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Degenerative aortic stenosis is a growing clinical problem owing to the high incidence in an aging population and its significant morbidity and mortality. Currently, aortic valve replacement remains the only treatment. Despite promising observational data, pharmacological management to slow or halt progression of aortic stenosis has remained elusive. Nevertheless, with a greater understanding of the mechanisms which underpin aortic stenosis, research has begun to explore novel treatment strategies. This review will explore the historical agents used to manage aortic stenosis and the emerging agents that are currently under investigation., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: We set out to explore associations between a 'mitral-specific' cardiac damage score (m-CDS) and survival outcomes in mitral regurgitation (MR) and compare the performance of the m-CDS and an 'aortic-specific' CDS (a-CDS) in patients with MR within the large National Echo Database of Australia., Methods: Among 620 831 unique adults investigated with echocardiography, there were 17 658 individuals (3.1%) with moderate or greater functional MR (aged 76±13 years, 51% female) who met inclusion criteria. A randomly selected cohort of 5000 of these patients was used to test seven different CDS models for prediction of subsequent all-cause mortality during an average 3.8-year follow-up. The best-performing CDS model in the derivation cohort was then applied to a validation cohort of the remaining 12 658 individuals (aged 76±13 years, 51% female)., Results: The best-performing m-CDS model stratified the full cohort into Stage 0: control (1046 patients, 8%); Stage 1: left atrial damage (3416 patients, 27%); Stage 2: left ventricular damage (3352 patients, 26%); Stage 3: right ventricular damage (1551 patients, 12%) and Stage 4: pulmonary hypertension (3293 patients, 26%). Increasing m-CDS stage was consistently and incrementally associated with both all-cause and cardiovascular mortality at 1 year, 5 years and all-time and remained so after adjustment for increasing age and severity of MR, with a ~35% increase in mortality for each increase in CDS stage (p<0.001)., Conclusion: A m-CDS was robustly and incrementally associated with short-, medium- and long-term risk of all-cause and cardiovascular mortality in patients with functional MR in this large registry study., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Increasing aortic dilation increases the risk of aortic dissection. Nevertheless, dissection occurs at dimensions below guideline-directed cut-offs for prophylactic surgery. Currently, there are no large-scale population imaging data assessing aortic dimensions before dissection., Methods and Results: Patients within the National Echo Database of Australia were stratified according to absolute, height-indexed, and body surface area (BSA)-indexed aortic dimensions. Fatal thoracic aortic dissections (ICD-10-AM Code I71) were identified via linkage with the National Death Index. A total of 524 994 individuals were assessed, comprising patients with normal aortic dimensions (n = 460 992), mild dilation (n = 53 402), moderate dilation (n = 10 029), and severe dilation (n = 572). A total of 274 992 (52.4%) were males, with a median age of 64 years and a median follow-up time of 6.9 years. Eight hundred and ninety-nine fatal aortic dissections occurred (normal diameter = 610, mildly dilated aorta = 215, moderately dilated = 53, and severely dilated = 21). Using normal aortas as the reference population, odds of fatal dissection increased with aortic diameter [mild = odds ratio (OR) 3.05, 95% confidence interval (CI) 2.61-3.56; moderate = OR 4.0, 95% CI 3.02-5.30; severe = OR 28.72, 95% CI 18.44-44.72]. Due to the much larger number of patients without severe aortic dilation, 97.7% of fatal aortic dissections occurred in non-severely dilated aortas. Following sensitivity analysis, severe aortic dilation was responsible for at most 24.4% of fatal aortic dissections. The results were robust for absolute, height-indexed, or BSA-indexed aortic measurements., Conclusion: Although severe aortic dilatation is associated with a near-30-fold increase in fatal dissections, severely dilated aortas are implicated in only 2.3-24.4% of fatal dissections. This highlights the 'aortic paradox' and limitations of current guidelines. Future studies should seek to refine risk predictors in patients without severe aortic dilation., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Identifying individuals with severe aortic stenosis (AS) at high risk of mortality remains challenging using current clinical imaging methods., Objectives: The purpose of this study was to evaluate an artificial intelligence decision support algorithm (AI-DSA) to augment the detection of severe AS within a well-resourced health care setting., Methods: Agnostic to clinical information, an AI-DSA trained to identify echocardiographic phenotype associated with an aortic valve area (AVA)<1 cm 2 using minimal input data (excluding left ventricular outflow tract measures) was applied to routine transthoracic echocardiograms (TTE) reports from 31,141 U.S. Medicare beneficiaries at an academic medical center (2003-2017)., Results: Performance of AI-DSA to detect the phenotype associated with an AVA<1 cm 2 was excellent (sensitivity 82.2%, specificity 98.1%, negative predictive value 9.2%, c-statistic = 0.986). In addition to identifying clinical severe AS cases, AI-DSA identified an additional 1,034 (3.3%) individuals with guideline-defined moderate AS but with a similar clinical and TTE phenotype to those with severe AS with low rates of aortic valve replacement (6.6%). Five-year mortality was 75.9% in those with known severe AS, 73.5% in those with a similar phenotype to severe AS, and 44.6% in those without severe AS. The AI-DSA continued to perform well to identify severe AS among those with a depressed left ventricular ejection fraction. Overall rates of aortic valve replacement remained low, even in those with an AVA<1 cm 2 (21.9%)., Conclusions: Without relying on left ventricular outflow tract measurements, an AI-DSA used echocardiographic reports to reliably identify the phenotype of severe AS. These results suggest possible utility for this AI-DSA to enhance detection of severe AS individuals at risk for adverse outcomes., Competing Interests: This work was supported by Echo IQ Pty Ltd. Dr Stewart is supported by the 10.13039/501100000925National Health and Medical Research Council of Australia (GNT1135894). Dr Strom is supported by the 10.13039/100000002National Institutes of Health (1K23HL144907, R01AG063937), 10.13039/100006520Edwards Lifesciences, Ultromics, HeartSciences, Anumana, and EchoIQ. Unrelated to this work, Dr Strom has served on the Scientific Advisory Board for Edwards Lifesciences and EchoIQ and has received consulting fees from Bracco Diagnostics, General Electric Healthcare, and Lantheus Medical Imaging. Prof Strange has received consulting fees from Edwards, Medtronic, and Echo IQ and has received speaker fees from Edwards, Medtronic, Abbott, and Echo IQ. Prof Playford has received consulting fees from Edwards, Medtronic, and Echo IQ. Prof Stewart has received consulting fees from Echo IQ., (© 2024 The Authors.)

Background: The mortality risk attributable to moderate aortic stenosis (AS) remains incompletely characterized and has historically been underestimated. We aim to evaluate the association between moderate AS and all-cause death, comparing it with no/mild AS (in a general referral population and in patients with heart failure with reduced ejection fraction)., Methods and Results: A systematic review and pooled meta-analysis of Kaplan-Meier-derived reconstructed time-to-event data of studies published by June 2023 was conducted to evaluate survival outcomes among patients with moderate AS in comparison with individuals with no/mild AS. Ten studies were included, encompassing a total of 409 680 patients (11 527 with moderate AS and 398 153 with no/mild AS). In the overall population, the 15-year overall survival rate was 23.3% (95% CI, 19.1%-28.3%) in patients with moderate AS and 58.9% (95% CI, 58.1%-59.7%) in patients with no/mild aortic stenosis (hazard ratio [HR], 2.55 [95% CI, 2.46-2.64]; P <0.001). In patients with heart failure with reduced ejection fraction, the 10-year overall survival rate was 15.5% (95% CI, 10.0%-24.0%) in patients with moderate AS and 37.3% (95% CI, 36.2%-38.5%) in patients with no/mild AS (HR, 1.83 [95% CI, 1.69-2.0]; P <0.001). In both populations (overall and heart failure with reduced ejection fraction), these differences correspond to significant lifetime loss associated with moderate AS during follow-up (4.4 years, P <0.001; and 1.9 years, P <0.001, respectively). A consistent pattern of elevated mortality rate associated with moderate AS in sensitivity analyses of matched studies was observed., Conclusions: Moderate AS was associated with higher risk of death and lifetime loss compared with patients with no/mild AS.

Background: The independent effect of pulmonary hypertension (PHT) severity on mortality in those with reduced left ventricular ejection fraction (LVEF) is not well known., Objectives: The authors aimed to examine the prognostic impact of increasingly elevated pulmonary pressures in a large clinical cohort of adults with reduced LVEF., Methods: The authors analyzed data from the National Echocardiography Database of Australia, a large clinical registry linking routine echocardiographic investigations to mortality. In 23,675 adults with a recorded tricuspid regurgitation peak velocity (TRV) and reduced LVEF (<50%), the authors evaluated the relationship between conventional thresholds of increasing risk of PHT and mortality during median follow-up of 2.9 years (Q1-Q3: 1.0-5.4 years)., Results: Mean age was 70 ± 15 years, and 7,498 (31.7%) individuals were female. Overall, 8,801 (37.2%) had normal (TRV <2.5 m/s), 7,061 (29.8%) had borderline (2.5-2.8 m/s), 5,676 (24.0%) intermediate (2.9-3.4 m/s), and 2,137 (9.0%) individuals had high-risk PHT (>3.4 m/s). With increasing risk of PHT, 1- and 5-year actuarial mortality increased from 13.3% and 43.8% to 41.5% and 81.4%, respectively (P < 0.0001) from normal to severely elevated TRV. The adjusted HR of mortality increased by 1.31-fold (95% CI: 1.23-1.38), 1.82-fold (95% CI: 1.72-1.93), and 2.38-fold (95% CI: 2.21-2.56) in those with borderline, intermediate, and high risk of PHT respectively, compared with normal TRV. Further analyses suggested a distinctive threshold with a TRV reached >2.41 m/s (adjusted HR: 1.18 [95% CI: 1.04-1.33])., Conclusions: The authors demonstrate the prevalence and negative prognostic impact of increasingly elevated TRV levels in individuals with reduced LVEF, with a threshold for mortality lying within the range of "borderline risk" PHT., Competing Interests: Funding Support and Author Disclosures This research did not receive any specific grants from funding agencies in the public, commercial, or not for profit sectors. However, the National Echo Database of Australia has received investigator-initiated funding support from Janssen, Novartis Pharmaceuticals, and Edwards Lifesciences in the past 3 years. Both the National Echo Database of Australia (grant 1055214) and Dr Stewart (grant 11358940) are supported by the National Health and Medical Research Council of Australia. Dr Ratwatte is supported by the National Heart Foundation of Australia (grant 106796). Drs Stewart, Strange, and Playford have previously received consultancy/speaker fees from Edwards Lifesciences. Drs Stewart and Playford have received consultancy fees from Medtronic, Edwards Lifesciences, Abbott Laboratories, and ECHO IQ Pty Ltd. Dr Celermajer has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Grading of diastolic function can be useful, but indeterminate classifications are common. We aimed to invasively derive and validate a quantitative echocardiographic estimation of pulmonary artery wedge pressure (PAWP) and to compare its prognostic performance to diastolic dysfunction grading., Methods and Results: Echocardiographic measures were used to derive an estimated PAWP (ePAWP) using multivariable linear regression in patients undergoing right heart catheterization (RHC). Prognostic associations were analysed in the National Echocardiography Database of Australia (NEDA). In patients who had undergone both RHC and echocardiography within 2 h (n = 90), ePAWP was derived using left atrial volume index, mitral peak early velocity (E), and pulmonary vein systolic velocity (S). In a separate external validation cohort (n = 53, simultaneous echocardiography and RHC), ePAWP showed good agreement with invasive PAWP (mean ± standard deviation difference 0.5 ± 5.0 mmHg) and good diagnostic accuracy for estimating PAWP >15 mmHg [area under the curve (95% confidence interval) 0.94 (0.88-1.00)]. Among patients in NEDA [n = 38,856, median (interquartile range) follow-up 4.8 (2.3-8.0) years, 2756 cardiovascular deaths], ePAWP was associated with cardiovascular death even after adjustment for age, sex, and diastolic dysfunction grading [hazard ratio (HR) 1.08 (1.07-1.09) per mmHg] and provided incremental prognostic information to diastolic dysfunction grading (improved C-statistic from 0.65 to 0.68, P < 0.001). Increased ePAWP was associated with worse prognosis across all grades of diastolic function [HR normal, 1.07 (1.06-1.09); indeterminate, 1.08 (1.07-1.09); abnormal, 1.08 (1.07-1.09), P < 0.001 for all]., Conclusion: Echocardiographic ePAWP is an easily acquired continuous variable with good accuracy that associates with prognosis beyond diastolic dysfunction grading., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective Data linkage is a very powerful research tool in epidemiology, however, establishing this can be a lengthy and intensive process. This paper reports on the complex landscape of conducting data linkage projects in Australia. Methods We reviewed the processes, required documentation, and applications required to conduct multi-jurisdictional data linkage across Australia, in 2023. Results Obtaining the necessary approvals to conduct linkage will likely take nearly 2 years (estimated 730 days, including 605 days from initial submission to obtaining all ethical approvals and an estimated further 125 days for the issuance of unexpected additionally required approvals). Ethical review for linkage projects ranged from 51 to 128 days from submission to ethical approval, and applications consisted of 9-25 documents. Conclusions Major obstacles to conducting multi-jurisdictional data linkage included the complexity of the process, and substantial time and financial costs. The process was characterised by inefficiencies at several levels, reduplication, and a lack of any key accountabilities for timely performance of processes. Data linkage is an invaluable resource for epidemiological research. Further streamlining, establishing accountability, and greater collaboration between jurisdictions is needed to ensure data linkage is both accessible and feasible to researchers.

Background: Right ventricular (RV) function is tightly coupled to afterload, yet echocardiographic indices of RV function are frequently assessed in isolation. Normalizing RV function for afterload (RV-PA coupling) using a simplified ratio of tricuspid annular plane systolic excursion (TAPSE)/ tricuspid regurgitant velocity (TRV) could help to identify RV decompensation and improve risk stratification in critically ill patients. This is the first study to explore the distribution of TAPSE/TRV ratio and its prognostic relevance in a large general critical care cohort., Methods: We undertook retrospective analysis of echocardiographic, clinical, and mortality data of intensive care unit (ICU) patients between January 2012 and May 2017. A total of 1077 patients were included and stratified into tertile groups based on TAPSE/TRV ratio: low (< 5.9 mm.(m/s) -1 ), middle (≥ 5.9-8.02 mm.(m/s) -1 ), and high (≥ 8.03 mm.(m/s) -1 ). The distribution of the TAPSE/TRV ratio across ventricular function subtypes of normal, isolated left ventricular (LV), isolated RV, and biventricular dysfunction was explored. The overall prognostic relevance of the TAPSE/TRV ratio was tested, including distribution across septic, cardiovascular, respiratory, and neurological subgroups., Results: Higher proportions of ventricular dysfunctions were seen in low TAPSE/TRV tertiles. TAPSE/TRV ratio is impacted by LV systolic function but to a lesser extent than RV dysfunction or biventricular dysfunction. There was a strong inverse relationship between TAPSE/TRV ratio and survival. After multivariate analysis, higher TAPSE/TRV ratios (indicating better RV-PA coupling) were independently associated with lower risk of death in ICU (HR 0.927 [0.872-0.985], p < 0.05). Kaplan-Meier analysis demonstrated higher overall survival in middle and high tertiles compared to low tertiles (log rank p < 0.0001). The prognostic relevance of TAPSE/TRV ratio was strongest in respiratory and sepsis subgroups. Patients with TAPSE/TRV < 5.9 mm (m/s) -1 had a significantly worse prognosis than those with higher TAPSE/TRV ratios., Conclusion: The TAPSE/TRV ratio has prognostic relevance in critically ill patients. The prognostic power may be stronger in respiratory and septic subgroups. Larger prospective studies are needed to investigate the role of TAPSE/TRV in pre-specified subgroups including its role in clinical decision-making., (© 2024. Crown.)

This manuscript on real-world evidence (RWE) in pulmonary hypertension (PH) incorporates the broad experience of members of the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative Real-World Evidence Working Group. We aim to strengthen the research community's understanding of RWE in PH to facilitate clinical research advances and ultimately improve patient care. Herein, we review real-world data (RWD) sources, discuss challenges and opportunities when using RWD sources to study PH populations, and identify resources needed to support the generation of meaningful RWE for the global PH community., Competing Interests: Boucly reports consulting fees from AOP Orphan; payment, honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AOP Orphan, MSD, and Janssen; and support for attending meetings/travel from MSD and Janssen. Moles reports grants or contracts from Acceleron Pharma, Janssen, and CVS Caremark; and leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, for Gossamer Bio. Elwing reports grants or contracts from United Therapeutics Corporation, Gossamer Bio, Bayer, Acceleron/Merck, Altavant, Aerovate, Tenax, Pharmosa, Actelion/Janssen, Arena, Lung, Liquidia, and Phase Bio; consulting fees for United Therapeutics Corporation; support for attending meetings and/or travel for United Therapeutics, Altavant, Aerovate, Bayer, Gossamer Bio, Liquida, Acceleron/Merck, Janssen/Actelion, and Insmed; and other financial or nonfinancial interests from Bayer as a grant reviewer. Jose reports grants or contracts from Team Phenomenal Hope Charity, Francis Family Foundation, United Therapeutics, and Janssen/Johnson & Johnson. Alves Jr. reports payment or honoraria from Bayer and Janssen; and support for attending meetings and/or travel from Janssen. Minty reports consulting fees from Janssen Pharmaceuticals and Orpyx Medical Technologies; and stock or stock options from Orpyx Medical Technologies. Weatherald reports grants or contracts from Janssen, Bayer, Merck, Canadian Institutes for Health Research, and the Heart & Stroke Foundation of Canada; consulting fees from Janssen and Merck; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Janssen and Merck; payment for expert testimony from Sprigings Intellectual Property Law; support for attending meetings and/or travel from Janssen; participation on a data safety monitoring board or advisory board from Janssen, Acceleron, and Université Laval; and leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, from the Pulmonary Hypertension Association of Canada. Mathai reports grants or contracts from NIH/NHLBI (HL125175) and DOD (W81XWH‐20‐1‐0768); consulting fees from Actelion/Janssen, Aerovate, Merck, United Therapeutics Corporation, and Theravance; and participation on a data safety monitoring board or advisory board from Bayer. Sahay reports grants or contracts from United Therapeutics Corporation, Janssen, Bayer, Merck, Liquidia, and Gossamer; consulting fees from Merck, Liquidia, and Gossamer; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from United Therapeutics Corporation (received by hospital rather than self); patents planned, issued, or pending with Janssen; and participation on a data safety monitoring board or advisory board with GSK, Bayer, United Therapeutics, and Janssen. Pulido reports grants or contracts from Janssen, MSD, and United Therapeutics; consulting fees from Janssen, Bayer, Gossamer, and MSD; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bayer, Janssen, and Pfizer. Badagliacca reports grants or contracts from United Therapeutics Corporation, Ferrer, and Janssen; consulting fees from MSD, United Therapeutics Corporation, Ferrer, Janssen, and AOP; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from MSD, United Therapeutics Corporation, Ferrer, Janssen, and AOP; and support for attending meetings and/or travel from MSD, United Therapeutics Corporation, Ferrer, Janssen, and AOP. Cirulis reports grants or contracts from Entelligence (now ATS); and leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, with ATS Web Committee Co‐Director and ATS Program Committee. Gerges reports grants or contracts from AOP Health; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AOP Health, Actelion/Janssen, and Ferrer; and support for attending meetings and/or travel from AOP Health, Actelion/Janssen, Ferrer, Daiichi Sankyo, and MSD. Gillmeyer reports grants or contracts from Parker B. Francis Fellowship Award, Doris Duke Charitable Foundation Award, and National Center for Advancing Translational Sciences, National Institutes of Health (BU‐CTSI Grant Number 1UL1TR001430); and leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, for the American Thoracic Society Program Committee (unpaid). Hobohm reports consulting fees for Janssen, Boston Consulting, and MSD. Lau reports grants or contracts from Janssen and GSK; consulting fees for Janssen; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Janssen. Morland reports grants or contracts from United Therapeutics Corporation; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, from the PVRI Innovative Drug Development Initiative (unpaid); and stock or stock options from United Therapeutics Corporation. Nikkho reports grants or contracts from Bayer AG; and leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, from the PVRI Innovative Drug Development Initiative (unpaid). The remaining authors declare no conflict of interest., (© 2023 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

An elevated estimated right ventricular systolic pressure (eRVSP) identified on echocardiography is present in one-third of individuals with type 2 diabetes, but its prognostic significance is unknown. To assess the relationship between eRVSP and mortality, prospective data from 1732 participants in the Fremantle Diabetes Study Phase II were linked with the National Echocardiographic Database of Australia. Of this cohort, 416 (mean age 70.6 years, 47.4% males) had an eRVSP measured and 381 (91.4%) had previously confirmed type 2 diabetes. Receiver- operating characteristic analysis of the relationship between eRVSP and all-cause mortality was conducted. Survival analyses were performed for participants with type 2 diabetes diagnosed before first measured eRVSP (n = 349). Cox regression identified clinical and echocardiographic associates of all-cause mortality. There were 141 deaths (40.4%) during 2348 person-years (mean ± SD 6.7 ± 4.0 years) of follow-up. In unadjusted Kaplan-Meier analysis, mortality rose with higher eRVSP (log-rank test, p < 0.001). In unadjusted pairwise comparisons, eRVSP >30 to 35, >35 to 40, and >40 mmHg had significantly increased mortality compared with eRVSP ≤ 30 mmHg ( p = 0.025, p = 0.001, p < 0.001, respectively). There were 50 deaths in 173 individuals (29.1%) with eRVSP ≤ 30 mmHg, and 91 in 177 (51.4%) with eRVSP > 30 mmHg (log-rank test, p < 0.001). In adjusted models including age, Aboriginal descent, Charlson Comorbidity Index ≥ 3 and left heart disease, eRVSP > 30 mmHg predicted a two-fold higher all-cause mortality versus ≤ 30 mmHg. An eRVSP > 30 mmHg predicts increased all-cause mortality in type 2 diabetes. Where available, eRVSP could inform type 2 diabetes outcome models.

Background: Regional wall motion abnormalities (WMAs) after myocardial infarction are associated with adverse remodeling and increased mortality in the short to medium term. Their long-term prognostic impact is less well understood., Methods and Results: Via the National Echo Database of Australia (2000-2019), we identified normal wall motion versus WMA for each left ventricular wall among 492 338 individuals aged 61.9±17.9 years. The wall motion score index was also calculated. We then examined actual 1- and 5-year mortality, plus adjusted risk of long-term mortality according to WMA status. Overall, 39 346/255 697 men (15.4%) and 17 834/236 641 women (7.5%) had a WMA. The likelihood of a WMA was associated with increasing age and greater systolic/diastolic dysfunction. A defect in the inferior versus anterior wall was the most and least common WMA in men (8.0% and 2.5%) and women (3.3% and 1.1%), respectively. Any WMA increased 5-year mortality from 17.5% to 29.7% in men and from 14.9% to 30.8% in women. Known myocardial infarction (hazard ratio [HR], 0.86 [95% CI, 0.80-0.93]) or revascularization (HR, 0.87 [95% CI, 0.82-0.92]) was independently associated with a better prognosis, whereas men (1.22-fold increase) and those with greater systolic/diastolic dysfunction had a worse prognosis. Among those with any WMA, apical (HR, 1.08 [95% CI, 1.02-1.13]) or inferior (HR, 1.09 [95% CI, 1.04-1.15]) akinesis, dyskinesis or aneurysm, or a wall motion score index >3.0 conveyed the worst prognosis., Conclusions: In a large real-world clinical cohort, twice as many men as women have a WMA, with inferior WMA the most common. Any WMA confers a poor prognosis, especially inferoapical akinesis/dyskinesis/aneurysm.

Body surface area (BSA) is the most commonly used metric for body size indexation of echocardiographic measures, but its use in patients who are underweight or obese is questioned (body mass index (BMI) < 18.5 kg/m 2 or ≥ 30 kg/m 2 , respectively). We aim to use survival analysis to identify an optimal body size indexation metric for echocardiographic measures that would be a better predictor of survival than BSA regardless of BMI. Adult patients with no prior valve replacement were selected from the National Echocardiography Database Australia. Survival analysis was performed for echocardiographic measures both unindexed and indexed to different body size metrics, with 5-year cardiovascular mortality as the primary endpoint. Indexation of echocardiographic measures (left ventricular end-diastolic diameter [n = 230,109] and mass [n = 224,244], left atrial volume [n = 150,540], aortic sinus diameter [n = 90,805], right atrial area [n = 59,516]) by BSA had better prognostic performance vs unindexed measures (underweight: C-statistic 0.655 vs 0.647; normal weight/overweight: average C-statistic 0.666 vs 0.625; obese: C-statistic 0.627 vs 0.613). Indexation by other body size metrics (lean body mass, height, and/or weight raised to different powers) did not improve prognostic performance versus BSA by a clinically relevant magnitude (average C-statistic increase ≤ 0.02), with smaller differences in other BMI subgroups. Indexing measures of cardiac and aortic size by BSA improves prognostic performance regardless of BMI, and no other body size metric has a clinically meaningful better performance., (© 2023. The Author(s).)

Decreased hydraulic forces during diastole contribute to reduced left ventricular (LV) filling and heart failure with preserved ejection fraction. However, their association with diastolic function and patient outcomes are unknown. The aim of this retrospective, cross-sectional study was to determine the mechanistic association between diastolic hydraulic forces, estimated by echocardiography as the atrioventricular area difference (AVAD), and both diastolic function and survival. Patients (n = 5176, median [interquartile range] 5.5 [5.0-6.1] years follow-up, 1213 events) were selected from the National Echo Database Australia (NEDA) based on the presence of relevant transthoracic echocardiographic measures, LV ejection fraction (LVEF) ≥ 50%, heart rate 50-100 beats/minute, the absence of moderate or severe valvular disease, and no prior prosthetic valve surgery. NEDA contains echocardiographic and linked national death index mortality outcome data from 1985 to 2019. AVAD was calculated as the cross-sectional area difference between the LV and left atrium. LV diastolic dysfunction was graded according to 2016 guidelines. AVAD was weakly associated with E/e', left atrial volume index, and LVEF (multivariable global R 2  = 0.15, p < 0.001), and not associated with e' and peak tricuspid regurgitation velocity. Decreased AVAD was independently associated with poorer survival, and demonstrated improved model discrimination after adjustment for diastolic function grading (C-statistic [95% confidence interval] 0.644 [0.629-0.660] vs 0.606 [0.592-0.621], p < 0.001) and E/e' (0.649 [0.635-0.664] vs 0.634 [0.618-0.649], p < 0.001), respectively. Therefore, decreased hydraulic forces, estimated by AVAD, are weakly associated with diastolic dysfunction and demonstrate an incremental prognostic association with survival beyond conventional measures used to grade diastolic dysfunction., (© 2023. Springer Nature Limited.)

Approximately 50% of patients with severe aortic stenosis (AS) in clinical practice present with 'low-gradient' haemodynamics. Stroke Volume Index (SVI) is a measure of left ventricular output, with 'normal-flow' considered as  > 35 ml/m 2 . The association between SVI and prognosis in severe low-gradient AS (LGAS) in currently not well-understood. We analysed the National Echo Database of Australia (NEDA) and identified 109,990 patients with sufficiently comprehensive echocardiographic data, linked to survival information. We identified 1,699 with severe LGAS and preserved ejection fraction (EF) (≥ 50%) and 774 with severe LGAS and reduced EF. One- and three-year survival in each subgroup were assessed (follow-up of 74 ± 43 months), according to SVI thresholds. In patients with preserved EF the mortality "threshold" was at SVI < 30 ml/m 2 ; 1- and 3-year survival was worse for those with SVI < 30 ml/m 2 relative to those with SVI > 35 ml/m 2 (HR 1.80, 95% CI 1.32-2.47 and HR 1.38, 95% CI 1.12-1.70), while survival was similar between those with SVI 30-35 ml/m 2 and SVI > 35 ml/m 2 . In patients with reduced EF the mortality "threshold" was 35 ml/m 2 ; 1- and 3-year survival was worse for both those with SVI < 30 ml/m 2 and 30-35 ml/m 2 relative to those with SVI > 35 ml/m 2 (HR 1.98, 95% CI 1.27-3.09 and HR 1.41, 95% CI 1.05-1.93 for SVI < 30 ml/m 2 and HR 2.02, 95% CI 1.23-3.31 and HR 1.56, 95% CI 1.10-2.21 for SVI 30-35 ml/m 2 ). The SVI prognostic threshold for medium-term mortality in severe LGAS patients is different for those with preserved LVEF (< 30 ml/m 2 ) compared to those with reduced LVEF (< 35 ml/m 2 )., (© 2023. The Author(s).)

Objective: The significance of pulmonary hypertension (PHT) complicating aortic stenosis (AS) is poorly characterised. In a large cohort of adults with at least moderate AS, we aimed to describe the prevalence and prognostic importance of PHT in such patients., Methods: In this retrospective study, we analysed the National Echocardiography Database of Australia (data from 2000 to 2019). Adults with an estimated right ventricular systolic pressure (eRVSP), left ventricular ejection fraction (LVEF) >50% and with moderate or greater AS were included (n=14 980). These subjects were then categorised according to their eRVSP. The relationship between PHT severity and mortality outcomes were evaluated (median follow-up of 2.6 years, IQR 1.0-4.6 years)., Results: Subjects were aged 77±13 years and 57.4% were female. Overall, 2049 (13.7%), 5085 (33.9%), 4380 (29.3%), 1956 (13.1%) and 1510 (10.1%) patients had no (eRVSP<30.00 mm Hg), borderline (30.00-39.99 mm Hg), mild (40.00-49.99 mm Hg), moderate (50.00-59.99 mm Hg) and severe PHT (>60.00 mm Hg), respectively. An echocardiographic phenotype was evident with worsening PHT, showing rising E:e' ratio and right and left atrial sizes(p<0.0001, for all). Adjusted analyses showed that the risk of long-term mortality progressively rose as eRVSP level increased (HR 1.14-2.94, borderline to severe PHT, p<0.0001 for all). A mortality threshold was identified in the 4th decile of eRVSP categories (35.01-38.00 mm Hg; HR 1.19, 95% CI 1.04 to 1.35), with risk progressively increasing through to the 10th decile (HR 2.86, 95% CI 2.54 to 3.21)., Conclusions: In this large cohort study, we find that PHT is common in ≥moderate AS and mortality increases as PHT becomes more severe. A threshold for higher mortality lies within the range of 'borderline-mild' PHT., Trial Registration Number: ACTRN12617001387314., Competing Interests: Competing interests: SS, DP and GS have previously received consultancy/speaking fees from Edwards LifeSciences. DP and GS have received consultancy fees from Medtronic, Edwards LifeSciences, Abbott Laboratories and ECHO IQ Pty Ltd. DSC is on the Editorial Board of BMJ HEART., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Aortic regurgitation (AR) can lead to pulmonary hypertension (PHT). There is a paucity of data on the prognostic importance of PHT in these patients. We therefore aimed to describe the prevalence and prognostic importance of PHT in such patients., Methods: In this retrospective study, we analysed the National Echocardiography Database of Australia (data from 2000 to 2019). Adults with an estimated right ventricular systolic pressure (eRVSP), left ventricular ejection fraction (LVEF) >50% and with moderate or greater AR were included (n=8392). These subjects were then categorised according to their eRVSP. The relationship between PHT severity and mortality outcomes were evaluated (median follow-up of 3.1 years, IQR 1.5-5.7 years)., Results: Subjects were aged 74±14 years and 58.4% (4901) were female. Overall, 1417 (16.9%) had no PHT, and 3253 (38.8%), 2249 (26.9%), 893 (10.6%) and 580 (6.9%) patients had borderline, mild, moderate and severe PHT, respectively. Mean eRVSP was slightly higher in females than males (41±13 vs 39±12 mm Hg, p<0.0001) and increased with age in both sexes. After adjustment for age and sex, the risk of long-term mortality increased as eRVSP increased (adjusted HR (aHR) 1.20, 95% CI 1.06 to 1.36 in borderline PHT, to aHR 3.32, 95% CI 2.85 to 3.86 in severe PHT, p<0.0001). There was a mortality threshold seen from mild PHT onwards (eRVSP 41.36-44.15 mm Hg; aHR 1.41, 95%CI 1.17 to 1.68)., Conclusions: In this large cohort study, we characterise the relationship between AR and PHT in adults. In patients with ≥moderate AR, PHT is associated with a progressive risk of mortality, even at mildly elevated levels., Competing Interests: Competing interests: SS, DP and GS have previously received consultancy/speaking fees from Edwards LifeSciences. DP and GS have received consultancy fees from Medtronic, Edwards Lifesciences, Abbott Laboratories and ECHO IQ Pty Ltd. DSC is on the Editorial Board of BMJ Heart., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives To provide insights into the obstacles which pose challenges to the set-up of any National Registry in Australia. Methods An analysis of our experience in executing a Multi-Institutional Agreement (MIA) and obtaining ethics and governance approvals, post-award of a large Medical Research Futures Fund grant in June 2020. Results From July 2020, our timeline to an executed MIA was 283 days, despite full-time staff working towards this goal. Subsequently, after lead site ethics approval, time to site governance approvals ranged from 9 to 291 days. A total of 214 emails were sent during the MIA development and signing. There were 11-71 emails sent to individual governance offices and the number of requested points of additional information ranged from 0 to 31 queries. Conclusions There were considerable time delays in executing the initial (pre-research) stages of a National Federal Government funded Registry project which required substantial time and resources. We report a wide variation in requirements between different states and institutions. We propose several strategies which could be implemented to facilitate a more streamlined approach to research ethics and governance. This centralised approach would allow for better use of funding and facilitate better progress in medical research.

Objective: We developed an artificial intelligence decision support algorithm (AI-DSA) that uses routine echocardiographic measurements to identify severe aortic stenosis (AS) phenotypes associated with high mortality., Methods: 631 824 individuals with 1.08 million echocardiograms were randomly spilt into two groups. Data from 442 276 individuals (70%) entered a Mixture Density Network (MDN) model to train an AI-DSA to predict an aortic valve area <1 cm 2 , excluding all left ventricular outflow tract velocity or dimension measurements and then using the remainder of echocardiographic measurement data. The optimal probability threshold for severe AS detection was identified at the f1 score probability of 0.235. An automated feature also ensured detection of guideline-defined severe AS. The AI-DSA's performance was independently evaluated in 184 301 (30%) individuals., Results: The area under receiver operating characteristic curve for the AI-DSA to detect severe AS was 0.986 (95% CI 0.985 to 0.987) with 4622/88 199 (5.2%) individuals (79.0±11.9 years, 52.4% women) categorised as 'high-probability' severe AS. Of these, 3566 (77.2%) met guideline-defined severe AS. Compared with the AI-derived low-probability AS group (19.2% mortality), the age-adjusted and sex-adjusted OR for actual 5-year mortality was 2.41 (95% CI 2.13 to 2.73) in the high probability AS group (67.9% mortality)-5-year mortality being slightly higher in those with guideline-defined severe AS (69.1% vs 64.4%; age-adjusted and sex-adjusted OR 1.26 (95% CI 1.04 to 1.53), p=0.021)., Conclusions: An AI-DSA can identify the echocardiographic measurement characteristics of AS associated with poor survival (with not all cases guideline defined). Deployment of this tool in routine clinical practice could improve expedited identification of severe AS cases and more timely referral for therapy., Competing Interests: Competing interests: Profs Stewart, Playford and Strange have previously received consultancy/speaking fees from Edwards Lifesciences. Profs Playford and Strange have received consultancy fees from Medtronic, Edwards Lifesciences, Abbott Laboratories and ECHO IQ Pty Ltd. Dr Watts is employed by ECHO IQ Pty Ltd., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Symptoms associated with severe aortic stenosis (AS) are used to guide management., Objectives: The purpose of this study was to examine the pattern of symptoms, comorbidities, and cardiac damage in moderate and severe AS., Methods: A total of 846,198 echocardiographic investigations from 330,940 individuals aged >18 years were selected for the most recent echocardiogram, moderate or severe AS (mean gradient 20.0-39.9 mm Hg, aortic valve peak gradient 3.0-3.9 m/s and aortic valve area >1.0 cm 2 ; or ≥ 40.0 mm Hg, ≥4.0 m/s or ≤1.0 cm 2 , respectively), and a cardiologist consultation. Natural Language Processing was applied to letters to extract comorbidities, dyspnea, chest pain, and syncope. Patients with prior aortic valve replacement were excluded., Results: 2,213 patients (0.7% overall, 32.8% females) had moderate and 3,416 (1.0%, 47.3% females) had severe AS. Comorbidities were common, including hypertension, (56.6% moderate AS, 53.1% severe AS, P  = 0.01), coronary disease (46.0% and 46.8%, respectively, P  = 0.58) and atrial fibrillation (29.6% and 34.8%, respectively, P  < 0.001). Symptoms were also common in both moderate (n = 915, 41.3%) and severe (n = 1,630, 47.7%) AS ( P  < 0.001). Comorbidities were more likely in symptomatic vs asymptomatic patients ( P  < 0.001). Dyspnea was more likely in severe AS, whereas angina and syncope were similar in moderate vs severe AS. In multivariable analysis, only dyspnea was associated with severe (vs moderate) AS (OR: 1.73, 95% CI: 1.41-2.13, P  < 0.001). In both adjusted and unadjusted models, the degree of cardiac damage did not relate to presence of any symptoms but was associated with AS severity., Conclusions: Dyspnea is common in both moderate and severe AS, is associated with comorbidities and is not related to the degree of cardiac damage. Symptom-guided management decisions in AS may need revision., Competing Interests: This study was supported by 10.13039/100006520Edwards Lifesciences Corporation. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Objective: Pulmonary hypertension (PHT) commonly coexists with significant mitral regurgitation (MR), but its prevalence and prognostic importance have not been well characterised. In a large cohort of adults with moderate or greater MR, we aimed to describe the prevalence and severity of PHT and assess its influence on outcomes., Methods: In this retrospective study, we analysed the National Echocardiography Database of Australia (data from 2000 to 2019). Adults with an estimated right ventricular systolic pressure (eRVSP), left ventricular ejection fraction >50% and with moderate or greater MR were included (n=9683). These subjects were then categorised according to their eRVSP. The relationship between PHT severity and mortality outcomes was evaluated (median follow-up of 3.2 years, IQR 1.3-6.2 years)., Results: Subjects were aged 76±12 years, and 62.6% (6038) were women. Overall, 959 (9.9%) had no PHT, and 2952 (30.5%), 3167 (32.7%), 1588 (16.4%) and 1017 (10.5%) patients had borderline, mild, moderate and severe PHT, respectively. A 'typical left heart disease' phenotype was identified with worsening PHT, showing rising E:e', right and left atrial sizes increasing progressively, from no PHT to severe PHT (p<0.0001, for all). With increasing PHT severity, 1- and 5-year actuarial mortality increased from 8.5% and 33.0% to 39.7% and 79.8%, respectively (p<0.0001). Similarly, adjusted survival analysis showed the risk of long-term mortality progressively increased with higher eRVSP levels (adjusted HR 1.20-2.86, borderline to severe PHT, p<0.0001 for all). A mortality inflection was apparent at an eRVSP level >34.00 mm Hg (HR 1.27, CI 1.00-1.36)., Conclusions: In this large study, we report on the importance of PHT in patients with MR. Mortality increases as PHT becomes more severe from an eRVSP of 34 mm Hg onwards., Competing Interests: Competing interests: SS, DP and GS have previously received consultancy/speaking fees from Edwards Lifesciences. DP and GS have received consultancy fees from Medtronic, Edwards Lifesciences, Abbott Laboratories and ECHO IQ Pty Ltd., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pulmonary arterial hypertension (PAH) has a progressive, unremitting clinical course. Vasoreactivity testing (VdT) during right heart catheterisation (RHC) identifies a subgroup with excellent long-term response to calcium channel blockade (CCB). Reporting on these patients is limited. Established in 2011, the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) registry offers the opportunity to assess the frequency of VdT during RHC, treatment and follow up of PAH patients., Methods: Registry data from 3,972 PAH patients with index RHC revealed 1,194 VdT appropriate patients. Data was analysed in three groups: 1) VdT+CCB+: VdT positive, CCB treated; 2) VdT+CCB-: VdT positive, no CCB prescribed, 3) VdT-/noVdT: VdT negative, or VdT not tested. Data was reviewed for adherence to guidelines, clinical response (World Health Organization functional class [WHO FC], 6-minute-walk-distance [6MWD], RHC), and outcomes (survival or lung transplantation)., Results: Patients included had idiopathic (IPAH=1,087), heritable (HPAH=67) and drug or toxin-induced PAH (DPAH=40). A VdT was performed in 22% (268/1,194), with incomplete data in 26% (70/268); 28% (55/198) were VdT+. Analysis group allocation was: VdT+CCB+ (33/55), VdT+CCB- (22/55), VdT- (143)/noVdT (996). From patients with 1-year data VdT+CCB+ and VdT-/noVdT patients improved WHO FC, 6MWD and cardiac index (CI); VdT+CCB- data remained similar. Within the VdT+CCB+ group, 30% (10/33) were long-term CCB responders with a 100% 5-year survival; non-responders had a 61% survival at 5.4 years. Long-term responders were younger at diagnosis (40 yrs vs 54 yrs)., Conclusion: Use of VdT testing and documentation is poor in this contemporary patient cohort. Nonetheless, survival in VdT+CCB+ patients from the PHSANZ registry is excellent, supporting guidelines promoting VdT testing. Strategies to promote the use of VdT are warranted., (Copyright © 2022 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Aims: Atrial functional mitral regurgitation (AFMR) is characterised by left atrial and consequent mitral annular dilatation causing mitral regurgitation. AFMR is likely to become more common with population ageing, alongside increases in atrial fibrillation and heart failure with preserved ejection fraction; conditions causing atrial dilatation. Here, we aim to define the prevalence and characterise the patient and survival characteristics of AFMR in the National Echocardiographic Database of Australia (NEDA)., Methods and Results: 14 004 adults with moderate or severe FMR were identified from NEDA. AFMR or ventricular FMR (VFMR) was classified by LA size, LV size and LVEF. AFMR was found in 40% (n=5562) and VFMR in 60% (n=8442). Compared with VFMR, the AFMR subgroup were significantly older (mean age 78±11 years), with a higher proportion of females and of AF. Participants were followed up for a median of 65 months (IQR 36-116 months). After adjustment for age, sex, AF, and pulmonary hypertension, the prognosis for VFMR was significantly worse than for AFMR (HR 1.57, 95% CI 1.47 to 1.68 for all-cause and 1.73, 95% CI 1.60 to 1.88, p<0.001 for both). After further adjustment for LVEF, mortality rates were similar in VFMR and AFMR patients (HR 0.93, p=NS), though advancing age and pulmonary hypertension remained independently associated with prognosis., Conclusions: AFMR is a common cause of significant functional MR that predominantly affects elderly female patients with AF. Advancing age and pulmonary hypertension independently associated with survival in FMR. Prognosis was better in AFMR compared with VFMR; however, this difference was accounted for by LV systolic impairment and not by MR severity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Pulmonary hypertension (PH) is a common and debilitating medical condition with high mortality. PH research has traditionally focused on pulmonary arterial hypertension and its management in expert PH centres. Other forms of PH such as PH associated with cardiac or respiratory disease are more common, less well-understood and associated with higher mortality. Epidemiology of PH in disadvantaged, remote and rural regions, remains largely undocumented. In this review, we discuss the unique challenges in identifying PH in rural and disadvantaged populations using the Top End region of the Northern Territory of Australia as an example. We propose a simple diagnostic approach, ideally suited to regions where resource allocation is scarce, using clinical skills, echocardiography, and an escalation algorithm. The brief history, epidemiology and current literature on PH are summarised to inform the busy clinicians. We highlight two case examples from the Top End to illustrate the challenges and potential solutions., (© 2022 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Background: Aortic stenosis (AS) is the most common valvular heart disease in high-income countries. Adjusted for clinical confounders, the risk associated with increasing AS severity across the spectrum of AS severity remains uncertain., Methods: The authors conducted an international, multicenter, parallel-cohort study of 217,599 Australian (mean age, 76.0 ± 7.3 years; 49.3% women) and 30,865 US (mean age, 77.4 ± 7.3 years; 52.2% women) patients aged ≥65 years who underwent echocardiography. Patients with previous aortic valve replacement were excluded. The risk of increasing AS severity, quantified by peak aortic velocity (Vmax), was assessed through linkage to 97,576 and 14,481 all-cause deaths in Australia and the United States, respectively., Results: The distribution of AS severity (mean Vmax, 1.7 ± 0.7 m/sec) was similar in both cohorts. Compared with those with Vmax of 1.0 to 1.49 m/sec, those with Vmax of 2.50 to 2.99 m/sec (US cohort) or Vmax of 3.0 to 3.49 m/sec (Australian cohort) had a 1.5-fold increase in mortality risk within 10 years, adjusting for age, sex, presence of left heart disease, and left ventricular ejection fraction. Overall, the adjusted risk for mortality plateaued (1.75- to 2.25-fold increased risk) above a Vmax of 3.5 m/sec. This pattern of mortality persisted despite adjustment for a comprehensive list of comorbidities and treatments within the US cohort., Conclusions: Within large, parallel patient cohorts managed in different health systems, similar patterns of mortality linked to increasingly severe AS were observed. These findings support ongoing clinical trials of aortic valve replacement in patients with nonsevere AS and suggest the need to develop and apply more proactive surveillance strategies in this high-risk population., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Aims: We sought to analyse the distribution of TR severity and survival in a large cohort of adults with CIED leads., Methods: The distribution of TR severity was analysed in 18,797 adults (mean age 73.8+/-13.9, 63.3% men) with CIED leads undergoing echocardiography across 25 centres. Survival status and cause of death were linked and the relationship between TR severity and mortality during 2.6 (interquartile range 1.1-4.6) years follow-up examined. Data from 439,558 individuals (mean age 62.1 ±17.8 years, 51.5% men) without a CIED were subsequently incorporated in a pooled cohort analysis., Results: Overall, 8,824/18,797 individuals (47%) with a CIED had no/trivial TR; 5,490 (29.2%) mild TR; 3,068 (16.3%) moderate TR; and 1,415 (7.5%) severe TR. Moderate or greater TR was independently associated with age, female sex, atrial fibrillation and significant left heart disease (p<0.001 for all). 8,868 individuals (47.2%) died from any cause (43.2% from cardiovascular causes). Individuals with moderate or severe TR had a 1.6 to 2.5-fold increased risk of all-cause mortality in adjusted models, compared to those with no TR (p<0.001 for both). In the pooled cohort analysis, CIEDs were associated with a near 2-fold (95% CI 1.81-1.99; p<0.001) increased probability of moderate or greater TR, on adjusted basis. However, the mortality associated with moderate or greater TR did not differ significantly with respect to the presence or absence of a device lead., Conclusions: Moderate or greater TR is more prevalent in those with CIED's, even in adjusted models, and was independently associated with incremental risks for all-cause and cardiovascular mortality., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The specific prevalence and outcome of pulmonary hypertension after mitral valve replacement (MVR) is not well documented. The aim of the study was to determine the prevalence and prognostic impact of pulmonary hypertension after MVR. In addition, we sought to determine the threshold of mortality risk according to echocardiography derived pulmonary pressures and those echocardiographic characteristics that are associated with increased mortality. Using the National Echocardiography Database of Australia, patients who had undergone MVR were identified with estimated right ventricular systolic pressure (eRVSP) assessed and linked to patient mortality during mean follow up of 1917 days. Classification and regression tree analysis was used to identify the most powerful predictors of mortality. A total of 10,994 patients who had undergone echocardiography following MVR (mean age 65.2 ± 16, 44.8% women) were studied (mean follow-up 1917 days). The prevalence of PH (defined as eRSVP ≥40 mmHg) was 64.1% (7042/10,994). Severe PH (eRVSP ≥60 mmHg) was seen in 42.3% (4671/10,994). Mortality in individuals with PH was greater than amongst individuals without PH (41.1% vs. 26.3%). Age, tricuspid regurgitation and left ventricular dysfunction were also associated with mortality. There is a high prevalence of PH after MVR which confers an adverse prognosis. Improved therapeutic approaches to mitral valve disease and the subsequent development of PH are essential., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Background: The prevalence and prognostic impact of tricuspid regurgitation (TR) remain incompletely characterized., Methods: The distribution of TR severity was analyzed in 439,558 adults (mean age, 62.1 ± 17.8 years; 51.5% men) being investigated for heart disease, from 2000 to 2019, by 25 centers contributing to the National Echocardiography Database of Australia. Survival status and cause of death were ascertained in all adults from the National Death Index of Australia. The relationship between TR severity and mortality was examined., Results: Of those studied, 311,604 (70.9%) had no/trivial TR; 94,172 (21.4%), mild TR; 26,056 (5.9%), moderate TR; and 7,726 (1.8%), severe TR. During a median 4.1 years (interquartile range, 2.2-7.0 years) of follow-up, 109,004 died (49% from cardiovascular causes). Moderate or greater TR was associated with older age and female sex (P < .001). Individuals with moderate and severe TR had a 2.0- to 3.2-fold increased risk of all-cause long-term mortality after adjustment for age and sex compared with those with no/trivial TR (P < .001 for both comparisons). Even those with mild TR had a significantly increased risk for mortality (hazard ratio [HR] = 1.29; 95% CI, 1.27-1.31). In fully adjusted models, including for RV systolic pressure, atrial fibrillation, and significant left heart disease, there remained a 1.24- to 2.65-fold increased risk of mortality with mild (HR = 1.24; 95% CI, 1.23-1.26), moderate (HR = 1.72; 95% CI, 1.68-1.75), or severe TR (HR = 2.65; 95% CI, 2.57-2.73), compared with those with no/trivial TR (P < .001 for all)., Conclusions: Tricuspid regurgitation is a common condition in adults referred for echocardiography. Moreover, even in the presence of other cardiac disease, increasing grades of TR are independently associated with increasing risks of cardiovascular and all-cause mortality. Furthermore, we show that even mild TR is independently associated with a significant increase in mortality., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: While large scientific and medical evidence has demonstrated the increased risk of death and cardiovascular mortality in patients with severe AS, the independent contribution of moderate AS to an increased risk of death remains uncertain., Methods and Findings: We conducted a multicenter study including a cohort of 30,865 US patients and another cohort of 217,599 Australian patients with equivalent echocardiographic and aortic valve profiling over the same period (2003-2017). During a median 5.2 years (US) and 4.4 years (Australian) follow-up, the risk of death (hazard ratio) of patients with moderate AS as compared to those without AS was 1.66 (95%CI 1.52-1.80) and 1.37 (95%CI 1.34-1.41) in the US and Australian cohorts, even after adjusting this analysis for age and sex. This increased risk of death and cardiovascular mortality (odds ratio) in patients with moderate AS was consistent also across subgroups of left ventricular ejection fraction (LVEF) (subgroups of LVEF < 40%, 40-49%, 50-59%, and ≥ 60%: OR of moderate AS for CV mortality 2.0 [95%CI 1.4-2.7], 1.7 [95%CI 1.2-2.4], 1.5 [95%CI 1.1-1.9], and 1.4 [95%CI 1.2-1.6], respectively)., Conclusions: The findings of this study suggest that patients with moderate AS have a potential increased risk of death and cardiovascular mortality, regardless of age, sex, and LVEF. Hence, these data suggest the need to develop specific strategies to detect and treat individuals with moderate AS., Competing Interests: Dr. Strom additionally reports grant funding from the NIH/NHLBI, Ultromics, HeartSciences, and Anumana, consulting for Bracco Diagnostics, and speaker honoraria from Northwest Imaging Forums. Dr. Strange reports consulting for Edwards Lifesciences. Changyu Shen is currently an employee of Biogen. All other authors report no relevant disclosures.

Aims: The interplay between aortic stenosis (AS), cardiovascular events, and mortality is poorly understood. In addition, how echocardiographic indices compare for predicting outcomes remains unexplored for the full range of AS severity., Methods and Results: We prospectively calculated peak jet velocity (Vmax) and aortic valve area (AVA) in 5994 adult subjects with and without AS. We linked ultrasound data to 5-year mortality and clinical events obtained from electronic medical records. Proportional-hazard and negative binomial regression models were adjusted for relevant covariables such as age, sex, comorbidities, stroke-volume, LV ejection fraction, left valve regurgitation, aortic valve sclerosis or calcification, and valve replacement. We observed a strong linear relationship between Vmax and all-cause mortality (hazard ratio: 1.26, 95% confidence interval: 1.19-1.33 per 100 cm/s), cardiovascular events, as well as incidental and recurrent heart failure (HF). Adjusted risks were highly significant even at Vmax values in the range of 150-200 cm/s, risk curves separating very early after the index exam. Vmax was not associated with coronary, arrhythmic, cerebrovascular, or non-cardiovascular events. Although risks were confirmed when AVA was entered in place of Vmax, the risks estimated for categories based on the two indices were mismatched, even in patients with normal flow. An external cohort comprising 112 690 patients confirmed augmented risks of all-cause and cardiovascular mortality starting at values of Vmax and AVA in the range of mild AS., Conclusions: Aortic stenosis is strongly associated to all-cause mortality, cardiovascular mortality, and cardiac events, specifically HF. Risks increase in parallel to the degree of outflow obstruction but are apparent very early in patients with mild disease. Criteria for grading AS based on Vmax and AVA are mismatched in terms of outcomes., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)

Non-rheumatic aortic stenosis (AS) is among the most common valvular diseases in the developed world. Current guidelines support aortic valve replacement (AVR) for severe symptomatic AS, which carries high morbidity and mortality when left untreated. In contrast, moderate AS has historically been thought to be a benign diagnosis for which the potential benefits of AVR are outweighed by the procedural risks. However, emerging data demonstrating the substantial mortality risk in untreated moderate AS and substantial improvements in periprocedural and perioperative mortality with AVR have challenged the traditional risk/benefit paradigm. As such, an appraisal of the contemporary data on morbidity and mortality associated with moderate AS and appropriate timing of valvular intervention in AS is warranted. In this review, we discuss the current understanding of moderate AS, including the epidemiology, current surveillance and management guidelines, clinical outcomes, and future studies., Competing Interests: Competing interests: JBS reports additional grant support from Edwards Lifesciences, Ultromics, HeartSciences and Anumana, consulting for Bracco Diagnostics, and speaker fees from Northwest Imaging Forums, unrelated to the submitted work. GS has served on the Scientific Advisory Board for Edwards Lifesciences Australia., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objective: Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious condition occurring in 2%-4% of patients after acute pulmonary embolism. Pulmonary endarterectomy (PEA) is a potential cure for technically operable disease. The epidemiology and long-term outcomes of CTEPH have not been previously described in Australia and New Zealand., Methods: Data were extracted from the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) registry for patients diagnosed with CTEPH between January 2004 and March 2020. Baseline characteristics, treatment strategies, outcome data and long-term survival are reported., Results: A total of 386 patients were included with 146 (37.8%) undergoing PEA and 240 (62.2%) in the non-PEA group. PEA patients were younger (55 ± 16 vs. 62 ± 16 years, p < 0.001) with higher baseline 6-min walk distance (6MWD; 405 ± 122 vs. 323 ± 146 m, p = 0.021), whilst both groups had similar baseline pulmonary haemodynamics. Pulmonary hypertension-specific therapy was used in 54% of patients post-PEA and 88% in the non-PEA group. The 1-, 3- and 5-year survival rates were 93%, 87% and 84% for the PEA group compared to 86%, 73% and 62%, respectively, for the non-PEA group (p < 0.001). Multivariate survival analysis showed baseline 6MWD was an independent predictor of survival in both operated and medically managed patients., Conclusion: In this first multicentre report of CTEPH in Australia and New Zealand, long-term survival is comparable to that in other contemporary CTEPH registries. However, PEA was only performed in a minority of CTEPH patients (37.8%) and significantly less than overseas reports. Greater awareness of PEA and improved patient access to experienced CTEPH centres are important priorities., (© 2021 Asian Pacific Society of Respirology.)

Background The prevalence and outcomes of the different subtypes of severe low-gradient aortic stenosis (AS) in routine clinical cardiology practice have not been well characterized. Methods and Results Data were derived from the National Echocardiography Database of Australia. Of 192 060 adults (aged 62.8±17.8 [mean±SD] years) with native aortic valve profiling between 2000 and 2019, 12 013 (6.3%) had severe AS. Of these, 5601 patients (47%) had high-gradient and 6412 patients (53%) had low-gradient severe AS. The stroke volume index was documented in 2741 (42.7%) patients with low gradient; 1750 patients (64%) with low flow, low gradient (LFLG); and 991 patients with normal flow, low gradient. Of the patients with LFLG, 1570 (89.7%) had left ventricular ejection fraction recorded; 959 (61%) had paradoxical LFLG (preserved left ventricular ejection fraction), and 611 (39%) had classical LFLG (reduced left ventricular ejection fraction). All-cause and cardiovascular-related mortality were assessed in the 8162 patients with classifiable severe AS subtype during a mean±SD follow-up of 88±45 months. Actual 1-year and 5-year all-cause mortality rates varied across these groups and were 15.8% and 49.2% among patients with high-gradient severe AS, 11.6% and 53.6% in patients with normal-flow, low-gradient severe AS, 16.9% and 58.8% in patients with paradoxical LFLG severe AS, and 30.5% and 72.9% in patients with classical LFLG severe AS. Compared with patients with high-gradient severe AS, the 5-year age-adjusted and sex-adjusted mortality risk hazard ratios were 0.94 (95% CI, 0.85-1.03) in patients with normal-flow, low-gradient severe AS; 1.01 (95% CI, 0.92-1.12) in patients with paradoxical LFLG severe AS; and 1.65 (95% CI, 1.48-1.84) in patients with classical LFLG severe AS. Conclusions Approximately half of those patients with echocardiographic features of severe AS in routine clinical practice have low-gradient hemodynamics, which is associated with long-term mortality comparable with or worse than high-gradient severe AS. The poorest survival was associated with classical LFLG severe AS.

Background: There are currently no established prognostic models for "low-gradient" severe aortic stenosis (AS), including those with low-flow, low-gradient (LFLG) or normal-flow, low-gradient (NFLG) severe AS. The "cardiac damage staging classification" has been validated as a clinically useful prognostic tool for high-gradient severe AS but not yet for these other common subtypes of severe AS, LFLG and NFLG., Methods: The authors analyzed data from the National Echo Database of Australia, a large national, multicenter registry with individual data linkage to mortality. Of 192,060 adults (mean age, 62.8 ± 17.8 years) with comprehensive ultrasound profiling of the native aortic valve studied between 2000 and 2019, 12,013 (6.3%) had severe AS. On the basis of standard echocardiographic parameters, 5,601 patients with high-gradient, 611 with classical and 959 with paradoxical LFLG, and 911 with NFLG severe AS were identified. Mean follow-up was 88 ± 45 months. All-cause and cardiovascular-related mortality were assessed for each group on an adjusted basis (age and sex) and analyzed by cardiac damage stage., Results: Patients with LFLG AS had greater associated cardiac damage at diagnosis (stages 3 and 4 in 34% of those with classical LFLG, 22.5% of those with paradoxical LFLG, 15.5% of those with NFLG, and 14% of those with high-gradient AS; P < .001). For all four major subtypes of severe AS, there was a progressive increase in 1- and 5-year mortality with increasing cardiac damage score. For example, for paradoxical LFLG severe AS, compared with stage 0 patients, adjusted 1-year all-cause mortality was 22% higher in stage 1 patients, 55% higher in stage 2 patients (P = .095), and 155% higher in stage 3 and 4 patients (P < .001). Among patients with classical LFLG severe AS, compared with stage 1 patients, adjusted 1-year all-cause mortality was 55% higher in stage 2 patients (P = .018) and 100% higher in stage 3 and 4 patients (P < .001)., Conclusions: Regardless of severe AS subtype, increasing severity denoted by the cardiac damage staging classification is strongly associated with increasing mortality risk., (Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)