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Objective Obesity is a risk factor for clinical cardiovascular disease, putatively via increased burden of atherosclerosis. It remains contentious as to whether weight loss in people with obesity is accompanied by a reduction in intima-media thickness, a noninvasive marker of subclinical atherosclerosis, consistent with a lowering of risk of cardiovascular events. Methods A systematic literature search was performed to identify all surgical and nonsurgical weight loss interventions that reported intima-media thickness. A meta-analysis was undertaken to obtain pooled estimates for change in intima-media thickness. Results From the 3,197 articles screened, 9 studies were included in the meta-analysis, with a total of 393 participants who lost an average of 16 kg (95% CI 9.4–22.5) of body weight over an average follow-up of 20 months. The pooled mean change in carotid intima-media thickness was −0.03 mm (95% CI −0.05 to −0.01), which was similar between surgical and nonsurgical interventions. Conclusions In people with obesity, weight loss was associated with a reduction in carotid intima-media thickness, consistent with a lowering in risk of cardiovascular events.

Background and objectives Pericardial effusion (PE) confers a poor prognosis in non-congenital pulmonary arterial hypertension (PAH). The clinical significance and prognostic implications of PE in Eisenmenger syndrome (ES) is much less well characterised. Accordingly, we aimed to define the frequency, echocardiographic characteristics, natural history and clinical sequelae of PE in those with ES. Patients and methods We retrospectively studied 55 consecutive individuals presenting since 2000, age >18 years, with ES. Analysis of clinical notes, transthoracic echocardiograms and vital status was undertaken via local records and the National Death Index. Results Mean age was 38 years (11.4SD), 22% had Down syndrome and the mean follow-up time was 14.7 years (13.4SD). Nine patients (16%) had a PE during their follow-up period with the majority being small (56%). No PE exhibited clinical or echocardiographic signs of tamponade and none required pericardiocentesis. At the time of last review, 42% of individuals had died. The presence of PE was not associated with mortality (p=0.83). Conclusions Pericardial effusion occurs relatively frequently in ES but is usually small and with no evidence of haemodynamic compromise. Pericardial effusion in this setting is not related to mortality.

Background: Objective multi-parametric risk assessment is recommended in pulmonary arterial hypertension (PAH) to identify patients at risk of early morbidity and mortality. The REVEAL 2.0 Risk Score is a new model proposed for the follow-up of PAH patients but it has not been externally validated. Methods: The REVEAL 2.0 Risk Score was applied to a mixed prevalent and incident cohort of PAH patients (n=1,011) from the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) Registry. Kaplan-Meier (KM) survival was estimated for each REVEAL 2.0 Risk Score strata and for a broader three-category (low, intermediate, high-risk) model. Results: The REVEAL 2.0 model effectively discriminated risk in the large external PHSANZ registry cohort, with c-statistic 0.74 (both for full 8-tier and three-category models). When applied to incident cases only, c-statistic was 0.73. The three-category REVEAL 2.0 model demonstrated robust separation of 12 and 60-months survival estimates (all risk categories comparisons p Conclusion: 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 PAH patients at follow-up. The simplified 3-category model may be preferred for clinical use and for future comparison with other prognostic models.

IntroductionCoronary artery disease (CAD) persists as a major cause of morbidity and mortality worldwide despite intensive identification and treatment of traditional risk factors. Data emerging over the past decade show a quarter of patients have disease in the absence of any known risk factor, and half have only one risk factor. Improvements in quantification and characterisation of coronary atherosclerosis by CT coronary angiography (CTCA) can provide quantitative measures of subclinical atherosclerosis—enhancing the power of unbiased ‘omics’ studies to unravel the missing biology of personal susceptibility, identify new biomarkers for early diagnosis and to suggest new targeted therapeutics.Methods and analysisBioHEART-CT is a longitudinal, prospective cohort study, aiming to recruit 5000 adult patients undergoing clinically indicated CTCA. After informed consent, patient data, blood samples and CTCA imaging data are recorded. Follow-up for all patients is conducted 1 month after recruitment, and then annually for the life of the study. CTCA data provide volumetric quantification of total calcified and non-calcified plaque, which will be assessed using established and novel scoring systems. Comprehensive molecular phenotyping will be performed using state-of-the-art genomics, metabolomics, proteomics and immunophenotyping. Complex network and machine learning approaches will be applied to biological and clinical datasets to identify novel pathophysiological pathways and to prioritise new biomarkers. Discovery analysis will be performed in the first 1000 patients of BioHEART-CT, with validation analysis in the following 4000 patients. Outcome data will be used to build improved risk models for CAD.Ethics and disseminationThe study protocol has been approved by the human research ethics committee of North Shore Local Health District in Sydney, Australia. All findings will be published in peer-reviewed journals or at scientific conferences.Trial registration numberACTRN12618001322224.

The Fontan circulation describes the circulatory state resulting from an operation in congenital heart disease where systemic venous return is directed to the lungs without an intervening active pumping chamber. As survival increases, so too does recognition of the potential health challenges. This document aims to allow clinicians, people with a Fontan circulation, and their families to benefit from consensus agreement about management of the person with a Fontan circulation. The document was crafted with input from a multidisciplinary group of health care providers as well as individuals with a Fontan circulation and families. It is hoped that the shared common vision of long-term wellbeing will continue to drive improvements in care and quality of life in this patient population and eventually translate into improved survival. KEYPOINTS.

Heterotaxy is considered a risk factor for poor outcomes after the Fontan operation. However, long-term data to support this notion are lacking. The aims of this study were to ascertain the long-term outcomes of patients with heterotaxy after hospital discharge after Fontan completion and to compare these outcomes with those of a contemporary nonheterotaxy cohort.A binational Fontan registry (n = 1540) was analyzed to identify patients with heterotaxy and compare them with patients without heterotaxy. The primary composite end point was Fontan failure, encompassing death, heart transplantation, Fontan takedown or conversion, protein-losing enteropathy, plastic bronchitis, or New York Heart Association functional class III or IV.A total of 109 patients with heterotaxy were identified and they were compared with 1431 nonheterotaxy patients after Fontan completion. There was no difference in unadjusted 15-year freedom from Fontan failure (heterotaxy, 78% vs nonheterotaxy, 85%; P = .2). Patients in the heterotaxy group had a significantly higher cumulative incidence of post-Fontan arrhythmias (P.001). Propensity-score matching for confounders yielded 73 patients with heterotaxy matched with 439 patients without heterotaxy, in whom 15-year freedom from Fontan failure was also not different (heterotaxy, 76% vs nonheterotaxy, 81%; P = .2). There was no difference in 15-year freedom from Fontan failure in patients with right vs left isomerism (right isomerism, 80% vs left isomerism, 76%; P = .7).Although heterotaxy may complicate the pre-Fontan course, once the Fontan procedure is successfully completed, heterotaxy does not appear to be an important risk factor for Fontan failure. Patients with heterotaxy are at a higher risk of post-Fontan arrhythmias compared with patients without heterotaxy.

ObjectivesThe mechanisms of attrition of the Fontan population have been poorly characterised and it is unclear whether some of the deaths are potentially preventable. We analysed the circumstances of late death in patients with a Fontan circulation, with a special focus on identifying lesions amenable to intervention that may have contributed to the decline of their circulation.MethodsBetween 1975 and 2018, a total of 105 patients from a Bi-National Registry died beyond 1 year after Fontan completion, at a median age of 18.6 (IQR 13.8–26.0) years old, 12.7 (IQR 6.0–19.3) years after Fontan completion.ResultsA total of 105 patients died—63 patients (60%) with an atriopulmonary (AP) Fontan, 21 patients (20%) with a lateral tunnel (LT) and 21 patients (20%) with an extracardiac conduit (ECC). 72 patients (69%) were reviewed within 2 years preceding death, with 32% (23/72) deemed to be clinically well. Fontan circulatory failure was the most common cause of death in 42 patients (45%). Other causes of death included sudden death/arrhythmia (19%), perioperative death (12%), neurological complication (7%) and thromboembolism (7%). All patients with an LT or ECC who died from Fontan failure had at least one surgical defect that was amenable to intervention at time of death.ConclusionsConventional clinical surveillance has been insensitive in detecting a significant proportion of patients at risk of late death. Fontan circulatory failure contributes to half of the late deaths. Patients with an LT or ECC Fontan who died with a clinical picture of circulation failure may have potentially correctable lesions.

Atherosclerosis underlies most myocardial infarctions and ischemic strokes. The timing of onset and the rate of progression of atherosclerosis differ between individuals and among arterial sites. Physical manifestations of atherosclerosis may begin in early life, particularly in the abdominal aorta. Measurement of the abdominal aortic intima-media thickness by external ultrasound is a non-invasive methodology for quantifying the extent and severity of early atherosclerosis in children, adolescents, and young adults. This review provides an evidence-based rationale for the assessment of abdominal aortic intima-media thickness—particularly as an age-appropriate methodology for studying the natural history of atherosclerosis in the young in comparison to other methodologies—establishes best practice methods for assessing abdominal aortic intima-media thickness, and identifies key gaps in the literature, including those that will identify the clinical relevance of this measure.

It has been 50 years since Francis Fontan pioneered the operation that today bears his name. Initially designed for patients with tricuspid atresia, this procedure is now offered for a vast array of congenital cardiac lesions when a circulation with 2 ventricles cannot be achieved. As a result of technical advances and improvements in patient selection and perioperative management, survival has steadily increased, and it is estimated that patients operated on today may hope for a 30-year survival of >80%. Up to 70 000 patients may be alive worldwide today with Fontan circulation, and this population is expected to double in the next 20 years. In the absence of a subpulmonary ventricle, Fontan circulation is characterized by chronically elevated systemic venous pressures and decreased cardiac output. The addition of this acquired abnormal circulation to innate abnormalities associated with single-ventricle congenital heart disease exposes these patients to a variety of complications. Circulatory failure, ventricular dysfunction, atrioventricular valve regurgitation, arrhythmia, protein-losing enteropathy, and plastic bronchitis are potential complications of the Fontan circulation. Abnormalities in body composition, bone structure, and growth have been detected. Liver fibrosis and renal dysfunction are common and may progress over time. Cognitive, neuropsychological, and behavioral deficits are highly prevalent. As a testimony to the success of the current strategy of care, the proportion of adults with Fontan circulation is increasing. Healthcare providers are ill-prepared to tackle these challenges, as well as specific needs such as contraception and pregnancy in female patients. The role of therapies such as cardiovascular drugs to prevent and treat complications, heart transplantation, and mechanical circulatory support remains undetermined. There is a clear need for consensus on how best to follow up patients with Fontan circulation and to treat their complications. This American Heart Association statement summarizes the current state of knowledge on the Fontan circulation and its consequences. A proposed surveillance testing toolkit provides recommendations for a range of acceptable approaches to follow-up care for the patient with Fontan circulation. Gaps in knowledge and areas for future focus of investigation are highlighted, with the objective of laying the groundwork for creating a normal quality and duration of life for these unique individuals. ispartof: CIRCULATION vol:140 issue:6 pages:E234-E284 ispartof: location:United States status: published

IntroductionRecurrence of cardiac events is common after a first event, leading to hospitalisations and increased health burden. Patients have difficulties achieving the lifestyle changes required for secondary prevention and access to secondary prevention programs is limited. This study aims to evaluate the impact of a game-based mobile app, MyHeartMate, which is designed to motivate engagement in secondary prevention behaviours for cardiovascular risk factors.Methods and analysisThe MyHeartMate study is a randomised controlled trial with 6-month follow-up and blinded assessment of the primary outcome. Participants (n=394) with coronary heart disease will be recruited from hospitals in metropolitan Sydney and randomly allocated to standard care or the MyHeartMate app intervention. The intervention group will receive the app, which uses game techniques to promote engagement and lifestyle behaviour change for secondary prevention. The primary outcome is difference between the groups in physical activity (metabolic equivalent of task minutes/week) at 6 months. Secondary outcomes include change in low-density lipoprotein cholesterol, systolic blood pressure, medication adherence, body mass index, waist circumference, mood and dietary changes at 6 months. Data on app engagement, and patient perspectives of usability and acceptability, will also be analysed.Ethics and disseminationThe study has received ethics approval from Northern Sydney Local Health District Human Research Ethics Committee. The study findings will be disseminated via peer-reviewed publications and presentation at international scientific meetings/conferences.Trial registration numberACTRN12617000869370; Pre-results.

This study sought to evaluate the effects of the Carillon device on mitral regurgitation severity and left ventricular remodeling.Functional mitral regurgitation (FMR) complicates heart failure with reduced ejection fraction and is associated with a poor prognosis.In this blinded, randomized, proof-of-concept, sham-controlled trial, 120 patients receiving optimal heart failure medical therapy were assigned to a coronary sinus-based mitral annular reduction approach for FMR or sham. The pre-specified primary endpoint was change in mitral regurgitant volume at 12 months, measured by quantitative echocardiography according to an intention-to-treat analysis.Patients (69.8 ± 9.5 years of age) were randomized to either the treatment (n = 87) or the sham-controlled (n = 33) arm. There were no significant differences in baseline characteristics between the groups. In the treatment group, 73 of 87 (84%) had the device implanted. The primary endpoint was met, with a statistically significant reduction in mitral regurgitant volume in the treatment group compared to the control group (decrease of 7.1 ml/beat [95% confidence interval [CI]: -11.7 to -2.5] vs. an increase of 3.3 ml/beat [95% CI: -6.0 to 12.6], respectively; p = 0.049). Additionally, there was a significant reduction in left ventricular volumes in patients receiving the device versus those in the control group (left ventricular end-diastolic volume decrease of 10.4 ml [95% CI: -18.5 to -2.4] vs. an increase of 6.5 ml [95% CI: -5.1 to 18.2]; p = 0.03 and left ventricular end-systolic volume decrease of 6.2 ml [95% CI: -12.8 to 0.4] vs. an increase of 6.1 ml [95% CI: -1.42 to 13.6]; p = 0.04).The Carillon device significantly reduced mitral regurgitant volume and left ventricular volumes in symptomatic patients with functional mitral regurgitation receiving optimal medical therapy. (Carillon Mitral Contour System for Reducing Functional Mitral Regurgitation [REDUCE FMR]; NCT02325830).

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.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.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.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.

This systematic review and meta-analysis was undertaken to investigate the short- and long-term clinical outcomes of concurrent repair of mild or moderate tricuspid regurgitation (TR) during left-sided valve surgery.Medline, PubMed, EMBASE, and Cochrane Libraries were searched, and 12 studies were identified, comprising 1373 patients who underwent TR repair during left-sided valve surgery and 1553 patients who did not. Of these studies, 6 were classified as having a low risk of bias (randomized controlled trials or propensity-matched studies), and 6 were considered as having a high risk of bias (nonmatched observational studies). The primary analysis included only studies with a low risk of bias (399 repair and 426 nonrepair).Primary analysis of studies at low risk of bias demonstrated that the addition of TR repair compared with nonrepair was associated with reduced risks of cardiovascular mortality, all-cause mortality, and progression of TR over a median of 5.3 years of follow-up (cardiovascular mortality: relative risk [RR], 0.46; 95% confidence interval [CI], 0.28 to 0.75; P = .002; all-cause mortality: RR, 0.68; 95% CI, 0.49 to 0.96; P = .03; and TR progression: RR, 0.26; 95% CI, 0.12 to 0.56; P.001). Cardiopulmonary bypass time was significantly shorter in the nonrepair group (mean weighted difference, 18 minutes; 95% CI, 6 to 30; P = .003), although the risk of perioperative mortality was comparable between the 2 groups (RR, 0.72; 95% CI, 0.27 to 1.97; P.05).Concurrent repair of mild or moderate TR during left-sided valve surgery is associated with improved long-term clinical outcomes without adversely affecting early survival. Should these results be validated by ongoing trials, there should be a revision of current guidelines to recommend a more aggressive approach toward TR repair.

OBJECTIVE AND PATIENTS This study aimed to characterize bone mineral density abnormalities and pathophysiological associations in young adults living with a Fontan circulation. DESIGN Participants underwent bone mineral density measurement using dual-energy X-ray absorptiometry and serum biochemical analysis, cardiopulmonary exercise and strength testing and transthoracic echocardiography. RESULTS In our cohort (n = 28), 29% had osteopenic-range bone mineral density and one patient was osteoporotic (average hip t score: -0.6 ± 1.1; spine t score: -0.6 ± 0.9). Four patients (14%) had z scores

Cardiovascular disease (CVD) is the leading cause of death and disability in women globally, accounting for 32% of deaths in females. There are several female-specific risk factors for CVD that are under appreciated clinically, insufficiently researched and not given adequate attention in CVD risk prediction. Hypertensive and metabolic disorders of pregnancy are independent risk factors for the development of premature CVD. They confer more than double the risk of CVD in exposed women, but are not included in any current, multivariable CVD risk prediction models. Failure to recognise this risk leads to a lost opportunity to identify at risk women, institute primary preventive strategies, and potentially improve their health trajectory. This also translates into a missed opportunity to educate women and their families about their CVD risks, and to a lack of awareness and prioritisation of CVD within the broader community. Improving CVD outcomes for women globally also requires attention to research methodology and analysis. Researchers should be encouraged to include a thorough pregnancy history in prospective CVD datasets and to power their studies to report on gender disaggregated CVD outcomes. Particular attention should be given to the inclusion of young women of child-bearing age in CVD intervention trials. Ultimately, women should be offered CVD assessment using gender specific risk prediction models that are validated across broad ethic and socioeconomic groups. These prediction models should account for female specific risk factors and their complex interactions with traditional risk factors. This will pave the way for a gender-specific approach to CVD diagnosis, investigation and management.

Metabolic syndrome (MS) is associated with atherosclerotic diseases. The prevalence of MS according to the Adult Treatment Panel III (ATPIII), World Health Organization (WHO), and International Diabetes Federation (IDF) criteria are variable but increasing in western countries and modernizing China. This study aimed to evaluate the prevalence of MS according to these three criteria, in farmers or ex-farming residents in three-gorges territories undergoing rapid lifestyle changes.We compared 95 residents (ex-farmers) in Wu Shan (WS) (28.4% men, aged 49.7 ± 9 years) resettled uphill for 3-5 years, and 87 age- and gender-matched farmers in Da Chang (DC) (27.6% men, aged 48.8 ± 10 years) before migration. MS and other traditional risk factors were assessed and carotid intima-media thickness (IMT) measured.Ninety-nine percent of WS residents were retired or adopted nonfarming jobs. Compared with DC farmers, WS ex-farmers had higher waist circumference, low density lipoprotein-cholesterol, and triglycerides (P 0.0001), but their blood pressures, HDL-cholesterol, and fasting glucose were similar. MS were identified in 43.2% (IDF), 36.8% (WHO), and 29.5% (ATPIII) respectively in WS ex-farmers, compared with 17.2%, 13.8%, and 11.5% respectively in DC farmers. Carotid IMT was significantly higher in WS ex-farmers (0.74 ± 0.16 mm) than in DC farmers (0.64 ± 0.11 mm) (P 0.0001). On multivariate regression analysis, prevalence of MS was correlated with job nature (beta = 0.425, P 0.0001). Carotid IMT was better correlated with IDF MS criteria (beta = 0.208, P = 0.021), independent of age and WS location (regression adjusted RIDF MS criteria is more sensitive, better correlates with atherosclerosis surrogate, and accordingly is more readily applicable to modernizing China.

Aims The optimal timing for pulmonary valve replacement in asymptomatic patients with repaired Tetralogy of Fallot (rTOF) and pulmonary regurgitation remains uncertain but is often guided by increases in right ventricular (RV) end-diastolic volume. As cardiopulmonary exercise testing (CPET) performance is a strong prognostic indicator, we assessed which cardiovascular magnetic resonance (CMR) parameters correlate with reductions in exercise capacity to potentially improve identification of high-risk patients. Methods and results In all, 163 patients with rTOF (mean age 24.5 ± 10.2 years) who had previously undergone CMR and standardized CPET protocols were included. The indexed right and left ventricular end-diastolic volumes (RVEDVi, LVEDVi), right and left ventricular ejection fractions (RVEF, LVEF), indexed RV stroke volume (RVSVi), and pulmonary regurgitant fraction (PRF) were quantified by CMR and correlated with CPET-determined peak oxygen consumption (VO2) or peak work. On univariable analysis, there was no significant correlation between RVEDVi and PRF with peak VO2 or peak work (% Jones-predicted). In contrast, RVEF and RVSVi had significant correlations with both peak VO2 and peak work that remained significant on multivariable analysis. For a previously established prognostic peak VO2 threshold of Conclusion In rTOF, CMR indices of RV systolic function are better predictors of CPET performance than RV size. An RVEF

Since the 1st World Symposium on Pulmonary Hypertension (WSPH) in 1973, pulmonary hypertension (PH) has been arbitrarily defined as mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest, measured by right heart catheterisation. Recent data from normal subjects has shown that normal mPAP was 14.0±3.3 mmHg. Two standard deviations above this mean value would suggest mPAP >20 mmHg as above the upper limit of normal (above the 97.5th percentile). This definition is no longer arbitrary, but based on a scientific approach. However, this abnormal elevation of mPAP is not sufficient to define pulmonary vascular disease as it can be due to an increase in cardiac output or pulmonary arterial wedge pressure. Thus, this 6th WSPH Task Force proposes to include pulmonary vascular resistance ≥3 Wood Units in the definition of all forms of pre-capillary PH associated with mPAP >20 mmHg. Prospective trials are required to determine whether this PH population might benefit from specific management. Regarding clinical classification, the main Task Force changes were the inclusion in group 1 of a subgroup “pulmonary arterial hypertension (PAH) long-term responders to calcium channel blockers”, due to the specific prognostic and management of these patients, and a subgroup “PAH with overt features of venous/capillaries (pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis) involvement”, due to evidence suggesting a continuum between arterial, capillary and vein involvement in PAH., State of the art and research perspectives of haemodynamic definitions and clinical classification of pulmonary hypertension http://ow.ly/TJeR30mgWKj

Carotid-femoral pulse wave velocity is associated with arterial stiffness in major elastic arteries, and predicts future cardiovascular events. However, little is known about carotid-femoral pulse wave velocity as a marker of vascular health in children. Semi-automated cuff-based devices for assessing pulse wave velocity are increasingly popular, although these utilize an algorithm developed and validated in adults. Physiological differences between adults and children may, however, reduce the accuracy of cuff-based methods. We sought to determine the accuracy of a cuff-based pulse wave velocity device in healthy children, and determine whether a novel age-appropriate algorithm increases accuracy. We recruited 29 healthy children between the ages of 2 and 20 years. Pulse wave velocity was measured both by using a tonometer on the carotid artery and an inflated cuff on the thigh, and using a tonometer on both the carotid artery and femoral artery as a reference standard. Accuracy of the cuff-based device with its standard algorithm developed in adults, and a novel age-appropriate algorithm corrected for physiological differences in leg pulse wave velocity was assessed with Regression analysis and Bland-Altman plots. Cuff-based device estimates of pulse wave velocity had excellent agreement to the reference standard (Δ = -0.26 ms

A patent foramen ovale (PFO) is a remnant interatrial communication, best diagnosed with transoesophageal echocardiography (TOE) and bubble study. Although quite common and often asymptomatic, PFO is associated with cryptogenic stroke and migraine. Approximately one-half of patients with a cryptogenic stroke have a PFO, and the dilemma regarding whether or not to proceed with percutaneous device closure, to reduce the risk of future recurrent events due to paradoxical embolism, has been subject to debate for nearly two decades. Despite promising observational data, initial randomised clinical trials failed to demonstrate superiority of closure over medical therapy. However, long-term follow-up data from one of these early trials, combined with two new randomised trials, have provided more evidence for the benefits of closure in selected patients. This new evidence suggests that younger patients with high-risk features such as an atrial septal aneurysm (ASA) or large interatrial shunt are more likely to benefit from PFO closure, after fastidious exclusion of an alternative cause for the index stroke. However, issues which require further clarification include whether anticoagulant therapy is preferable to antiplatelet therapy for medical management, and which particular type of closure device is optimal. Finally, despite promising retrospective observational data suggesting improvement in migraine attacks after PFO closure, high quality evidence is lacking in this regard.

Background: Carotid femoral pulse wave velocity (cfPWV) is directly associated with arterial stiffness in major elastic arteries and predicts future cardiovascular events (1). Little is known of cfPWV as a marker of vascular health in children. Semi-automated cuff-based devices for assessing cfPWV are increasingly popular, although these utilize an algorithm developed and validated in adults (2). Physiological differences between adults and children may thus reduce the accuracy of cuff-based. Methods: We sought to determine the accuracy of a cuff-based cfPWV device in healthy children and determine whether an age-appropriate algorithm increases accuracy. Methods we prospectively recruited 29 healthy children (mean age = 11.5 ± 5.2 years old). cfPWV was measured using a tonometer on the carotid artery and an inflated cuff on the thigh (Sphygmocor XCEL; AtCor Medical, Australia), and using a tonometer on both the carotid artery and femoral artery (SphygmoCor CvMS; AtCor Medical, Australia) as a reference method. We assessed the accuracy of the cuff-based device with its standard algorithm that was developed in adults, and an adjusted algorithm corrected for physiological differences in leg (femoral to thigh cuff) PWV between adult and children (3). Results: Cuff-based device estimates of cfPWV in children had excellent agreement to the reference standard (r = 0.85; Δ = −0.26 ms−1 [SD 0.44]). The adjusted algorithm improved the accuracy of the cuff-based method (r = 0.84; Δ=0.02 ms−1 [SD 0.44]) (Figure 1). Conclusions: Although the cuff-based semi-automatic approach estimates cfPWV with excellent agreement to the reference standard, adjusting the algorithm for known differences in leg PWV improves the accuracy of cuff-based measurement in children.

Objectives: Carotid-femoral pulse wave velocity (cfPWV) is a validated non-invasive measure of aortic stiffness. Risk factors for cfPWV are well described in adulthood, and furthermore cfPWV is associated with incident cardiovascular disease in adults (1). However, risk factors for arterial stiffness in childhood are poorly described (2). Accordingly, we sought to determine the risk factors for cfPWV in childhood and adolescence and hypothesized that cfPWV would be higher amongst those with greater adiposity. Methods: We prospectively recruited 88 healthy children (mean age = 11.0 ± 5.3 years old). Age, weight, height, and blood pressure were measured. cfPWV was assessed using a semi-automated cuff-based device (Sphygmocor XCEL; AtCor Medical, Australia), and body composition using air displacement plethysmography (BOD POD; Cosmed, Italy) (3). Associations with cfPWV were determined by multivariable linear regression, with subsequent mediation analyses to inform likely causal pathways. Results: After adjusting for age and sex, cfPWV was significantly associated with weight, body mass index (BMI), systolic blood pressure, mean blood pressure, heart rate, and lean body mass (LBM), while LBM was significantly associated with height, weight, BMI and fat mass (Table 1). After further adjusting for weight, mean blood pressure and heart rate, LBM remained significantly associated with cfPWV (ß = 0.68; p = 0.007). Mediation analyses indicate that weight mediates the association between age and cfPWV (PM = 76%), and that LBM mediates the relationship between weight and cfPWV (Figure 1). Conclusion: Higher cfPWV in healthy children and adolescents is a function of growth, and this association may be in turn mediated by higher LBM rather than adiposity.

Background: Bicuspid aortic valve (BAV) is a common congenital heart disease which is associated with aortic dilatation. There is controversy in the literature regarding the various measures of the biomechanical properties of the aorta in these patients and their relationship to aortic dilatation. The present study aimed to assess both conventional 2D Cardiac Magnetic Resonance Imaging (CMRI) measurements of aortic biomechanics (compliance and distensibility) and a computational fluid dynamics (CFD) approach in patients with BAV and either normal or dilated ascending aorta. Methods: 2D CMRI was performed in 18 patients (6 controls, 6 BAV with dilated ascending aorta and 6 BAV with normal ascending aorta i.e.

Objectives A significant proportion of renal transplant patients have cardiovascular comorbidities for which they receive treatment with antiplatelet agents. The aim of this study was to systematically review the current literature reporting perioperative outcomes for patients receiving dual antiplatelet therapy compared to single antiplatelet therapy at the time of kidney transplantation with particular reference to the risks of postoperative haemorrhage. Materials and Methods Embase, Medline and Cochrane databases were utilized to identify articles reporting outcomes of renal transplant recipients on single antiplatelet therapy and dual antiplatelet therapy. These outcomes were compared using a random effects model meta-analysis where appropriate. Results Six articles were incorporated in the analysis, including 130 receiving dual antiplatelet therapy, and 781 in the single antiplatelet therapy group. There was a significantly higher risk of post-operative haemorrhagic events in the dual antiplatelet therapy group compared to the single antiplatelet therapy group (RR 1.58, 95% CI 1.19–2.09, p = 0.001). Post-operative cardiovascular event rates were similar between both groups in individual studies, although this could not be quantitatively analysed. Conclusions The use of dual antiplatelet therapy was associated with a higher risk of post-operative haemorrhage compared to the use of single antiplatelet therapy without increased rates of surgical intervention. However, the use of dual antiplatelet therapy may provide protection from cardiovascular events in an inherently higher risk patient group.

ObjectivesLong-term single-site ventricular pacing may adversely affect ventricular function, due to dyssynchronous systemic ventricular contraction. We sought to determine the incidence, predictors and outcomes of pacing-associated cardiomyopathy (PACM) in an adult congenital heart disease (ACHD) cohort.MethodsWe retrospectively identified all patients in our database with a permanent pacemaker from 2000 to 2019. Patients were followed for the primary endpoint of unexplained decline in systemic ventricular function (PACM) and the secondary endpoint of heart failure admission.ResultsOf 2073 patients in our database, 106 had undergone pacemaker implantation. Over a median follow-up of 9.4 years, 25 patients (24%) developed PACM, but only in those with ventricular pacing percentage (VP%) ≥70%; PACM occurred in 0% of those with VP ConclusionsIn a cohort of patients with ACHD followed long-term post-pacing, 24% developed cardiomyopathy that was significantly associated with a higher burden of ventricular pacing (VP ≥70%). Given promising response rates to CRT, patients with ACHD expected to pace in the ventricle should be closely monitored for systemic ventricular decline.

ObjectivesA small proportion of patients undergoing bicuspid aortic valve (BAV) intervention have had prior repair of aortic coarctation (CoA). We aimed to describe phenotypic differences between BAV patients, comparing those with versus those without previous coarctation repair.Methods556 adults with BAV who had undergone aortic valve and/or ascending aortic surgery were identified, and relevant clinical and operative details were retrospectively analysed.ResultsOf the total cohort, 532 patients (95.7%) had isolated BAV (‘BAV-only’), and 24 (4.3%) had had a previous successful CoA repair (‘BAV-CoA’). The median age at surgery was significantly lower in BAV-CoA patients compared with BAV-only (median, IQR: 40 years, 26–57 vs 62 years, 51–69, pConclusionIn adult patients undergoing aortic valve surgery for BAV disease, those with a prior history of repaired CoA underwent surgery at a very much younger age, and a higher proportion required intervention for aortic regurgitation.

Purpose To quantitatively characterize the central role of vortex formation on the flow patterns and energy transfer within the right atrium (RA). Materials and Methods 4D-flow magnetic resonance imaging (MRI) data with multiple encoding velocities was acquired in 12 healthy subjects at 3T. Particles entering the RA were classified according to the origin of entry. Vortex membership was numerically derived by assessing the location of pathline center of curvature relative to the vortex core, defined by Q-criteria. Flow dynamics and energetics were assessed using paired t-tests. Results The majority of flow (74%) passes through the RA in a single beat, with a very small volume fraction retained longer than two beats (

Background The number and age demographic of the future Fontan population is unknown. Methods Population projections were calculated probabilistically using microsimulation. Mortality hazard rates for each Fontan recipient were calculated from survivorship of 1353 Fontan recipients in the Australia and New Zealand Fontan Registry, based on Fontan type, age at Fontan, gender and morphology. Projected rates of new Fontan procedures were generated from historical rates of Fontan procedures per population births. Results At the end of 2014, the living Fontan population of Australia and New Zealand was 1265 people from an Australian and New Zealand regional population of 28 million (4.5 per 100,000 population). Of those, 165 (13%) received an atrio-pulmonary (AP) procedure, 262 (21%) a lateral tunnel (LT) procedure and 838 (66%) an extra-cardiac conduit (ECC) procedure. This population is expected to grow to 1917 (95% CI: 1846: 1986) by 2025 (5.8 per 100,000 population), with 149 (8%) AP procedures, 254 (13%) LT procedures, and 1514 (79%) ECC procedures. By 2045, the living Fontan population is expected to reach 2986 (95% CI: 2877: 3085; 7.2 per 100,000 population). The average age of the Fontan population is expected to increase from 18years in 2014 to 23years (95% CI: 22–23) by 2025, and 31years (95% CI: 30–31) by 2045. Conclusion The Australian and New Zealand population of patients alive after a Fontan procedure will double over the next 20years increasing the demand for heart-failure services and cardiac transplantation. Greater consideration for the needs of this mostly adult Fontan population will be necessary.

Tropical endomyocardial fibrosis (EMF) is a neglected disease of poverty that afflicts rural populations in tropical low-income countries, with some certain high-prevalence areas. Tropical EMF is characterized by the deposition of fibrous tissue in the endomyocardium, leading to restrictive physiology. Since the first descriptions in Uganda in 1948, high-frequency areas for EMF have included Africa, Asia, and South America. Although there is no clear consensus on a unified hypothesis, it seems likely that dietary, environmental, and infectious factors may combine in a susceptible individual to give rise to an inflammatory process leading to endomyocardial damage and scar formation. The natural history of EMF includes an active phase with recurrent flare-ups of inflammation evolving to a chronic phase leading to restrictive heart failure. In the chronic phase, biventricular involvement is the most common presentation, followed by isolated right-sided heart disease. Marked ascites out of proportion to peripheral edema usually develops as a typical feature of EMF. EMF carries a very poor prognosis. In addition to medical management of heart failure, early open heart surgery (endocardectomy and valve repair/replacement) appears to improve outcomes to some extent; however, surgery is technically challenging and not available in most endemic areas. Increased awareness among health workers and policy makers is the need of the hour for the unhindered development of efficient preventive and therapeutic strategies.

Disordered neovascularization and impaired wound healing are important contributors to diabetic vascular complications. We recently showed that high-density lipoproteins (HDLs) enhance ischemia-mediated neovascularization, and mounting evidence suggests HDL have antidiabetic properties. We therefore hypothesized that HDL rescue diabetes-impaired neovascularization. Streptozotocin-induced diabetic mice had reduced blood flow recovery and neovessel formation in a hindlimb ischemia model compared with nondiabetic mice. Reconstituted HDL (rHDL) infusions in diabetic mice restored blood flow recovery and capillary density to nondiabetic levels. Topical rHDL application rescued diabetes-impaired wound closure, wound angiogenesis, and capillary density. In vitro, rHDL increased key mediators involved in hypoxia-inducible factor-1α (HIF-1α) stabilization, including the phosphoinositide 3-kinase/Akt pathway, Siah1, and Siah2, and suppressed the prolyl hydroxylases (PHD) 2 and PHD3. rHDL rescued high glucose–induced impairment of tubulogenesis and vascular endothelial growth factor (VEGF) A protein production, a finding associated with enhanced phosphorylation of proangiogenic mediators VEGF receptor 2 and endothelial nitric oxide synthase. Siah1/2 small interfering RNA knockdown confirmed the importance of HIF-1α stability in mediating rHDL action. Lentiviral short hairpin RNA knockdown of scavenger receptor class B type I (SR-BI) in vitro and SR-BI−/− diabetic mice in vivo attenuated rHDL rescue of diabetes-impaired angiogenesis, indicating a key role for SR-BI. These findings provide a greater understanding of the vascular biological effects of HDL, with potential therapeutic implications for diabetic vascular complications.

In the second year of this journal, Timothy Cartmill (Figure 1a) provided a succinct history of the development of paediatric cardiac surgery, which had benefitted greatly from the contribution of local figures like Sir Brian Barratt-Boyes [1]. By the 1970s, three of the premier units in the world for the care of complex congenital heart disease (CHD) had been established in Australia and New Zealand (ANZ): in Auckland, Sydney and Melbourne. The tradition of multidisciplinary care established by these units – between dedicated surgeons, cardiologists, radiologists and anaesthetists – pervaded the region through generations of their trainees. The 1980s and 90s saw mortality for repair of most lesions in infancy and childhood fall to 2% overall [2]. Echocardiography and prenatal ultrasound enabled foetal detection and early accurate diagnosis, and the ready availability of prostaglandin ensured survival to transfer to tertiary referral centres. Once lesions were repaired, the technological developments available in intensive care allowed effective multi-organ support for even the smallest bodies. Cartmill concluded that, ‘‘It remains to understand the pathology more clearly, to develop the techniques . . . and to refine preoperative and postoperative care.’’ [1] Teams in Australia and New Zealand have led too many clinical and research developments in the field of congenital heart disease in the last 25 years to list comprehensively. In this editorial, we chronicle some of the most influential and innovative work from the region. These achievements have led to a better understanding of the pathology and natural history Figure 1 Legends whose legacies still shape congenital heart disease today: (a) Timothy Cartmill, (b) Roger Mee, (c) Sir Brian Barratt-Boyes.

Cardiac disease accounts for a large burden of premature mortality and morbidity in patients with type 1 myotonic dystrophy (MD). However, little is known about structural cardiac abnormalities particularly in asymptomatic patients with MD. We sought to describe the prevalence and extent of structural cardiac abnormalities in patients with MD and to assess their association with functional, electrical, biochemical and genetic disturbances.In this case-control study, 40 adults with MD who had no contraindications to cardiac MRI (CMR) were identified from the Grampian region genetic database. Forty-one age-and-gender-matched healthy volunteers were also recruited. All subjects underwent detailed assessment including CMR, echocardiography, electrocardiography, signal-averaged electrocardiography, Holter monitoring and quantification of serum B-type natriuretic peptide (BNP). Genetic testing of patients with MD was performed with quantification of CTG trinucleotide repeat sequences. Results of clinical, electrical, genetic and biochemical investigations were correlated with cardiac structural and functional abnormalities detected on CMR.Electrical disturbances including prolongation of PR (187±29 vs 156±23 ms, p0.001) and QRS intervals (99±11 vs 89±9 ms, p0.001) were the most prevalent abnormality. Patients with MD had a significantly lower left ventricular (LV) mass (142±44 vs 172±73 g, p=0.03) and lower right ventricular (RV) ejection fraction (46±9 vs 50±7%, p=0.02) compared with controls, although LV ejection fraction was similar between the groups (58±8 vs 59±6%, p=0.34). LV non-compaction was also significantly more prevalent in the MD cohort (35% vs 12%, p=0.019). Late gadolinium enhancement was present in 13% of patients with MD. Muscular disability scores correlated with electrical changes (r=0.529, p0.001); however, the number of CTG repeat sequences did not correlate with either electrical or structural abnormalities.Patients with MD have a high prevalence of both electrical and structural abnormalities. These include reduced LV mass, impaired RV contractility, a high prevalence of LV non-compaction and myocardial fibrosis. These findings illustrate the potential utility of CMR detecting subclinical disease in otherwise asymptomatic patients with MD.

Despite a lack of evidence supporting the use of angiotensin-converting enzyme (ACE) inhibitors in patients with a Fontan circulation, their use is frequent. We decided to identify the rationale for ACE inhibitor therapy in patients within the Australia and New Zealand Fontan Registry.All patients in the Registry taking an ACE inhibitor at last follow up were identified, and a review of medical records was undertaken to determine the rationale for treatment initiation and reasons for treatment continuation or dose increase.In 2015, 36% of the surviving patients in the Registry (462/1268) were taking an ACE inhibitor. Indications for initiation of therapy were ventricular systolic or diastolic dysfunction (29%), atrioventricular valve regurgitation (19%), preservation of normal ventricular function (7%), prolonged effusions at Fontan (6%), hypertension (6%), other (6%) and unknown (2%). No indication was stated in the remaining patients (25%). Those with hypoplastic left heart syndrome were more likely to be on an ACE inhibitor than those with an alternative primary morphology (70% vs 32%; p0.001). Only 36% of the patients treated with an ACE inhibitor at last follow up (166/462) had an indication that would generally justify treatment in a two-ventricle circulation.It is likely that the use of ACE inhibitors in patients with a Fontan circulation is excessive within our region. The coordination of prospective, multicentre studies and initiatives such as the Australia and New Zealand Fontan Registry will facilitate further investigations to guide treatment decisions in the growing Fontan population.

Background: Elevated maternal blood glucose concentrations may contribute to macrosomia, adiposity, and poorer vascular health in the offspring. Objective: The aim was to explore the effect of a low-glycemic index (low-GI) diet during pregnancy on offspring growth, adiposity, and arterial wall thickness during infancy. Design: This was a longitudinal follow-up study in a self-selected subgroup of mother-infant pairs (n = 59) participating in a larger randomized trial comparing the effects on perinatal outcomes of a low-GI diet and a conventional high-fiber (HF) diet during pregnancy. Infant anthropometric measurements were taken every month for 6 mo and then at 9 and 12 mo of age. Adiposity was assessed at birth and at 3 mo by air-displacement plethysmography by using the Pea Pod system (Cosmed) and at 6 and 12 mo by bioimpedance analysis (Bodystat). Aortic intima-media thickness was assessed at 12 mo by high-resolution ultrasound (Philips). Results: Maternal dietary GI was lower in the low-GI group than in the HF group (51 ± 1 compared with 57 ± 1; P , 0.001). No differences in neonatal outcomes were observed in the main trial. In the self-selected subsample, birth weight and length z scores were lower in the low-GI group than in the HF group (birth weight z score: 0.2 ± 0.2 compared with 0.7 ± 0.2, respectively; P = 0.04; birth length z score: 0.3 ± 0.2 compared with 0.9 ± 0.2, respectively; P = 0.04), but adiposity from birth to 12 mo of age and growth trajectories from 1 to 12 mo of age were similar. Aortic intima-media thickness was lower in the low-GI group than in the HF group (657 612 compared with 696 ± 12 mm, respectively; P = 0.02), which was partly mediated by differences in birth weight. Conclusion: In women at risk of gestational diabetes mellitus, a low-GI diet influences offspring birth weight, birth length, and arterial wall thickness in early childhood, but not adiposity or growth trajectory during the first year of life. This trial was registered at anzctr.org.au as ACTRN12610000681055.

Experimental evidence suggests that structural changes to the arterial adventitia may be a key vascular determinant of early arterial stiffening, although this has not been directly studied. Accordingly, we hypothesized that in young children, in whom this relationship would not be altered by atheroma, carotid extramedial thickness (EMT), a measure that incorporates the thickness of the arterial adventitia, perivascular tissues and the internal jugular venous wall, would be associated with localized arterial stiffness of the same arterial region.We studied 248 healthy prepubescent children (aged 8 years). Carotid diameter and carotid EMT were measured by high-resolution ultrasound. Carotid blood pressure was derived from brachial blood pressure and carotid tonometry. Three measures of localized arterial stiffness (β stiffness index, distensibility coefficient and incremental modulus of elasticity) were calculated for the common carotid artery. Results were adjusted for heart rate and DBP, two important hemodynamic determinants of arterial stiffness.Carotid EMT was associated with all three measures of arterial stiffness (β stiffness index: standardized β = 0.121, P = 0.03; distensibility coefficient: standardized β = -0.121, P = 0.05; incremental modulus of elasticity: standardized β = 0.140, P = 0.02). These associations remained significant after adjustment for potential confounders such as sex, height, waist circumference, BMI and body surface area.Carotid EMT is associated with the stiffness of the same arterial segment in children, suggesting that the arterial adventitia may be involved in early changes in arterial stiffness during childhood.

Percutaneous coronary intervention has revolutionized the treatment of coronary artery disease. Successive improvements in implantation techniques, stent materials and design, combined with dual antiplatelet therapy have improved stent safety. However, optimal biocompatibility and long-term effectiveness in the absence of pharmaceutical intervention remains elusive. Drug-eluting stents, introduced to combat in-stent restenosis was found to impair endothelial regeneration, increasing thrombotic risk. Innovations in polymer technology and new stent designs have improved, but not solved, these issues. Despite the drawbacks of drug elution it remains a key component of stent platforms, leaving the need for a truly biocompatible platform with lasting clinical efficacy and safety unmet. This review will examine current stent designs and explore proactive approaches to enhance stent biocompatibility.

The Fontan operation for single ventricle palliation consists of the creation of a complete cavopulmonary connection, usually by incorporating inferior vena caval flow into a pulmonary arterial circulation already receiving flow from the superior vena cava. In single ventricle palliated in this way, the anatomy is complex, and the pathophysiological complications are frequent; so, cardiac imaging is a key aspect of clinical surveillance. Common problems that echocardiography and MRI may disclose and characterise in the Fontan palliation of single ventricle include obstruction of systemic venous and pulmonary arterial flow, atrioventricular and semilunar valve dysfunction, unintended collateral flow patterns, ventricular dysfunction, aortic arch obstruction, interatrial obstruction, fenestration flow and patch leaks. Despite the broad scope of these modalities for detection of such problems, often no single imaging method is comprehensive in any given patient. Therefore, physicians must recognise the limitations of each modality, and circumvent these by application of suitable alternatives. New imaging tools are becoming available, which may ultimately prove to be of value in the Fontan circulation. Proper application of diverse new technologies such as four dimensional flow, computational fluid dynamics and three-dimensional printing will require critical evaluation in the single ventricle population.

A 28-year-old male was admitted to hospital with an acute ST-elevation myocardial infarction. This was in the context of recreational abuse of nitrous oxide. The prevalence of nitrous oxide use in Australia has not been formally quantified, however it is the second most commonly used recreational drug in the United Kingdom. Nitrous oxide has previously been shown to increase serum homocysteine levels. This patient was discovered to have an elevated homocysteine level at baseline, which was further increased after nitrous oxide consumption. Homocysteine has been linked to endothelial dysfunction and coronary atherosclerosis and this case report highlights one of the dangers of recreational abuse of nitrous oxide.

There are limited data to describe the relationship between the transvalvular gradient and mortality among patients who undergo aortic valve replacement.Using the National Echo Database Australia, valvular hemodynamics were characterized in 3,943 men (mean age, 62 ± 18 years) and 2,107 women (mean age, 62 ± 19 years) who underwent aortic valve replacement (median follow-up duration, 770 days; interquartile range, 381-1,584 days). The degree of impaired valvular hemodynamics (IVH) was categorized as mild (mean gradient 10.0-19.9 mm Hg, peak velocity 2.0-2.9 m/sec), moderate (mean gradient 20.0-39.9 mm Hg, peak velocity 3.0-3.9 m/sec), or severe (mean gradient ≥ 40.0 mm Hg, peak velocity ≥ 4 m/sec or effective orifice area0.8 cmOverall, 2,175 (36.0%), 2,598 (42.9%), 698 (11.5%), and 579 (9.6%) patients had no, mild, moderate, and severe IVH, respectively. Those with residual moderate or severe IVH had 5-year mortality of 45.5% and 57.3%, respectively, and higher adjusted long-term all-cause mortality (adjusted hazard ratios, 1.44 and 2.02; P .001) compared with "no IVH." Patients with mild IVH had similar mortality rates to those without IVH. A mortality threshold was evident above a mean transvalvular gradient22.5 mm Hg after adjusting for age, sex, stroke volume index, aortic regurgitation, and effective orifice area.After aortic valve replacement, most patients displayed an acceptable aortic valve hemodynamic profile. Moderate to severe IVH, however, was associated with poor long-term survival, with a threshold for increased mortality similar to that of native valvular aortic stenosis evident.

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 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.

PFO-associated platypnea-orthodeoxia syndrome (POS) is characterised by dyspnoea and hypoxaemia when upright. The pathogenesis is thought to involve an increase in right atrial pressure or change in degree of right to left shunting with upright posture due to structural change. We sought to