Point-of-care AI-enhanced novice echocardiography for screening heart failure (PANES-HF).

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.

Safety and efficacy of cerebral embolic protection in transcatheter aortic valve implantation: an updated meta-analysis.

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.

Myocardial Aging among a Population-Based Cohort Is Associated with Adverse Cardiovascular Outcomes and Sex-Specific Differences among Older Adults.

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 <0.8 (28%), E/A 0.8-1.2 (39%), E/A (29%), E/A >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 <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 <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.

Echocardiographic Imaging in Transcatheter Structural Intervention: An AAE Review Paper.

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.

Longitudinal analysis of thoracic aortic expansion in non-syndromic real-world patients.

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; CI95: 1.87-1.99) mm per decade, and for ascending aorta as 1.76 (CI95: 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.

An Updated Meta-Analysis on the Clinical Outcomes of Percutaneous Left Atrial Appendage Closure Versus Direct Oral Anticoagulation in Patients With Atrial Fibrillation.

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), CHA2DS2-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.

Network Meta-Analysis Comparing Transcatheter, Minimally Invasive, and Conventional Surgical Aortic Valve Replacement.

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.

Managing Patients With Moderate Aortic Stenosis.

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.

The impact of atrial fibrillation on prognosis in aortic stenosis.

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.

Adverse cardiovascular and metabolic perturbations among older women: 'fat-craving' hearts.

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/m2 vs 24 ± 3.4 kg/m2, 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.

Prognostic Value of Left Atrial Strain in Aortic Stenosis: A Competing Risk Analysis.

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.

Impact of aortic annular size and valve type on haemodynamics and clinical outcomes after transcatheter aortic valve implantation.

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.

Factors Affecting Rate of Progression of Aortic Stenosis and Its Impact on Outcomes.

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 cm1) 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.

Prevalence and Prognostic Implications of Discordant Grading and Flow-Gradient Patterns in Moderate Aortic Stenosis.

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 cm2) 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/m2, and LVEF ≥50%); "paradoxical" low-flow, low-gradient moderate AS (MG <20 mm Hg, SVi <35 mL/m2, 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.

Prognostic implications of left ventricular diastolic dysfunction in moderate aortic stenosis.

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 cm2) 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.

Obesity in Older Adults and Associations with Cardiovascular Structure and Function.

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 (ß = -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.

Novel predictive role for mid-regional proadrenomedullin in moderate to severe aortic stenosis.

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.

Left Ventricular Global Longitudinal Strain in Patients with Moderate Aortic Stenosis.

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 cm2) 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.

Left ventricular remodelling patterns in patients with moderate aortic stenosis.

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.