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 -dis-tance [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.

ABSTRACT 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.

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.

Background: Progressive right ventricular (RV) dysfunction in pulmonary arterial hypertension (PAH) which is contributed by RV ischemia leads to adverse clinical outcomes. Oxygen-sensitive (OS) cardiovascular magnetic resonance (CMR) has been used to determine the in vivo myocardial oxygenation of the left ventricle (LV). The aims of the present study were therefore to determine the feasibility of RV targeted rest/stress OS-CMR imaging in PAH patients and healthy volunteers. Methods: We prospectively recruited 20 patients with right heart catheter proven PAH and 9 healthy age matched controls (NC). The CMR examination involved standard functional imaging and OS-CMR imaging. An OS-CMR signal intensity (SI) index (stress/rest SI) was acquired at RV anterior, RV free-wall and RV inferior segments. In the LV, the OS-CMR SI index was acquired globally. Results: Reliable OS SI changes were only obtained from the RV inferior segment. As RV dysfunction in PAH is a global process, hence this segment was used in both patients and NC for further comparison. RV OS-CMR SI change between rest and stress in the NC was 17%+/- 5% (mean +/- SD). Nine of 20 (45%) of the PAH patients had a mean OS SI change of less than 9% (or >= 2 SD different from the mean values in NC). Overall, RV OS SI index between the PAH patients and NC was 11%+/- 9% vs. 17%+/- 5% (P=0.045) in the RV inferior segment. In the LV, the global OS-CMR SI index between the PAH patients and NC was 11%+/- 7% vs. 21%+/- 9% (P=0.019). There was a strong correlation between RV Inf OS-CMR SI and LV OS-CMR SI (r=0.86, P<0.001). Conclusions: In this small pilot study, pharmacological induced OS-CMR is a feasible and safe technique to identify and study myocardial oxygenation in the RV of PAH patients.

Abstract Background Progressive right ventricular (RV) dysfunction is a natural progression of pulmonary arterial hypertension (PAH) which is associated with adverse clinical outcomes. The main contributor to progressive RV dysfunction is RV ischemia. Oxygen-sensitive (OS) cardiovascular magnetic resonance (CMR) has been used to determine the in-vivo myocardial oxygenation of the left ventricle (LV). Purpose The aim of the present study was to (1) Determine the feasibility of RV targeted rest/stress OS-CMR imaging in PAH patients and normal volunteers; (2) To define the presence and extent of RV myocardial ischaemia in patients with known PAH. Methods We prospectively recruited 20 patients with right heart catheter proven PAH and 9 normal (NC), age matched controls with no heart disease. The CMR examination involved standard functional imaging and OS-CMR imaging. OS-CMR images were acquired using a T2* sequence at rest and adenosine-induced stress vasodilatation. The RV was divided into 3 segments - RV anterior, RV free-wall and RV inferior. An OS-CMR signal intensity (SI) index (stress/rest signal intensity) was acquired at RV anterior, RV free-wall and RV inferior segments. Results All the PAH patients tolerated and completed the adenosine induced stress OS-CMR without any complications or adverse effects. In NC, reliable OS signal intensity changes was only obtained from the RV inferior segment. As RV dysfunction in PAH is a global process, hence this segment was used in both patients and NC for further comparison. RV OS-CMR signal intensity change between rest and stress in the normal volunteers was 17±4% (mean ± SD). 9 out of twenty (45%) of the PAH patients had a mean BOLD signal intensity change of less than 9% (or 2SD different from the mean values in normal volunteers). Overall, RV OS SI index between the PAH patients and controls was 11±9% vs 17±5% (p-value = 0.045) in RV inferior segment. Conclusion Pharmacological induced OS-CMR is a feasible and safe technique to identify and study myocardial oxygenation in the RV of PAH patients.

BACKGROUND: Pulmonary arterial hypertension (PAH) prognosis has improved with targeted therapies; however, the long-term outlook remains poor. Objective multiparametric risk assessment is recommended to identify patients at risk of early morbidity and mortality, and for optimization of treatment. The US Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) 2.0 risk score is a new model proposed for the follow-up of patients with PAH but has not been externally validated. METHODS: The REVEAL 2.0 risk score was applied to a mixed prevalent and incident cohort of patients with PAH (n = 1,011) from the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) Registry. Kaplan-Meier survival was estimated for each REVEAL 2.0 risk score strata and for a simplified three-category (low, intermediate, and high risk) model. Sensitivity analysis was performed on an incident-only cohort. RESULTS: The REVEAL 2.0 model effectively discriminated risk in the large external PHSANZ Registry cohort, with a C statistic of 0.74 (both for full eight-tier and three-category models). When applied to incident cases only, the C statistic was 0.73. The three-category REVEAL 2.0 model demonstrated robust separation of 12- and 60-month survival estimates (all risk category comparisons P < .001). Although the full eight-tier REVEAL 2.0 model separated patients at low, intermediate, and high risk, survival estimates overlapped within some of the intermediate- and high-risk strata. CONCLUSIONS: The REVEAL 2.0 risk score was validated in a large external cohort from the PHSANZ Registry. The REVEAL 2.0 model can be applied for risk assessment of patients with PAH at follow-up. The simplified three-category model may be preferred for clinical use and for future comparison with other prognostic models.

Introduction: A pulmonary vascular resistance (PVR) criterion of >3 Wu was introduced into the haemodynamic definition of pulmonary arterial hypertension (PAH) in 2013. Lower levels of PVR can be abnormal, particularly in the younger population. There is limited data on the natural history and response to PAH therapy in patients with precapillary pulmonary hypertension with PVR <3 Wu. Methods: Using the PHSANZ registry, we analysed outcomes of all patients fulfilling the haemodynamic criteria: mPAP ≥25 mmHg, PAWP ≤15 mmHg and PVR <3 Wu. Patients with left-to-right cardiac shunts, chronic liver, lung, and left heart disease were excluded. Results: 82 patients (mean age 63 ± 11 years, 82% female) were included. Underlying diagnosis included idiopathic (n = 39), connective tissue disease (n = 42) and HIV infection (n = 1). At diagnosis, haemodynamics showed mPAP 28 ± 4 mmHg, PAWP 12 ± 2 mmHg and PVR 2.3 ± 0.5 Wu. Baseline exercise capacity revealed mean 6MWD of 341 ± 124 m with 77% in NYHA FC 3/4. All patients were commenced on initial monotherapy with endothelin receptor antagonists (n = 66) or phosphodiesterase type 5 inhibitors (n = 16). At first post-treatment evaluation (median 5 months; IQR 4-12), 6MWD increased by 46 m (IQR 7-96) and 35% demonstrated improvement in NYHA FC status. After a median follow-up of 65 months (IQR 32-101), 22% were deceased, with estimated 1-yr, 3-yr and 5-yr survivals of 98%, 88%, 84%, respectively. Conclusions: Our data suggest that selected patients with precapillary PH with PVR <3 Wu may benefit from PAH therapy. Further studies are needed to determine whether early treatment of these patients confers beneficial impact on exercise capacity and outcomes.

Pericardial effusion is a clinical condition often due to pericarditis or malignancy. Primary cardiac sarcomas are extremely rare with a non-specific clinical presentation which may include effusion. A 45-year old woman presented to hospital with pleuritic chest pain after a viral illness.

Background: Progressive right ventricular (RV) dysfunction in pulmonary arterial hypertension (PAH) which is contributed by RV ischaemia leads to adverse clinical outcomes. Oxygen-sensitive (OS) cardiovascular magnetic resonance (CMR) has been used to determine the in-vivo myocardial oxygenation of the left ventricle (LV). The aim of the present study was to (1) Determine the feasibility of RV targeted rest/stress OS-CMR imaging in PAH patients and normal volunteers; (2) To define the presence and extent of RV myocardial ischaemia in patients with known PAH. Methods: We prospectively recruited 20 patients with right heart catheter proven PAH and 9 normal healthy volunteers (NV). The CMR examination involved standard functional imaging and OS-CMR Imaging. An OS-CMR signal intensity (SI) index (stress/rest signal intensity) was acquired at RV anterior, RV free-wall and RV inferior segments. Results: Reliable OS signal intensity changes were only obtained from the RV inferior segment. As RV dysfunction in PAH is a global process, this segment was used in both patients and NV for further comparison. RV OS SI change between rest and stress in the NV was 17 ± 4% (mean ± SD). 9/20 (45%) of the PAH patients had a mean OS-CMR signal intensity change of less than 9% (or 2SD different from the mean values in normal volunteers). Overall, RV OS SI index between the PAH patients and NV was 11 ± 9% vs 17 ± 5% (p-value = 0.04) in RV inferior segment. Conclusion: Pharmacological induced OS-CMR is a feasible and safe technique to identify and study myocardial oxygenation in the RV of PAH patients.

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 +/- 18.7 years, 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 82.592.4%) and 77.0% (CI 70.3-84.3%), respectively. Multivariate analysis showed that male sex and lower 6minute 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.

Making Australia the benchmark in echocardiography databases: The National Echo Database Australia (NEDA) D Playford, G. Strange, G. Scalia, S. Stewart, T. Marwick, A. Keogh, D. Prior, P. Steele, M. Ilton, E. Gabbay, J. Codde, B. Sheehan and D. Celermajer University of Notre Dame, Fremantle, Australia The Prince Charles Hospital, Brisbane, Australia Mary MacKillop Institute for Health Research, Melbourne, Australia Baker IDI, Melbourne, Australia St Vincents Hospital, Sydney, Australia St Vincents Hospital, Melbourne, Australia NT Heart Centre, Darwin, Australia University of Notre Dame, Fremantle, Australia Pulmonary Hypertension Society of ANZ, Australia Royal Pri

No unified method exists to effectively predict and monitor progression of pulmonary arterial hypertension (PAH). We assessed the longitudinal relationship between a novel marker of cardiopulmonary reserve and established prognostic surrogate markers in patients with pulmonary vascular disease.

Background: We have previously demonstrated that PHT identified using echocardiography (Echo) is common and that left heart disease accounts for the majority of PHT. Echo measurements of left heart disease may be helpful in predicting the cause of PHT. Aims: To examine prevalence of PHT within NEDA, and uncover left heart Echo predictors of PHT. Methodology: NEDA utilises novel database engineering to combine individual databases into a single database. 307,656 Echos from two laboratories have been included in this analysis. We defined PHT as a right ventricular systolic pressure (RVSP) over 40 mmHg. Results: 180,374 Echos (59%) had a measurable tricuspid regurgitation (TR) velocity profile from which an RVSP could be calculated. PHT from any cause was identified in 39,699 (22%) Echos. Of those in which PHT was identified, the mean RVSP was 51+/-11 mmHg, compared with 29.5+/-5.8 in those without PHT (p<0.0001). These patients were older than the overall average for NEDA (mean age 74.9+/-12.1 vs 62.9+/-16.6 years, p<0.0001). The ejection fraction (EF) was similar but significantly different between those with PHT and those without (58.1+/-13.7 vs 61.9+/-8.7%, p<0.0001). Measures of diastolic function were markedly different (E:E’ ratio 17.1+/-8.5 vs 11.3+/-5.5, p<0.0001). Conclusions: Pulmonary hypertension is common, representing 22% of those with a measurable RVSP in a large echo cohort (over 300,000 Echos). Overall, the EF was similar in PHT compared to those without PHT, whereas surrogate markers of filling pressure such as E:E’ ratio were markedly different, underpinning the importance of measuring diastolic function in the evaluation of PHT.

Background: Epidemiological research from population-based cohort studies have shaped public health strategies. Echocardiography (echo) is one of the most commonly performed cardiac investigations in Australia, however there is limited epidemiological data quantifying cardiovascular risk for various echo measurements. From Medicare Australia data, 919,309 echos were processed in 2015, excluding State Government hospital echo data. Aims: To develop the National Echocardiography Database Australia (NEDA), capturing measurement data from digital echo labs across Australia, and to link this data with national death index (NDI). We seek to obtain mortality risk statistics for each cardiac abnormality studied. Methodology: We have developed an architectural prototype and a “scraper” tool to retrieve every variable from each echo lab, including retrospective data. We identified 650 unique measurements obtained from a comprehensive echo exam. We wrote a unique data dictionary to account for differing variable names from different labs. Text was converted into variables using a parsing algorithm. Results: Two complete echo databases from different software vendors, have been scraped and combined totalling 307,656 echocardiograms collected between 2001 and 2015. Conversion of variable names and measurement units was performed to unify data formats. A total of 5,477,019 valid data points were collected, mean age 62.9+/-16.95. Conclusions: Using novel database engineering we combined two echo databases from different echo software manufacturers into one database containing over 300,000 individual echocardiograms. Phased roll-out of NEDA to multiple sites is now planned along with linkage to the NDI, allowing large scale epidemiological research.

Background: Echocardiography (echo) is pivotal in evaluation of valvular heart disease. Traditionally, aortic valve replacement is delayed until symptoms develop, due to the long latent period. Recent data suggests earlier intervention in asymptomatic patients reduces mortality and hospitalisations. Aim: To examine prevalence of severe AS within the National Echo Database Australia (NEDA), and compare with Medicare Australia data on surgical interventions. Methodology: The NEDA database utilises novel database engineering to combine echo databases into a single database. To date, 307,656 echocardiograms from two laboratories have been included in this analysis (patient age 62.9±16.9 years). Data was extracted and Medicare data was compared for 2014. Results: Within NEDA database (2001-2015), an aortic valve area (AVA) was calculated in 139,372 patients (mean 2.4±0.89cm2), mean transaortic gradient (MG) in 250,138 patients (mean 6.7±8.0mmHg). We defined severe AS as a MG >40mmHg or an AVA <1.0cm2. 8182 patients met our definition (age 73.9±17.1, AVA 0.82±0.25, MG 37.4±18.5), and 892 in the 2014 year (age 75.9±17.1, AVA 0.82±0.25, MG 33.7±18.3). In 2014, 3907 aortic valve replacements (AVR) were performed in Australia, and 189 in the NEDA geographical area. 703 patients (79%) of those with severe AS did not undergo AVR. Conclusion: Severe AS is common, but AVR is only performed in 21% of these patients. Even accounting for comorbidities, age and transcatheter intervention, there appears to be a disparity between severe AS and AVR rates. In the era of earlier intervention to improve outcome, further investigation into this mismatch may be warranted.

Background: Pericardial effusions are a common presentation encountered by multiple medical specialties. We sought to evaluate the indications, aetiology, characteristics and outcomes of pericardiocentesis for pericardial effusions at the Royal Adelaide Hospital over a 1 year period. Methods: We performed a retrospective clinical audit on consecutive patients who underwent percutaneous pericardiocentesis within the Royal Adelaide Hospital between July 2014 and June 2015 in the electronic cardiac database. All procedures were performed by registrars with senior supervision in the cardiac laboratory utilising echo and fluoroscopic guidance. A 6Fr pigtail drain was inserted in all cases. Results: A total of 26 percutaneous pericardiocentesis procedures were performed on 25 patients within the study period. Mean age was 64.3 ±17.3 years and 52% (13/25) were male. Indications included cardiac tamponade (27%), symptomatic effusion with (42%) and without (23%) echocardiographic haemodynamic compromise, and diagnostic (4%). Aetiologies included malignancy (37%), pericarditis (19%), post pericardiotomy (15%), overanticoagulation (7%), idiopathic (11%), infective [MRSA, TB] (7%) and trauma (4%). Subxiphoid was more often utilised (81%) than an apical approach (15%) with only 1 failed attempt (4%). Mean effusion size on echo was 2.5 ± 0.6cm and total fluid drained was 694±416mL. Majority were heavily blood stained (50%) with the remainder haemoserous (25%) and serous (25%). 96% were exudative. Cytology was positive in 8 out of 10 malignancies, identifying all 4 new malignancies. Median duration of drain insertion was 3 (range 1-5) days and length of stay 9.5 (range 1-30) days. There were 7 clinical recurrences (28%) up to 3 months follow-up. One patient required repeat percutaneous drain and 3 referred for surgical pericardial window. Complications included 1 pneumopericardium and 1 death in the setting of multiorgan failure and adenocarcinoma. Conclusion: Percutaneous pericardiocentesis is an effective therapy for symptomatic pericardial effusion. Clinical recurrence was common, particularly with malignancy.

We report the case of a 58-year-old woman who presented with progressive dyspnoea and exercise intolerance. Transthoracic echocardiography revealed pulmonary hypertension with no identifiable cause, including after 3D and contrast imaging. A nuclear ventilation/perfusion pulmonary scan was negative. Right heart catheterisation with oximetry detected elevated pulmonary pressures, a normal pulmonary capillary wedge pressure, and significant left to right intracardiac shunting without an identifiable cause. Further evaluation with cardiovascular magnetic resonance (CMR) imaging was performed and identified and characterised a sinus venosus-type atrial septal defect (ASD), associated partial anomalous pulmonary venous drainage, and significant intracardiac shunting. CMR facilitated surgical closure of the ASD and correction of pulmonary venous drainage. Her pulmonary hypertension, intracardiac shunt and symptoms resolved. Intracardiac shunting is an important cause of pulmonary hypertension, and its cause may be missed on routine cardiac investigations. CMR is a valuable non-invasive investigation in this setting. [CMR Image A shows a sinus venosus ASD (single arrow) involving the SVC (double arrow), with right superior and middle pulmonary veins draining into the SVC (arrow heads). CMR Image B shows a persistent left-sided SVC (single arrow) draining into a dilated coronary sinus (double arrow)].