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.

Pulmonary hypertension in remote and disadvantaged population: overcoming unique challenges for improved outcomes.

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.

Acute Vasoreactivity Testing and Outcomes in Pulmonary Arterial Hypertension: A Call for Increased Testing.

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.

Chronic thromboembolic pulmonary hypertension in Australia and New Zealand: An analysis of the PHSANZ registry.

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.

Uncovering the treatable burden of severe aortic stenosis in Australia: current and future projections within an ageing population.

BACKGROUND: We aimed to address the paucity of information describing the treatable burden of disease associated with severe aortic stenosis (AS) within Australia's ageing population. METHODS: A contemporary model of the population prevalence of symptomatic, severe AS and treatment pathways in Europe and North America was applied to the 2019 Australian population aged ≥ 55 years (7 million people) on an age-specific basis. Applying Australian-specific data, these estimates were used to further calculate the total number of associated deaths and incident cases of severe AS per annum. RESULTS: Based on an overall point prevalence of 1.48 % among those aged ≥ 55 years, we estimate that a minimum of 97,000 Australians are living with severe AS. With a 2-fold increased risk of mortality without undergoing aortic valve replacement (AVR), more than half of these individuals (∼56,000) will die within 5-years. From a clinical management perspective, among those with concurrent symptoms (68.3 %, 66,500 [95 % CI 59,000-74,000] cases) more than half (58.4 %, 38,800 [95 % CI 35,700 - 42,000] cases) would be potentially considered for surgical AVR (SAVR) - comprising 2,400, 5,400 and 31,000 cases assessed as high-, medium- or low peri-operative mortality risk, respectively. A further 17,000/27,700 (41.6 % [95 % CI 11,600 - 22,600]) of such individuals would be potentially considered to a transthoracic AVR (TAVR). During the subsequent 5-year period (2020-2024), each year, we estimate an additional 9,300 Australians aged ≥ 60 years will subsequently develop severe AS (6,300 of whom will experience concurrent symptoms). Of these symptomatic cases, an estimated 3,700 and 1,600 cases/annum, will be potentially suitable for SAVR and TAVR, respectively. CONCLUSIONS: These data suggest there is likely to be a substantive burden of individuals living with severe AS in Australia. Many of these cases may not have been diagnosed and/or received appropriate treatment (based on the evidence-based application of SAVR and TAVR) to reduce their high-risk of subsequent mortality.

Top End Pulmonary Hypertension Study: Understanding Epidemiology, Therapeutic Gaps and Prognosis in Remote Australian Setting.

INTRODUCTION: The Top End of Australia has a high proportion of Indigenous people with a high burden of chronic cardiac and pulmonary diseases likely to contribute to pulmonary hypertension (PH). The epidemiology of PH has not been previously studied in this region. METHODS: Patients with PH were identified from the Northern Territory echocardiography database from January 2010 to December 2015 and followed to the end of 2019 or death. Pulmonary hypertension was defined as a tricuspid regurgitation velocity ≥2.75 m/s measured by Doppler echocardiography. The aetiology of PH, as categorised by published guidelines, was determined by reviewing electronic health records. RESULTS: 1,764 patients were identified comprising 49% males and 45% Indigenous people. The prevalence of PH was 955 per 100,000 population (with corresponding prevalence of 1,587 for Indigenous people). Hypertension, atrial fibrillation, diabetes and respiratory disease were present in 85%, 45%, 41% and 39%, respectively. Left heart disease was the leading cause for PH (58%), the majority suffering from valvular disease (predominantly rheumatic). Pulmonary arterial hypertension (PAH), respiratory disease related PH, chronic thromboembolic PH (CTEPH) and unclear multifactorial PH represented 4%, 16%, 2% and 3%, respectively. Underlying causes were not identifiable in 17% of the patients. Only 31% of potentially eligible patients were on PAH-specific therapy. At census, there was 40% mortality, with major predictors being age, estimated pulmonary artery systolic pressure (ePASP) and Indigenous ethnicity. CONCLUSION: Pulmonary hypertension is prevalent in Northern Australia, with a high frequency of modifiable risk factors and other treatable conditions. Whether earlier diagnosis, interpretation and intervention improve outcomes merits further assessment.

Risk stratification in pulmonary arterial hypertension using Bayesian analysis.

BACKGROUND: Current risk stratification tools in pulmonary arterial hypertension (PAH) are limited in their discriminatory abilities, partly due to the assumption that prognostic clinical variables have an independent and linear relationship to clinical outcomes. We sought to demonstrate the utility of Bayesian network-based machine learning in enhancing the predictive ability of an existing state-of-the-art risk stratification tool, REVEAL 2.0. METHODS: We derived a tree-augmented naïve Bayes model (titled PHORA) to predict 1-year survival in PAH patients included in the REVEAL registry, using the same variables and cut-points found in REVEAL 2.0. PHORA models were validated internally (within the REVEAL registry) and externally (in the COMPERA and PHSANZ registries). Patients were classified as low-, intermediate- and high-risk (<5%, 5-20% and >10% 12-month mortality, respectively) based on the 2015 European Society of Cardiology/European Respiratory Society guidelines. RESULTS: PHORA had an area under the curve (AUC) of 0.80 for predicting 1-year survival, which was an improvement over REVEAL 2.0 (AUC 0.76). When validated in the COMPERA and PHSANZ registries, PHORA demonstrated an AUC of 0.74 and 0.80, respectively. 1-year survival rates predicted by PHORA were greater for patients with lower risk scores and poorer for those with higher risk scores (p<0.001), with excellent separation between low-, intermediate- and high-risk groups in all three registries. CONCLUSION: Our Bayesian network-derived risk prediction model, PHORA, demonstrated an improvement in discrimination over existing models. This is reflective of the ability of Bayesian network-based models to account for the interrelationships between clinical variables on outcome, and tolerance to missing data elements when calculating predictions.

Diagnostic delay in pulmonary arterial hypertension: Insights from the Australian and New Zealand pulmonary hypertension registry.

BACKGROUND AND OBJECTIVE: Early diagnosis of PAH is clinically challenging. Patterns of diagnostic delay in Australian and New Zealand PAH populations have not been explored in large-scale studies. We aimed to evaluate the magnitude, risk factors and survival impact of diagnostic delay in Australian and New Zealand PAH patients. METHODS: A cohort study of PAH patients from the PHSANZ Registry diagnosed from 2004 to 2017 was performed. Diagnostic interval was the time from symptom onset to diagnostic right heart catheterization as recorded in the registry. Factors associated with diagnostic delay were analysed in a multivariate logistic regression model. Survival rates were compared across patients based on the time to diagnosis using Kaplan-Meier method and Cox regression. RESULTS: A total of 2044 patients were included in analysis. At diagnosis, median age was 58 years (IQR: 43-69), female-to-male ratio was 2.8:1 and majority of patients were in NYHA FC III-IV (82%). Median diagnostic interval was 1.2 years (IQR: 0.6-2.7). Age, CHD-PAH, obstructive sleep apnoea and peripheral vascular disease were independently associated with diagnostic interval of ≥1 year. No improvement in diagnostic interval was seen during the study period. Longer diagnostic interval was associated with decreased 5-year survival. CONCLUSION: PAH patients experience significant diagnostic interval, which has not improved despite increased community awareness. Age, cardiovascular and respiratory comorbidities are significantly associated with longer time to diagnosis. Mortality rates appear higher in patients who experience longer diagnostic interval.

Living With, and Caring for, Congenital Heart Disease in Australia: Insights From the Congenital Heart Alliance of Australia and New Zealand Online Survey.

BACKGROUND: There is a paucity of data describing the day-to-day experiences of adult Australians personally living with or caring for a child born with congenital heart disease (CHD). Such data would be of great practical importance to inform health care initiatives to improve outcomes. METHODS: 588 men (38.3 ± 11.9 years) and women (39.6 ± 12.6 years, 78% of respondent patients) living with CHD and 1,091 adult carers (93% mothers) of children with CHD (median age 7.3 [IQR 3.5-13.3 years], 54% male), representing all Australian states and territories, responded to a comprehensive online survey designed and hosted by the Congenital Heart Alliance of Australia and New Zealand. Data on demographic factors, the nature of underlying CHD, interactions with health care services, psychological wellbeing and wider impacts of CHD were collected. RESULTS: Most respondents were able to identify the type of CHD they (29% with a simple lesion such atrial septal defect, 17% tetralogy of Fallot) or their child had (21% with a simple lesion, 15% tetralogy of Fallot), whilst 90% cases of CHD had undergone cardiac surgery. Patients with CHD were mostly employed (70%) or studying (8.8%), whilst 9.1% were receiving disability benefits. In terms of transition care, 52% of adult patients had been referred by a paediatric to adult cardiologist with 84% still actively managed by a specialist. Overall, 31% of patients with CHD sought emergency care and required >10 days sick leave in the past 12 months. Moreover, 71% and 55% of patients, respectively, reported recent feelings of anxiety/worry or depressive thoughts related to their CHD (61% sought professional assistance). Consistent with high levels of disruption to daily living, 59% of carer respondents (24%>10 days) had taken carer's leave in the past 12 months. CONCLUSIONS: These contemporary, self-reported, Australian data reveal the burden of living and caring for CHD from an adult's perspective. Survey respondents highlighted the potential disconnect between paediatric and adult CHD services and suggest an important, unmet need for dedicated health services/community care to cost-effectively manage high levels of health care utilisation coupled with associated psychological distress.

Pharmacological Treatment of Pulmonary Arterial Hypertension in Australia: Current Trends and Challenges.

BACKGROUND: Combination drug therapy for pulmonary arterial hypertension (PAH) is the international standard of care for most patients, however in Australia there are barriers to drug access. This study evaluates current treatment of PAH patients in Australia and the consistency of therapy with international guidelines. METHODS: Cross-sectional analysis of patients with Group 1 PAH enrolled in the Pulmonary Hypertension Society of Australia and New Zealand Registry (PHSANZ) at 31 December 2017. Drug treatment was classified as monotherapy or combination therapy and adequacy of treatment was determined by risk status assessment using the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) 2.0 risk calculator. Predictors of monotherapy were assessed using a generalised linear model with Poisson distribution and logarithmic link function. RESULTS: 1,046 patients met the criteria for analysis. Treatment was classified as monotherapy in 536 (51%) and combination therapy in 510 (49%) cases. Based on REVEAL 2.0, 184 (34%) patients on monotherapy failed to meet low-risk criteria and should be considered inadequately treated. Independent predictors of monotherapy included age greater than 60 years (risk ratio [RR] 1.23, 95% confidence interval [CI] 1.09-1.38; p=0.001), prevalent enrolment in the registry (RR 1.21 [95%CI 1.08-1.36]; p=0.001) and comorbid systemic hypertension (RR 1.17 [95%CI 1.03-1.32]; p=0.014), while idiopathic/heritable/drug-induced PAH subtype (RR 0.85 [95%CI 0.76-0.96]; p=0.006), functional class IV (RR 0.50 [95%CI 0.29-0.86]; p=0.012), increased right ventricular systolic pressure (RR 0.99 [95%CI 0.99-1.00]; p<0.001) and increased pulmonary vascular resistance (RR 0.96 [95%CI 0.95-0.98]; p<0.001) were less likely to be associated with monotherapy. CONCLUSIONS: Most Australian PAH patients are treated with monotherapy and a significant proportion remain at risk of poor outcomes. This is below the standard of care recommended by international guidelines and at risk patients should be escalated to combination therapy.

Adult Congenital Heart Disease in Australia and New Zealand: A Call for Optimal Care.

BACKGROUND: Adult congenital heart disease (ACHD) is a relatively new subspecialty in the cardiology field. The prevalence of ACHD is estimated at ∼ 3,000 per million adult population. The ACHD patient group is estimated to grow at ∼ 5% per year and in the next decade it is forecast that 1 in 150 young adults will carry some form of ACHD diagnosis. These estimates translate to ∼ 72,000 ACHD patients in Australia and ∼ 14,000 in New Zealand, although no current numbers are available. The Cardiac Society of Australia and New Zealand (CSANZ) has recently published Recommendations for Standards of Care for Adult Congenital Heart Disease (ACHD) in 2016. There is currently no long-term plan or proposal to address this huge health care burden within the federal government. This document details the size of the problem insofar as it is known and recommends solutions to be implemented. METHODS: This document was developed by the Adult Congenital Heart Disease Working Group of the Paediatric and Congenital Council (the Congenital Heart Alliance of Australia and New Zealand) as a response to the chronic under resourcing in this area, the risk this poses to patients and clinicians, and the clear need for long-term planning to develop safe care pathways. RESULTS: These issues were raised with the CSANZ Board in December 2015 and the document was developed in response to the Board's request for more information. The current iteration was finalised on 14 November 2017. CONCLUSIONS: The authorship group comprised participants in the CSANZ adult CHD standards of care recommendations from 2013 with the inclusion of some newly trained ACHD cardiologists, who represented most states and territories across ANZ. None of the authors has any academic or professional conflict of interest.

The National Echocardiography Database Australia (NEDA): Rationale and methodology.

The National Echocardiography Database Australia (NEDA) is a new echocardiography database collecting digital measurements on both a retrospective and prospective basis. To date, echocardiographic data from 435,133 individuals (aged 61.6 ±â€¯17.9 years) with linkage to 59,725 all-cause deaths during a median of 40 months follow-up have been collected. These data will inform a number of initial analyses focusing on pulmonary hypertension, aortic stenosis and the role of artificial intelligence to facilitate accurate diagnoses of cardiac abnormalities.

Left Heart Disease and Pulmonary Hypertension: Are We Seeing the Full Picture?

Pulmonary hypertension (PH) is common, under diagnosed and associated with a high mortality. There are significant delays in the diagnosis of pulmonary hypertension leading to increased morbidity and delays in the initiation of treatment. Once PH is diagnosed, establishing the degree of pulmonary vascular resistance (PVR) enables clinicians to broadly divide the underlying pathology into pre-capillary or post-capillary causes, a crucial step in tailoring management. Pulmonary hypertension is most commonly due to left heart disease (PH-LHD) and echocardiography (echo) is the most widely accessible investigation in its diagnosis. Regardless of the underlying pathophysiology of LHD, the sequelae lead to pressure overload on the left heart and a reactive increase in pulmonary pressures. In this review article, we will discuss the prevalence of PH, examine the pathophysiology of PH-LHD, establish how echo can be used to identify patients with PH-LHD and discuss surrogate echo markers of PVR.

Survival of Idiopathic Pulmonary Arterial Hypertension Patients in the Modern Era in Australia and New Zealand.

BACKGROUND: Epidemiology and treatment strategies continue to evolve in pulmonary arterial hypertension (PAH). We sought to define the characteristics and survival of patients with idiopathic, heritable and drug-induced PAH in the current management era. METHODS: Consecutive cases of idiopathic, heritable and drug-induced PAH were prospectively enrolled into an Australian and New Zealand Registry. RESULTS: Between January 2012 and December 2016, a total of 220 incident cases were enrolled (mean age 57.2±18.7years, female 69.5%) and followed for a median duration of 26 months (IQR17-39). Co-morbidities were common such as obesity (34.1%), systemic hypertension (30.5%), coronary artery disease (16.4%) and diabetes mellitus (19.5%). Initial combination therapy was used in 54 patients (dual, n=50; triple, n=4). Estimated survival rates at 1-year, 2-years and 3-years were 95.6% (CI 92.8-98.5%), 87.3% (CI 82.5-92.4%) and 77.0% (CI 70.3-84.3%), respectively. Multivariate analysis showed that male sex and lower 6-minute distance at diagnosis independently predicted worse survival, whereas obesity was associated with improved survival. Co-morbidities other than obesity did not impact survival. Initial dual oral combination therapy was associated with a trend towards better survival compared with initial oral monotherapy (adjusted HR=0.27, CI 0.06-1.18, p=0.082) CONCLUSIONS: The epidemiology and survival of patients with idiopathic PAH in Australia and New Zealand are similar to contemporary registries reported in Europe and North America. Male sex and poorer exercise capacity are predictive of mortality whereas obesity appears to exert a protective effect. Despite current therapies, PAH remains a life-threatening disease associated with significant early mortality.

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.

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.

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 aortic paradox: a nationwide analysis of 523,994 individual echocardiograms exploring fatal aortic dissection.

BACKGROUND: Increasing aortic dilation increases the risk of aortic dissection. Nevertheless, dissection occurs at dimensions below guideline-directed cut-offs for prophylactic surgery. There is no current large-scale population imaging data assessing aortic dimensions before dissection. METHODS: Patients within the National Echo Database of Australia (NEDA) were stratified according to absolute, height-indexed and body surface area (BSA)-indexed aortic dimensions. Fatal thoracic aortic dissections (ICD-10-AM code I79) were identified via linkage with the National Death Index. RESULTS: 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). 274,992 (52.4%) were male, with median age 64 years and median follow-up time 6.9 years. 899 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 = 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. Results were robust for absolute, height-indexed or BSA-indexed aortic measurements. CONCLUSION: Although severe aortic dilatation is associated with a near-thirty-fold increase in fatal dissection, 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.

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.

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.