVI exhibits significantly reduced periprocedural complications, indicating the positive impact of accumulated expertise.

Clinical phenotypes among patients with normal cardiac perfusion using unsupervised learning: a retrospective observational study.

BACKGROUND: Myocardial perfusion imaging (MPI) is one of the most common cardiac scans and is used for diagnosis of coronary artery disease and assessment of cardiovascular risk. However, the large majority of MPI patients have normal results. We evaluated whether unsupervised machine learning could identify unique phenotypes among patients with normal scans and whether those phenotypes were associated with risk of death or myocardial infarction. METHODS: Patients from a large international multicenter MPI registry (10 sites) with normal perfusion by expert visual interpretation were included in this cohort analysis. The training population included 9849 patients, and external testing population 12,528 patients. Unsupervised cluster analysis was performed, with separate training and external testing cohorts, to identify clusters, with four distinct phenotypes. We evaluated the clinical and imaging features of clusters and their associations with death or myocardial infarction. FINDINGS: Patients in Clusters 1 and 2 almost exclusively underwent exercise stress, while patients in Clusters 3 and 4 mostly required pharmacologic stress. In external testing, the risk for Cluster 4 patients (20.2% of population, unadjusted hazard ratio [HR] 6.17, 95% confidence interval [CI] 4.64-8.20) was higher than the risk associated with pharmacologic stress (HR 3.03, 95% CI 2.53-3.63), or previous myocardial infarction (HR 1.82, 95% CI 1.40-2.36). INTERPRETATION: Unsupervised learning identified four distinct phenotypes of patients with normal perfusion scans, with a significant proportion of patients at very high risk of myocardial infarction or death. Our results suggest a potential role for patient phenotyping to improve risk stratification of patients with normal imaging results. FUNDING: This work was supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health [R35HL161195 to PS]. The REFINE SPECT database was supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health [R01HL089765 to PS]. MCW was supported by the British Heart Foundation [FS/ICRF/20/26002].

Artificial intelligence in detecting left atrial appendage thrombus by transthoracic echocardiography and clinical features: the Left Atrial Thrombus on Transoesophageal Echocardiography (LATTEE) registry.

AIMS: Transoesophageal echocardiography (TOE) is often performed before catheter ablation or cardioversion to rule out the presence of left atrial appendage thrombus (LAT) in patients on chronic oral anticoagulation (OAC), despite associated discomfort. A machine learning model [LAT-artificial intelligence (AI)] was developed to predict the presence of LAT based on clinical and transthoracic echocardiography (TTE) features. METHODS AND RESULTS: Data from a 13-site prospective registry of patients who underwent TOE before cardioversion or catheter ablation were used. LAT-AI was trained to predict LAT using data from 12 sites (n = 2827) and tested externally in patients on chronic OAC from two sites (n = 1284). Areas under the receiver operating characteristic curve (AUC) of LAT-AI were compared with that of left ventricular ejection fraction (LVEF) and CHA2DS2-VASc score. A decision threshold allowing for a 99% negative predictive value was defined in the development cohort. A protocol where TOE in patients on chronic OAC is performed depending on the LAT-AI score was validated in the external cohort. In the external testing cohort, LAT was found in 5.5% of patients. LAT-AI achieved an AUC of 0.85 [95% confidence interval (CI): 0.82-0.89], outperforming LVEF (0.81, 95% CI 0.76-0.86, P < .0001) and CHA2DS2-VASc score (0.69, 95% CI: 0.63-0.7, P < .0001) in the entire external cohort. Based on the proposed protocol, 40% of patients on chronic OAC from the external cohort would safely avoid TOE. CONCLUSION: LAT-AI allows accurate prediction of LAT. A LAT-AI-based protocol could be used to guide the decision to perform TOE despite chronic OAC.

Noninvasive Coronary Atherosclerotic Plaque Imaging.

Coronary artery disease is the leading cause of morbidity and mortality worldwide. Despite remarkable advances in the management of coronary artery disease, the prediction of adverse coronary events remains challenging. Over the preceding decades, considerable effort has been made to improve risk stratification using noninvasive imaging. Recently, these efforts have increasingly focused on the direct imaging of coronary atherosclerotic plaque. Modern imaging now allows imaging of coronary plaque burden, plaque type, atherosclerotic plaque activity, and plaque thrombosis, which have major potential to refine patient risk stratification, aid decision making, and advance future clinical practice.

Computed tomography perfusion and angiography in patients with chronic total occlusion undergoing percutaneous coronary intervention.

BACKGROUND AND AIMS: Myocardial perfusion imaging (MPI) and anatomical imaging with coronary computed tomography angiography (CCTA) can play an important role in the preprocedural planning of a chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We aimed to establish the feasibility of a novel dynamic computed tomography perfusion (CTP) analysis for the assessment of myocardial perfusion before and after a successful recanalization of CTO in patients undergoing CCTA as part of a standard preprocedural workup. METHODS: In a prospective observational study symptomatic patients underwent dynamic CTP on a dual-source CT scanner both before and 3 months after successful CTO PCI. RESULTS: Twenty-seven patients completed the study (63 ± 8 years old, 78% male). Following successful CTO PCI, there was a significant reduction in the ischemic burden (5 [5-7] versus 1 [0-2] segments, p < 0.001), and improvement in myocardial blood flow (85.3 [71.7-94.1] versus 134.6 [123.8-156.9] mL/min, p < 0.001) resulting in an increase in the relative flow reserve (0.49 [0.41-0.57] versus 0.88 [0.74-0.95], p < 0.001). CONCLUSIONS: CTP emerges as a robust and safe method for MPI in CTO patients. The single imaging session assessment of both coronary anatomy and perfusion with CT lends itself to precise disease phenotyping in the challenging population of CTO patients.

Coronary Atherosclerotic Plaque Activity and Future Coronary Events.

Importance: Recurrent coronary events in patients with recent myocardial infarction remain a major clinical problem. Noninvasive measures of coronary atherosclerotic disease activity have the potential to identify individuals at greatest risk. Objective: To assess whether coronary atherosclerotic plaque activity as assessed by noninvasive imaging is associated with recurrent coronary events in patients with myocardial infarction. Design, Setting, and Participants: This prospective, longitudinal, international multicenter cohort study recruited participants aged 50 years or older with multivessel coronary artery disease and recent (within 21 days) myocardial infarction between September 2015 and February 2020, with a minimum 2 years' follow-up. Intervention: Coronary 18F-sodium fluoride positron emission tomography and coronary computed tomography angiography. Main Outcomes and Measures: Total coronary atherosclerotic plaque activity was assessed by 18F-sodium fluoride uptake. The primary end point was cardiac death or nonfatal myocardial infarction but was expanded during study conduct to include unscheduled coronary revascularization due to lower than anticipated primary event rates. Results: Among 2684 patients screened, 995 were eligible, 712 attended for imaging, and 704 completed an interpretable scan and comprised the study population. The mean (SD) age of participants was 63.8 (8.2) years, and most were male (601 [85%]). Total coronary atherosclerotic plaque activity was identified in 421 participants (60%). After a median follow-up of 4 years (IQR, 3-5 years), 141 participants (20%) experienced the primary end point: 9 had cardiac death, 49 had nonfatal myocardial infarction, and 83 had unscheduled coronary revascularizations. Increased coronary plaque activity was not associated with the primary end point (hazard ratio [HR], 1.25; 95% CI, 0.89-1.76; P = .20) or unscheduled revascularization (HR, 0.98; 95% CI, 0.64-1.49; P = .91) but was associated with the secondary end point of cardiac death or nonfatal myocardial infarction (47 of 421 patients with high plaque activity [11.2%] vs 19 of 283 with low plaque activity [6.7%]; HR, 1.82; 95% CI, 1.07-3.10; P = .03) and all-cause mortality (30 of 421 patients with high plaque activity [7.1%] vs 9 of 283 with low plaque activity [3.2%]; HR, 2.43; 95% CI, 1.15-5.12; P = .02). After adjustment for differences in baseline clinical characteristics, coronary angiography findings, and Global Registry of Acute Coronary Events score, high coronary plaque activity was associated with cardiac death or nonfatal myocardial infarction (HR, 1.76; 95% CI, 1.00-3.10; P = .05) but not with all-cause mortality (HR, 2.01; 95% CI, 0.90-4.49; P = .09). Conclusions and Relevance: In this cohort study of patients with recent myocardial infarction, coronary atherosclerotic plaque activity was not associated with the primary composite end point. The findings suggest that risk of cardiovascular death or myocardial infarction in patients with elevated plaque activity warrants further research to explore its incremental prognostic implications.

Pericoronary adipose tissue density is increased in patients with recent spontaneous coronary dissection.

OBJECTIVE: Inflammatory activity is one of the potential mechanisms of spontaneous coronary artery dissection (SCAD). Recently, the pericoronary adipose tissue attenuation (PCAT) derived from CT angiography (CTA) has been established as a method for measuring vascular inflammation. We aimed to characterise the pancoronary and vessel-specific PCAT in patients with and without recent SCAD. METHODS: The study comprised patients with SCAD referred to a tertiary centre between 2017 and 2022 who underwent CTA and were compared with individuals with no prior SCAD. PCAT was analysed on end-diastolic CTA reconstructions along proximal 40 mm of all major coronary vessels as well as the SCAD-related vessel. We analysed 48 patients with recent SCAD (median 6.1 (IQR 3.5-14.9) months since SCAD, 95.8% female) and 48 patients in the group without SCAD. RESULTS: Pancoronary PCAT was higher in patients with SCAD compared with those without SCAD (-80.6±7.9 vs -85.3 HU±6.1, p=0.002). Vessel-specific PCAT in patients with SCAD compared with patients without SCAD was higher for both the RCA (-80.9±9.5 vs -87.1±6.9 HU, p=0.001) and the LCA (-80.3±7.8 vs -83.4±7.2 HU, p=0.04). In patients with SCAD, PCAT of the SCAD-related vessel was not significantly different from averaged PCAT of unaffected vessels (-81.2±9.2 vs -80.6±7.6, p=0.74). There was no association between PCAT and the interval from SCAD to CTA. CONCLUSIONS: Patients with recent SCAD have higher PCAT compared with patients without SCAD, suggesting an increased perivascular inflammatory activity. This association is not restricted to the dissected vessel.

Time and event-specific deep learning for personalized risk assessment after cardiac perfusion imaging.

Standard clinical interpretation of myocardial perfusion imaging (MPI) has proven prognostic value for predicting major adverse cardiovascular events (MACE). However, personalizing predictions to a specific event type and time interval is more challenging. We demonstrate an explainable deep learning model that predicts the time-specific risk separately for all-cause death, acute coronary syndrome (ACS), and revascularization directly from MPI and 15 clinical features. We train and test the model internally using 10-fold hold-out cross-validation (n = 20,418) and externally validate it in three separate sites (n = 13,988) with MACE follow-ups for a median of 3.1 years (interquartile range [IQR]: 1.6, 3.6). We evaluate the model using the cumulative dynamic area under receiver operating curve (cAUC). The best model performance in the external cohort is observed for short-term prediction - in the first six months after the scan, mean cAUC for ACS and all-cause death reaches 0.76 (95% confidence interval [CI]: 0.75, 0.77) and 0.78 (95% CI: 0.78, 0.79), respectively. The model outperforms conventional perfusion abnormality measures at all time points for the prediction of death in both internal and external validations, with improvement increasing gradually over time. Individualized patient explanations are visualized using waterfall plots, which highlight the contribution degree and direction for each feature. This approach allows the derivation of individual event probability as a function of time as well as patient- and event-specific risk explanations that may help draw attention to modifiable risk factors. Such a method could help present post-scan risk assessments to the patient and foster shared decision-making.

Latent Coronary Plaque Morphology From Computed Tomography Angiography, Molecular Disease Activity on Positron Emission Tomography, and Clinical Outcomes.

BACKGROUND: Assessments of coronary disease activity with 18F-sodium fluoride positron emission tomography and radiomics-based precision coronary plaque phenotyping derived from coronary computed tomography angiography may enhance risk stratification in patients with coronary artery disease. We sought to investigate whether the prognostic information provided by these 2 approaches is complementary in the prediction of myocardial infarction. METHODS: Patients with known coronary artery disease underwent coronary 18F-sodium fluoride positron emission tomography and coronary computed tomography angiography on a hybrid positron emission tomography/computed tomography scanner. Coronary 18F-NaF uptake was determined by the coronary microcalcification activity. We performed quantitative plaque analysis of coronary computed tomography angiography datasets and extracted 1103 radiomic features for each plaque. Using weighted correlation network analysis, we derived latent morphological features of coronary lesions which were aggregated to patient-level radiomics nomograms to predict myocardial infarction. RESULTS: Among 260 patients with established coronary artery disease (age, 65±9 years; 83% men), 179 (69%) participants showed increased coronary 18F-NaF activity (coronary microcalcification activity>0). Over 53 (40-59) months of follow-up, 18 patients had a myocardial infarction. Using weighted correlation network analysis, we derived 15 distinct eigen radiomic features representing latent morphological coronary plaque patterns in an unsupervised fashion. Following adjustments for calcified, noncalcified, and low-density noncalcified plaque volumes and 18F-NaF coronary microcalcification activity, 4 radiomic features remained independent predictors of myocardial infarction (hazard ratio, 1.46 [95% CI, 1.03-2.08]; P=0.03; hazard ratio, 1.62 [95% CI, 1.04-2.54]; P=0.02; hazard ratio, 1.49 [95% CI, 1.07-2.06]; P=0.01; and hazard ratio, 1.50 (95% CI, 1.05-2.13); P=0.02). CONCLUSIONS: In patients with established coronary artery disease, latent coronary plaque morphological features, quantitative plaque volumes, and disease activity on 18F-sodium fluoride positron emission tomography are additive predictors of myocardial infarction.

Advanced Cardiac Imaging in the Assessment of Aortic Stenosis.

Aortic stenosis is the most common form of valve disease in the Western world and a major healthcare burden. Although echocardiography remains the central modality for the diagnosis and assessment of aortic stenosis, recently, advanced cardiac imaging with cardiovascular magnetic resonance, computed tomography, and positron emission tomography have provided invaluable pathological insights that may guide the personalized management of the disease. In this review, we discuss applications of these novel non-invasive imaging modalities for establishing the diagnosis, monitoring disease progression, and eventually planning the invasive treatment of aortic stenosis.

The Role of Positron Emission Tomography in Advancing the Understanding of the Pathogenesis of Heart and Vascular Diseases.

Cardiovascular disease remains the leading cause of morbidity and mortality worldwide. For developing new therapies, a better understanding of the underlying pathology is required. Historically, such insights have been primarily derived from pathological studies. In the 21st century, thanks to the advent of cardiovascular positron emission tomography (PET), which depicts the presence and activity of pathophysiological processes, it is now feasible to assess disease activity in vivo. By targeting distinct biological pathways, PET elucidates the activity of the processes which drive disease progression, adverse outcomes or, on the contrary, those that can be considered as a healing response. Given the insights provided by PET, this non-invasive imaging technology lends itself to the development of new therapies, providing a hope for the emergence of strategies that could have a profound impact on patient outcomes. In this narrative review, we discuss recent advances in cardiovascular PET imaging which have greatly advanced our understanding of atherosclerosis, ischemia, infection, adverse myocardial remodeling and degenerative valvular heart disease.

Novel PET Applications and Radiotracers for Imaging Cardiovascular Pathophysiology.

PET allows the assessment of cardiovascular pathophysiology across a wide range of cardiovascular conditions. By imaging processes directly involved in disease progression and adverse events, such as inflammation and developing calcifications (microcalcifications), PET can not only enhance our understanding of cardiovascular disease, but also, as shown for 18F-sodium fluoride, has the potential to predict hard endpoints. In this review, the recent advances in disease activity assessment with cardiovascular PET, which provide hope that this promising technology could be leveraged in the clinical setting, shall be discussed.

Unsupervised learning to characterize patients with known coronary artery disease undergoing myocardial perfusion imaging.

PURPOSE: Patients with known coronary artery disease (CAD) comprise a heterogenous population with varied clinical and imaging characteristics. Unsupervised machine learning can identify new risk phenotypes in an unbiased fashion. We use cluster analysis to risk-stratify patients with known CAD undergoing single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). METHODS: From 37,298 patients in the REFINE SPECT registry, we identified 9221 patients with known coronary artery disease. Unsupervised machine learning was performed using clinical (23), acquisition (17), and image analysis (24) parameters from 4774 patients (internal cohort) and validated with 4447 patients (external cohort). Risk stratification for all-cause mortality was compared to stress total perfusion deficit (< 5%, 5-10%, ≥10%). RESULTS: Three clusters were identified, with patients in Cluster 3 having a higher body mass index, more diabetes mellitus and hypertension, and less likely to be male, have dyslipidemia, or undergo exercise stress imaging (p < 0.001 for all). In the external cohort, during median follow-up of 2.6 [0.14, 3.3] years, all-cause mortality occurred in 312 patients (7%). Cluster analysis provided better risk stratification for all-cause mortality (Cluster 3: hazard ratio (HR) 5.9, 95% confidence interval (CI) 4.0, 8.6, p < 0.001; Cluster 2: HR 3.3, 95% CI 2.5, 4.5, p < 0.001; Cluster 1, reference) compared to stress total perfusion deficit (≥10%: HR 1.9, 95% CI 1.5, 2.5 p < 0.001; < 5%: reference). CONCLUSIONS: Our unsupervised cluster analysis in patients with known CAD undergoing SPECT MPI identified three distinct phenotypic clusters and predicted all-cause mortality better than ischemia alone.

Advances in the Assessment of Coronary Artery Disease Activity with PET/CT and CTA.

Non-invasive testing plays a pivotal role in the diagnosis, assessment of progression, response to therapy, and risk stratification of coronary artery disease. Although anatomical plaque imaging by computed tomography angiography (CTA) and ischemia detection with myocardial perfusion imaging studies are current standards of care, there is a growing body of evidence that imaging of the processes which drive atherosclerotic plaque progression and rupture has the potential to further enhance risk stratification. In particular, non-invasive imaging of coronary plaque inflammation and active calcification has shown promise in this regard. Positron emission tomography (PET) with newly-adopted radiotracers provides unique insights into atheroma activity acting as a powerful independent predictor of myocardial infarctions. Similarly, by providing a quantitative measure of coronary inflammation, the pericoronary adipose tissue density (PCAT) derived from standard coronary CTA enhances cardiac risk prediction and allows re-stratification over and above current state-of-the-art assessments. In this review, we shall discuss the recent advances in the non-invasive methods of assessment of disease activity by PET and CTA, highlighting how these methods could improve risk stratification and ultimately benefit patients with coronary artery disease.

Serum lipoprotein(a) and bioprosthetic aortic valve degeneration.

AIMS: Bioprosthetic aortic valve degeneration demonstrates pathological similarities to aortic stenosis. Lipoprotein(a) [Lp(a)] is a well-recognized risk factor for incident aortic stenosis and disease progression. The aim of this study is to investigate whether serum Lp(a) concentrations are associated with bioprosthetic aortic valve degeneration. METHODS AND RESULTS: In a post hoc analysis of a prospective multimodality imaging study (NCT02304276), serum Lp(a) concentrations, echocardiography, contrast-enhanced computed tomography (CT) angiography, and 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) were assessed in patients with bioprosthetic aortic valves. Patients were also followed up for 2 years with serial echocardiography. Serum Lp(a) concentrations [median 19.9 (8.4-76.4) mg/dL] were available in 97 participants (mean age 75 ± 7 years, 54% men). There were no baseline differences across the tertiles of serum Lp(a) concentrations for disease severity assessed by echocardiography [median peak aortic valve velocity: highest tertile 2.5 (2.3-2.9) m/s vs. lower tertiles 2.7 (2.4-3.0) m/s, P = 0.204], or valve degeneration on CT angiography (highest tertile n = 8 vs. lower tertiles n = 12, P = 0.552) and 18F-NaF PET (median tissue-to-background ratio: highest tertile 1.13 (1.05-1.41) vs. lower tertiles 1.17 (1.06-1.53), P = 0.889]. After 2 years of follow-up, there were no differences in annualized change in bioprosthetic hemodynamic progression [change in peak aortic valve velocity: highest tertile [0.0 (-0.1-0.2) m/s/year vs. lower tertiles 0.1 (0.0-0.2) m/s/year, P = 0.528] or the development of structural valve degeneration. CONCLUSION: Serum lipoprotein(a) concentrations do not appear to be a major determinant or mediator of bioprosthetic aortic valve degeneration.

Relationship between impaired myocardial blood flow by positron emission tomography and low-attenuation plaque burden and pericoronary adipose tissue attenuation from coronary computed tomography: From the prospective PACIFIC trial.

BACKGROUND: Positron emission tomography (PET) is the clinical gold standard for quantifying myocardial blood flow (MBF). Pericoronary adipose tissue (PCAT) attenuation may detect vascular inflammation indirectly. We examined the relationship between MBF by PET and plaque burden and PCAT on coronary CT angiography (CCTA). METHODS: This post hoc analysis of the PACIFIC trial included 208 patients with suspected coronary artery disease (CAD) who underwent [15O]H2O PET and CCTA. Low-attenuation plaque (LAP, < 30HU), non-calcified plaque (NCP), and PCAT attenuation were measured by CCTA. RESULTS: In 582 vessels, 211 (36.3%) had impaired per-vessel hyperemic MBF (≤ 2.30 mL/min/g). In multivariable analysis, LAP burden was independently and consistently associated with impaired hyperemic MBF (P = 0.016); over NCP burden (P = 0.997). Addition of LAP burden improved predictive performance for impaired hyperemic MBF from a model with CAD severity and calcified plaque burden (P < 0.001). There was no correlation between PCAT attenuation and hyperemic MBF (r = - 0.11), and PCAT attenuation was not associated with impaired hyperemic MBF in univariable or multivariable analysis of all vessels (P > 0.1). CONCLUSION: In patients with stable CAD, LAP burden was independently associated with impaired hyperemic MBF and a stronger predictor of impaired hyperemic MBF than NCP burden. There was no association between PCAT attenuation and hyperemic MBF.

Machine learning for prediction of all-cause mortality after transcatheter aortic valve implantation.

AIMS: Prediction of adverse events in mid-term follow-up after transcatheter aortic valve implantation (TAVI) is challenging. We sought to develop and validate a machine learning model for prediction of 1-year all-cause mortality in patients who underwent TAVI and were discharged following the index procedure. METHODS AND RESULTS: The model was developed on data of patients who underwent TAVI at a high-volume centre between January 2013 and March 2019. Machine learning by extreme gradient boosting was trained and tested with repeated 10-fold hold-out testing using 34 pre- and 25 peri-procedural clinical variables. External validation was performed on unseen data from two other independent high-volume TAVI centres. Six hundred four patients (43% men, 81 ± 5 years old, EuroSCORE II 4.8 [3.0-6.3]%) in the derivation and 823 patients (46% men, 82 ± 5 years old, EuroSCORE II 4.7 [2.9-6.0]%) in the validation cohort underwent TAVI and were discharged home following the index procedure. Over the 12 months of follow-up, 68 (11%) and 95 (12%) subjects died in the derivation and validation cohorts, respectively. In external validation, the machine learning model had an area under the receiver-operator curve of 0.82 (0.78-0.87) for prediction of 1-year all-cause mortality following hospital discharge after TAVI, which was superior to pre- and peri-procedural clinical variables including age 0.52 (0.46-0.59) and the EuroSCORE II 0.57 (0.51-0.64), P < 0.001 for a difference. CONCLUSION: Machine learning based on readily available clinical data allows accurate prediction of 1-year all-cause mortality following a successful TAVI.