Ischaemia with no obstructive coronary arteries: a review with focus on the Asian population.

ABSTRACT: Ischaemia with no obstructive coronary arteries (INOCA) has been a diagnostic and therapeutic challenge for decades. Several studies have demonstrated that INOCA is associated with an increased risk of death, adverse cardiovascular events, poor quality of life and high healthcare cost. Although there is increasing recognition of this entity in the Western population, in the Asian population, INOCA remains elusive and its prevalence uncertain. Despite its prognostic significance, diagnosis of INOCA is often delayed. In this review, we identified the multiple barriers to its diagnosis and management, and proposed strategies to overcome them.

Propensity-score matched analysis of patent foramen ovale closure in real-world study cohort with cryptogenic ischemic stroke.

INTRODUCTION: Patent foramen ovale (PFO) occurs in 25% of the general population and in 40% of cryptogenic ischemic stroke patients. Recent trials support PFO closure in selected patients with cryptogenic stroke. We examined the outcomes of transcatheter PFO closure in a real-world study cohort with cryptogenic stroke. METHODS: Consecutive ischemic stroke patients who were classified as cryptogenic on the TOAST aetiology and diagnosed with a PFO were included. All patients underwent either transcatheter PFO closure or medical therapy. A 2:1 propensity score matching by sex and Risk-of-Paradoxical-Embolism (RoPE) score was performed. Multivariable regression models adjusted for sex and RoPE score. RESULTS: Our cohort comprised 232 patients with mean age 44.3 years (SD 10.8) and median follow-up 1486.5 days. 33.2% were female. PFO closure (n=84) and medical therapy (n=148) groups were well-matched with <10% mean-difference in sex and RoPE score. Two patients in the treated group (2.4%) and seven in the control group (4.7%) had a recurrent ischemic stroke event. Multivariable Cox regression demonstrated a hazard-ratio of 0.26 (95%CI 0.03-2.13, P=0.21) for PFO closure compared to control. The incidence of atrial fibrillation (AF) detected post-PFO closure was similar between the treated and control (1.19% vs 1.35%, multivariable logistic regression odds-ratio 0.90, 95%CI 0.04-9.81, P=0.94). There were no major periprocedural complications documented. The difference in restricted mean survival-time free from stroke at two years between treated and control was 26.2 days (95%CI 5.52-46.85, P=0.013). CONCLUSIONS: In this Asian cohort, we report a low incidence of ischemic stroke recurrence and new-onset AF in patients who underwent PFO closure. When compared to the medical therapy group, there was no significant difference in the incidence of stroke recurrence and new-onset AF. Further studies involving larger real-world cohorts are warranted to identify patients who are more likely to benefit from PFO closure.

Age- and sex-specific reference values of biventricular flow components and kinetic energy by 4D flow cardiovascular magnetic resonance in healthy subjects.

BACKGROUND: Advances in four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) have allowed quantification of left ventricular (LV) and right ventricular (RV) blood flow. We aimed to (1) investigate age and sex differences of 4D flow CMR-derived LV and RV relative flow components and kinetic energy (KE) parameters indexed to end-diastolic volume (KEiEDV) in healthy subjects; and (2) assess the effects of age and sex on these parameters. METHODS: We performed 4D flow analysis in 163 healthy participants (42% female; mean age 43 ± 13 years) of a prospective registry study (NCT03217240) who were free of cardiovascular diseases. Relative flow components (direct flow, retained inflow, delayed ejection flow, residual volume) and multiple phasic KEiEDV (global, peak systolic, average systolic, average diastolic, peak E-wave, peak A-wave) for both LV and RV were analysed. RESULTS: Compared with men, women had lower median LV and RV residual volume, and LV peak and average systolic KEiEDV, and higher median values of RV direct flow, RV global KEiEDV, RV average diastolic KEiEDV, and RV peak E-wave KEiEDV. ANOVA analysis found there were no differences in flow components, peak and average systolic, average diastolic and global KEiEDV for both LV and RV across age groups. Peak A-wave KEiEDV increased significantly (r = 0.458 for LV and 0.341 for RV), whereas peak E-wave KEiEDV (r = - 0.355 for LV and - 0.318 for RV), and KEiEDV E/A ratio (r = - 0.475 for LV and - 0.504 for RV) decreased significantly, with age. CONCLUSION: These data using state-of-the-art 4D flow CMR show that biventricular flow components and kinetic energy parameters vary significantly by age and sex. Age and sex trends should be considered in the interpretation of quantitative measures of biventricular flow. Clinical trial registration  https://www. CLINICALTRIALS: gov . Unique identifier: NCT03217240.

Pulmonary Artery Strain Predicts Prognosis in Pulmonary Arterial Hypertension.

BACKGROUND: Current cardiac magnetic resonance (CMR) imaging in pulmonary arterial hypertension (PAH) focuses on measures of ventricular function and coupling. OBJECTIVES: The purpose of this study was to evaluate pulmonary artery (PA) global longitudinal strain (GLS) as a prognostic marker in patients with PAH. METHODS: The authors included 169 patients with PAH from the ASPIRE (Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre) and INITIATE (Integrated computatioNal modelIng of righT heart mechanIcs and blood flow dynAmics in congeniTal hEart disease) registries, and 82 normal controls with similar age and gender distributions. PA GLS was derived from CMR feature tracking. Right ventricular measurements including volumes, ejection fraction, and right ventricular GLS were also derived from CMR. Patients were followed up a median of 34 months with all-cause mortality as the primary endpoint. Other known risk scores were collected, including the REVEAL (Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management) 2.0 and COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension) 2.0 scores. RESULTS: Of 169 patients (mean age: 57 ± 15 years; 80% female), 45 (26.6%) died (median follow-up: 34 months). Mean PA GLS was 23% ± 6% in normal controls and 10% ± 5% in patients with PAH (P < 0.0001). Patients with PA GLS <9% had a higher risk of mortality than those with PA GLS ≥9% (P < 0.001), and this was an independent predictor of mortality in PAH on multivariable analysis after adjustment for known risk factors (HR: 2.93; P = 0.010). Finally, in patients with PAH, PA GLS provided incremental prognostic value over the REVEAL 2.0 (global chi-square; P = 0.001; C statistic comparison; P = 0.030) and COMPERA 2.0 (global chi-square; P = 0.001; C statistic comparison; P = 0.048). CONCLUSIONS: PA GLS confers incremental prognostic utility over the established risk scores for identifying patients with PAH at higher risk of death, who may be targeted for closer monitoring and/or intensified therapy.

First use of large-bore suction thrombectomy for acute pulmonary embolism in Asia-Pacific: feasibility and short-term clinical outcomes.

Clinical outcomes for intermediate or high-risk pulmonary emboli (PE) remain sub-optimal, with limited improvements in survival for the past 15 years. Anticoagulation alone results in slow thrombus resolution, persistent right ventricular (RV) dysfunction, patients remaining at risk of haemodynamic decompensation and increased likelihood of incomplete recovery. Thrombolysis elevates risk of major bleeding and is thus reserved for high-risk PE. Thus, a huge clinical need exists for an effective technique to restore pulmonary perfusion with minimal risk and avoidance of lytic therapy. In 2021, large bore suction thrombectomy (ST) was introduced in Asia for the first time and this study assessed the feasibility and short-term outcomes of Asian patients undergoing ST for acute PE. 40 consecutive patients (58% male, mean age of 58.3 ± 16.6 years) with intermediate (87.5%) or high-risk PE (12.5%) were enrolled in this prospective registry. 20% had prior VTE, 42.5% had contraindications to thrombolysis, and 10% failed to respond to thrombolysis. PE was idiopathic in 40%, associated with active cancer in 15% and post-operative status in 12.5%. Procedural time was 124 ± 30 min. Emboli were aspirated in all patients without the need for thrombolytics, resulting in a 21.4% reduction in mean pulmonary arterial pressures and 123% increase TASPE-PASP ratio, a prognostic measure of RV-arterial coupling. (both p < 0.001) Procedural complications were 5% and 87.5% patients survived to discharge without symptomatic VTE recurrence during 184 days of mean follow-up. ST affords an effective reperfusion option for PE without thrombolytics, normalises RV overload and provides excellent short-term clinical outcomes.

Association of Shunt Size and Long-Term Clinical Outcomes in Patients with Cryptogenic Ischemic Stroke and Patent Foramen Ovale on Medical Management.

INTRODUCTION: Patent foramen ovale (PFO) is a potential source of cardiac embolism in cryptogenic ischemic stroke, but it may also be incidental. Right-to-left shunt (RLS) size may predict PFO-related stroke, but results have been controversial. In this cohort study of medically-managed PFO patients with cryptogenic stroke, we aimed to investigate the association of shunt size with recurrent stroke, mortality, newly detected atrial fibrillation (AF), and to identify predictors of recurrent stroke. METHODS: Patients with cryptogenic stroke who screened positive for a RLS using a transcranial Doppler bubble study were included. Patients who underwent PFO closure were excluded. Subjects were divided into two groups: small (Spencer Grade 1, 2, or 3; n = 135) and large (Spencer Grade 4 or 5; n = 99) shunts. The primary outcome was risk of recurrent stroke, and the secondary outcomes were all-cause mortality and newly detected AF. RESULTS: The study cohort included 234 cryptogenic stroke patients with medically-managed PFO. The mean age was 50.5 years, and 31.2% were female. The median period of follow-up was 348 (IQR 147-1096) days. The rate of recurrent ischemic stroke was higher in patients with large shunts than in those with small shunts (8.1% vs. 2.2%, p = 0.036). Multivariate analyses revealed that a large shunt was significantly associated with an increased risk of recurrent ischemic stroke [aOR 4.09 (95% CI 1.04-16.0), p = 0.043]. CONCLUSIONS: In our cohort of cryptogenic stroke patients with medically managed PFOs, those with large shunts were at a higher risk of recurrent stroke events, independently of RoPE score and left atrium diameter.

Extrapulmonary manifestations and complications of severe acute respiratory syndrome coronavirus-2 infection: a systematic review.

Introduction: We aimed to describe the extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including their frequency, onset with respect to respiratory symptoms, pathogenesis and association with disease severity. Methods: We searched the MEDLINE and Embase databases for SARS-CoV-2-related studies. Meta-analysis, observational studies, case series and case reports published in English or Chinese between 1 January 2020 and 1 May 2020 were included. Reports with only paediatric or obstetric cases were excluded. Results: 169 articles were included. Early manifestations (preceding respiratory symptoms until Day 6 of onset) included olfactory and gustatory disturbance (self-reported in up to 68% and 85% of cases, respectively), gastrointestinal symptoms (up to 65.9%) and rash (up to 20.4%). From Day 7 onwards, hypercytokinaemia, paralleled multi-organ complications including acute cardiac injury (pooled incidence of 17.7% in 1,412 patients, mostly with severe disease and 17.4% mortality), kidney and liver injury (up to 17% and 33%, respectively) and thrombocytopenia (up to 30%). Hypercoagulability resulted in venous thromboembolic events in up to 31% of all patients. Uncommon disease presentation and complications comprised Guillain-Barré syndrome, rhabdomyolysis, otitis media, meningoencephalitis and spontaneous pneumomediastinum. Conclusion: Although the systemic manifestations of SARS-CoV-2 infection are variegated, they are deeply interwoven by shared mechanisms. Two phases of extrapulmonary disease were identified: (a) an early phase with possible gastrointestinal, ocular and cutaneous involvement; and (b) a late phase characterised by multiorgan dysfunction and clinical deterioration. A clear, multidisciplinary consensus to define and approach thromboinflammation and cytokine release syndrome in SARS-CoV-2 is needed.

Effects of sex on clinical outcomes of hypertrophic cardiomyopathy in Singapore.

Introduction: Despite the growing recognition that sex can affect the presentation and outcomes in hypertrophic cardiomyopathy (HCM), this relationship is understudied in Asians. Therefore, we aimed to explore sex differences in Asian patients with HCM. Method: A total of 295 consecutive patients diagnosed with HCM were recruited from a tertiary cardiology centre from 2010 to 2017 over a mean of 3.9±2.7 years. We evaluated the effects of sex on the outcomes of HCM in Asian patients. Results: HCM patients were more commonly men (72%). Women were older and had more comorbidities, including hypertension and atrial fibrillation. On transthoracic echocardiography, the indexed left ventricular end-systolic and end-diastolic volumes were similar, but more women had more-than-moderate mitral regurgitation and had a smaller left ventricular outflow tract (LVOT). Women more commonly had findings of obstructive physiology with significant LVOT obstruction, defined as >30 mmHg at rest. The use of implantable cardioverter defibrillators was similar across sexes. On multivariable analysis, women were found to be more likely to develop progressive heart failure requiring admission (hazard ratio [HR] 2.10, 95% confidence interval [CI] 1.05-4.71, P=0.021) but had a lower rate of all-cause mortality (HR 0.36, 95% CI 0.19-0.70, P=0.003). Conclusion: Women diagnosed with HCM were older, had more comorbidities and were more likely to develop heart failure while men had a higher risk of all-cause mortality.

Right ventricular energetic biomarkers from 4D Flow CMR are associated with exertional capacity in pulmonary arterial hypertension.

BACKGROUND: Cardiovascular magnetic resonance (CMR) offers comprehensive right ventricular (RV) evaluation in pulmonary arterial hypertension (PAH). Emerging four-dimensional (4D) flow CMR allows visualization and quantification of intracardiac flow components and calculation of phasic blood kinetic energy (KE) parameters but it is unknown whether these parameters are associated with cardiopulmonary exercise test (CPET)-assessed exercise capacity, which is a surrogate measure of survival in PAH. We compared 4D flow CMR parameters in PAH with healthy controls, and investigated the association of these parameters with RV remodelling, RV functional and CPET outcomes. METHODS: PAH patients and healthy controls from two centers were prospectively enrolled to undergo on-site cine and 4D flow CMR, and CPET within one week. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes (EDV). Phasic (peak systolic, average systolic, and peak E-wave) LV and RV blood flow KE indexed to EDV (KEIEDV) and ventricular LV and RV flow components (direct flow, retained inflow, delayed ejection flow, and residual volume) were calculated. Oxygen uptake (VO2), carbon dioxide production (VCO2) and minute ventilation (VE) were measured and recorded. RESULTS: 45 PAH patients (46 ± 11 years; 7 M) and 51 healthy subjects (46 ± 14 years; 17 M) with no significant differences in age and gender were analyzed. Compared with healthy controls, PAH had significantly lower median RV direct flow, RV delayed ejection flow, RV peak E-wave KEIEDV, peak VO2, and percentage (%) predicted peak VO2, while significantly higher median RV residual volume and VE/VCO2 slope. RV direct flow and RV residual volume were significantly associated with RV remodelling, function, peak VO2, % predicted peak VO2 and VE/VCO2 slope (all P < 0.01). Multiple linear regression analyses showed RV direct flow to be an independent marker of RV function, remodelling and exercise capacity. CONCLUSION: In this 4D flow CMR and CPET study, RV direct flow provided incremental value over RVEF for discriminating adverse RV remodelling, impaired exercise capacity, and PAH with intermediate and high risk based on risk score. These data suggest that CMR with 4D flow CMR can provide comprehensive assessment of PAH severity, and may be used to monitor disease progression and therapeutic response. TRIAL REGISTRATION NUMBER: https://www. CLINICALTRIALS: gov . Unique identifier: NCT03217240.

EFFECTIVENESS OF RESIN INFILTRATION IN CARIES INHIBITION AND AESTHETIC APPEARANCE IMPROVEMENT OF WHITE-SPOT LESIONS: AN UMBRELLA REVIEW.

OBJECTIVES: Resin infiltration technique is a minimal interventive approach to manage white-spot lesions. The present umbrella review aimed to comprehensively appraise the previously published systematic reviews on the effectiveness of resin infiltration in arresting caries progression and improving the aesthetic appearance of white-spot lesions. MATERIAL AND METHODS: Ten electronic databases were searched between January 1960 and May 2021. Only systematic reviews published in English on the use of resin infiltration in primary or permanent teeth were included. The degree of overlap across each review was calculated using the Corrected Covered Areas method and their evidence quality were assessed using A MeaSurement Tool to Assess systematic Reviews 2 assessment tool. Umbrella meta-analysis was carried out using a random-effects model. RESULTS: Thirteen systematic reviews were chosen, but only eight were eligible for an umbrella meta-analysis. The overall Corrected Covered Areas value was very high (19.8%), whereas only three studies were classified as 'High Quality'. Qualitative synthesis suggested that resin infiltration demonstrated acceptable aesthetic results, whereas quantitative analysis showed favourable outcomes in minimizing the risk of caries progression (RR: 0.32; 95% CI: 0.29-0.36). White-spot lesions treated with resin infiltrant in permanent teeth demonstrated a lower risk of caries progression (P < .001) than primary teeth. Overall, low data heterogeneity was observed (I2: 0%-20%). However, quantitative umbrella analysis on the aesthetic outcome was unable to perform due to limited data. CONCLUSION: Resin infiltration can be regarded as an effective treatment modality in minimizing the risk of caries progression and improving the aesthetic appearance of white-spot lesions. Future well-designed high-quality systematic reviews with long-term follow-up and more control of confounding variables are warranted.

Prevalence, Risk Factors and Intervention for Depression and Anxiety in Pulmonary Hypertension: A Systematic Review and Meta-analysis.

BACKGROUND: Current guidelines recommend psychological support for patients with pulmonary hypertension suffering from psychological adversity. However, little is known about the prevalence and risk factors of depression and anxiety in patients with pulmonary hypertension (PH). METHODS: Medline and Embase were searched from inception to 6 May 2021. Meta-analysis of proportions using the generalized linear mixed model was conducted to analyze the pooled prevalence rates of depression and anxiety in PH patients. Risk factors for depression and anxiety in PH patients were evaluated using meta regression. RESULTS: A total of 24 studies involving 2,161 PH patients were included. The pooled prevalence of depression in PH was 28.0% (95% CI: 20.5-36.8) and pooled prevalence of anxiety was 37.1% (95% CI: 28.7-46.4). There was a significantly higher prevalence of anxiety (p = 0.0013) amongst PH patients in Asia (61.1%) compared to Europe (40.3%) and North America (22.9%). In terms of risk factors, congenital heart disease-related pulmonary arterial hypertension (PAH-CHD) were significantly associated with both depression (OR: 1.68, 95% CI: 1.27-2.23, p = 0.024) and anxiety (OR: 1.63, 95% CI: 1.45-1.83, p = 0.002). On the other hand, chronic thromboembolic pulmonary hypertension (CTEPH, OR: 1.18, 95% CI: 1.10-1.26, p = 0.004) was significantly associated with depression, whereas worse pulmonary vascular resistance (ß: 0.30, 95% CI: 0.09-0.52, p = 0.005) and cardiac index (ß: -0.96, 95% CI: -1.58 to -0.35, p = 0.002) were significantly correlated with anxiety. CONCLUSION: The prevalence of anxiety and depression in PH patients is alarmingly high, with an increased prevalence of anxiety in Asia compared to Europe or North America. Psychological support is warranted for patients with PH, particularly those with underlying congenital heart disease, CTEPH, and severe disease. SYSTEMATIC REVIEW REGISTRATION: CRD42021251733.

Is pulpotomy a promising modality in treating permanent teeth? An umbrella review.

Emerging evidence suggests the use of less invasive therapy such as pulpotomy in treating permanent teeth with pulp exposure and signs of pulpitis. Hence, this umbrella review aims to evaluate the available systematic reviews on pulpotomy treated permanent teeth. Articles published between January 1970 and May 2021 were searched in ten electronic databases and five textbooks. Only systematic reviews published in English that examined the use of pulpotomy on either carious or traumatic pulpal exposed in mature or immature permanent teeth with signs of pulpitis were selected. The Corrected Covered Areas (CCAs) were calculated to identify the overlap in primary studies, whereas the AMSTAR 2 assessment tool was used to analyze the risk of bias in each included review. Nine systematic reviews were chosen of which two systematic reviews focused solely on coronal pulpotomy, one on partial pulpotomy, and the remaining focused on both coronal and partial pulpotomies. Overall, only two reviews were rated as 'High Quality'. Umbrella analyses showed that both coronal and partial pulpotomies revealed overall high success rates ranging from 88.5% to 90.6%. However, the currently available evidence on the effects of different pulpal medicaments and restorative materials on the success rate of pulpotomy were still inconclusive. Pulpotomy can be regarded as a promising modality in treating mature and immature permanent teeth with carious pulpal exposure or signs of pulpitis. Nonetheless, further high-quality clinical trials with long-term follow-up and better control of confounding factors are warranted in the future.

Does pulmonary artery pulsatility index predict mortality in pulmonary arterial hypertension?

AIMS: Pulmonary artery pulsatility index (PAPi), defined as [(pulmonary artery systolic pressure - diastolic pulmonary artery pressure)/mean right atrial pressure], is a novel haemodynamic index that predicts right ventricular failure after myocardial infarction and left ventricular assist device implantation. We analysed if a low PAPi is associated with death in our 14 - â€‹year pulmonary arterial hypertension (PAH) registry. METHODS: Consecutive patients with newly diagnosed PAH and complete haemodynamic data were prospectively enrolled into our standing registry between January 2003 and December 2016. PAPi was calculated from baseline invasive right heart catheterization data. A prognostic cut-off value was determined with a decision tree. Baseline characteristics of 'high' and 'low' PAPi groups based on this cut-off were compared, as well as odds of death and time-to-death. RESULTS: One hundred and two patients were included. Mean age was 53 years, and 77% were women. Our multi-ethnic cohort was 64% Chinese, 23% Malay, and 10% Indian. The aetiologies were idiopathic (33%), connective tissue disease (31%), congenital heart disease (24%), and others (12%). The low PAPi group (<5.3) had a greater age (56 years vs. 49 years), lower pulmonary artery systolic pressure (71 mmHg vs. 85 mmHg), and higher mean right atrial pressure (14 mmHg vs. 6 mmHg). Mortality risk was higher in the low PAPi group (adjusted odds ratio: 2.98 and adjusted hazard ratio: 2.23). Mean right atrial pressure was the strongest predictor (hazard ratio 1.114, P = 0.009) when components of PAPi were analysed. CONCLUSIONS: Pulmonary artery pulsatility index was found to be predictive of mortality in PAH and may be a valuable marker for risk stratification. Its prognostic strength may be driven by mean right atrial pressure.

Pulmonary arterial hypertension in pregnancy-a systematic review of outcomes in the modern era.

Pregnancy is hazardous with pulmonary arterial hypertension, but maternal mortality may have fallen in recent years. We sought to systematically evaluate pulmonary arterial hypertension and pregnancy-related outcomes in the last decade. We searched for articles describing outcomes in pregnancy cohorts published between 2008 and 2018. A total of 3658 titles were screened and 13 studies included for analysis. Pooled incidences and percentages of maternal and perinatal outcomes were calculated. Results showed that out of 272 pregnancies, 214 pregnancies advanced beyond 20 gestational weeks. The mean maternal age was 28 ± 2 years, mean pulmonary artery systolic pressure on echocardiogram was 76 ± 19 mmHg. Etiologies include idiopathic pulmonary arterial hypertension (22%), congenital heart disease (64%), and others (15%). Majority (74%) had good functional class I/II. Only 48% of women received pulmonary arterial hypertension-specific therapy. Premature deliveries occur in 58% of pregnancies at mean of 34 ± 1 weeks, most (76%) had Cesarean section. Maternal mortality rate was 12% overall (n = 26); even higher for idiopathic pulmonary arterial hypertension etiology alone (20%). Reported causes of death included right heart failure, cardiac arrest, pulmonary arterial hypertension crises, pre-eclampsia, and sepsis; 61% of maternal deaths occur at 0-4 days postpartum. Stillbirth rate was 3% and neonatal mortality rate was 1%. In conclusion, pulmonary arterial hypertension in pregnancy continues to be perilous with high maternal mortality rate. Continued prospective studies are needed.

An Asian Perspective on Gender Differences in Clinical Outcomes and Echocardiographic Profiles of Patients With Medically Managed Severe Aortic Stenosis.

BACKGROUND: Gender differences in valvular heart disease are increasingly recognised. A prior study has suggested better surgical outcomes in women with symptomatic aortic stenosis (AS). We investigate gender differences in medically managed severe AS. METHOD: We studied 347 patients with severe AS (aortic valve area index <0.6 cm2/m2) in terms of baseline clinical background, echocardiographic characteristics, and clinical outcomes. Appropriate univariate and multivariate models were employed, while Kaplan-Meier curves were constructed to compare mortality outcomes. RESULTS: In total, 205 (59%) patients were women. Despite higher incidences of hypertension (75.6% vs 47.3%) and diabetes mellitus (46.5% vs 29.5%) in women, women had improved survival (Kaplan-Meier log-rank = 6.24, p = 0.012). After adjusting for age (hazard ratio [HR], 1.034; 95% confidence interval [CI], 1.014-1.054), hypertension (HR, 1.469; 95% CI, 0.807-2.673), diabetes (HR, 1.219; 95% CI, 0.693-2.145), and indexed aortic valve area (HR 0.145, 95% CI 0.031-0.684) on multivariate analyses, female gender remained independently associated with lower mortality (HR, 0.561; 95%, CI 0.332-0.947). Women tended to have smaller body surface area (BSA), left ventricular (LV) internal diastolic diameter, and smaller LV outflow tract diameter but were similar to men in terms of LV ejection fraction, AS severity, and patterns of LV remodelling. CONCLUSIONS: Women appeared to have better outcomes compared to men in medically managed severe AS. These gender differences warrant further study and may affect prognosis, follow-up, and timing of valve surgery.

Help-seeking patterns and funding strategies in patients with pulmonary arterial hypertension on phosphodiesterase-5 inhibitors: an orphan disease with effective but costly treatment.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is associated with high medical and pharmaceutical costs. Phosphodiesterase type 5 (PDE5) inhibitors have been found to be beneficial but costly. They are not subsidised in Singapore except via the Medication Assistance Fund (MAF) Plus scheme. In this study, we described the help-seeking behaviour of patients and funding strategies for Singaporean patients on PDE5 inhibitors in our registry. METHODS: We consecutively recruited all patients with PAH who presented to our pulmonary hypertension specialty centre between 1 January 2003 and 29 December 2016. Singaporean patients on PDE5 inhibitors were included. Data recorded and analysed for this study included baseline demographics, whether the patients received MAF Plus funding, percentage of funding, and any additional source of subsidies. RESULTS: 114 (77.0%) of 148 patients in the registry were Singapore citizens on PDE5 inhibitors. 75 (65.8%) of these 114 patients had been seen by a medical social worker, of whom 16 were on MAF Plus funding. 14 of the remaining 59 patients were subsidised by MediFund, whereas the remainder were self-paying. 30 (26.3%) patients in total were on some form of subsidy, and 28 (24.6%) patients were on combination therapy. Of this group, nine were receiving MAF Plus subsidies. CONCLUSION: Fewer than expected patients were found to be receiving drug subsidies for PAH. This was partly due to insufficient referrals and lack of requests for financial assistance. Patients on combination therapy had greater financial challenges. This study should spur us on to study funding gaps further and address them.