An Artificial Intelligence Algorithm for Detection of Severe Aortic Stenosis: A Clinical Cohort Study.

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 cm2 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 cm2 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 cm2 (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.

Mitral-specific cardiac damage score (m-CDS) predicts risk of death in functional mitral regurgitation: a study from the National Echo Database of Australia.

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.

Moderate Aortic Valve Stenosis Is Associated With Increased Mortality Rate and Lifetime Loss: Systematic Review and Meta-Analysis of Reconstructed Time-to-Event Data of 409 680 Patients.

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.

Association of Pulmonary Artery Pressures With Mortality in Adults With Reduced Left Ventricular Ejection Fraction.

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.

Clinical to Population Prevalence of Hypertrophic Cardiomyopathy Phenotype: Insights From the National Echo Database Australia.

BACKGROUND: There is a paucity of data describing the underlying prevalence of hypertrophic cardiomyopathy (HCM), a primary genetic disorder characterised by progressive left ventricular (LV) hypertrophy and sudden death, from both a clinical and a population perspective. METHODS: We screened the echocardiographic reports of 155,668 men and 147,880 women within the multicentre National Echo Database Australia (NEDA) (2001-2019). End-diastolic wall thickness ≥15 mm anywhere in the left ventricle was identified as a characteristic of an HCM phenotype according to current guideline recommendations. Applying a septal-to-posterior wall thickness ratio >1.3 and LV outflow tract obstruction ≥30 mmHg (when documented), we further identified asymmetric septal hypertrophy and obstructive HCM (oHCM), respectively. The observed pattern of phenotypical HCM within the overall NEDA cohort (>650,000 cases) was then extrapolated to the ∼539,000 (5.7% of adult population) and ∼474,000 (4.8%) Australian men and women, respectively, who were investigated with echocardiography in 2021 on an age-specific basis. RESULTS: Overall, 15,380 cases (mean age 71.1±14.6 years, 10,138 men [65.9%]) with the characteristic HCM phenotype within the NEDA cohort were identified. Of these 15,380 cases, 5,552 (36.1%) had asymmetric septal hypertrophy, and 2,276 of the 10,290 cases with LV outflow tract obstruction profiling data (22.1%) had obstructive HCM. A further 3,389 of 13,715 cases (24.7%) had evidence of LV systolic dysfunction (LV ejection fraction <55%). Within the entire NEDA cohort (including those without LV profiling), HCM was found in 10,138 of 342,161 men (2.96%; 95% confidence interval [CI] 2.91%-3.02%) and 5,242 of 308,539 women (1.70%; 95% CI 1.65%-1.75%). When extrapolated to the Australian population, we estimate that a minimum of 15,971 men and 8,057 women presented with echocardiographic features of phenotypical HCM in 2021. This translates into a minimum caseload/prevalence of ∼17 adult men (∼2.5 in those aged ≤50 years) and eight adult women (∼1 in those aged ≤50 years) per 10,000 population meeting phenotypical HCM criteria. CONCLUSIONS: Using contemporary Australian echocardiographic and population data, we estimate that a minimum of 15,971 (17.5 cases/10,000) men and 8,057 women (8.2 cases/10,000) had echocardiographic evidence of phenotypical HCM in 2021. These disease burden data are particularly relevant as new treatment options are emerging.

Echocardiographic estimation of pulmonary artery wedge pressure: invasive derivation, validation, and prognostic association beyond diastolic dysfunction grading.

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.

The burdensome logistics of data linkage in Australia - the example of a national registry for congenital heart disease.

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.

Real-world evidence to advance knowledge in pulmonary hypertension: Status, challenges, and opportunities. A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative's Real-world Evidence Working Group.

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.

The Relationship between Pulmonary Artery Pressure and Mortality in Type 2 Diabetes: A Fremantle Diabetes Study Phase II and National Echocardiographic Database of Australia Data Linkage Study.

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.

Pattern and Prognostic Impact of Regional Wall Motion Abnormalities in 255 697 Men and 236 641 Women Investigated with Echocardiography.

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.

Enhanced detection of severe aortic stenosis via artificial intelligence: a clinical cohort study.

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 cm2, 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.

The prognostic significance of stroke volume index in low gradient severe aortic stenosis: from the national echo database of Australia.

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/m2. 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/m2; 1- and 3-year survival was worse for those with SVI < 30 ml/m2 relative to those with SVI > 35 ml/m2 (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/m2 and SVI > 35 ml/m2. In patients with reduced EF the mortality "threshold" was 35 ml/m2; 1- and 3-year survival was worse for both those with SVI < 30 ml/m2 and 30-35 ml/m2 relative to those with SVI > 35 ml/m2 (HR 1.98, 95% CI 1.27-3.09 and HR 1.41, 95% CI 1.05-1.93 for SVI < 30 ml/m2 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/m2). The SVI prognostic threshold for medium-term mortality in severe LGAS patients is different for those with preserved LVEF (< 30 ml/m2) compared to those with reduced LVEF (< 35 ml/m2).

Prevalence of pulmonary hypertension in mitral regurgitation and its influence on outcomes.

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.

Obstacles in establishing a national disease registry in Australia: lessons from the development of the CHAANZ Congenital Heart Disease Registry.

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.

Prevalence of pulmonary hypertension in aortic stenosis and its influence on outcomes.

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.

Prevalence of pulmonary hypertension in aortic regurgitation and its influence on outcomes.

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.

Medical Therapy to Prevent or Slow Progression of Aortic Stenosis: Current Evidence and Future Directions.

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.

Atrial functional mitral regurgitation: prevalence, characteristics and outcomes from the National Echo Database of Australia.

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.