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Patients undergoing transcatheter aortic valve implantation (TAVI) commonly have co-morbidities requiring anticoagulation. However, the optimal post-procedural anticoagulation regimen is not well-established. This meta-analysis investigates safety and efficacy outcomes of direct oral anticoagulants (DOACs) and Vitamin K Antagonist (VKA), with or without concomitant antiplatelet therapy. We searched EMBASE and MEDLINE for appropriate studies. Subgroup analyses were performed for anticoagulant monotherapy and combined therapy with antiplatelet agents. Eleven studies (6359 patients) were included. Overall, there were no differences between DOACs and VKA for all-cause mortality (Odds Ratio [OR]: .69; Credible Interval [CrI]: .40–1.06), cardiovascular-related mortality (OR: .76; Crl: .13–3.47), bleeding (OR: .95; CrI: .75–1.17), stroke (OR: 1.04; CrI: .65–1.63), myocardial infarction (OR: 1.51; CrI: .55–3.84), and valve thrombosis (OR: .29; CrI: .01–3.54). For DOACs vs VKA monotherapy subgroup, there were no differences in outcomes. For the combined therapy subgroup, there was decreased odds of all-cause mortality in the DOACs group compared with the VKA group (OR: .13; CrI: .02–.65), but no differences for bleeding and stroke. DOACs and VKA have similar safety and efficacy profiles for post-TAVI patients with anticoagulation indication. However, if concomitant antiplatelet therapy is required, DOACs were more favorable than VKA for all-cause mortality.

BackgroundHeart failure (HF) and diabetes epidemiologically share a bidirectional relationship, with each increasing the incidence and worsening the prognosis of the other. Global longitudinal strain (GLS) measured by feature tracking cardiovascular magnetic resonance (CMR) has prognostic value in HF. However, this has not been established in HF patients with diabetes.ObjectivesThis study aimed to assess the prognostic value of GLS in HF patients with diabetes.MethodsConsecutive patients (n=315) with HF from six tertiary cardiac centres in Singapore underwent CMR at 3T, including GLS, late gadolinium enhancement (LGE), native T1 mapping, and extracellular volume fraction (ECV) mapping. The primary outcome was a composite of all-cause mortality or HF hospitalisation.ResultsCompared to those without diabetes (n=156), the diabetes group (n=159) had a higher prevalence of LGE (76 vs 60%, pConclusionCompared to heart failure patients without diabetes, those with diabetes have worse CMR markers of fibrosis and adverse prognosis. GLS is a powerful and independent prognostic marker in heart failure patients with diabetes.

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.

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, post-operative pacing requirement, arrhythmic recurrence and one-year all-cause mortality. RESULTS Among 2,260 patients (mean age 45±18years, 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

Objective Brown adipose tissue (BAT) controls metabolic rate through thermogenesis. As its regulatory factors during the transition from hyperthyroidism to euthyroidism are not well established, our study investigated the relationships between supraclavicular brown adipose tissue (sBAT) activity and physiological/metabolic changes with changes in thyroid status. Design Participants with newly diagnosed Graves’ disease were recruited. A thionamide antithyroid drug (ATD) such as carbimazole (CMZ) or thiamazole (TMZ) was prescribed in every case. All underwent energy expenditure (EE) measurement and supraclavicular infrared thermography (IRT) within a chamber calorimeter, as well as 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scanning, with clinical and biochemical parameters measured during hyperthyroidism and repeated in early euthyroidism. PET sBAT mean/maximum standardized uptake value (SUV mean/max), MR supraclavicular fat fraction (sFF) and mean temperature (Tscv) quantified sBAT activity. Results Twenty-one (16 female/5 male) participants aged 39.5 ± 2.5 years completed the study. The average duration to attain euthyroidism was 28.6 ± 2.3 weeks. Eight participants were BAT-positive while 13 were BAT-negative. sFF increased with euthyroidism (72.3 ± 1.4% to 76.8 ± 1.4%; P < 0.01), but no changes were observed in PET SUV mean and Tscv. Significant changes in serum-free triiodothyronine (FT3) levels were related to BAT status (interaction P value = 0.04). FT3 concentration at hyperthyroid state was positively associated with sBAT PET SUV mean (r = 0.58, P = 0.01) and resting metabolic rate (RMR) (P < 0.01). Conclusion Hyperthyroidism does not consistently lead to a detectable increase in BAT activity. FT3 reduction during the transition to euthyroidism correlated with BAT activity.

Study Objectives Respiratory sleep indices are traditionally reported on the basis of the average total sleep time. The relationship between the hour-to-hour variability of these parameters and blood pressure (BP) has not been reported. Methods We evaluated the associations of the hour-to-hour variability of the apnea–hypopnea index (AHI), oxygen desaturation index (ODI), and lowest oxygen saturation with the 24-h ambulatory BP in patients with hypertension and newly diagnosed obstructive sleep apnea. A total of 147 patients underwent polysomnography, based on which obstructive sleep apnea was diagnosed in 106 patients; these patients underwent 24-h ambulatory BP monitoring within the next 30 days. Each polysomnogram was divided into hourly reports to calculate the variability of the respiratory sleep indices. Variability independent of the mean was considered the primary measure of variability. Results The median number of hourly polysomnogram reports was 7 (range, 4–8). The hour-to-hour variability of both AHI and ODI, but not of the lowest oxygen saturation, was correlated with the 24-h pulse pressure, 24-h systolic BP, and awake systolic BP (p Conclusions The hour-to-hour variability of AHI and ODI is independently associated with the 24-h pulse pressure. Further investigations are warranted to evaluate the clinical relevance of this new-found association.

Acute myocardial infarction (AMI) is associated with heightened thrombin generation. There are limited data relating to thrombin generation and left ventricular (LV) scarring and LV dilatation in post-MI LV remodeling. We studied 113 patients with ST-segment elevation myocardial infarction (STEMI) who had undergone primary percutaneous coronary intervention (PPCI) (n = 76) or pharmaco-invasive management (thrombolysis followed by early PCI, n = 37). Endogenous thrombin potential (ETP) was measured at baseline, 1 month and 6 months. Cardiovascular magnetic resonance imaging was performed at baseline and 6 months post-MI. Outcomes studied were an increase in scar change, which was defined as an increase in left ventricular infarct size of any magnitude detected by late gadolinium enhancement, adverse LV remodeling, defined as dilatation (increase) of left ventricular end-diastolic volume (LVEDV) by more than 20% and an increase in left ventricular ejection fraction (LVEF). The mean age was 55.19 ± 8.25 years and 91.2% were men. The baseline ETP was similar in the PPCI and pharmaco-invasive groups (1400.3 nM.min vs. 1334.1 nM.min, p = 0.473). Each 10-unit increase in baseline ETP was associated with a larger scar size (adjusted OR 1.020, 95% CI 1.002–1.037, p = 0.027). Baseline ETP was not associated with adverse LV remodeling or an increase in LVEF. There was no difference in scar size or adverse LV remodeling among patients undergoing PPCI vs. pharmaco-invasive management or patients receiving ticagrelor vs. clopidogrel. Enhanced thrombin generation after STEMI is associated with a subsequent increase in myocardial scarring but not LV dilatation or an increase in LVEF at 6 months post-MI.

Background The relative contribution of pathophysiological mechanisms in acute coronary syndrome (ACS) towards obstructive sleep apnea (OSA) is not well-studied. We examined the correlation between severity of OSA and inflammation, myocardial necrosis, wall stress, and fibrosis. Methods A total of 89 patients admitted with ACS underwent a sleep study during index admission. Plasma levels of high-sensitivity C-reactive protein (hs-CRP), troponin I, N-terminal pro-brain natriuretic peptide (NT-proBNP), and suppression of tumorigenicity 2 (ST2) were prospectively analyzed. Two patients diagnosed with central sleep apnea were excluded. Results The recruited patients were divided into no (AHI Conclusion Severe OSA during the acute phase of ACS was associated with extensive myocardial necrosis and high myocardial wall stress, but not with inflammation and myocardial fibrosis.

IntroductionAlthough treatment of obstructive sleep apnoea (OSA) using continuous positive airway pressure (CPAP) reduces blood pressure (BP), adherence to CPAP is often suboptimal. A mandibular advancement device (MAD) is a guideline-endorsed alternative therapy for OSA. Still, there is limited evidence on the relative efficacy between MAD and CPAP on BP reduction. We evaluate whether treatment of moderate-to-severe OSA using MAD can improve BP and other health-related outcomes compared with CPAP.Methods and analysisThis is a randomised, controlled, non-inferiority trial conducted. We will recruit 220 Asians with a history of hypertension and high cardiovascular risk for an overnight polysomnography screening. Those with moderate-to-severe OSA (apnoea–hypopnoea index ≥15 events/hour) will be randomised to treatment with either MAD or CPAP in a 1:1 ratio. Stratified by age (60 vs 2) and apnoea–hypopnoea index (30 vs Ethics and disseminationThe Domain Specific Review Board-C, National Healthcare Group under approved the study protocol (NHG DSRB Ref: 2019/00359, approved on 28 August 2019). Study findings will be disseminated to various local, national, and international audiences through abstract presentations and publication in peer-reviewed journals.Trial registration numberNCT04119999.

BackgroundAcute 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.MethodsA 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.ResultsA 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).ConclusionThe 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.

Aims: Extracellular vesicles (EVs) are small double-membrane plasma vesicles that play key roles in cellular crosstalk and mechanisms such as inflammation. The role of EVs in combined organ failure such as cardiorenal syndrome has not been investigated. The aim of this study is to identify EV proteins that are associated with renal dysfunction, heart failure, and their combination in dyspnoeic patients. Methods and results: Blood samples were prospectively collected in 404 patients presenting with breathlessness at the emergency department at National University Hospital, Singapore. Renal dysfunction was defined as estimated glomerular filtration rate ' 60 mL/min/1.73 m2. The presence of heart failure was independently adjudicated by two clinicians on the basis of the criteria of the European Society of Cardiology guidelines. Protein levels of SerpinG1, SerpinF2, Cystatin C, and CD14 were measured with a quantitative immune assay within three EV sub-fractions and in plasma and were tested for their associations with renal dysfunction, heart failure, and the concurrence of both conditions using multinomial regression analysis, thereby correcting for confounders such as age, gender, ethnicity, and co-morbidities. Renal dysfunction was found in 92 patients (23%), while heart failure was present in 141 (35%). In total, 58 patients (14%) were diagnosed with both renal dysfunction and heart failure. Regression analysis showed that Cystatin C was associated with renal dysfunction, heart failure, and their combination in all three EV sub-fractions and in plasma. CD14 was associated with both renal dysfunction and the combined renal dysfunction and heart failure in all EV sub-fractions, and with presence of heart failure in the high density lipoprotein sub-fraction. SerpinG1 and SerpinF2 were associated with heart failure in, respectively, two and one out of three EV sub-fractions and in plasma, but not with renal dysfunction. Conclusions: We provide the first data showing that Cystatin C and CD14 in circulating EVs are associated with both renal dysfunction and heart failure in patients presenting with acute dyspnoea. This suggests that EV proteins may be involved in the combined organ failure of the cardiorenal syndrome and may represent possible targets for prevention or treatment.

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. 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 (

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.

The role of left atrial (LA) strain as an imaging biomarker in aortic stenosis is not well established. The aim of this study was to investigate the prognostic performance of phasic LA strain in relation to clinical and echocardiographic variables and N-terminal pro-B-type natriuretic peptide in asymptomatic and minimally symptomatic patients with moderate to severe aortic stenosis and left ventricular ejection fraction50%.LA reservoir strain (LASr), LA conduit strain (LAScd), and LA contractile strain (LASct) were measured using speckle-tracking echocardiography. The primary outcome was a composite of all-cause mortality, heart failure hospitalization, progression to New York Heart Association functional class III or IV, acute coronary syndrome, or syncope. Secondary outcomes 1 and 2 comprised the same end points but excluded acute coronary syndrome and additionally syncope, respectively. The prognostic performance of phasic LA strain cutoffs was evaluated in competing risk analyses, aortic valve replacement being the competing risk.Among 173 patients (mean age, 69 ± 11 years; mean peak transaortic velocity, 4.0 ± 0.8 m/sec), median LASr, LAScd, and LASct were 27% (interquartile range [IQR], 22%-32%), 12% (IQR, 8%-15%), and 16% (IQR, 13%-18%), respectively. Over a median of 2.7 years (IQR, 1.4-4.6 years), the primary outcome and secondary outcomes 1 and 2 occurred in 66 (38%), 62 (36%), and 59 (34%) patients, respectively. LASr20%, LAScd6%, and LASct12% were identified as optimal cutoffs of the primary outcome. In competing risk analyses, progressing from echocardiographic to echocardiographic-clinical and combined models incorporating N-terminal pro-B-type natriuretic peptide, LA strain parameters outperformed other key echocardiographic variables and significantly predicted clinical outcomes. LASr20% was associated with the primary outcome and secondary outcome 1, LAScd6% with all clinical outcomes, and LASct12% with secondary outcome 2. LAScd6% had the highest specificity (95%) and positive predictive value (82%) for the primary outcome, and competing risk models incorporating LAScd6% had the best discriminative value.In well-compensated patients with moderate to severe aortic stenosis and preserved left ventricular ejection fractions, LA strain was superior to other echocardiographic indices and incremental to N-terminal pro-B-type natriuretic peptide for risk stratification. LAScd6%, LASr20%, and LASct12% identified patients at higher risk for adverse outcomes.

Lack of validation and standardization of research-use-only (RUO) immunoassays brings with it inherent threats to authenticity and functional quality. Poor correlation between different commercial neprilysin RUO immunoassays is concerning and discordant findings need to be resolved. We seek to identify and validate reliable neprilysin immunoassays to strengthen the scientific rigor and reproducibility of neprilysin-related investigation and of biomarker research in general.Soluble neprilysin (sNEP) concentrations were determined in cohorts (n = 532) from Spain (Cohort 1), New Zealand (NZ, Cohort 2) and Singapore (Cohort 3), using commercial kits from six vendors. Apparent sNEP concentrations were correlated between different assays and with plasma neprilysin activity. Assay reliability was further validated by performance verification, MS analysis and cross-reactivity tests.sNEP in Cohorts 1 and 2 measured concurrently in Spain and NZ showed significant inter-laboratory correlation only for the Aviscera Bioscience sNEP ELISA SK00724-01. Neprilysin concentrations obtained with the RD systems and SK00724-01 ELISAs correlated with each other but not with neprilysin activity. In Cohort 3, sNEP concentrations from the Perkin Elmer AlphaLISA and Biotechne ELLA assays agreed (r = 0.89) and both correlated with neprilysin activity (r = 0.87, 0.77 respectively). MS analysis detected authentic neprilysin in the AlphaLISA kit calibrator and in antibody pull-down material from human plasma. The AlphaLISA assay performed within acceptable limits (spike and recovery, dilutional linearity, inter- and intra-assay CV) and showed no cross-reactivity against neprilysin substrates and closely-related analogues.AlphaLISA and ELLA assays provide reliable measures of sNEP concentrations. Reliability of other commercial neprilysin assays remains in question.

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.We studied patients with severe fTR to assess predictors of mortality.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.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.For patients diagnosed with severe fTR, advanced age on diagnosis, prior heart failure admission, LVEF50%, and PASP50 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.

Background:Asian representation in sport is increasing, yet there remains a lack of reference values for the Asian athlete's heart. Consequently, current guidelines for cardiovascular screening recommend using Caucasian athletes' norms to evaluate Asian athletes. This study aims to outline electrocardiographic and echocardiographic characteristics of the Asian athlete's heart using a Singaporean prospective registry of Southeast (SE) Asian athletes.Methods and Results:One hundred and fifty elite athletes, mean age of 26.1 ± 5.7 years (50% males, 88% Chinese), were evaluated using a questionnaire, 12-lead electrocardiogram (ECG) and transthoracic echocardiogram. All ECGs were analyzed using the 2017 International Recommendations. Echocardiographic data were presented by gender and sporting discipline. The prevalence of abnormal ECGs among SE Asian athletes was 6.7%—higher than reported figures for Caucasian athletes. The abnormal ECGs comprised mainly anterior T wave inversions (ATWI) beyond lead V2, predominantly in female athletes from mixed/endurance sport (9.3% prevalence amongst females). None had echocardiographic structural abnormalities. Male athletes had reduced global longitudinal strain compared to females (−18.7 ± 1.6 vs. −20.7 ± 2.1%,p< 0.001). Overall, SE Asian athletes had smaller left ventricular cavity sizes and wall thickness compared to non-Asian athletes.Conclusion:SE Asian athletes have higher abnormal ECG rates compared to Caucasian athletes, and also demonstrate structural differences that should be accounted for when interpreting their echocardiograms compared to athletes of other ethnicities.

Summary Aims The primary aim of this study was to provide normative formant frequency (F) values for male and female speakers of Australian English. The secondary aim was to examine the effects of speaker sex, age, vowel quality, and geographical location on F. Method The first three monophthong formant frequencies (F1, F2, and F3) for 244 female and 135 male speakers aged 18–60 years from a recent large-scale corpus of Australian English were analysed on a passage reading task. Results Mixed effects linear regression models suggested that speaker sex, speaker age, and vowel quality significantly predicted F1, F2, and F3 (P = 0.000). Effect sizes suggested that speaker sex and vowel quality contributed most to the variations in F1, F2, and F3 whereas speaker age and geographical location contributed a smaller amount. Conclusion Both clinicians and researchers are provided with normative F data for 18–60 year-old speakers of Australian English. Such data have increased internal and external validity relative to previous literature. F normative data for speakers of Australian English should be considered with reference to speaker sex and vowel but it may not be practically necessary to adjust for speaker age and geographical location.

ObjectiveST segment elevation myocardial infarction (STEMI) is associated with significant mortality leading to loss of productive life years, especially in younger patients. This study aims to compare the characteristics and outcomes of young versus older patients with STEMI undergoing primary percutaneous coronary intervention (PPCI) to help focus public health efforts in STEMI prevention.MethodsData from the Coronary Care Unit database of the National University Hospital, Singapore from July 2015 to June 2019 were reviewed. Patients were divided into young (ResultsOf the 1818 consecutive patients with STEMI who underwent PPCI, 465 (25.6%) were ConclusionYoung patients with STEMI are more often smokers, of Indian ethnicity and had family history of IHD, although cardiometabolic risk factors are also prevalent. Mortality is lower, but not negligible, among the young patients with STEMI. Public health efforts are needed to reduce the prevalence of these risk factors among the constitutionally susceptible population.

The association of diabetes mellitus (DM) with cardiac resynchronization therapy (CRT) response and cardiovascular outcomes in Asian patients with heart failure (HF) is unclear. This study aims to investigate the effects of DM on CRT response and cardiovascular outcomes in Asian HF patients. Consecutive Asian HF patients receiving CRT were enrolled in the Prospective Evaluation of Asian with CRT for Heart Failure (PEACH) study from 2011 to 2017. CRT response and super-response were defined as decrease in end-systolic volume index ≥15% and ≥30%, respectively. Primary endpoint was time to composite of HF-hospitalization and all-cause mortality. Among 161 patients followed for 3.3 ± 1.5 years (age 66.7 ± 11.2 years, 22% females, mean QRS duration 154.3 ± 22.4 ms, 83% left bundle branch block), 84 (52%) were CRT responders and 57 (35%) were super-responders. Of 82 (51%) patients with DM (100% type 2, mean HbA1c 7.3 ± 1.9%), 35 (43%) were responders. DM attenuated reverse remodeling (CRT response: AOR 0.44, 95% confidence interval [CI] 0.20 to 0.98, p 0.05; super-response: AOR 0.42, 95% CI 0.18 to 0.97, p0.05), and DM increased HF-hospitalization and all-cause mortality (AHR 1.68, 95% CI 1.00 to 2.82, p = 0.05). The extent of CRT-response correlates with higher event-free survival (CRT response: AHR 0.5, 95% CI 0.30 to 0.81, p = 0.005; super-response: AHR 0.27, 95% CI 0.14 to 0.52, p 0.001). In conclusion, the extent of reverse remodeling post-CRT is the strongest predictor of event free survival. However, DM is detrimental to the CRT recipient by attenuating reverse remodeling, inducing end organ dysfunction and is independently associated with worsened clinical outcomes among Asian HF patients.

It is unclear whether universal access to primary percutaneous coronary intervention (pPCI) may reduce sex differences in 1-year rehospitalization for heart failure (HF) and myocardial infarction (MI) after ST-elevation myocardial infarction (STEMI). We studied 7,597 consecutive STEMI patients (13.8% women, n = 1,045) who underwent pPCI from January 2007 to December 2013. Cox regression models adjusted for competing risk from death were used to assess sex differences in rehospitalization for HF and MI within 1 year from discharge. Compared with men, women were older (median age 67.6 vs 56.0 years, p0.001) with higher prevalence of co-morbidities and multivessel disease. Women had longer median door-to-balloon time (76 vs 66 minutes, p0.001) and were less likely to receive drug-eluting stents (19.5% vs 24.1%, p = 0.001). Of the medications prescribed at discharge, fewer women received aspirin (95.8% vs 97.6%, p = 0.002) and P2Y

Background Clinicians need improved tools to better identify nonacute heart failure with preserved ejection fraction (HFpEF). Objectives The purpose of this study was to derive and validate circulating microRNA signatures for nonacute heart failure (HF). Methods Discovery and validation cohorts (N = 1,710), comprised 903 HF and 807 non-HF patients from Singapore and New Zealand (NZ). MicroRNA biomarker panel discovery in a Singapore cohort (n = 546) was independently validated in a second Singapore cohort (Validation 1; n = 448) and a NZ cohort (Validation 2; n = 716). Results In discovery, an 8-microRNA panel identified HF with an area under the curve (AUC) 0.96, specificity 0.88, and accuracy 0.89. Corresponding metrics were 0.88, 0.66, and 0.77 in Validation 1, and 0.87, 0.58, and 0.74 in Validation 2. Combining microRNA panels with N-terminal pro–B-type natriuretic peptide (NT-proBNP) clearly improved specificity and accuracy from AUC 0.96, specificity 0.91, and accuracy 0.90 for NT-proBNP alone to corresponding metrics of 0.99, 0.99, and 0.93 in the discovery and 0.97, 0.96, and 0.93 in Validation 1. The 8-microRNA discovery panel distinguished HFpEF from HF with reduced ejection fraction with AUC 0.81, specificity 0.66, and accuracy 0.72. Corresponding metrics were 0.65, 0.41, and 0.56 in Validation 1 and 0.65, 0.41, and 0.62 in Validation 2. For phenotype categorization, combined markers achieved AUC 0.87, specificity 0.75, and accuracy 0.77 in the discovery with corresponding metrics of 0.74, 0.59, and 0.67 in Validation 1 and 0.72, 0.52, and 0.68 in Validation 2, as compared with NT-proBNP alone of AUC 0.71, specificity 0.46, and accuracy 0.62 in the discovery; with corresponding metrics of 0.72, 0.44, and 0.57 in Validation 1 and 0.69, 0.48, and 0.66 in Validation 2. Accordingly, false negative (FN) (81% Singapore and all NZ FN cases were HFpEF) as classified by a guideline-endorsed NT-proBNP ruleout threshold, were correctly reclassified by the 8-microRNA panel in the majority (72% and 88% of FN in Singapore and NZ, respectively) of cases. Conclusions Multi-microRNA panels in combination with NT-proBNP are highly discriminatory and improved specificity and accuracy in identifying nonacute HF. These findings suggest potential utility in the identification of nonacute HF, where clinical assessment, imaging, and NT-proBNP may not be definitive, especially in HFpEF.

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

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