Prognostic benefits of His-Purkinje capture in physiological pacemakers for bradycardia.

INTRODUCTION: Clinical outcomes of long-term ventricular septal pacing (VSP) without His-Purkinje capture remain unknown. This study evaluated the differences in clinical outcomes between conduction system pacing (CSP), VSP, and right ventricular pacing (RVP). METHODS: Consecutive patients with bradycardia indicated for pacing from 2016 to 2022 were prospectively followed for the clinical endpoints of heart failure (HF)-hospitalizations and all-cause mortality at 2 years. VSP was defined as septal pacing due to unsuccessful CSP implant or successful CSP followed by loss of His-Purkinje capture within 90 days. RESULTS: Among 1016 patients (age 73.9 ± 11.2 years, 47% female, 48% atrioventricular block), 612 received RVP, 335 received CSP and 69 received VSP. Paced QRS duration was similar between VSP and RVP, but both significantly longer than CSP (p < .05). HF-hospitalizations occurred in 130 (13%) patients (CSP 7% vs. RVP 16% vs. VSP 13%, p = .001), and all-cause mortality in 143 (14%) patients (CSP 7% vs. RVP 19% vs. VSP 9%, p < .001). The association of pacing modality with clinical events was limited to those with ventricular pacing (Vp) > 20% (pinteraction < .05). Adjusting for clinical risk factors among patients with Vp > 20%, VSP (adjusted hazard ratio [AHR]: 4.74, 95% confidence interval [CI]: 1.57-14.36) and RVP (AHR: 3.08, 95% CI: 1.44-6.60) were associated with increased hazard of HF-hospitalizations, and RVP (2.52, 95% CI: 1.19-5.35) with increased mortality, compared to CSP. Clinical endpoints did not differ between VSP and RVP with Vp > 20%, or amongst groups with Vp < 20%. CONCLUSION: Conduction system capture is associated with improved clinical outcomes. CSP should be preferred over VSP or RVP during pacing for bradycardia.

The prognostic value of metabolic dysfunction-associated steatotic liver disease in acute myocardial infarction: A propensity score-matched analysis.

AIM: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at increased risk of incident cardiovascular disease. However, the clinical characteristics and prognostic importance of MASLD in patients presenting with acute myocardial infarction (AMI) have yet to be examined. METHODS: This study compared the characteristics and outcomes of patients with and without MASLD presenting with AMI at a tertiary centre in Singapore. MASLD was defined as hepatic steatosis, with at least one of five metabolic criteria. Hepatic steatosis was determined using the Hepatic Steatosis Index. Propensity score matching was performed to adjust for age and sex. The Kaplan-Meier curve was constructed for long-term all-cause mortality. Cox regression analysis was used to investigate independent predictors of long-term all-cause mortality. RESULTS: In this study of 4446 patients with AMI, 2223 patients with MASLD were matched with patients without MASLD using propensity scores. The mean follow-up duration was 3.4 ± 2.4 years. The MASLD group had higher rates of obesity, diabetes and chronic kidney disease than their counterparts. Patients with MASLD had early excess all-cause mortality (6.8% vs. 3.6%, p < .001) at 30 days, with unfavourable mortality rates sustained in the long-term (18.3% vs. 14.5%, p = .001) compared with those without MASLD. After adjustment, MASLD remained independently associated with higher long-term all-cause mortality (hazard ratio 1.330, 95% confidence interval 1.106-1.598, p = .002). CONCLUSION: MASLD embodies a higher burden of metabolic dysfunction and is an independent predictor of long-term mortality in the AMI population. Its early identification may be beneficial for risk stratification and provide therapeutic targets for secondary preventive strategies in AMI.

Global longitudinal strain and plasma biomarkers for prognosis in heart failure complicated by diabetes: a prospective observational study.

BACKGROUND: Heart failure (HF) and diabetes are associated with increased incidence and worse prognosis of each other. The prognostic value of global longitudinal strain (GLS) measured by cardiovascular magnetic resonance (CMR) has not been established in HF patients with diabetes. METHODS: In this prospective, observational study, consecutive patients (n = 315) with HF underwent CMR at 3T, including GLS, late gadolinium enhancement (LGE), native T1, and extracellular volume fraction (ECV) mapping. Plasma biomarker concentrations were measured including: N-terminal pro B-type natriuretic peptide(NT-proBNP), high-sensitivity troponin T(hs-TnT), growth differentiation factor 15(GDF-15), soluble ST2(sST2), and galectin 3(Gal-3). The primary outcome was a composite of all-cause mortality or HF hospitalisation. RESULTS: Compared to those without diabetes (n = 156), the diabetes group (n = 159) had a higher LGE prevalence (76 vs. 60%, p < 0.05), higher T1 (1285±42 vs. 1269±42ms, p < 0.001), and higher ECV (30.5±3.5 vs. 28.8±4.1%, p < 0.001). The diabetes group had higher NT-pro-BNP, hs-TnT, GDF-15, sST2, and Gal-3. Diabetes conferred worse prognosis (hazard ratio (HR) 2.33 [95% confidence interval (CI) 1.43-3.79], p < 0.001). In multivariable Cox regression analysis including clinical markers and plasma biomarkers, sST2 alone remained independently associated with the primary outcome (HR per 1 ng/mL 1.04 [95% CI 1.02-1.07], p = 0.001). In multivariable Cox regression models in the diabetes group, both GLS and sST2 remained prognostic (GLS: HR 1.12 [95% CI 1.03-1.21], p = 0.01; sST2: HR per 1 ng/mL 1.03 [95% CI 1.00-1.06], p = 0.02). CONCLUSIONS: Compared to HF patients without diabetes, those with diabetes have worse plasma and CMR markers of fibrosis and a more adverse prognosis. GLS by CMR is a powerful and independent prognostic marker in HF patients with diabetes.

Remote intensive management to improve antiplatelet adherence in acute myocardial infarction: a secondary analysis of the randomized controlled IMMACULATE trial.

This study aim to investigate if remote intensive coaching for the first 6 months post-AMI will improve adherence to the twice-a-day antiplatelet medication, ticagrelor. Between July 8, 2015, to March 29, 2019, AMI patients were randomly assigned to remote intensive management (RIM) or standard care (SC). RIM participants underwent 6 months of weekly then two-weekly consultations to review medication side effects and medication adherence coaching by a centralized nurse practitioner team, whereas SC participants received usual cardiologist face-to-face consultations. Adherence to ticagrelor were determined using pill counting and serial platelet reactivity measurements for 12 months. A total of 149 (49.5%) of participants were randomized to RIM and 152 (50.5%) to SC. Adherence to ticagrelor was similar between RIM and SC group at 1 month (94.4 ± 0.7% vs. 93.6±14.7%, p = 0.537), 6 months (91.0±14.6% vs. 90.6±14.8%, p = 0.832) and 12 months (87.4±17.0% vs. 89.8±12.5%, p = 0.688). There was also no significant difference in platelet reactivity between the RIM and SC groups at 1 month (251AU*min [212-328] vs. 267AU*min [208-351], p = 0.399), 6 months (239AU*min [165-308] vs. 235AU*min [171-346], p = 0.610) and 12 months (249AU*min [177-432] vs. 259AU*min [182-360], p = 0.678). Sensitivity analysis did not demonstrate any association of ticagrelor adherence with bleeding events and major adverse cardiovascular events. RIM, comprising 6 months of intensive coaching by nurse practitioners, did not improve adherence to the twice-a-day medication ticagrelor compared with SC among patients with AMI. A gradual decline in ticagrelor adherence over 12 months was observed despite 6 months of intensive coaching.

Conduction system versus biventricular pacing in heart failure with non-left bundle branch block.

INTRODUCTION: The benefits of cardiac resynchronization therapy (CRT) with biventricular pacing (BiV) is significantly lower when applied to heart failure (HF) patients with non-left bundle branch block (LBBB) conduction delay. We investigated clinical outcomes of conduction system pacing (CSP) for CRT in non-LBBB HF. METHODS: Consecutive HF patients with non-LBBB conduction delay undergoing CSP were propensity matched for age, sex, HF-etiology, and atrial fibrillation (AF) in a 1:1 ratio to BiV from a prospective registry of CRT recipients. Echocardiographic response was defined as an increase in left ventricular ejection fraction (LVEF) by ≥10%. The primary outcome was the composite of HF-hospitalizations or all-cause mortality. RESULTS: A total of 96 patients were recruited (mean age 70 ± 11years, 22% female, 68% ischemic HF and 49% AF). Significant reductions in QRS duration and LV dimensions were seen only after CSP, while LVEF improved significantly in both groups (p < 0.05). Echocardiographic response occurred more frequently in CSP than BiV (51% vs. 21%, p < 0.01), with CSP independently associated with four-fold increased odds (adjusted odds ratio 4.08, 95% confidence interval [CI] 1.34-12.41). The primary outcome occurred more frequently in BiV than CSP (69% vs. 27%, p < 0.001), with CSP independently associated with 58% risk reduction (adjusted hazard ratio [AHR] 0.42, 95% CI 0.21-0.84, p = 0.01), driven by reduced all-cause mortality (AHR 0.22, 95% CI 0.07-0.68, p < 0.01), and a trend toward reduced HF-hospitalization (AHR 0.51, 95% CI 0.21-1.21, p = 0.12). CONCLUSIONS: CSP provided greater electrical synchrony, reverse remodeling, improved cardiac function and survival compared to BiV in non-LBBB, and may be the preferred CRT strategy for non-LBBB HF.

Outcomes of supraventricular tachycardia ablation: Results from the Singapore ablation and cardiac devices registry.

BACKGROUND: The Singapore Cardiac Databank was designed to monitor the performance and outcomes of catheter ablation. We investigated the outcomes of paroxysmal supraventricular tachycardia (PSVT)-ablation in a prospective, nationwide, cohort study. METHODS: Atrioventricular nodal re-entrant tachycardia (AVNRT), atrioventricular re-entry tachycardia (AVRT), or atrial tachycardia (AT)-ablations in Singapore from 2010 to 2018 were studied. Outcomes include acute success, periprocedural-complications, postoperative pacing requirement, arrhythmic recurrence and 1-year all-cause mortality. RESULTS: Among 2260 patients (mean age 45 ± 18 years, 50% female, 57% AVNRT, 37% AVRT, 6% AT), overall acute success rates of PSVT-ablation was 98.4% and increased in order of AT, AVRT, and AVNRT (p < .001). Periprocedural cardiac tamponade occurred in two AVRT patients. A total of 15 pacemakers (6 within first 30-days, 9 after 30-days) were implanted (seven AV block, eight sinus node dysfunction [SND]), with the highest incidence of pacemaker implantation after AT-ablation (5% vs. 0.6% AVNRT vs. 0.1% AVRT, p < .001). Repeat ablations (0.9% AVNRT, 7% AVRT, 4% AT, p < .001) were performed in 78 (3.5%) patients and 13 (0.6%) patients died within a year of ablation. Among outcomes considered adjusting for age, sex, PSVT-type and procedure-time, AT was independently associated with 6-fold increased odds of total (adjusted odds ratio [AOR] 6.32, 95% confidence interval [CI] 1.95-20.53) and late (AOR 6.38, 95% CI 1.39-29.29) pacemaker implantation, while AVRT was associated with higher arrhythmic recurrence with repeat ablations (AOR 4.72, 95% CI 2.36-9.44) compared to AVNRT. CONCLUSIONS: Contemporary PSVT ablation is safe with high acute success rates. Long-term outcomes differed by nature of the PSVT.

Comparison of biodegradable and newer generation durable polymer drug-eluting stents with short-term dual antiplatelet therapy: a systematic review and Bayesian network meta-analysis of randomized trials comprising of 43,875 patients.

Newer generation durable polymer drug-eluting stents (DP-DES) and biodegradable polymer DES (BP-DES) have similar efficacy with dual-antiplatelet therapy (DAPT) duration of > 6 months. However, this difference in outcomes have not been well studied in shorter DAPT regime. This study compares the safety and efficacy profiles of DP-DES and BP-DES based on short-term (1-3 months), intermediate-term (4-6 months) and standard DAPT (6-12 months) durations. A search was conducted on Embase and Medline for Randomized Controlled Trials (RCTs) comparing stent types, and DAPT durations. Primary endpoints include cardiac death, myocardial infarction (MI), definite stent thrombosis, stroke, target vessel revascularization (TVR) and major bleeding. Network analysis was conducted to summarize the evidence. A total of 15 RCTs involving 43,875 patients were included. DP-DES was associated with significantly lower major bleeding rates compared to BP-DES (RR 0.44, Crl 0.22-0.83) in short-term DAPT. Among DP-DES patients, short-term DAPT was associated with lower major bleeding risk compared to standard DAPT (RR 0.47, CrI 0.32-0.69). This favorable bleeding profile with short DAPT was not found in BP-DES patients. Cardiac death, MI, definite stent thrombosis, stroke and TVR rates were similar across the various DAPT durations and stent types. Our preliminary findings demonstrated comparable efficacy and safety outcomes between BP-DES and newer generation BP-DES across various DAPT durations. In patients requiring short DAPT, DP-DES had more favourable major bleeding profile compared to BP-DES, without compromising anti-thrombotic efficacy.

Temporal Changes in Extracellular Vesicle Hemostatic Protein Composition Predict Favourable Left Ventricular Remodeling after Acute Myocardial Infarction.

The subset of plasma extracellular vesicles (EVs) that coprecipitate with low-density lipoprotein (LDL-EVs) carry coagulation and fibrinolysis pathway proteins as cargo. We investigated the association between LDL-EV hemostatic/fibrinolysis protein ratios and post-acute myocardial infarction (post-AMI) left ventricular (LV) remodeling which precedes heart failure. Protein concentrations of von Willebrand factor (VWF), SerpinC1 and plasminogen were determined in LDL-EVs extracted from plasma samples obtained at baseline (within 72 h post-AMI), 1 month and 6 months post-AMI from 198 patients. Patients were categorized as exhibiting adverse (n = 98) or reverse (n = 100) LV remodeling based on changes in LV end-systolic volume (increased or decreased ≥15) over a 6-month period. Multiple level longitudinal data analysis with structural equation (ML-SEM) model was used to assess predictive value for LV remodeling independent of baseline differences. At baseline, protein levels of VWF, SerpinC1 and plasminogen in LDL-EVs did not differ between patients with adverse versus reverse LV remodeling. At 1 month post-AMI, protein levels of VWF and SerpinC1 decreased whilst plasminogen increased in patients with adverse LV remodeling. In contrast, VWF and plasminogen decreased whilst SerpinC1 remained unchanged in patients with reverse LV remodeling. Overall, compared with patients with adverse LV remodeling, higher levels of SerpinC1 and VWF but lower levels of plasminogen resulted in higher ratios of VWF:Plasminogen and SerpinC1:Plasminogen at both 1 month and 6 months post-AMI in patients with reverse LV remodeling. More importantly, ratios VWF:Plasminogen (AUC = 0.674) and SerpinC1:Plasminogen (AUC = 0.712) displayed markedly better prognostic power than NT-proBNP (AUC = 0.384), troponin-I (AUC = 0.467) or troponin-T (AUC = 0.389) (p < 0.001) to predict reverse LV remodeling post-AMI. Temporal changes in the ratios of coagulation to fibrinolysis pathway proteins in LDL-EVs outperform current standard plasma biomarkers in predicting post-AMI reverse LV remodeling. Our findings may provide clinical cues to uncover the cellular mechanisms underpinning post-AMI reverse LV remodeling.

Severe Functional Tricuspid Valve Regurgitation: Predictors of Mortality After Initial Diagnosis.

BACKGROUND: Severe functional tricuspid regurgitation (fTR) is associated with adverse clinical outcomes and remains under-treated. There is recent interest in this disease due to emerging tricuspid valve therapies. However, the timing and selection of patients who may benefit from treatment is uncertain. Risk factors associated with mortality after diagnosis of severe fTR may help guide treatment. AIM: We studied patients with severe fTR to assess predictors of mortality. METHODS: We retrospectively identified consecutive patients who had severe fTR diagnosed on transthoracic echocardiography in a single academic tertiary hospital. These were categorised into atrial fibrillation (AF)- and non-AF-related groups. Patient characteristics and echocardiographic parameters were collected. We then analysed the collected parameters on their impact on occurrence of mortality and also on the time to mortality. RESULTS: A total of 635 patients with severe fTR were studied (41.6 % male, mean age of 68.6±15.4 yrs). There were 130 (20.5%) in the AF-related group and 505 (79.5%) in the non-AF related-group. Median follow-up duration was 774 days, during which 154 (24.3%) deaths occurred within the first year. Older age on diagnosis, reduced left ventricular ejection fraction (LVEF) (<50%), high pulmonary systolic pressure (PASP) (>50 mmHg) and a prior history of heart failure admissions were associated with occurrence of mortality. Older age on diagnosis, reduced LVEF, and high PASP were also found to be associated with time to mortality. CONCLUSIONS: For patients diagnosed with severe fTR, advanced age on diagnosis, prior heart failure admission, LVEF <50%, and PASP >50 mmHg are associated with mortality. These factors could form the basis of future studies that determine the timing and decision to intervene in patients with severe fTR.

Atrial Fibrillation and the Prognostic Performance of Biomarkers in Heart Failure.

BACKGROUND: Consideration of circulating biomarkers for risk stratification in heart failure (HF) is recommended, but the influence of atrial fibrillation (AF) on prognostic performance of many markers is unclear. We investigated the influence of AF on the prognostic performance of circulating biomarkers in HF. METHODS: N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional-pro-atrial natriuretic peptide, C-type natriuretic peptide (CNP), NT-proCNP, high-sensitivity troponin-T, high-sensitivity troponin-I, mid-regional-propeptide adrenomedullin, co-peptin, growth differentiation factor-15, soluble Suppressor of Tumorigenicitiy (sST2), galectin-3, and procalcitonin plasma concentrations were measured in a prospective, multicenter study of adults with HF. AF was defined as a previous history of AF, and/or presence of AF/flutter on baseline 12-lead electrocardiogram. The primary outcome was the composite of HF-hospitalization or all-cause mortality at 2 years. RESULTS: Among 1099 patients (age 62 ± 12years, 28% female), 261(24%) patients had AF. Above-median concentrations of all biomarkers were independently associated with increased risk of the primary outcome. Significant interactions with AF were detected for galectin-3 and sST2. In considering NT-proBNP for additive risk stratification, sST2 (adjusted hazard ratio [AHR]1.85, 95%confidence interval [C.I.] 1.17-2.91) and galectin-3 (AHR1.85, 95%C.I. 1.09-2.45) were independently associated with increased primary outcome only in the presence of AF. The prognostic performance of sST2 was also stronger in AF for all-cause mortality (AF: AHR2.82, 95%C.I. 1.26-6.21; non-AF: AHR1.78, 95% C.I. 1.14-2.76 without AF), while galectin-3 predicted HF-hospitalization only in AF (AHR1.64, 95%C.I. 1.03-2.62). CONCLUSIONS: AF modified the prognostic utility of selected guideline-endorsed HF-biomarkers. Application of markers for prognostic purposes in HF requires consideration of the presence or absence of AF. CLINICAL TRIAL REGISTRATION: ACTRN12610000374066.

Obstructive sleep apnea during rapid eye movement sleep in patients after percutaneous coronary intervention: a multicenter study.

PURPOSE: Obstructive sleep apnea (OSA) during the rapid eye movement (REM) stage of the sleep cycle is associated with intense hypoxemia and cardiovascular instability. We characterized OSA during REM sleep in patients after percutaneous coronary intervention. METHODS: In this multicenter study, 204 patients who had undergone percutaneous coronary intervention in the prior 6 to 36 months were recruited for in-laboratory polysomnography. The primary measure was respiratory events during REM sleep. The patients were divided into 2 groups: (1) OSA during REM sleep (≥ 15 events/h) and (2) absence of OSA during REM sleep (< 15 events/h). RESULTS: Based on the overall apnea-hypopnea index ≥ 15, 148 patients (74.0%) had OSA. After excluding patients with failed polysomnography or REM sleep < 30 min, 163 patients formed the cohort for this analysis. OSA during REM sleep was diagnosed in 132 patients (81%). Compared with the patients without OSA during REM sleep, those with OSA during REM sleep had a higher body mass index (p = 0.003) and systolic blood pressure (p = 0.041), and a higher prevalence of diabetes mellitus (p = 0.029). Logistic regression analysis, including age, sex, diabetes mellitus, indication for percutaneous coronary intervention, and indication for multi-vessel percutaneous coronary intervention, showed that diabetes mellitus was the only independent predictor of OSA during REM sleep (odds ratio 2.83; 95% CI, 1.17 to 6.83; p = 0.021). CONCLUSION: In patients treated with percutaneous coronary intervention, there was a high prevalence of OSA during REM sleep. Diabetes mellitus was an independent predictor of OSA during REM sleep.

Assessment of acute kidney injury risk using a machine-learning guided generalized structural equation model: a cohort study.

BACKGROUND: Acute kidney injury is common in the surgical intensive care unit (ICU). It is associated with poor patient outcomes and high healthcare resource usage. This study's primary objective is to help identify which ICU patients are at high risk for acute kidney injury. Its secondary objective is to examine the effect of acute kidney injury on a patient's prognosis during and after the ICU admission. METHODS: A retrospective cohort of patients admitted to a Singaporean surgical ICU between 2015 to 2017 was collated. Patients undergoing chronic dialysis were excluded. The outcomes were occurrence of ICU acute kidney injury, hospital mortality and one-year mortality. Predictors were identified using decision tree algorithms. Confirmatory analysis was performed using a generalized structural equation model. RESULTS: A total of 201/940 (21.4%) patients suffered acute kidney injury in the ICU. Low ICU haemoglobin levels, low ICU bicarbonate levels, ICU sepsis, low pre-ICU estimated glomerular filtration rate (eGFR) and congestive heart failure was associated with the occurrence of ICU acute kidney injury. Acute kidney injury, together with old age (> 70 years), and low pre-ICU eGFR, was associated with hospital mortality, and one-year mortality. ICU haemoglobin level was discretized into 3 risk categories for acute kidney injury: high risk (haemoglobin ≤9.7 g/dL), moderate risk (haemoglobin between 9.8-12 g/dL), and low risk (haemoglobin > 12 g/dL). CONCLUSION: The occurrence of acute kidney injury is common in the surgical ICU. It is associated with a higher risk for hospital and one-year mortality. These results, in particular the identified haemoglobin thresholds, are relevant for stratifying a patient's acute kidney injury risk.

Patients with acute and chronic coronary syndromes have elevated long-term thrombin generation.

Coronary artery disease is a leading cause of morbidity and mortality worldwide. Despite significant advances in revascularization strategies and antiplatelet therapy with aspirin and/or P2Y12 receptor antagonist, patients with acute coronary syndrome (ACS) continue to be at long-term risk of further cardiovascular events. Besides platelet activation, the role of thrombin generation (TG) in atherothrombotic complications is widely recognized. In this study, we hypothesized that there is an elevation of coagulation activation persists beyond 12 months in patients with ACS and chronic coronary syndrome (CCS) when compared with healthy controls. We measured TG profiles of patients within 72 h after percutaneous coronary intervention, at 6-month, 12-month and 24-month. Our results demonstrated that TG of patients with ACS (n = 114) and CCS (n = 40) were persistently elevated when compared to healthy individuals (n = 50) in peak thrombin (ACS 273.1 nM vs CCS 287.3 nM vs healthy 234.3 nM) and velocity index (ACS 110.2 nM/min vs CCS 111.0 nM/min vs healthy 72.9 nM/min) at 24-month of follow-up. Our results suggest a rationale for addition of anticoagulation to antiplatelet therapy in preventing long-term ischemic events after ACS. Further research could clarify whether the use of TG parameters to enable risk stratification of patients at heightened long-term procoagulant risk who may benefit most from dual pathway inhibition.

Pulmonary arterial hypertension in a multi-ethnic Asian population: Characteristics, survival and mortality predictors from a 14-year follow-up study.

BACKGROUND AND OBJECTIVE: Pulmonary arterial hypertension (PAH) is a rare and fatal disease. Data from Asia are lacking compared with the West. We aim to describe disease characteristics in an ethnically diverse South-East Asian population and assess predictors for survival. METHODS: We consecutively enrolled patients with PAH referred to our pulmonary hypertension specialty centre from January 2003 to December 2016. Baseline characteristics and survival were analysed. Based on a forward predictor selection procedure, a multi-level structural equation model was applied to identify predictors associated with mortality. RESULTS: Out of 148 patients enrolled, 77% were females and mean age was 50.8 ± 15.9 years. Racial distribution was consistent with our population census. The most common aetiologies were congenital heart disease-associated PAH (35.8%), idiopathic PAH (29.7%) and then connective tissue disease-associated PAH (24.3%). Most patients presented in World Health Organization (WHO) Functional Class (FC) II (48.6%), followed by FC III (28.8%). Majority of patients (54.1%) were on phosphodiesterase type 5 (PDE5) inhibitor monotherapy. Survival rates were 85.8% at the end of the first year, 70.9% at 3 years, 66.9% at 5 years, 61.5% at 7 years and 55.4% at 10 years. The Registry to Evaluate Early And Long-term PAH Disease Management (REVEAL) score (RS) was found to be the best predictor of mortality. A score > 6 was identified as a cut-off. Other predictors include mean right atrial pressure, heart rate, aetiology, age and N-terminal pro-brain natriuretic peptide. CONCLUSION: In this first registry study from a South-East Asian population, our survival rates are comparable with other national registries. The RS is validated in our population to be a good predictor of mortality.

Incidence and predictors of target lesion failure in a multiethnic Asian population receiving the SYNERGY coronary stent: A prospective all-comers registry.

OBJECTIVES: To evaluate the target lesion failure (TLF) rate of the SYNERGY stent in all-comers, multiethnic Asian population. BACKGROUND: Currently, most drug eluting stents deliver anti-proliferative drugs from a durable polymer which is associated with a risk of late stent thrombosis. The novel everolimus-eluting, platinum chromium SYNERGY stent is coated with a bioabsorbable abluminal polymer that resolves within 4 months. METHODS: This was a prospective, single center registry of consecutive patients treated with the SYNERGY stent between December 2012 and April 2015. The primary outcome was the incidence of TLF, defined as the combination of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization (TLR) at 1 year. RESULTS: A total of 807 patients received the SYNERGY stent during the study period. One-year clinical outcome data was available for 765 patients (94.8%) and were considered for statistical analysis. The mean age was 60.7 ± 10.8 years, and 83.4% were males. Patients with acute myocardial infarction consisted of 50.3% (ST-segment elevation myocardial infarction: 23.0%, Non-ST-segment elevation myocardial infarction: 27.3%) of the study population. The treated lesions were complex (ACC/AHA type B2/C: 72.7%). The primary end point of TLF at 1 year was 5.8%. Rates of cardiac mortality, target vessel myocardial infarction, and TLR were 4.2, 1.0, and 1.3%, respectively, at 1 year. Predictors of the incidence and time to early TLF were female gender, Malay ethnicity, diabetes mellitus, acute myocardial infarction at presentation, a prior history of coronary artery bypass surgery and the presence of lesion calcification. The incidence of definite stent thrombosis was 0.4% at 1 year. CONCLUSIONS: In this registry, the use of the SYNERGY stent was associated with low rates of TLF at 1 year.

The Neighborhood Built Environment and Cognitive Function of Older Persons: Results from the Singapore Longitudinal Ageing Study.

BACKGROUND: We investigated the association of subjective (perceived) and objective (geographical information system [GIS]-based) measures of the neighborhood built environment (BE) attributes with cognitive function among older persons, and the mediating effect of transportation physical activity (TPA) and leisure time (physical, social and productive) activities (LTA). METHOD: A cross-sectional study of 402 residents aged 55 years and above in the Singapore Longitudinal Ageing Study. Perceived neighborhood BE attributes (residential density, street connectivity, land use mix - diversity, land use mix - access, infrastructure for walking or cycling, aesthetics, traffic safety, and crime safety) and objective GIS measures of walkability and accessibility were related to participants' cognitive global and domain-specific performance measured by Repeatable Battery for the Assessment of Neurocognitive Status (RBANS). RESULTS: Controlling for age, sex, education, race, chronic medical illnesses, self-rated health, Geriatric Depression Scale depression score, POMA measures of balance and gait, and other BE attributes, the subjective measure of land use mix-diversity (standardized coefficient ß = 0.161, p = 0.008) and GIS measure of walkability (ß = 0.163, p = 0.002) were positively and significantly associated with RBANS global z-score, and immediate and delayed memory recall, visuospatial/ constructional ability and language, except attention. In hierarchical modeling, TPA and LTA attenuated the effect estimates, but the associations remained significant. CONCLUSION: BE features which increase opportunities and easy access to a diversity of destinations for services and facilities that promote physical, social and cognitively stimulating activities is associated with better cognitive functioning in older people.

The women's heart health programme: a pilot trial of sex-specific cardiovascular management.

BACKGROUND: There is increasing knowledge of sex-specific differences in cardiovascular disease and recognition of sex disparities in management. In our study, we investigated whether a cardiovascular programme tailored to the specific needs of women could lead to improved outcomes. METHODS: We randomised 100 female patients to receive cardiology follow-up with the conventional sex-neutral cardiac programme (control), or the sex-tailored Women's Heart Health Programme (intervention). The intervention group was managed by an all-women multidisciplinary team and received culture-centred health intervention workshops, designed through in-depth interviews with the participants. The primary outcome was cardiovascular risk factor improvement at 1 year. Secondary outcomes include cardiovascular event rates, quality of life scores, and self-reported improvement in knowledge, attitudes, intentions and practices. Generalised structural equation model analysis was used to determine if the intervention group had better outcomes at alpha level 0.1. RESULTS: The mean age was 67.3 ± 12.7 years, with an ethnic distribution of 70% Chinese, 18% Malays, and 12% Indians. The majority of these patients had no formal or primary level of education (63%), and were mostly unemployed (78%). Patients in intervention group had better control of diabetes mellitus (lower HbA1c of 0.63% [CI 0.21-1.04], p = 0.015) and lower body-mass-index (0.74 kg/m2 [CI 0.02-1.46], p = 0.092) at 1 year, but there was no significant difference in blood pressure or lipid control. Overall, there was a trend towards better risk factor control, 31.6% of intervention group versus 26.5% of control group achieved improvement in at least 1 CV risk factor control to target range. There was no significant difference in incidence of cardiovascular events, quality of life, or domains in knowledge, attitudes, intention and practices. CONCLUSION: This pilot study is the first of its kind evaluating a new model of care for women with heart disease. The potential to improve outcomes needs to be studied in a larger trial with longer follow up. TRIAL REGISTRATION: This trial was prospectively registered clinicaltrials.gov on 6 May 2013. Trial Number: 2013/00088. Identifier: NCT02017470.

High Incidence of Occult Atrial Fibrillation in Asian Patients with Cryptogenic Stroke.

BACKGROUND: Occult atrial fibrillation (AF) is not uncommon in patients with stroke. In western cohorts, insertable loop recorders (ILRs) have been shown to be the gold-standard and are cost-effective for AF detection. Anticoagulation for secondary stroke prevention is indicated if AF is detected. The incidence of occult AF among Asian patients with cryptogenic stroke is unclear. METHODS: Patients with cryptogenic stroke referred between August 2014 and February 2017 had ILRs implanted. Episodes of AF >2 minutes duration were recorded using proprietary algorithms within the ILRs, whereupon clinicians and patients were alerted via remote monitoring. All AF episodes were adjudicated using recorded electrograms. Once AF was detected, patients were counseled for anticoagulation. RESULTS: Seventy-one patients with cryptogenic stroke, (age 61.9 ± 13.5 years, 77.5% male, mean CHA2DS2VASc score of 4.2 ± 1.3) had ILRs implanted. Time from stroke to the ILR implant was a median of 66 days. Duration of ILR monitoring was 345 ± 229 days. The primary endpoint of AF detection at 6 months was 12.9%; and at 12 months it was 15.2%. Median time to detection of AF was 50 days. The AF episodes were all asymptomatic and lasted a mean of 77 minutes (± 118.9). Anticoagulation was initiated in all but 1 patient found to have AF. CONCLUSIONS: The incidence of occult AF is high in Asian patients with cryptogenic stroke and comparable to western cohorts. The combination of ILR and remote monitoring is a highly automated, technologically driven, and clinically effective technique to screen for AF.

Relationship between soluble Semaphorin4D and cognitive impairment in patients with obstructive sleep apnea-hypopnea syndrome.

To investigate the relationship between plasma soluble semaphorin4D (sSema4D) and obstructive sleep apnea-hypopnea syndrome (OSAHS), and to ascertain the effect of sSema4D on cognitive dysfunction in patients with OSAHS. We prospectively recruited 30 men with moderate-severe OSAHS diagnosed by polysomnography, and 30 healthy controls with matched gender, age and education level. Montreal Cognitive Assessment (MoCA) was administered to determine cognitive impairment. Plasma sSema4D levels were measured. Among the total of 60 study patients, the overall plasma sSema4D level was 7.81 ± 1.91 ng/ml. Plasma sSema4D level in OSAHS group was significantly higher than that in controls (8.92 ± 1.79 vs 6.70 ± 1.28 ng/ml, p < 0.001). In OSAHS subgroup, patients with cognition impairment (CI) had higher plasma sSema4D level (10.50 ± 1.16 vs 8.00 ± 1.41 ng/ml, p < 0.001) and apnea-hypopnea index (AHI) (48.1 ± 14.0 vs 30.3 ± 9.2, p < 0.001) than those in non-CI group. Multiple logistic regression revealed that plasma sSema4D level (AOR 2.824, 95 % CI 1.562-5.103; p = 0.001) and BMI (AOR 2.237, 95 % CI 1.345-3.722; p = 0.002) were significantly associated with OSAHS, and plasma sSema4D was a significant predictor of CI after adjustment for other confounders (AOR 4.956, 95 % CI 1.581-15.538; p = 0.006). OSAHS patients, especially those with cognition impairment, are featured by elevated plasma sSema4D level, and sSema4D is significantly associated with cognition impairment induced by OSAHS.

Epidemiological risk factors for adult dengue in Singapore: an 8-year nested test negative case control study.

BACKGROUND: Understanding changes in the ecology and epidemiology of dengue is important to ensure resource intensive control programmes are targeted effectively as well as to inform future dengue vaccination strategies. METHODS: We analyzed data from a multicentre longitudinal prospective study of fever in adults using a nested test negative case control approach to identify epidemiological risk factors for dengue disease in Singapore. From April 2005 to February 2013, adult patients presenting with fever within 72 h at selected public primary healthcare clinics and a tertiary hospital in Singapore were recruited. Acute and convalescent blood samples were collected and used to diagnose dengue using both PCR and serology methods. A dengue case was defined as having a positive RT-PCR result for DENV OR evidence of serological conversion between acute and convalescent blood samples. Similarly, controls were chosen from patients in the cohort who tested negative for dengue using the same laboratory methods. RESULTS: The host epidemiological factors which increased the likelihood of dengue disease amongst adults in Singapore were those aged between 21 and 40 years old (2 fold increase) while in contrast, Malay ethnicity was protective (OR 0.57, 95%CI 0.35 to 0.91) against dengue disease. Spatial factors which increased the odds of acquiring dengue was residing at a foreign workers dormitory or hostel (OR 3.25, 95 % CI 1.84 to 5.73) while individuals living in the North-West region of the country were less likely to get dengue (OR 0.50, 95%CI 0.29 to 0.86). Other factors such as gender, whether one primarily works indoors or outdoors, general dwelling type or floor, the type of transportation one uses to work, travel history, as well as self-reported history of mosquito bite or household dengue/fever were not useful in helping to inform a diagnosis of dengue. CONCLUSIONS: We have demonstrated a test negative study design to better understand the epidemiological risk factors of adult dengue over multiple seasons. We were able to discount other previously speculated factors such as gender, whether one primarily works indoors or outdoors, dwelling floor in a building and the use of public transportation as having no effect on one's risk of getting dengue.