Prevalence and Cost of Managing Paediatric Cardiac Disease in Queensland.

BACKGROUND: There is a paucity of contemporary information regarding the prevalence and related health care expenditure of the most common cardiac conditions in Australian children, including congenital heart disease (CHD). METHODS: The 10 most common cardiac conditions managed by Queensland Paediatric Cardiac Service during 2014-2015 were identified from an electronic database: ventricular septal defect (VSD), pulmonary stenosis, aortic stenosis, tetralogy of Fallot, atrioventricular septal defect, transposition, Ebstein's anomaly, long QT syndrome, dilated cardiomyopathy, and rheumatic carditis. Demographic data, clinic attendance, investigational procedures, and therapeutic interventions were extracted from the electronic health records to derive indicative population estimates and direct health care expenditure relating to CHD. RESULTS: A total of 2,519 patients diagnosed with the 10 target conditions were being actively managed, including 456 (18.1%) new-born and 787 prevalent cases (2.5/1,000 population) aged <5 years. A total of 12,180 (4.8/case) investigations were performed (6,169 echocardiographic and 279 cardiac catheterisation procedures) costing $2.25 million/annum. A further 5,326 clinic visits (2.1/case, 22% regional) were conducted at a cost of $550,000/annum. A combined total of 804 catheter-based interventions and surgical procedures were performed in 300 cases (11.9%) at a cost of $13.6 million/annum. VSD (38.6% of cases) was the single greatest contributor ($5.1 million/annum) to total combined direct health care costs of $13.6 million/annum for the 2,519 patients. CONCLUSIONS: These pilot data indicate a significant patient population and health care burden imposed by CHD in Queensland. Future initiatives to better quantify this burden, from an individual to health system perspective, are urgently needed.

Pulmonary arterial hypertension with below threshold pulmonary vascular resistance.

Pulmonary vascular resistance (PVR) >3 Wood units is a criterion of the haemodynamic definition of pulmonary arterial hypertension (PAH). However, this cut-off is conservative and arbitrarily defined. Data is lacking on the natural history, response to therapy and survival of patients diagnosed with precapillary pulmonary hypertension (PH) with mild or borderline elevation of PVR.In Australia, PAH therapy could be prescribed solely on mean pulmonary arterial pressure (PAP) and pulmonary arterial wedge pressure (PAWP) criteria. Using the Australian and New Zealand Pulmonary Hypertension Registry, we aimed to study a population diagnosed with PAH between January 2004 and December 2017 with the pre-defined haemodynamic characteristics of mean PAP ≥25 mmHg, PAWP ≤15 mmHg and PVR <3 Wood units.Eighty-two patients met the pre-defined haemodynamic inclusion criteria (mean age 63±11 years; 67 females). Underlying aetiologies included idiopathic disease (n=39), connective tissue disease (CTD; n=42) and HIV infection (n=1). At diagnosis, mean PAP was 27 mmHg (interquartile range (IQR) 25-30 mmHg), PAWP 13 mmHg (IQR 11-14 mmHg) and PVR 2.2 Wood units (IQR 1.9-2.7 Wood units). Baseline 6-min walk distance (6MWD) was 352 m (IQR 280-416 m) and 77% of subjects were in New York Heart Association (NYHA) functional class 3 or 4. All patients were commenced on initial monotherapy with an endothelin receptor antagonist (ERA; n=66) or phosphodiesterase type-5 inhibitor (PDE5i; n=16). At first re-evaluation, 6MWD increased by 46 m (IQR 7-96 m) and 35% of subjects demonstrated improvement in NYHA functional class. After a median follow-up of 65 months (IQR 32-101 months), 18 out of 82 subjects (22.0%) had died, with estimated 1-year and 5-year survival rates of 98% and 84%, respectively. Death attributed to PAH occurred in six out of these 18 patients (33.3%, 7% of total cohort).Patients with precapillary PH and "borderline" PVR falling outside the current definition have adverse outcomes. Such patients appear to respond to PAH therapy; however, this requires further study in randomised trials.

The value of right ventricular to pulmonary arterial coupling in the critically ill: a National Echocardiography Database of Australia (NEDA) substudy.

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

Incident pulmonary hypertension in 13 488 cases investigated with repeat echocardiography: a clinical cohort study.

Background: We addressed the paucity of data describing the characteristics and natural history of incident pulmonary hypertension. Methods: Adults (n=13 448) undergoing routine echocardiography without initial evidence of pulmonary hypertension (estimated right ventricular systolic pressure, eRVSP <30.0 mmHg) or left heart disease were studied. Incident pulmonary hypertension (eRVSP ≥30.0 mmHg) was detected on repeat echocardiogram a median of 4.1 years apart. Mortality was examined according to increasing eRVSP levels (30.0-39.9, 40.0-49.9 and ≥50.0 mmHg) indicative of mild-to-severe pulmonary hypertension. Results: A total of 6169 men (45.9%, aged 61.4±16.7 years) and 7279 women (60.8±16.9 years) without evidence of pulmonary hypertension were identified (first echocardiogram). Subsequently, 5412 (40.2%) developed evidence of pulmonary hypertension, comprising 4125 (30.7%), 928 (6.9%) and 359 (2.7%) cases with an eRVSP of 30.0-39.9 mmHg, 40.0-49.9 mmHg and ≥50.0 mmHg, respectively (incidence 94.0 and 90.9 cases per 1000 men and women, respectively, per year). Median (interquartile range) eRVSP increased by +0.0 (-2.27 to +2.67) mmHg and +30.68 (+26.03 to +37.31) mmHg among those with eRVSP <30.0 mmHg versus ≥50.0 mmHg. During a median 8.1 years of follow-up, 2776 (20.6%) died from all causes. Compared to those with eRVSP <30.0 mmHg, the adjusted risk of all-cause mortality was 1.30-fold higher in 30.0-39.9 mmHg, 1.82-fold higher in 40.0-49.9 mmHg and 2.11-fold higher in ≥50.0 mmHg groups (all p<0.001). Conclusions: New-onset pulmonary hypertension, as indicated by elevated eRVSP, is a common finding among older patients without left heart disease followed-up with echocardiography. This phenomenon is associated with an increased morality risk even among those with mildly elevated eRVSP.

Prognostic association supports indexing size measures in echocardiography by body surface area.

Body surface area (BSA) is the most commonly used metric for body size indexation of echocardiographic measures, but its use in patients who are underweight or obese is questioned (body mass index (BMI) < 18.5 kg/m2 or ≥ 30 kg/m2, respectively). We aim to use survival analysis to identify an optimal body size indexation metric for echocardiographic measures that would be a better predictor of survival than BSA regardless of BMI. Adult patients with no prior valve replacement were selected from the National Echocardiography Database Australia. Survival analysis was performed for echocardiographic measures both unindexed and indexed to different body size metrics, with 5-year cardiovascular mortality as the primary endpoint. Indexation of echocardiographic measures (left ventricular end-diastolic diameter [n = 230,109] and mass [n = 224,244], left atrial volume [n = 150,540], aortic sinus diameter [n = 90,805], right atrial area [n = 59,516]) by BSA had better prognostic performance vs unindexed measures (underweight: C-statistic 0.655 vs 0.647; normal weight/overweight: average C-statistic 0.666 vs 0.625; obese: C-statistic 0.627 vs 0.613). Indexation by other body size metrics (lean body mass, height, and/or weight raised to different powers) did not improve prognostic performance versus BSA by a clinically relevant magnitude (average C-statistic increase ≤ 0.02), with smaller differences in other BMI subgroups. Indexing measures of cardiac and aortic size by BSA improves prognostic performance regardless of BMI, and no other body size metric has a clinically meaningful better performance.

Decreased diastolic hydraulic forces incrementally associate with survival beyond conventional measures of diastolic dysfunction.

Decreased hydraulic forces during diastole contribute to reduced left ventricular (LV) filling and heart failure with preserved ejection fraction. However, their association with diastolic function and patient outcomes are unknown. The aim of this retrospective, cross-sectional study was to determine the mechanistic association between diastolic hydraulic forces, estimated by echocardiography as the atrioventricular area difference (AVAD), and both diastolic function and survival. Patients (n = 5176, median [interquartile range] 5.5 [5.0-6.1] years follow-up, 1213 events) were selected from the National Echo Database Australia (NEDA) based on the presence of relevant transthoracic echocardiographic measures, LV ejection fraction (LVEF) ≥ 50%, heart rate 50-100 beats/minute, the absence of moderate or severe valvular disease, and no prior prosthetic valve surgery. NEDA contains echocardiographic and linked national death index mortality outcome data from 1985 to 2019. AVAD was calculated as the cross-sectional area difference between the LV and left atrium. LV diastolic dysfunction was graded according to 2016 guidelines. AVAD was weakly associated with E/e', left atrial volume index, and LVEF (multivariable global R2 = 0.15, p < 0.001), and not associated with e' and peak tricuspid regurgitation velocity. Decreased AVAD was independently associated with poorer survival, and demonstrated improved model discrimination after adjustment for diastolic function grading (C-statistic [95% confidence interval] 0.644 [0.629-0.660] vs 0.606 [0.592-0.621], p < 0.001) and E/e' (0.649 [0.635-0.664] vs 0.634 [0.618-0.649], p < 0.001), respectively. Therefore, decreased hydraulic forces, estimated by AVAD, are weakly associated with diastolic dysfunction and demonstrate an incremental prognostic association with survival beyond conventional measures used to grade diastolic dysfunction.

Incident aortic stenosis in 49 449 men and 42 229 women investigated with routine echocardiography.

OBJECTIVE: We addressed the paucity of data describing the characteristics and consequences of incident aortic stenosis (AS). METHODS: Adults undergoing echocardiography with a native aortic valve (AV) and no AS were studied. Subsequent age-specific and sex-specific incidence of AS were derived from echocardiograms conducted a median of 2.8 years apart. Progressive AV dysfunction and individually linked mortality were examined per AS category. RESULTS: 49 449 men (53.9%, 60.9±15.8 years) and 42 229 women (61.6±16.9 years) with no initial evidence of AS were identified. Subsequently, 6293 (6.9%) developed AS-comprising 5170 (5.6%), 636 (0.7%), 339 (0.4%) and 148 (0.2%) cases of mild, moderate, severe low-gradient and severe high-gradient AS, respectively. Age-adjusted incidence rates of all grades of AS were 17.5 cases per 1000 men/annum and 18.7 cases per 1000 women/annum: rising from ~5 to ~40 cases per 1000/annum in those aged <30 years vs >80 years. Median peak AV velocity increased by +0.57 (+0.36 to +0.80) m/s in mild AS compared with +2.75 (+2.40 to +3.19) m/s in severe high-gradient AS cases between first and last echocardiograms. During subsequent median 7.7 years follow-up, 24 577 of 91 678 cases (26.8%) died. Compared with no AS, the adjusted risk of all-cause mortality was 1.42-fold higher in mild AS, 1.92-fold higher in moderate AS, 1.95-fold higher in severe low-gradient AS and 2.27-fold higher in severe, high-gradient AS cases (all p<0.001). CONCLUSIONS: New onset AS is a common finding among older patients followed up with echocardiography. Any grade of AS is associated with higher mortality, reinforcing the need for proactive vigilance.

Counting the cost of premature mortality with progressively worse aortic stenosis in Australia: a clinical cohort study.

BACKGROUND: Aortic stenosis is the most common cardiac valve disorder requiring clinical management. However, there is little evidence on the societal cost of progressive aortic stenosis. We sought to quantify the societal burden of premature mortality associated with progressively worse aortic stenosis. METHODS: In this observational clinical cohort study, we examined echocardiograms on native aortic valves of 98 565 men and 99 357 women aged 65 years or older across 23 sites in Australia, from Jan 1, 2003, to Dec 31, 2017. Individuals were grouped according to their peak aortic valve velocity in 0·50 m/s increments up to 4·00 m/s or more (severe aortic stenosis), using 1·00-1·99 m/s (no aortic stenosis) as the reference group. Sex-specific premature mortality and years of life lost during a 5-year follow-up were calculated, along with willingness-to-pay to regain quality-adjusted life years (QALYs). FINDINGS: Overall, 20 701 (21·0%) men and 18 576 (18·7%) women had evidence of mild-to-severe aortic stenosis. The actual 5-year mortality in men with normal aortic valves was 32·1% and in women was 26·1%, increasing to 40·9% (mild aortic stenosis) and 52·2% (severe aortic stenosis) in men and to 35·9% (mild aortic stenosis) and 55·3% (severe aortic stenosis) in women. Overall, the estimated societal cost of premature mortality associated with aortic stenosis was AU$629 million in men and $735 million in women. Per 1000 men and women investigated, aortic stenosis was associated with eight more premature deaths in men resulting in 32·5 more QALYs lost (societal cost of $1·40 million) and 12 more premature deaths in women resulting in 57·5 more QALYs lost (societal cost of $2·48 million) when compared with those without aortic stenosis. INTERPRETATION: Any degree of aortic stenosis in older individuals is associated with premature mortality and QALYs. In this context, there is a crucial need for cost-effective strategies to promptly detect and optimally manage this common condition within our ageing populations. FUNDING: Edwards LifeSciences, National Health and Medical Research Council of Australia, and the National Heart, Lung, and Blood Institute.

Uncovering the treatable burden of severe aortic stenosis in the UK.

OBJECTIVE: To estimate the population prevalence and treatable burden of severe aortic stenosis (AS) in the UK. METHODS: We adapted a contemporary model of the population profile of symptomatic and asymptomatic severe AS in Europe and North America to estimate the number of people aged ≥55 years in the UK who might benefit from surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI). RESULTS: With a point prevalence of 1.48%, we estimate that 291 448 men and women aged ≥55 years in the UK had severe AS in 2019. Of these, 68.3% (199 059, 95% CI 1 77 201 to 221 355 people) would have been symptomatic and, therefore, more readily treated according to their surgical risk profile; the remaining 31.7% of cases (92 389, 95% CI 70 093 to 144 247) being asymptomatic. Based on historical patterns of intervention, 58.4% (116 251, 95% CI 106 895 to 1 25 606) of the 199 059 symptomatic cases would qualify for SAVR, with 7208 (95% CI 7091 to 7234) being assessed as being in a high, preoperative surgical risk category. Among the remaining 41.6% (82 809, 95% CI 73 453 to 92 164) of cases potentially unsuitable for SAVR, an estimated 61.7% (51 093, 95% CI 34 780 to 67 655) might be suitable for TAVI. We estimate that 172 859 out of 291 448 prevalent cases of severe AS (59.3%) will subsequently die within 5 years without proactive management. CONCLUSIONS: These data suggest a high burden of severe AS in the UK requiring surgical or transcatheter intervention that challenges the ongoing capacity of the National Health Service to meet the needs of those affected.

Preserved ejection fraction and structural heart disease in 446 848 patients investigated with echocardiography.

BACKGROUND: Sex-specific differences in left ventricular ejection fraction (LVEF) and responses to neurohormonal modulating therapies are relevant to clinical trials of treatment for heart failure with preserved ejection fraction (HFpEF). AIMS: This study aimed to identify the proportion and characteristics of patients presenting with possible or confirmed HFpEF within the National Echo Database of Australia. RESULTS: A total of 237 046 women (48.1%) and 256 019 men (aged 61.0 ± 18.3 vs. 60.6 ± 17.1 years, respectively) had sex-specific distributions of LVEF: 94.3% of women had LVEF ≥ 45% (mean LVEF 66.0 ± 8.6%), compared with 87.2% of men (mean LVEF 63.4 ± 8.7%). The presence of structural heart disease (SHD) according to the PARAGON-HF criteria could be calculated in 93.8% of women and 93.4% of men with an LVEF ≥ 45%. Of these, 64 502 (30.8%) women and 104 344 (50.0%) of men had left ventricular hypertrophy, and 78 948 (35.3%) and 95 846 (42.9%), respectively, had left atrial enlargement. As a result, the proportion of women vs. men fulfilling echocardiographic criteria for HFpEF was very different: 111 497 (53.2%) vs. 146 359 (70.1%). SHD markedly increased with age, associated with a greater increase in women than men. The same signal was observed in those referred for suspected or previously confirmed HFpEF. CONCLUSIONS: Double the number of men than women had LVEF < 45%, and the distribution of SHD had was highly sex specific. Left ventricular hypertrophy and left atrial enlargement were more common in men and becoming more frequent in women with advancing age. The echocardiographic SHD distribution was similar in those referred with suspected or confirmed HFpEF. The findings are relevant to sex-specific recruitment criteria for future clinical trials.