Search

Background: Transcatheter valve-in-valve (VIV) or valve-in-ring (VIR) therapies for degenerated mitral bioprosthetic valves and rings are still evolving. We aimed to characterize short- and long-term outcomes of these procedures., Methods: An electronic literature search was conducted to retrieve articles describing mitral VIV or VIR implantation with at least 10 patients. Meta-analysis of proportions was carried out for 30-day or in-hospital outcomes of mortality, stroke, major bleeding, transfusion, acute kidney injury, procedural success, valve embolization, paravalvular leak, pacemaker implantation, and hospital stay. Individual patient data meta-analysis using Kaplan-Meier curve reconstruction was used to estimate long-term mortality of VIV, VIR and redo surgical mitral valve replacement (SMVR)., Results: We analyzed 34 studies (7047 patients). Pooled procedural success was 94.8% in VIV and 80.5% in VIR. Pooled short-term mortality and stroke risk was 6.4% and 1.9% respectively in VIV, 9.1% and 1.6% respectively in VIR, and 8.4% and 5.5% respectively in SMVR., Conclusions: This study provides prognostic information on clinical outcomes for redo SMVR and transcatheter mitral VIV and VIR implantation., (© 2024 Wiley Periodicals LLC.)

Background: Glycated haemoglobin (HbA1c) is a well-established biomarker for diabetes diagnosis and management and is linked to risk of cardiovascular death. However, among adults without cardiovascular disease (CVD) and diabetes, the value of HbA1c in predicting distinct signatures of myocardial ageing has not been explored., Methods: Subjects, from among older adults without CVD, underwent comprehensive cardiovascular and metabolic assessment. Transthoracic echocardiography measured left ventricular structure and function. Longitudinal left atrial (LA) strain comprising reservoir strain (Ɛs), conduit strain (Ɛe) and booster strain (Ɛa) and their corresponding peak strain rates (SRs, SRe, SRa) were measured using cardiac magnetic resonance (CMR). Blood sampling for biomarkers and cardiovascular examinations were performed., Results: 247 subjects (mean age 71 years, 44.1% female, mean HbA1c 6.0%) were included. HbA1c was significantly associated with E/A ratio (p < 0.0001), conduit strain (Ɛe) (p < 0.0001), conduit strain rate SRe (p < 0.0001), and conduit strain rate to booster strain rate SRe:SRa ratio (p < 0.0001). Multivariate models adjusting for clinical variables such as body mass index, blood pressure, heart rate, diabetes mellitus, smoking, and associated cardiac parameters, demonstrated a persistent independent association. Each unit increase in HbA1c was associated with lower E/A ratio, lower Ɛe, higher SRe and lower SRe:SRa ratio. These associations remained significant after diabetic subjects were excluded., Conclusion: Distinct associations were found between HbA1c and myocardial functions of interest in the ageing heart. HbA1c may be useful biomarker for stratifying risks associated with myocardial ageing, independent of diabetes status., Trial Registration: ClinicalTrials.gov Identifier: NCT02791139., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Background: Echocardiographic indexes of aortic stenosis may not comprehensively reflect disease morbidity. Plasma proteomic profiling may add prognostic value in these patients., Methods and Results: Proximity extension assays (Olink) of 183 circulating cardiovascular and inflammatory proteins were performed in a prospective follow-up study of 122 asymptomatic/minimally symptomatic patients (mean±SD age, 69.1±10.9 years; 61% men) with moderate to severe aortic stenosis and preserved left ventricular ejection fraction. Protein signatures of higher-risk echocardiographic subgroups were determined. Associations of proteins with the primary composite outcome (heart failure hospitalization, progression to New York Heart Association class III-IV, or all-cause mortality) were evaluated using competing risk analyses, with aortic valve replacement being the competing risk. Network analysis unveiled mutually exclusive communities of proteins and echocardiographic parameters, connected only through NT-proBNP (N-terminal pro-B-type natriuretic peptide). Members of the tumor necrosis factor receptor superfamily (TNFRSF1A, TNFRSF1B, and TNFRSF14), and trefoil factor-3 were major hub proteins among the circulating biomarkers. Left ventricular global longitudinal strain >-15% was associated with higher levels of proteins, primarily of inflammation and immune regulation, whereas aortic valve area <1 cm 2 , E/e' >15, and left atrial reservoir strain <20% were associated with higher levels of NT-proBNP. Of 14 proteins associated with the primary end point, phospholipase-C, C-X-C motif chemokine-9, and interleukin-10 receptor subunit β demonstrated the highest hazard ratios after adjusting for clinical factors ( q <0.05)., Conclusions: Plasma proteins involved in inflammation and immune regulation were differentially expressed in patients with aortic stenosis with reduced left ventricular global longitudinal strain, and associated with adverse clinical outcomes. Their incorporation into aortic stenosis risk stratification warrants further assessment.

The increasing prevalence of heart failure (HF) in ageing populations drives demand for echocardiography (echo). There is a worldwide shortage of trained sonographers and long waiting times for expert echo. We hypothesised that artificial intelligence (AI)-enhanced point-of-care echo can enable HF screening by novices. The primary endpoint was the accuracy of AI-enhanced novice pathway in detecting reduced LV ejection fraction (LVEF) < 50%. Symptomatic patients with suspected HF (N = 100, mean age 61 ± 15 years, 56% men) were prospectively recruited. Novices with no prior echo experience underwent 2-weeks' training to acquire echo images with AI guidance using the EchoNous Kosmos handheld echo, with AI-automated reporting by Us2.ai (AI-enhanced novice pathway). All patients also had standard echo by trained sonographers interpreted by cardiologists (reference standard). LVEF < 50% by reference standard was present in 27 patients. AI-enhanced novice pathway yielded interpretable results in 96 patients and took a mean of 12 min 51 s per study. The area under the curve (AUC) of the AI novice pathway was 0.880 (95% CI 0.802, 0.958). The sensitivity, specificity, positive predictive and negative predictive values of the AI-enhanced novice pathway in detecting LVEF < 50% were 84.6%, 91.4%, 78.5% and 94.1% respectively. The median absolute deviation of the AI-novice pathway LVEF from the reference standard LVEF was 6.03%. AI-enhanced novice pathway holds potential to task shift echo beyond tertiary centres and improve the HF diagnostic workflow., (© 2024. The Author(s).)

Background: The use of cerebral embolic protection devices during transcatheter aortic valve implantation (TAVI) reveals conflicting data., Aims: This updated meta-analysis aims to evaluate the efficacy and safety of the SENTINEL Cerebral Protection System., Methods: A literature search for relevant studies up to September 2022 was performed. Study outcomes were divided based on time period - overall (up to 30 days) and short (≤7 days). The outcomes studied include stroke (disabling, non-disabling), mortality, neuroimaging findings, transient ischaemic attack, acute kidney injury and major vascular and bleeding complications., Results: A total of 15 studies involving 294,134 patients were included. Regarding overall outcomes, significant reductions were noted for mortality (odds ratio [OR] 0.60, 95% confidence interval [CI]: 0.41-0.88; p=0.008), all stroke (OR 0.64, 95% CI: 0.46-0.88; p=0.006) and disabling stroke (OR 0.42, 95% CI: 0.23-0.74; p=0.003) using the SENTINEL device. No significant differences were noted for other outcomes. There was significant heterogeneity across the studies for mortality (p=0.013) and all stroke (p=0.003). Including only randomised data (n=4), there was only significant reduction in the incidence of disabling stroke (OR 0.39, 95% CI: 0.17-0.89; p=0.026) in the SENTINEL group. In studies reporting ≤7-day outcomes (n=8), use of the SENTINEL device demonstrated significantly lower rates of all stroke (p<0.001), disabling stroke (p<0.001) and major bleeding complications (p=0.02). No differences in neuroimaging outcomes were noted., Conclusions: In this updated meta-analysis, use of the SENTINEL Cerebral Protection System was associated with lower rates of mortality, all stroke and disabling stroke, although significant heterogeneity was noted for mortality and all stroke. Including exclusively randomised data, there was only significant reduction in the incidence of disabling stroke. No significant adverse outcomes with device use were noted., Competing Interests: J. Yap received speaker honoraria from Biosensors, Biotronik, Boston Scientific, Edwards Lifesciences, Johnson & Johnson, Kaneka, Medtronic, and Terumo. K.W. Ho received speaker fees from Edwards Lifesciences, Medtronic, and Abbott Medical. S.H. Ewe received speaker fees from Abbott Medical, Philips, and GE HealthCare. The other authors have no conflicts of interest to declare.

Introduction: Despite growing calls to tackle aging-related cardiovascular disease (CVD), the role of detecting early diastolic dysfunction such as those observed in aging, prior to clinical disease, is of unclear clinical benefit., Methods: Myocardial function determined by echocardiography was examined in association with incident cardiovascular outcomes or all-cause death by Cox proportional hazards model. Sex-based differences in outcomes were included., Results: A total of 956 participants (mean age 63 ± 12.9 years, n = 424 males [44%]) were categorized based on mitral peak early-to-late diastolic filling velocity (E/A) ratios: E/A &lt;0.8 (28%), E/A 0.8-1.2 (39%), E/A (29%), E/A &gt;2.0 (4%). Incidence rate (IR) for non-fatal cardiovascular outcomes was 2.83 per 100 person-years (95% CI: 2.24-3.56) and 0.45 per 100 person-years (95% CI: 0.26-0.80) for all-cause death. Event-free survival from non-fatal cardiovascular outcomes was significantly different among E/A categories (log-rank p = 0.0269). E/A &lt;0.8 (HR 1.80, 95% CI: 1.031, 3.14, p = 0.039) was associated with non-fatal cardiovascular outcomes. Among men, IR for cardiovascular outcomes was 3.56 per 100 person-years (95% CI: 2.62-4.84) and 0.75 per 100 person-years (95% CI: 0.39-1.44) for all-cause death. Among women, IR for cardiovascular outcomes was 2.22 per 100 person-years (95% CI: 1.56-3.16) and 0.21 per 100 person-years (95% CI: 0.067-0.64) for all-cause death. For E/A &lt;0.8 category, women had significantly higher risks of non-fatal cardiovascular outcomes, compared to E/A 0.8-1.2 category (HR 2.49, 95% CI: 1.18, 5.23, p = 0.017)., Conclusion: Myocardial aging was an independent predictor of cardiovascular outcomes in community-dwelling older adults prior to clinical CVD. Impaired myocardial relaxation was prevalent in both sexes but associated with worse outcomes in women, suggestive of sex differences in age-related biology., (© 2024 S. Karger AG, Basel.)

Background: Atrial fibrillation (AF) and aortic stenosis (AS) are both highly prevalent and often coexist. Various studies have focused on the prognostic value of AF in patients with AS, but rarely considered left ventricular (LV) diastolic function as a prognostic factor., Objective: To evaluate the prognostic impact of AF in patients with AS while correcting for LV diastolic function., Methods: Patients with first diagnosis of significant AS were selected and stratified according to history of AF. The endpoint was all-cause mortality., Results: In total, 2849 patients with significant AS (mean age 72 ± 12 years, 54.8% men) were evaluated, and 686 (24.1%) had a history of AF. During a median follow-up of 60 (30-97) months, 1182 (41.5%) patients died. Ten-year mortality rate in patients with AF was 46.8% compared to 36.8% in patients with sinus rhythm (SR) (log-rank P < 0.001). On univariable (HR: 1.42; 95% CI: 1.25-1.62; P < 0.001) and multivariable Cox regression analysis (HR: 1.19; 95% CI: 1.02-1.38; P = 0.026), AF was independently associated with mortality. However, when correcting for indexed left atrial volume, E/e' or both, AF was no longer independently associated with all-cause mortality., Conclusion: Patients with significant AS and AF have a reduced survival as compared to patients with SR. Nonetheless, when correcting for markers of LV diastolic function, AF was not independently associated with outcomes in patients with significant AS., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Despite known sex-based differences in cardiovascular aging, differences in aging biology are poorly understood. We hypothesize that circulating metabolites studied cross-sectionally with cardiac aging may be associated with cardiovascular changes that distinguish cardiac aging in women., Methods: A population-based cohort of community men and women without cardiovascular disease from Singapore underwent detailed clinical and echocardiography examinations. Cross-sectional associations between cardiac functional characteristics and metabolomics profiles were examined., Results: Five hundred sixty-seven adults (48.9% women) participated. Women were younger (72 ± 4.4 years vs 73 ± 4.3 years, p = 0.022), had lower diastolic blood pressures (71 ± 11.0 mmHg vs 76 ± 11.2 mmHg, p < 0.0001, and less likely to have diabetes mellitus (18.0% vs 27.6%, p = 0.013) and smoking (3.8% vs 34.5%, p < 0.001). Body mass indices were similar (24 ± 3.8 kg/m 2 vs 24 ± 3.4 kg/m 2 , p = 0.29), but women had smaller waist circumferences (81 ± 10.1 cm vs 85 ± 9.2 cm, p < 0.001). Women had a significantly higher E/e' ratios (10.9 ± 3.4 vs 9.9 ± 3.3, p = 0.007) and mitral A peak (0.86 ± 0.2 m/s vs 0.79 ± 0.2 m/s, p < 0.001) than men. Among women, lower E/e' ratio was associated with higher levels of C16 (OR 1.019, 95%CI 1.002-1.036, p = 0.029), C16:1 (OR 1.06, 95%CI 1.006-1.118, p = 0.028), serine (OR 1.019, 95%CI 1.002-1.036, p = 0.025), and histidine (OR 1.045, 95%CI 1.013-1.078, p = 0.006). Lower mitral A peak was associated with higher levels of histidine (OR 1.039, 95%CI 1.009-1.070, p = 0.011), isoleucine (OR 1.013, 95%CI 1.004-1.021, p = 0.004), and C20 (OR 1.341, 95%CI 1.067-1.684, p = 0.012)., Conclusion: Impairments in diastolic functions were more frequent among older women compared to men, despite lower prevalence of vascular risk factors and preserved cardiac structure. Cardiac aging in women correlated with metabolites involved in fatty acid oxidation and tricyclic acid cycle fuelling., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

The availability of direct oral anticoagulants (DOACs) with known lower bleeding risk compared with warfarin have raised questions about the role of left atrial appendage closure (LAAC). We aimed to perform a meta-analysis to compare the clinical outcomes for LAAC versus DOACs. All studies directly comparing LAAC with DOACs up to January 2023 were included. The outcomes studied included the combined major adverse cardiovascular (CV) events outcomes, ischemic stroke and thromboembolic events, major bleeding, CV mortality, and all-cause mortality. Hazard ratios (HRs) and their 95% confidence interval were extracted or estimated from the data and pooled together with a random-effects model. A total of 7 studies (1 randomized controlled trial, 6 propensity-matched observational studies) were finally included, with a pooled population of 4,383 patients who underwent LAAC and 4,554 patients on DOACs. There were no significant differences between patients who underwent LAAC and patients on DOACs in terms of baseline age (75.0 vs 74.7, p = 0.27), CHA 2 DS 2 -VASc score (5.1 vs 5.1, p = 0.33), or HAS-BLED score (3.3 vs 3.3, p = 0.36). After a mean weighted follow-up of 22.0 months, LAAC was associated with significantly lower rates of combined major adverse CV event outcomes (HR 0.73 [0.56 to 0.95], p = 0.02), all-cause mortality (HR 0.68 [0.54 to 0.86], p = 0.02), and CV mortality (HR 0.55 [0.41 to 0.72], p<0.01). There were no significant differences in the rates of ischemic stroke or systemic embolism (HR 1.12 [0.92 to 1.35], p = 0.25), major bleeding (HR 0.94 [0.67 to 1.32], p = 0.71), or hemorrhagic stroke (HR 1.07 [0.74 to 1.54], p = 0.74) between LAAC and DOAC. In conclusion, percutaneous LAAC was found to be as efficacious as DOACs for stroke prevention, with lower all-cause and CV mortality. The rates of major bleeding and hemorrhagic stroke were similar. LAAC has a potential role to play in stroke prevention in patients with atrial fibrillation in the era of DOACs, but further randomized data are needed., Competing Interests: Declaration of Competing Interest Dr. Koh received speaker's honorarium from Abbott and Boston Scientific. Dr. Ewe received speaker's honorarium from Abbott and Philips. Dr. Yap received speaker's honorarium from Abbott, Biosensors, Biotronik, Boston Scientific, Edwards, GE healthcare, J&J, Kaneka, Medtronic, and Terumo. The remaining authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Transcatheter structural heart intervention (TSHI) has gained popularity over the past decade as a means of cardiac intervention in patients with prohibitive surgical risks. Following the exponential rise in cases and devices developed over the period, there has been increased focus on developing the role of "structural imagers" amongst cardiologists. This review, as part of a growing initiative to develop the field of interventional echocardiography, aims to highlight the role of echocardiography in myriad TSHIs available within Asia. We first discuss the various echocardiography-based imaging modalities, including 3-dimensional echocardiography, fusion imaging, and intracardiac echocardiography. We then highlight a selected list of structural interventions available in the region-a combination of established interventions alongside novel approaches-describing key anatomic and pathologic characteristics related to the relevant structural heart diseases, before delving into various aspects of echocardiography imaging for each TSHI., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Current guidelines recommend that clinical surveillance for patients with moderate aortic stenosis (AS) and aortic valve replacement (AVR) may be considered if there is an indication for coronary revascularization. Recent observational studies, however, have shown that moderate AS is associated with an increased risk of cardiovascular events and mortality. Whether the increased risk of adverse events is caused by associated comorbidities, or to the underlying moderate AS itself, is incompletely understood. Similarly, which patients with moderate AS need close follow-up or could potentially benefit from early AVR is also unknown. In this review, the authors provide a comprehensive overview of the current published reports on moderate AS. They first provide an algorithm that helps to diagnose moderate AS correctly, especially when discordant grading is observed. Although the traditional focus of AS assessment has been on the valve, it is increasingly acknowledged that AS is not only a disease of the aortic valve but also of the ventricle. The authors therefore discuss how multimodality imaging can help to evaluate the left ventricular remodeling response and improve risk stratification in patients with moderate AS. Finally, they summarize current evidence on the management of moderate AS and highlight ongoing trials on AVR in moderate AS., Competing Interests: Funding Support and Author Disclosures Dr Stassen has received funding from the European Society of Cardiology (ESC Training Grant App 000064741). Dr Pio has received funding from the European Society of Cardiology (ESC Training Grant T-2018-17405). The Department of Cardiology of the Leiden University Medical Centre has received unrestricted research grants from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, and Medtronic. Dr Ewe has received speaker fees from Abbott Vascular, Philips, and GE Healthcare. Dr Pibarot has received funding from Edwards Lifesciences, Medtronic, Pi-Cardia, and Cardiac Phoenix for echocardiography core laboratory analyses and research studies in the field of transcatheter valve therapies, for which he received no personal compensation; and he has received speaker fees from Edwards Lifesciences and Medtronic. Dr Leipsic holds institutional core laboratory grants with Edwards Lifesciences, Medtronic, Abbott, Boston Scientific, Conformal, Neovasc, and Pi Cardia; and is a consultant to Circle CVI. Dr Genereux has served as consultant and advisor and has received speaker fees from Abiomed and BioTrace Medical; has served as consultant for Boston Scientific, Cardiovascular System Inc, and the PI Eclipse Trial; has served as consultant and advisor, received speaker fees, and served as proctor for Edwards Lifesciences, from whom he has received research grants for the PI EARLY-TAVR and PI PROGRESS trials; has served as consultant for GE Healthcare, Siemens, Teleflex, and iRhythm Technologies; has served as consultant and advisor to Medtronic and has received speaker fees; has served as consultant to Opsens; has served as consultant and holds equity in Pi-Cardia, Puzzle Medical, and Saranas; has served as consultant and has received speaker fees from Shockwave; has served as consultant and holds equity in Soundbite Medical Inc; and has served as consultant, and as feasibility study PI for 4C Medical. Dr Van Mieghem has received research grant support from Abbott Vascular, Biotronik, Boston Scientific, Medtronic, Edwards Lifesciences, Abiomed, PulseCath BV, Daiichi Sankyo, Pie Medical, and Siemens. Dr Makkar has received consultant and research grants from Edwards, Medtronic, Abbott, Boston Scientific, and Philips. Dr Hahn has received speaker fees from Abbott Vascular, Baylis Medical, and Edwards Lifesciences; institutional consulting for Abbott Structural, Edwards Lifesciences, Medtronic; equity with Navigate; and is Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored trials, for which she receives no direct industry compensation. Dr Playford has received unrestricted research grants from Edwards Lifesciences, Janssen, Novartis, and Pfizer; and has received speaker fees from Edwards Lifesciences. Dr Ajmone Marsan has received speaker fees from Abbott Vascular and GE Healthcare. Dr Delgado has received speaker fees from Abbott Vascular, Edwards Lifesciences, Medtronic, Novartis, Merck Sharp & Dohme, and GE Healthcare. Dr Leon has received institutional clinical research grants from Abbott, Boston Scientific, Edwards, and Medtronic. Dr Bax has received speaker fees from Abbott Vascular. All other authors have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The landscape of aortic valve replacement (AVR) has evolved dramatically over the years, but time-varying outcomes have yet to be comprehensively explored. This study aimed to compare the all-cause mortality among 3 AVR techniques: transcatheter (TAVI), minimally invasive (MIAVR), and conventional AVR (CAVR). An electronic literature search was performed for randomized controlled trials (RCTs) comparing TAVI with CAVR and RCTs or propensity score-matched (PSM) studies comparing MIAVR with CAVR or MIAVR to TAVI. Individual patient data for all-cause mortality were derived from graphical reconstruction of Kaplan-Meier curves. Pairwise comparisons and network meta-analysis were conducted. Sensitivity analyses were performed in the TAVI arm for high risk and low/intermediate risk, as well as patients who underwent transfemoral (TF) TAVI. A total of 27 studies with 16,554 patients were included. In the pairwise comparisons, TAVI showed superior mortality to CAVR until 37.5 months, beyond which there was no significant difference. When restricted to TF TAVI versus CAVR, a consistent mortality benefit favoring TF TAVI was seen (shared frailty hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.76 to 0.98, p = 0.024). In the network meta-analysis involving majority PSM data, MIAVR demonstrated significantly lower mortality than TAVI (HR = 0.70, 95% CI = 0.59 to 0.82) and CAVR (HR = 0.69, 95% CI = 0.59 to 0.80); this association remained compared with TF TAVI but with a lower extent of benefit (HR = 0.80, 95% CI = 0.65 to 0.99). In conclusion, the initial short- to medium-term mortality benefit for TAVI over CAVR was attenuated over the longer term. In the subset of patients who underwent TF TAVI, a consistent benefit was found. Among majority PSM data, MIAVR showed improved mortality compared with TAVI and CAVR but less than the TF TAVI subset, which requires validation by robust RCTs., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Remodeling of the thoracic aorta is commonly seen and viewed as a precursor to an aortic aneurysm. However, while aneurysms have been shown to expand at a rate of approximately 1 mm annually, the expansion of the pre-aneurysmal aorta is poorly characterized, especially in relation to age, gender, and aortic size per se . We identified patients that had undergone echocardiography at least twice at a large university medical center. Diagnosis codes, medications, and blood test results were obtained from hospital records. Syndromic patients were excluded (e.g., Marfan's syndrome, bicuspid aortic valve). Final population comprised n = 24,928 patients (median age 61.2 years (inter-quartile range (IQR): 50.6-71.5); 55.8% males) that had undergone a median of 3 echocardiograms (2-4; range 2-27) during a median of 4.0 years (IQR: 2.3-6.2). Hypertension was present in 39.6% of patients and diabetes in 20.7%, median LV ejection fraction was 56.0% (IQR: 41.0-62.0). Aortic size measurements were analyzed in mixed models while clustering on individual patients. Mean expansion was determined for sinus of Valsalva as 1.93 (95% confidence interval; CI 95 : 1.87-1.99) mm per decade, and for ascending aorta as 1.76 (CI 95 : 1.70-1.82) mm per decade. Faster expansion was found in males, with larger aortic size, and younger age ( p for interaction <0.05 for all). In conclusion, expansion of the thoracic aorta, in real world, non-syndromic patients, is slow and averages <2 mm per decade. This will help to inform management of this large patient group., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (© 2023 The Authors.)

Background: The role of left atrial (LA) strain as an imaging biomarker in aortic stenosis is not well established. The aim of this study was to investigate the prognostic performance of phasic LA strain in relation to clinical and echocardiographic variables and N-terminal pro-B-type natriuretic peptide in asymptomatic and minimally symptomatic patients with moderate to severe aortic stenosis and left ventricular ejection fraction > 50%., Methods: LA reservoir strain (LASr), LA conduit strain (LAScd), and LA contractile strain (LASct) were measured using speckle-tracking echocardiography. The primary outcome was a composite of all-cause mortality, heart failure hospitalization, progression to New York Heart Association functional class III or IV, acute coronary syndrome, or syncope. Secondary outcomes 1 and 2 comprised the same end points but excluded acute coronary syndrome and additionally syncope, respectively. The prognostic performance of phasic LA strain cutoffs was evaluated in competing risk analyses, aortic valve replacement being the competing risk., Results: Among 173 patients (mean age, 69 ± 11 years; mean peak transaortic velocity, 4.0 ± 0.8 m/sec), median LASr, LAScd, and LASct were 27% (interquartile range [IQR], 22%-32%), 12% (IQR, 8%-15%), and 16% (IQR, 13%-18%), respectively. Over a median of 2.7 years (IQR, 1.4-4.6 years), the primary outcome and secondary outcomes 1 and 2 occurred in 66 (38%), 62 (36%), and 59 (34%) patients, respectively. LASr < 20%, LAScd < 6%, and LASct < 12% were identified as optimal cutoffs of the primary outcome. In competing risk analyses, progressing from echocardiographic to echocardiographic-clinical and combined models incorporating N-terminal pro-B-type natriuretic peptide, LA strain parameters outperformed other key echocardiographic variables and significantly predicted clinical outcomes. LASr < 20% was associated with the primary outcome and secondary outcome 1, LAScd < 6% with all clinical outcomes, and LASct < 12% with secondary outcome 2. LAScd < 6% had the highest specificity (95%) and positive predictive value (82%) for the primary outcome, and competing risk models incorporating LAScd < 6% had the best discriminative value., Conclusions: In well-compensated patients with moderate to severe aortic stenosis and preserved left ventricular ejection fractions, LA strain was superior to other echocardiographic indices and incremental to N-terminal pro-B-type natriuretic peptide for risk stratification. LAScd < 6%, LASr < 20%, and LASct < 12% identified patients at higher risk for adverse outcomes., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

The rate of aortic stenosis (AS) progression in patients with moderate AS is unclear. This study examined the risk factors of progression from moderate to severe AS and its impact on clinical outcomes. A total of 954 patients with moderate AS (valve area >1.0 and ≤1.5 cm²) and follow-up echocardiograms were included. AS progressed to severe (valve area <1.0 cm 1 ) in 589 patients (61.7%) over a median follow-up of 2.46 (interquartile range [IQR] 1.29 to 3.91) years. Of those who progressed to severe AS, patients were subdivided into Slow (n = 294, over 3.91 [IQR 3.11 to 5.10] years) versus Fast (n = 295, over 1.29 [IQR 0.85 to 1.85] years) Progressors, according to the median time between the 2 echocardiograms. The correlates of fast AS progression and its impact on cumulative survival and freedom from valve intervention were evaluated. On multivariate analysis, age, thickened left ventricle posterior wall, severe renal impairment, and aortic valve area were significantly associated with fast AS progression. Over a median follow-up of 6.34 (IQR 4.05 to 9.55) years, 228 patients (38.7%) died. Despite similar aortic valve intervention rates, Fast Progressors had worse 5-year survival (61.2% vs 81.9%, log-rank p <0.001) and event-free (valve intervention and all-cause mortality) survival rates (16.2% vs 55.9%, log-rank p <0.001). On multivariable Cox analysis, shorter progression to severe AS (in years) was independently associated with increased risk of all-cause mortality (hazard ratio 1.26, 95% confidence interval 1.16 to 1.37, p <0.001), or combined aortic valve intervention and death (hazard ratio 1.46, 95% confidence interval 1.38 to 1.55, p <0.001). In conclusion, fast progression from moderate to severe AS is associated with worse outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Data on patients with small aortic annuli (SAA) undergoing transcatheter aortic valve implantation (TAVI) are limited. We aim to describe the impact of aortic annular size, particularly SAA and TAVI valve type on valve haemodynamics, durability and clinical outcomes., Method: All patients in National Heart Centre Singapore who underwent transfemoral TAVI for severe symptomatic native aortic stenosis from July 2012 to December 2019 were included. Outcome measures include valve haemodynamics, prosthesis-patient mismatch (PPM), structural valve degeneration (SVD) and mortality., Results: A total of 244 patients were included. The mean Society of Thoracic Surgeons score was 6.22±6.08, with 52.5% patients with small aortic annulus (<23mm), 33.2% patients with medium aortic annulus (23-26mm) and 14.3% patients with large aortic annulus (>26mm). There were more patients with self-expanding valve (SEV) (65.2%) versus balloon-expandable valve (BEV) (34.8%). There were no significant differences in indexed aortic valve area (iAVA), mean pressure gradient (MPG), PPM, SVD or mortality across all aortic annular sizes. However, specific to the SAA group, patients with SEV had larger iAVA (SEV 1.19±0.35cm2/m2 vs BEV 0.88±0.15cm2/m2, P <0.01) and lower MPG (SEV 9.25±4.88 mmHg vs BEV 14.17±4.75 mmHg, P <0.01) at 1 year, without differences in PPM or mortality. Aortic annular size, TAVI valve type and PPM did not predict overall mortality up to 7 years. There was no significant difference in SVD between aortic annular sizes up to 5 years., Conclusion: Valve haemodynamics and durability were similar across the different aortic annular sizes. In the SAA group, SEV had better haemodynamics than BEV at 1 year, but no differences in PPM or mortality. There were no significant differences in mortality between aortic annular sizes, TAVI valve types or PPM.

Aims: Moderate aortic stenosis (AS) is associated with an increased risk of adverse events. Because outcomes in patients with AS are ultimately driven by the condition of the left ventricle (LV) and not by the valve, assessment of LV remodelling seems important for risk stratification. This study evaluated the association between different LV remodelling patterns and outcomes in patients with moderate AS., Methods and Results: Patients with moderate AS (aortic valve area 1.0-1.5 cm2) were identified and stratified into four groups according to the LV remodelling pattern: normal geometry (NG), concentric remodelling (CR), concentric hypertrophy (CH), or eccentric hypertrophy (EH). Clinical outcomes were defined as all-cause mortality and a composite endpoint of all-cause mortality and aortic valve replacement (AVR). Of 1931 patients with moderate AS (age 73 ± 10 years, 52% men), 344 (18%) had NG, 469 (24%) CR, 698 (36%) CH, and 420 (22%) EH. Patients with CH and EH showed higher 3-year mortality rates (28% and 32%, respectively) when compared with patients with NG (19%) (P < 0.001). After multivariable adjustment, CH remained independently associated with mortality (HR 1.258, 95% CI 1.016-1.558; P = 0.035), whereas both CH (HR 1.291, 95% CI 1.088-1.532; P = 0.003) and EH (HR 1.217, 95% CI 1.008-1.470; P = 0.042) were associated with the composite endpoint of death or AVR., Conclusion: In patients with moderate AS, those who develop CH already have an increased risk of all-cause mortality. Assessment of the LV remodelling patterns may identify patients at higher risk of adverse events, warranting closer surveillance, and possibly earlier intervention., Competing Interests: Conflict of interest: The Department of Cardiology of the Leiden University Medical Centre received unrestricted research grants from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, and Medtronic. J.J.B. received speaker fees from Abbott Vascular. N.A.M. received speaker fees from Abbott Vascular and GE Healthcare. V.D. received speaker fees from Abbott Vascular, Edwards Lifesciences, MSD, and GE Healthcare. The remaining authors have nothing to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The prognostic implications of discordant grading in severe aortic stenosis (AS) are well known. However, the prevalence of different flow-gradient patterns and their prognostic implications in moderate AS are unknown., Objectives: The purpose of this study was to investigate the occurrence and prognostic implications of different flow-gradient patterns in patients with moderate AS., Methods: Patients with moderate AS (aortic valve area >1.0 and ≤1.5 cm 2 ) were identified and divided in 4 groups based on transvalvular mean gradient (MG), stroke volume index (SVi), and left ventricular ejection fraction (LVEF): concordant moderate AS (MG ≥20 mm Hg) and discordant moderate AS including 3 subgroups: normal-flow, low-gradient moderate AS (MG <20 mm Hg, SVi ≥35 mL/m 2 , and LVEF ≥50%); "paradoxical" low-flow, low-gradient moderate AS (MG <20 mm Hg, SVi <35 mL/m 2 , and LVEF ≥50%) and "classical" low-flow, low-gradient moderate AS (MG <20 mm Hg and LVEF <50%). The primary endpoint was all-cause mortality., Results: Of 1,974 patients (age 73 ± 10 years, 51% men) with moderate AS, 788 (40%) had discordant grading, and these patients showed significantly higher mortality rates than patients with concordant moderate AS (P < 0.001). On multivariable analysis, "paradoxical" low-flow, low-gradient (HR: 1.458; 95% CI: 1.072-1.983; P = 0.014) and "classical" low-flow, low-gradient (HR: 1.710; 95% CI: 1.270-2.303; P < 0.001) patterns but not the normal-flow, low-gradient moderate AS pattern were independently associated with all-cause mortality., Conclusions: Discordant grading is frequently (40%) observed in patients with moderate AS. Low-flow, low-gradient patterns account for an important proportion of the discordant cases and are associated with increased mortality. These findings underline the need for better phenotyping patients with discordant moderate AS., Competing Interests: Funding Support and Author Disclosures The Department of Cardiology of the Leiden University Medical Centre has received unrestricted research grants from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, and Medtronic. Dr Stassen has received funding from the European Society of Cardiology (ESC Training Grant App000064741). Dr Butcher has received funding from the European Society of Cardiology (ESC Research Grant App000080404). Dr Pibarot has received funding from Edwards Lifesciences, Medtronic, Pi-Cardia, and Cardiac Phoenix for echocardiography core laboratory analyses and research studies in the field of transcatheter valve therapies, for which he received no personal compensation; and has received lecture fees from Edwards Lifesciences and Medtronic. Dr Delgado has received speaker fees from Abbott Vascular, Edwards Lifesciences, Merck Sharp and Dohme, and GE Healthcare. Dr Marsan has received speaker fees from Abbott Vascular and GE Healthcare. Dr Bax received speaker fees from Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the prognostic impact of left ventricular (LV) diastolic dysfunction in patients with moderate aortic stenosis (AS) and preserved LV systolic function., Methods: Patients with a first diagnosis of moderate AS (aortic valve area >1.0 and ≤1.5 cm 2 ) and preserved LV systolic function (LV ejection fraction ≥50%) were identified. LV diastolic function was evaluated using echocardiographic criteria according to the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Clinical outcomes were defined as all-cause mortality and a composite of all-cause mortality and aortic valve replacement (AVR)., Results: Of 1247 patients (age 74±10 years, 47% men), 535 (43%) had LV diastolic dysfunction at baseline. Patients with LV diastolic dysfunction showed significantly higher mortality rates at 1-year, 3-year and 5-year follow-up (13%, 30% and 41%, respectively) when compared with patients with normal LV diastolic function (6%, 17% and 29%, respectively) (p<0.001). On multivariable analysis, LV diastolic dysfunction was independently associated with all-cause mortality (HR 1.368; 95% CI 1.085 to 1.725; p=0.008) and the composite endpoint of all-cause mortality and AVR (HR 1.241; 95% CI 1.035 to 1.488; p=0.020)., Conclusions: LV diastolic dysfunction is independently associated with all-cause mortality and the composite endpoint of all-cause mortality and AVR in patients with moderate AS and preserved LV systolic function. Assessment of LV diastolic function therefore contributes significantly to the risk stratification of patients with moderate AS. Future clinical trials are needed to investigate whether patients with moderate AS and LV diastolic dysfunction may benefit from earlier valve intervention., Competing Interests: Competing interests: The Department of Cardiology of the Leiden University Medical Centre received unrestricted research grants from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare and Medtronic. JJB received speaker fees from Abbott Vascular. NAM received speaker fees from Abbott Vascular and GE Healthcare. VD received speaker fees from Abbott Vascular, Edwards Lifesciences, MSD and GE Healthcare. The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Moderate aortic stenosis (AS) is associated with an increased risk for adverse events. Although reduced left ventricular (LV) global longitudinal strain (GLS) is associated with worse outcomes in patients with severe AS, its prognostic value in patients with moderate AS is unknown. The aim of this study was to investigate the prognostic implications of LV GLS in patients with moderate AS., Methods: LV GLS was evaluated using speckle-tracking echocardiography in patients with moderate AS (aortic valve area 1.0-1.5 cm 2 ) and reported as absolute (i.e., positive) values. Patients were divided into three groups: LV ejection fraction (LVEF) < 50% (group 1), LVEF ≥ 50% but LV GLS < 16% (group 2), and LVEF ≥ 50% and LV GLS ≥ 16% (group 3). The LV GLS value of 16% was based on spline curve analysis. The primary end point was all-cause mortality., Results: A total of 760 patients (mean age, 71 ± 12 years; 61% men) were analyzed. During a median follow-up period of 50 months (interquartile range, 26-94 months), 257 patients (34%) died. Patients with LVEF < 50% and LVEF ≥ 50% but LV GLS < 16% showed significantly higher mortality rates at 1-, 3-, and 5-year follow-up (82%, 71%, and 58%; and 92%, 77%, and 58%, respectively) compared with those with LVEF ≥ 50% and LV GLS ≥ 16% (96%, 91%, and 85%, respectively; P < .001). Long-term outcomes were not different between patients with LVEF < 50% and those with LVEF ≥ 50% but LV GLS < 16% (P = .592). LV GLS discriminated higher risk patients even among those with LVEF ≥ 60% (P < .001) or those who were asymptomatic (P < .001). On multivariable analysis, LVEF < 50% (hazard ratio, 2.384; 95% CI, 1.614-3.522; P < .001) and LVEF ≥ 50% but LV GLS < 16% (hazard ratio, 2.467; 95% CI, 1.802-3.378; P < .001) were independently associated with all-cause mortality., Conclusions: In patients with moderate AS, reduced LV GLS is associated with an increased risk for all-cause mortality, even if LVEF is still preserved., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Objective: We investigated the prognostic significance of selected known and novel circulating biomarkers in aortic stenosis (AS)., Methods: N-terminal pro-BNP (NT-proBNP), high-sensitivity troponin-T (hsTnT), growth differentiation factor-15 (GDF-15), suppression of tumorigenicity-2 (ST2), mid-regional proadrenomedullin (MR-proADM) and mid-regional proatrial natriuretic peptide (MR-proANP) were measured in patients with moderate to severe AS, New York Heart Association (NYHA) class I-II and left ventricular ejection fraction ≥50%, recruited consecutively across five centres from 2011 to 2018. Their ability to predict both primary (all-cause mortality, heart failure hospitalisation or progression to NYHA class III-IV) and secondary (additionally incorporating syncope and acute coronary syndrome) outcomes was determined by competing risk analyses., Results: Among 173 patients with AS (age 69±11 years, 55% male, peak transaortic velocity (Vmax) 4.0±0.8 m/s), the primary and secondary outcomes occurred in 59 (34%) and 66 (38%), respectively. With aortic valve replacement as a competing risk, the primary outcome was determined consistently by the comorbidity index and each selected biomarker except ST2 (p<0.05), independent of NYHA class, Vmax, LV-global longitudinal strain and serum creatinine. MR-proADM had the highest discriminative value for both primary (subdistribution HR (SHR) 11.3, 95% CI 3.9 to 32.7) and secondary outcomes (SHR 12.6, 95% CI 4.7 to 33.5). Prognostic assessment of dual-biomarker combinations identified MR-proADM plus either hsTnT or NT-proBNP as the best predictive model for both clinical outcomes. Paired biomarker models were not superior to those including MR-proADM as the sole circulating biomarker., Conclusion: MR-proADM most powerfully portended worse prognosis and should be further assessed as possibly the biomarker of choice for risk stratification in AS., Competing Interests: Competing interests: SHE reports personal fees from Medtronic, Edwards Lifesciences and Abbott Medical, outside the submitted work. ZPD reports personal/speaker fees from GE and Phillips, and non-financial support from Phillips, outside the submitted work. AMR reports grants from National Medical Research Council of Singapore during the conduct of the study, is a long-term collaborator with Roche Diagnostics, the provider of assays central to this submission, and received support in kind, grants, speaker’s honoraria and acted on advisory boards for Roche Diagnostics. LHHL reports grants from National Medical Research Council of Singapore during the conduct of the study., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Recent data showed poor long-term survival in patients with moderate AS. Although sex differences in left ventricular (LV) remodeling and outcome are well described in severe AS, it has not been evaluated in moderate AS., Methods: In this retrospective, multicenter study, patients with a first diagnosis of moderate AS diagnosed between 2001 and 2019 were identified. Clinical and echocardiographic parameters were recorded at baseline and compared between men and women. Patients were followed up for the primary endpoint of all-cause mortality with censoring at the time of aortic valve replacement., Results: A total of 1895 patients with moderate AS (age 73 ± 10 years, 52% male) were included. Women showed more concentric hypertrophy and had more pronounced LV diastolic dysfunction than men. During a median follow-up of 34 (13-60) months, 682 (36%) deaths occurred. Men showed significantly higher mortality rates at 3- and 5-year follow-up (30% and 48%, respectively) than women (26% and 39%, respectively) ( p = 0.011). On multivariable analysis, male sex remained independently associated with mortality (hazard ratio 1.209; 95% CI: 1.024-1.428; p = 0.025). LV remodeling (according to LV mass index) was associated with worse outcomes (hazard ratio 1.003; CI: 1.001-1.005; p = 0.006), but no association was observed between the interaction of LV mass index and sex with outcomes., Conclusions: LV remodeling patterns are different between men and women having moderate AS. Male sex is associated with worse outcomes in patients with medically treated moderate AS. Further studies investigating the management of moderate AS in a sex-specific manner are needed., Competing Interests: The Department of Cardiology, Heart Lung Center, Leiden University Medical Centre, received research grants from 10.13039/100011949Abbott Vascular, 10.13039/100004326Bayer, 10.13039/501100005035Biotronik, Bioventrix, 10.13039/100008497Boston Scientific, 10.13039/100006520Edwards Lifesciences, 10.13039/100006775GE Healthcare, Ionis, and 10.13039/100004374Medtronic. Jeroen J. Bax received speaker fees from Abbott Vascular. Nina Ajmone Marsan received speaker fees from Abbott Vascular and GE Healthcare. Victoria Delgado received speaker fees from Abbott Vascular, Edwards Lifesciences, GE Healthcare, Medtronic, MSD, and Novartis. The remaining authors have nothing to disclose., (© 2022 The Authors.)

Aims: The aim of this study is to investigate the independent determinants of survival in patients with moderate aortic stenosis (AS), stratified by severity of symptoms and left ventricular ejection fraction (LVEF)., Methods and Results: Patients with a first diagnosis of moderate AS (aortic valve area >1.0 and ≤1.5 cm2) were identified. Patients were stratified by New York Heart Association (NYHA) functional class (NYHA I, NYHA II, or NYHA III-IV) and LVEF (LVEF ≥60%, LVEF 50-59%, or LVEF <50%) at the time of moderate AS diagnosis. The primary endpoint was all-cause mortality, while the secondary endpoint included all-cause mortality and aortic valve replacement. Of 1961 patients with moderate AS (mean age 73 ± 10 years, 51% men), 1108 (57%) patients were in NYHA class I, while 527 (27%) and 326 (17%) patients had symptoms of NYHA class II and III-IV, respectively. Regarding LVEF, 1032 (53%) had LVEF ≥60%, 544 (28%) LVEF 50-59%, and 385 (20%) LVEF <50%. During a median follow-up of 50 (23-82) months, 868 (44%) patients died. On multivariable analysis, NYHA class II [hazard ratio (HR): 1.633; 95% confidence interval (CI): 1.431-1.864; P < 0.001], NYHA class III-IV (HR: 2.084; 95% CI: 1.797-2.417; P < 0.001), LVEF 50-59% (HR: 1.194; 95% CI: 1.013-1.406; P = 0.034), and LVEF <50% (HR: 1.694; 95% CI: 1.417-2.026; P < 0.001) were independently associated with increased mortality., Conclusion: Moderate AS is associated with poor long-term survival. Baseline symptom severity and LVEF are associated with worse outcomes in these patients. Patients with low-normal LVEF (<60%) and mild symptoms (NYHA II) already have an increased risk of adverse events., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Introduction: Body mass index (BMI), despite being widely used as a marker of obesity, fails to fully capture cardiovascular risks as it is an insufficient biomarker of abdominal adiposity, unlike waist circumference (WC). We aimed to characterize associations between BMI and WC with cardiovascular structure and function in older adults., Methods: Among an observational cohort study of a community of older adults, transthoracic echocardiography determined cardiovascular structure and function, while aerobic capacity was determined by peak oxygen uptake (VO2) metrics. The cut-offs for obesity were 27.5 kg/m2 for BMI, and >90 cm for males and >80 cm for females for WC., Results: Of 970 older adults without cardiovascular disease (mean age 73 ± 4 years, 432 [44%] males), 124 (12.8%) were obese by BMI definition while 347 (35.7%) were obese by WC definition. Inter-definitional agreement was fair (Cohen's κ = 0.345). Unlike the BMI definition, participants defined as obese by WC were more likely to be women (65% vs. 50%, p < 0.001), older (65 ± 11 vs. 63 ± 14 years, p = 0.007), and had lower handgrip strength (24 ± 0.6 vs. 26 ± 0.4 kg, p = 0.022). Across BMI categories, high WC was associated with more impaired myocardial relaxation (E/A), and VO2 measurements (all p < 0.05). Among those with low BMI, high WC was associated with larger left atrial (LA) volumes (p = 0.003). WC, but not BMI, was independently associated with E/A (β = -0.114, SE -0.114 ± 0.024, p < 0.001) in regression analysis., Conclusion: WC identified a higher prevalence of obesity, possibly related to central adiposity. Across BMI categories, WC identified more adverse measurements in E/A, aerobic capacity, and LA structure., Trial Registration: ClinicalTrials.gov Identifier: NCT02791139., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Aims: Left ventricular ejection fraction is the conventional measure used to guide heart failure management, regardless of underlying etiology. Left ventricular global longitudinal strain (LV-GLS) by speckle tracking echocardiography (STE) is a more sensitive measure of intrinsic myocardial function. We aim to establish LV-GLS as a marker of replacement myocardial fibrosis on cardiovascular magnetic resonance (CMR) and validate the prognostic value of LV-GLS thresholds associated with fibrosis. Methods and results: LV-GLS thresholds of replacement fibrosis were established in the derivation cohort: 151 patients (57 ± 10 years; 58% males) with hypertension who underwent STE to measure LV-GLS and CMR. Prognostic value of the thresholds was validated in a separate outcome cohort: 261 patients with moderate-severe aortic stenosis (AS; 71 ± 12 years; 58% males; NYHA functional class I-II) and preserved LVEF ≥50%. Primary outcome was a composite of cardiovascular mortality, heart failure hospitalization, and myocardial infarction. In the derivation cohort, LV-GLS demonstrated good discrimination (c-statistics 0.74 [0.66-0.83]; P < 0.001) and calibration (Hosmer-Lemeshow χ 2 = 6.37; P = 0.605) for replacement fibrosis. In the outcome cohort, 47 events occurred over 16 [3.3, 42.2] months. Patients with LV-GLS > -15.0% (corresponding to 95% specificity to rule-in myocardial fibrosis) had the worst outcomes compared to patients with LV-GLS < -21.0% (corresponding to 95% sensitivity to rule-out myocardial fibrosis) and those between -21.0 and -15.0% (log-rank P < 0.001). LV-GLS offered independent prognostic value over clinical variables, AS severity and echocardiographic LV mass and E/e'. Conclusion: LV-GLS thresholds associated with replacement myocardial fibrosis is a novel approach to risk-stratify patients with AS and preserved LVEF., Competing Interests: The department of Cardiology at Leiden University receives unrestricted research grants from Abbott Vascular, Bayer, Biotronik, BIoventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Ionis and Medtronic. VD received speaker fees from Abbott Vascular, Edwards Lifesciences, GE Healthcare, MSD, Medtronic and Novartis. JJB received speaker fees from Abbott Vascular. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Le, Huang, Singh, Toh, Ewe, Tang, Loo, Bryant, Ang, Tay, Soo, Yip, Oon, Gong, Lunaria, Yong, Lee, Yeo, Chai, Goh, Ling, Ong, Richards, Delgado, Bax, Ding, Ling and Chin.)

Aims: Clinical guidelines recommend that the exercise protocol of a stress echocardiogram is selected to induce volitional exhaustion after a target duration of at least 8 minutes. While the Bruce protocol is very commonly used for clinical stress tests, it is known to be "steep", and many patients therefore fail to reach 8 minutes. We studied predictors of failure and developed a method for identifying patients not suitable for Bruce protocol which was accurate and yet simple enough to be used as a point-of-care decision support tool., Methods and Results: We studied data out-patients undergoing Bruce protocol stress echocardiograms (n = 11 086) and analyzed predictors of inappropriate early termination (defined as test duration < 8 min as per current practice guidelines) using logistic regression. A prediction model was constructed as follows: .5 points were given for each of hypertension, diabetes, smoking, and E/e' > 7.9 in the resting echocardiogram; .1 point was added for each 1-unit increment in body mass index; 1 point was added for patient age by decade; 2.0 points were subtracted for male sex (p for all < 0.001). In tests on held-out validation data, the model was well calibrated (in plots of predicted vs actual risk) and discriminated failure versus non-failure well (C-statistic .86 for a score of 6.0 points; p < 0.001)., Conclusion: These data may help to standardize protocol selection in stress echocardiography, by identifying patients pre-hoc where Bruce protocol will be inappropriately steep., (© 2021 Wiley Periodicals LLC.)

Background: Ageing and insulin resistant states such as diabetes mellitus frequently coexist and increase the risk of cardiovascular disease development among older adults. Here we investigate metabolic differences in amino acid profiles between ageing and diabetes mellitus, and their associations with cardiovascular function., Methods: In a group of community older adults we performed echocardiography, cardiac magnetic resonance imaging as well as cross sectional and longitudinal metabolomics profiling based on current and archived sera obtained fifteen years prior to examination., Results: We studied a total of 515 participants (women 50%, n = 255) with a mean age 73 (SD = 4.3) years. Diabetics had higher alanine (562 vs 448, p < 0.0001), higher glutamate (107 vs 95, p = 0.016), higher proline (264 vs 231, p = 0.008) and lower arginine (107 vs 117, p = 0.043), lower citrulline (30 vs 38, p = 0.006) levels (μM) compared to non-diabetics. Over time, changes in amino acid profiles differentiated diabetic older adults from non-diabetic older adults, with greater accumulation of alanine (p = 0.002), proline (p = 0.008) and (non-significant) trend towards greater accumulation of glycine (p = 0.057) among the older diabetics compared to the older non-diabetics. However, independent of diabetes status, amino acids were associated with cardiovascular functions in ageing, [archived valine (p = 0.011), leucine (p = 0.011), archived isoleucine (p = 0.0006), archived serine (p = 0.008), archived glycine (p = 0.006) methionine (p = 0.003)] which were associated with impairments in E/A ratio., Conclusion: Markers of branched chain amino acids and one ‑carbon metabolism pathways were associated with changes in cardiovascular function in older adults regardless of diabetes status. However, nitrogen handling pathways were specifically altered among older adults with diabetes. These findings broaden our understanding into specific amino acid pathways that may be altered between diabetic and non-diabetic older adults, and their relevance to cardiovascular function in ageing., Trial Registration: ClinicalTrials.gov Identifier: NCT02791139., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: This study aimed to evaluate the prevalence and prognostic value of the extent of extra-aortic valvular cardiac abnormalities in a large multicenter registry of patients with moderate AS., Background: The prognostic significance of a new classification system that incorporates the extent of cardiac injury (beyond the aortic valve) has been proposed in patients with severe aortic stenosis (AS). Whether this can be applied to patients with moderate AS is unclear., Methods: Based on the echocardiographic findings at the time of diagnosis of moderate AS (aortic valve area between 1.0 and 1.5 cm 2 and dimensionless velocity index ratio of ≥0.25), a total of 1,245 patients were included and analyzed retrospectively. They were recategorized into 5 groups according to the extent of extra-aortic valvular cardiac abnormalities: none (Group 0), involving the left ventricle (Group 1), the left atrial or mitral valve (Group 2), the pulmonary artery vasculature or tricuspid valve (Group 3), or the right ventricle (Group 4). Patients were followed for all-cause mortality and combined endpoint (all-cause mortality, stroke, heart failure, or myocardial infarction)., Results: The distribution of patients according to the proposed classification was 13.1%, 26.8%, 42.6%, 10.6%, and 6.9% in Groups 0, 1, 2, 3, and 4, respectively. During a median follow-up of 4.3 (2.4 to 6.9) years, 564 (45.3%) patients died. There was a significant higher mortality rates with increasing extent of extra-aortic valvular cardiac abnormalities (log-rank p < 0.001). On multivariable analysis, the presence of extra-aortic valvular cardiac abnormalities remained independently associated with all-cause mortality and combined outcome, adjusted for aortic valve replacement as a time-dependent covariable. In particular, Group 2 and above were independently associated with all-cause mortality., Conclusions: In patients with moderate AS, the presence of extra-aortic valvular cardiac abnormalities is associated with poor outcome., Competing Interests: Funding Support and Author Disclosures The Department of Cardiology, Heart Lung Center, Leiden University Medical Center has received grants from Biotronik, Medtronic, Boston Scientific, GE Healthcare, and Edwards Lifesciences. Dr. Marsan has received speaker fees from Abbott and Philips Ultrasound. Dr. Ding has received speaker fees from Philips. Dr. Ewe has received speaker fees from Edwards Lifesciences and Abbott Vascular. Dr. Delgado has received speaker fees from Abbott Vascular. Dr. Bax has received speaker fees from Abbott Vascular and Boehringer Ingelheim. Dr. Pio has received funding from European Society of Cardiology in the form of an ESC Training Grant (reference of application number: T-2018-17405). Dr. Genereux has received speaker fees from Edwards Lifesciences, Cordis, and Medtronic; has served as consultant for Abiomed, Boston Scientific, Cardiovascular System Inc., Cordis, Edwards Lifesciences, Medtronic, Opsens, Soundbite Medical Solutions Inc., Pi-Cardia, Saranas, Siemens, Shockwave Medical Inc., SIG.NUM, Teleflex, and 4C Medical; and holds shares in Soundbite Medical Solutions Inc., SIG.NUM, Pi-Cardia, and Puzzle Medical. Dr. Leon is an early physician founder of Mitralign and has an equity relationship (<1% of the company). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To demonstrate differences in cardiovascular structure and function between diabetic and non-diabetic older adults. To investigate associations between acyl-carnitines and cardiovascular function as indexed by imaging measurements., Methods: A community-based cohort of older adults without cardiovascular disease underwent current cardiovascular imaging and metabolomics acyl-carnitines profiling based on current and archived sera obtained fifteen years prior to examination., Results: A total of 933 participants (women 56%, n=521) with a mean age 63±13 years were studied. Old diabetics compared to old non-diabetics had lower myocardial relaxation (0.8±0.2 vs 0.9±0.3, p=0.0039); lower left atrial conduit strain (12±4.3 vs 14±4.1, p=0.045), lower left atrial conduit strain rate (-1.2±0.4 vs -1.3±0.5, p=0.042) and lower ratio of left atrial conduit strain to left atrial booster strain (0.5±0.2 vs 0.7±0.3, p=0.0029). Higher levels of archived short chain acyl-carnitine were associated with present-day impairments in myocardial relaxation (C5:1; OR 1.03, p=0.011), worse left atrial conduit strain function (C5:1; OR 1.03, p=0.037). Increases in hydroxylated acyl-carnitines were associated with worse left atrial conduit strain [(C4-OH; OR 1.05, p=0.0017), (C16:2-OH; OR 1.18, p=0.037)]. Current, archived and changes in long chain acyl-carnitines were associated with cardiovascular functions [(C16; OR 1.02, p=0.002), (C20:3; OR 1.01, p=0.014), (C14:3; OR 1.12, p=0.033), (C18:1; OR 1.01, p=0.018), (C18:2; OR 1.01, p=0.028), (C20:4; OR 1.10, p=0.038)] (all p<0.05)., Conclusion: Older diabetic adults had significant impairments in left ventricular myocardial relaxation and left atrial strain, compared to older non-diabetic adults. Short chain and long chain, di-carboxyl and hydroxylated acyl-carnitines were associated with these cardiovascular functional differences.

Transcatheter mitral valve repair with the MitraClip, a catheter-based percutaneous edge-to-edge repair technique to correct mitral regurgitation (MR), has been demonstrated in Western studies to be an effective and safe MR treatment strategy. However, randomised clinical trial data on its use in Asian-Pacific patients is limited. Hence, the Asian Pacific Society of Cardiology convened an expert panel to review the available literature on MitraClip and to develop consensus recommendations to guide clinicians in the region. The panel developed statements on the use of MitraClip for the management of degenerative MR, functional MR, and other less common indications, such as acute MR, dynamic MR, hypertrophic obstructive cardiomyopathy, and MR after failed surgical repair. Each statement was voted on by each panel member and consensus was reached when 80% of experts voted 'agree' or 'neutral'. This consensus-building process resulted in 10 consensus recommendations to guide general cardiologists in the evaluation and management of patients in whom MitraClip treatment is being contemplated., Competing Interests: Disclosure: This work was funded through Asian Pacific Society of Cardiology by unrestricted educational grants from Abbott Vascular, Amgen, AstraZeneca, Bayer and Roche Diagnostics. YKK has received research funding from Medtronic, Boston Scientific, Amgen, AstraZeneca and Shockwave Medical (all significant, via institution); consulting or honoraria fees (all modest) from Medtronic, Boston Scientific, Abbott Vascular, Amgen, Bayer and Novartis; and speaker or proctor fees from Abbott Vascular, Boston Scientific, Medtronic, Philips, Shockwave Medical, Alvimedica, Menarini, AstraZeneca, Amgen and Bayer. JWCT has received honoraria from AstraZeneca, Bayer, Amgen, Medtronic, Abbott Vascular, Biosensors, Alvimedica, Boehringer Ingelheim and Pfizer; research and educational grants from Medtronic, Biosensors, Biotronik, Philips, Amgen, AZ, Roche, Ostuka, Terumo and Abbott Vascular; and consulting fees from Elixir, CSL Behring. ET and SHS have received honoraria from Abbott Vascular. JL has received research funding from AstraZeneca, Sensible Medical and Volumetrix; and consulting fees from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Boston Scientific, CVRx, Edwards Lifesciences, Impulse Dynamics and VWave. XP has received proctor fees from Medtronic and Abbott Vascular. DWMM has received research funding and consulting or proctor fees from Abbott Vascular, Medtronic and Edwards Lifesciences. KM has received modest research funding and consulting or proctor fees from CSL Behring, Boston Scientific, Abbott Vascular, Medtronic, Thai Osuka, AstraZeneca and Daiichi Sankyo. SHE has received speaker fees from Edwards Lifesciences and Abbott Vascular. MA has received speaker fees from Abbott Medical Japan. JSK has received proctoring fees from Abbott Vascular and Occlutech. All other authors have no conflicts of interest to declare., (Copyright © 2021, Radcliffe Cardiology.)

Background: The criteria to define the grade of aortic stenosis (AS)-aortic valve area (AVA) and mean gradient (MG) or peak jet velocity-do not always coincide into one grade. Although in severe AS, this discrepancy is well characterised, in moderate AS, the phenomenon of discordant grading has not been investigated and its prognostic implications are unknown., Objectives: To investigate the occurrence of discordant grading in patients with moderate AS (defined by an AVA between 1.0 cm² and 1.5 cm² but with an MG <20 mm Hg) and how these patients compare with those with concordant grading moderate AS (AVA between 1.0 cm² and 1.5 cm² and MG ≥20 mm Hg) in terms of clinical outcomes., Methods: From an ongoing registry of patients with AS, patients with moderate AS based on AVA were selected and classified into discordant or concordant grading (MG <20 mm Hg or ≥20 mm Hg, respectively). The clinical endpoint was all-cause mortality., Results: Of 790 patients with moderate AS, 150 (19.0%) had discordant grading, moderate AS. Patients with discordant grading were older, had higher prevalence of previous myocardial infarction and left ventricular (LV) hypertrophy, larger LV end-diastolic and end-systolic volume index, higher LV filling pressure and lower LV ejection fraction and stroke volume index as compared with their counterparts. After a median follow-up of 4.9 years (IQR 3.0-8.2), patients with discordant grading had lower aortic valve replacement rates (26.7% vs 44.1%, p<0.001) and higher mortality rates (60.0% vs 43.1%, p<0.001) as compared with patients with concordant grading. Discordant grading moderate AS, combined with low LV ejection fraction, presented the higher risk of mortality (HR 2.78 (2.00-3.87), p<0.001)., Conclusion: Discordant-grading moderate AS is not uncommon and, when combined with low LV ejection fraction, is associated with high risk of mortality., Competing Interests: Competing interests: The Department of Cardiology, Heart Lung Center, Leiden University Medical Center has received grants from Biotronik, Medtronic, Boston Scientific, GE Healthcare, and Edwards Lifesciences. NAM has received speaker fees from Abbott and Philips Ultrasound. ZPD has received speaker fees from Philips. PP has received grant support from Edwards Lifesciences and Medtronic. SHE has received speaker fees from Edwards Lifesciences and Abbott Vascular. VD has received speaker fees from Abbott Vascular. JJB has received speaker fees from Abbott Vascular and Boehringer Ingelheim. PG reports speaker fee from Edwards Lifesciences, Cordis, Medtronic; Consultant: Abiomed, Boston Scientific, Cardiovascular System Inc., Cordis, Edwards Lifesciences, Medtronic, Opsens, Soundbite Medical Solutions Inc., Pi-Cardia, Saranas, Siemens, Shockwave Medical Inc., SIG.NUM; Teleflex, 4C Medical, Shareholder: Soundbite Medical Solutions Inc., SIG.NUM, Pi-Cardia, Puzzle Medical. MBL is an early physician founder of Mitralign and has an equity relationship (< 1% of the company)., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Yeo Khung Keong is a speaker, consultant and proctor for Abbott Vascular (MitraClip) and reports receiving honoraria from Abbott Vascular. The other authors have no conflicts of interest to declare.

Aims: Cardiac damage in severe aortic stenosis (AS) can be classified according to a recently proposed staging classification. The present study investigated the incremental prognostic value of left ventricular (LV) global longitudinal strain (GLS) over stages of cardiac damage in patients with severe AS., Methods and Results: From an ongoing registry, a total of 616 severe symptomatic AS patients with available LV GLS by speckle tracking echocardiography were selected and retrospectively analysed. Patients were categorized according to cardiac damage on echocardiography: Stage 0 (no damage), Stage 1 (LV damage), Stage 2 (mitral valve or left atrial damage), Stage 3 (tricuspid valve or pulmonary artery vasculature damage), or Stage 4 (right ventricular damage). LV GLS was divided by quintiles and assigned to the different stages. The endpoint was all-cause mortality. Over a median follow-up of 44 [24-89] months, 234 (38%) patients died. LV GLS was associated with all-cause mortality independent of stage of cardiac damage. After incorporation of LV GLS by quintiles into the staging classification, Stages 2-4 were independently associated with outcome. LV GLS showed incremental prognostic value over clinical characteristics and stages of cardiac damage., Conclusion: In this large single-centre cohort of severe AS patients, incorporation of LV GLS by quintiles in a novel proposed staging classification resulted in refinement of risk stratification by identifying patients with more advanced cardiac damage. LV GLS was shown to provide incremental prognostic value over the originally proposed staging classification., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

There are no studies evaluating comprehensive predictors of transcatheter aortic valve implantation (TAVI) outcomes encompassing frailty assessments in a South-East Asian cohort. In this longitudinal single-center cohort, all patients who underwent TAVI in a tertiary cardiac center and comprehensively assessed for frailty at baseline were included in a registry. The primary outcome was to investigate frailty indices predictive of prolonged index hospitalization after TAVI. Seventy-six patients with a mean age of 77.6 ± 8.5 years were included. Mean Society of Thoracic Society Predicted Risk of Mortality score was 5.2 ± 3.0, with 11 (14.5%) patients classified as high-risk (Society of Thoracic Society Predicted Risk of Mortality >8). Mean and median index hospitalization duration were 9.2 ± 5.6 and 7 [4.5 to 9.5] days, respectively. Univariate analysis demonstrated that lower hemoglobin (Hb) (p <0.01), longer 5-meter walk test (5MWT) (p <0.01), lower dominant hand grip strength (p <0.01), the use of transaortic access (p = 0.01), new atrial fibrillation post-TAVI (p <0.01), and lower postprocedural Hb (p <0.01) were associated with longer index hospitalization duration. Multivariate linear regression demonstrated preoperative Hb, preoperative atrial fibrillation and 5MWT were independent baseline predictors of index hospitalization duration (p <0.05). Additionally, a 5MWT cutoff of 11 seconds (0.45 m/s) had a high specificity (88.6%) in predicting prolonged index hospitalization duration. In conclusion, this is the first comprehensive frailty assessment in a South-East Asian cohort demonstrating 5MWT to be a significant predictor of prolonged index hospitalization. This simple and effective frailty assessment index may be considered to optimize patient selection for TAVI., (Copyright © 2020 Elsevier Inc. All rights reserved.)