Global burden of cardiovascular diseases: projections from 2025 to 2050.

AIMS: The prediction of future trends in cardiovascular disease (CVD) mortality and their risk factors can assist policy-makers in healthcare planning. This study aims to project geospatial trends in CVDs and their underlying risk factors from 2025 to 2050. METHODS AND RESULTS: Using historical data on mortality and disability-adjusted life years (DALYs) from the Global Burden of Disease (GBD) 2019 study, encompassing the period of 1990 to 2019, Poisson regression was performed to model mortality and DALYs associated with CVD and its associated risk factors from 2025 to 2050. Subgroup analysis was based on GBD super-regions. Between 2025 and 2050, a 90.0% increase in cardiovascular prevalence, 73.4% increase in crude mortality, and 54.7% increase in crude DALYs are projected, with an expected 35.6 million cardiovascular deaths in 2050 (from 20.5 million in 2025). However, age-standardized cardiovascular prevalence will be relatively constant (-3.6%), with decreasing age-standardized mortality (-30.5%) and age-standardized DALYs (-29.6%). In 2050, ischaemic heart disease will remain the leading cause of cardiovascular deaths (20 million deaths) while high systolic blood pressure will be the main cardiovascular risk factor driving mortality (18.9 million deaths). Central Europe, Eastern Europe, and Central Asia super-region is set to incur the highest age-standardized cardiovascular mortality rate in 2050 (305 deaths per 100 000 population). CONCLUSION: In the coming decades, the relatively constant age-standardized prevalence of global CVD suggests that the net effect of summative preventative efforts will likely continue to be unchanged. The fall in age-standardized cardiovascular mortality reflects the improvement in medical care following diagnosis. However, future healthcare systems can expect a rapid rise in crude cardiovascular mortality, driven by the ageing global populace. The continued rise in CVD burden will largely be attributed to atherosclerotic diseases. REGISTRATION: Not applicable.

The global cardiovascular disease (CVD) burden is expected to rise in the next few decades, driven primarily by an ageing populace worldwide. When standardized by age and population, CVD prevalence is expected to remain relatively constant, while mortality is expected to fall. This suggests that the effects of primary prevention efforts are set to remain roughly constant, while worldwide treatment outcomes are anticipated to improve.High blood pressures, dietary risks, and high cholesterol are the predominant risk factors expected to drive cardiovascular diseases from 2025 to 2050. A high body-mass index is likely to see a rapid rise in certain regions. Effective region-specific interventions are vital to arrest the CVD trajectory.

Clinical phenotypes and outcomes of patients with left ventricular thrombus: an unsupervised cluster analysis.

BACKGROUND: Left ventricular thrombus (LVT) can develop in a diverse group of patients with various underlying causes, resulting in divergent natural histories and trajectories with treatment. Our aim was to use cluster analysis to identify unique clinical profiles among patients with LVT and then compare their clinical characteristics, treatment strategies, and outcomes. METHODS: We conducted a retrospective study involving 472 patients with LVT whose data were extracted from a tertiary center's echocardiography database, from March 2011 to January 2021. We used the TwoStep cluster analysis method, examining 19 variables. RESULTS: Our analysis of the 472 patients with LVT revealed two distinct patient clusters. Cluster 1, comprising 247 individuals (52.3%), was characterized by younger patients with a lower incidence of traditional cardiovascular risk factors and relatively fewer comorbidities compared with Cluster 2. Most patients had LVT attributed to an underlying ischemic condition, with a larger proportion being due to post-acute myocardial infarction in Cluster 1 (68.8%), and due to ischemic cardiomyopathy in Cluster 2 (57.8%). Notably, patients in Cluster 2 exhibited a reduced likelihood of LVT resolution (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.44-0.77, p < 0.001) and a higher risk of all-cause mortality (HR 2.27, 95% CI 1.43-3.60, p = 0.001). These associations persisted even after adjusting for variables such as anticoagulation treatment, the presence of left ventricular aneurysms, and specific LVT characteristics such as mobility, protrusion, and size. CONCLUSION: Through TwoStep cluster analysis, we identified two distinct clinical phenotypes among patients with LVT, each distinguished by unique baseline clinical attributes and varying prognoses.

The burden of cardiovascular disease in Asia from 2025 to 2050: a forecast analysis for East Asia, South Asia, South-East Asia, Central Asia, and high-income Asia Pacific regions.

Background: Given the rapidly growing burden of cardiovascular disease (CVD) in Asia, this study forecasts the CVD burden and associated risk factors in Asia from 2025 to 2050. Methods: Data from the Global Burden of Disease 2019 study was used to construct regression models predicting prevalence, mortality, and disability-adjusted life years (DALYs) attributed to CVD and risk factors in Asia in the coming decades. Findings: Between 2025 and 2050, crude cardiovascular mortality is expected to rise 91.2% despite a 23.0% decrease in the age-standardised cardiovascular mortality rate (ASMR). Ischaemic heart disease (115 deaths per 100,000 population) and stroke (63 deaths per 100,000 population) will remain leading drivers of ASMR in 2050. Central Asia will have the highest ASMR (676 deaths per 100,000 population), more than three-fold that of Asia overall (186 deaths per 100,000 population), while high-income Asia sub-regions will incur an ASMR of 22 deaths per 100,000 in 2050. High systolic blood pressure will contribute the highest ASMR throughout Asia (105 deaths per 100,000 population), except in Central Asia where high fasting plasma glucose will dominate (546 deaths per 100,000 population). Interpretation: This forecast forewarns an almost doubling in crude cardiovascular mortality by 2050 in Asia, with marked heterogeneity across sub-regions. Atherosclerotic diseases will continue to dominate, while high systolic blood pressure will be the leading risk factor. Funding: This was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03), National Medical Research Council Research Training Fellowship (MH 095:003/008-303), National University of Singapore Yong Loo Lin School of Medicine's Junior Academic Fellowship Scheme, NUHS Clinician Scientist Program (NCSP2.0/2024/NUHS/NCWS) and the CArdiovascular DiseasE National Collaborative Enterprise (CADENCE) National Clinical Translational Program (MOH-001277-01).

Feasibility, safety and outcomes of conduction system pacing for bradycardia amongst the very elderly.

The impact of age (≥ 85 vs < 85 years) on clinical outcomes and pacemaker performance of conduction system pacing (CSP) compared to right ventricular pacing (RVP) were examined. Consecutive patients from a prospective, observational, multicenter study with pacemakers implanted for bradycardia were studied. The primary endpoint was a composite of heart failure (HF)-hospitalizations, pacing-induced cardiomyopathy requiring cardiac resynchronization therapy or all-cause mortality. Secondary endpoints were acutely successful CSP, absence of pacing-complications, optimal pacemaker performance defined as pacing thresholds < 2.5 V, R-wave amplitude ≥ 5 V and absence of complications, threshold stability (no increases of > 1 V) and persistence of His-Purkinje capture on follow-up. Among 984 patients (age 74.1 ± 11.2 years, 41% CSP, 16% ≥ 85 years), CSP was independently associated with reduced hazard of the primary endpoint compared to RVP, regardless of age-group (< 85 years: adjusted hazard ratio [AHR] 0.63, 95% confidence interval [CI] 0.40-0.98; ≥ 85 years: AHR 0.40, 95% CI 0.17-0.94). Among patients with CSP, age did not significantly impact the secondary endpoints of acute CSP success (86% vs 88%), pacing complications (19% vs 11%), optimal pacemaker performance (64% vs 69%), threshold stability (96% vs 96%) and persistent His-Purkinje capture (86% vs 91%) on follow-up (all p > 0.05). CSP improves clinical outcomes in all age-groups, without compromising procedural safety or pacemaker performance in the very elderly.

Validation of the NULL-EASE Score for Predicting Survival in a Multiethnic Asian Cohort of Out-of-Hospital Cardiac Arrest.

BACKGROUND: NULL-PLEASE is a simple and accurate clinical scoring system developed in a Western cohort of patients with out-of-hospital cardiac arrest (OHCA). The need for blood test results limits its use in early stages of care. We adapted and validated the NULL-EASE score (without laboratory tests) in an independent, multiethnic Asian cohort of patients with out-of-hospital cardiac arrest. METHODS AND RESULTS: Using the Singapore OHCA registry, we included consecutive adult patients with out-of-hospital cardiac arrest who survived to hospital admission between April 2010 to December 2020. In-hospital mortality was the primary outcome. Logistic regression analyses were performed with STATA MP v18. Of 3274 patients (median age 64, interquartile range 54-75; 67.9% male) included in the study, 2476 (75.6%) had in-hospital mortality. NULL-EASE score was significantly lower in survivors compared with nonsurvivors (median [inter quartile range] 3 [1-4] versus 6 [4-7]; P<0.001) and strongly predictive of mortality (area under receiver operating characteristic, 0.81 [95% CI, 0.79-0.83]). Patients with a score of ≥3 had higher odds of mortality (adjusted odds ratio, 8.11 [95% CI, 6.57-10.00]) when compared with those with lower scores, after adjusting for sex, residential arrest, diabetes, respiratory disease, and stroke. A cutoff value of ≥3 predicted mortality with 92.2% sensitivity, 84.1% positive predictive value, 46.1% specificity, and 65.5% negative predictive value. NULL-EASE score performed better in younger compared with older patients (area under receiver operating characteristic, 0.82 versus 0.77, P=0.008). CONCLUSIONS: The NULL-EASE score has good discriminative performance (sensitivity and accuracy) in our multiethnic Asian cohort, but the cutoff of ≥3 falls short of the desired level of specificity for therapeutic decision-making.

Predictors of Mortality in Acute Myocardial Infarction Complicated by Cardiogenic Shock despite Intra-Aortic Balloon Pump: Opportunities for Advanced Mechanical Circulatory Support in Asia.

Introduction: Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) mortality remains high despite revascularization and the use of the intra-aortic balloon pump (IABP). Advanced mechanical circulatory support (MCS) devices, such as catheter-based ventricular assist devices (cVAD), may impact mortality. We aim to identify predictors of mortality in AMI-CS implanted with IABP and the proportion eligible for advanced MCS in an Asian population. Methods: We retrospectively analyzed a cohort of Society for Cardiovascular Angiography and Intervention (SCAI) stage C and above AMI-CS patients with IABP implanted from 2017-2019. We excluded patients who had IABP implanted for indications other than AMI-CS. Primary outcome was 30-day mortality. Binary logistic regression was used to calculate adjusted odds ratios (aOR) for patient characteristics. Results: Over the 3-year period, 242 patients (mean age 64.1 ± 12.4 years, 88% males) with AMI-CS had IABP implanted. 30-day mortality was 55%. On univariate analysis, cardiac arrest (p < 0.001), inotrope/vasopressor use prior to IABP (p = 0.004) was more common in non-survivors. Non-survivors were less likely to be smokers (p = 0.001), had lower ejection fraction, higher creatinine/ lactate and lower pH (all p < 0.001). On multi-variate analysis, predictors of mortality were cardiac arrest prior to IABP (aOR 4.00, CI 2.28-7.03), inotrope/vasopressor prior to IABP (aOR 2.41, CI 1.18-4.96), lower arterial pH (aOR 0.02, CI 0.00-0.31), higher lactate (aOR 2.42, CI 1.00-1.19), and lower hemoglobin (aOR 0.83, CI 0.71-0.98). Using institutional MCS criteria, 106 patients (44%) would have qualified for advanced MCS. Conclusions: Early mortality in AMI-CS remains high despite IABP. Many patients would have qualified for higher degrees of MCS.

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.

Prognostic performance of soluble urokinase plasminogen activator receptor for heart failure or mortality in Western and Asian patients with acute breathlessness.

AIMS: The performance of circulating soluble urokinase plasminogen activator receptor (suPAR) for predicting the composite endpoint of subsequent heart failure (HF) hospitalisation and/or death at 1 year was assessed in (i) patients with undifferentiated breathlessness, and generalisability was compared in (ii) disparate Western versus Asian sub-cohorts, and in (iii) the sub-cohort adjudicated with HF. METHODS AND RESULTS: Patients with acute breathlessness were recruited from the emergency departments in New Zealand (NZ, n = 612) and Singapore (n = 483). suPAR measured in the presentation samples was higher in patients incurring the endpoint (n = 281) compared with survivors (5.2 ng/mL vs 3.1 ng/mL, P < 0.0001). The discriminative power of suPAR for endpoint prediction was c-statistic of 0.77 in the combined population, but was superior in Singapore than NZ (c-statistic: 0.83 vs 0.71, P < 0.0001). Although the highest suPAR tertile (>4.37 ng/mL) was associated with risks of >4-fold in NZ, >20-fold in Singapore, and ≥3-fold in HF for incurring the outcome, there was no interaction between country and suPAR levels after adjustment. Multivariable analysis indicated suPAR to be robust in predicting HF/death at 1-year [hazard ratio: 1.9 (95% CI:1.7 to 2.0) per SD increase] and improved risk discrimination for outcome prediction in HF (∆0.06) and for those with NT-proBNP >1000 pg/mL (∆0.02). CONCLUSION: suPAR is a strong independent predictor of HF and/or death at 1 year in acutely breathless patients, in both Asian and Western cohorts, and in HF. suPAR may improve stratification of acutely breathless patients, and in acute HF, for risk of later onset of heart failure or mortality.

Mandibular Advancement vs CPAP for Blood Pressure Reduction in Patients With Obstructive Sleep Apnea.

BACKGROUND: Hypertension guidelines recommend diagnosis and treatment of obstructive sleep apnea (OSA) in patients with hypertension. The mandibular advancement device (MAD) is an oral appliance therapy for patients who decline or cannot tolerate continuous positive airway pressure (CPAP). OBJECTIVES: We compared the relative effectiveness of MAD vs CPAP in reducing 24-hour ambulatory blood pressure (BP). METHODS: In an investigator-initiated, randomized, noninferiority trial (prespecified margin 1.5 mm Hg), 321 participants aged ≥40 years with hypertension and increased cardiovascular risk were recruited at 3 public hospitals for polysomnography. Of these, 220 participants with moderate-to-severe OSA (apnea-hypopnea index ≥15 events per hour) were randomized to either MAD or CPAP (1:1). The primary outcome was the difference between the 24-hour mean arterial BP at baseline and 6 months. RESULTS: Compared with baseline, the 24-hour mean arterial BP decreased by 2.5 mm Hg (P = 0.003) at 6 months in the MAD group, whereas no change was observed in the CPAP group (P = 0.374). The between-group difference was -1.6 mm Hg (95% CI: -3.51 to 0.24, noninferiority P < 0.001). The MAD group demonstrated a larger between-group reduction in all secondary ambulatory BP parameters compared with the CPAP group, with the most pronounced effects observed in the asleep BP parameters. Both the MAD and CPAP improved daytime sleepiness, with the between-group difference similar (P = 0.384). There were no between-group differences in cardiovascular biomarkers. CONCLUSIONS: MAD is noninferior to CPAP for reducing 24-hour mean arterial BP in participants with hypertension and increased cardiovascular risk. (Cardiosleep Research Program on Obstructive Sleep Apnea, Blood Pressure Control and Maladaptive Myocardial Remodeling-Non-inferiority Trial [CRESCENT]; NCT04119999).

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.

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.

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.

Differential Associations of A-/B-Type Natriuretic Peptides With Cardiac Structure, Function, and Prognosis in Heart Failure.

BACKGROUND: Natriuretic peptide (NP) elevations are prognostic in heart failure (HF), but relative atrial NP deficiency in acute HF has been suggested. OBJECTIVES: The authors compared plasma concentrations and relative strength of associations of A- and B-type NPs with cardiac structure/function and clinical outcomes in HF. METHODS: Midregional pro-atrial natriuretic peptide (MR-proANP), B-type natriuretic peptide (BNP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured in patients with compensated HF in a prospective, multicenter study. The primary outcome was a composite of HF-hospitalization or all-cause mortality. Secondary outcomes included individual primary outcome components and cardiovascular admission. RESULTS: Among 1,278 patients (age 60.1 ± 12.1 years, 82% men, left ventricular ejection fraction [LVEF] 34% ± 14%), median concentrations of MR-proANP were 990 pg/mL (Q1-Q3: 557-1,563 pg/mL), NT-proBNP 1,648 pg/mL (Q1-Q3: 652-3,960 pg/mL), and BNP 291 pg/mL (Q1-Q3: 103-777 pg/mL). No subpopulation with inappropriately low MR-proANP (relative to BNP/NT-proBNP) was observed. Clinical event rates were similar for biomarker tertiles. Increments in MR-proANP exhibited steeper associations with concurrent shifts in left ventricular size, diastolic indexes and LVEF than BNP/NT-proBNP at baseline and serially (P < 0.05), and lower odds of beneficial left ventricular reverse remodeling: OR: 0.35 (95% CI: 0.18-0.70). In single-biomarker models, MR-proANP(log10) was associated with the highest hazard (4 to 6 times) for each outcome. In multimarker models, independent associations were observed for the primary outcome (MR-proANP and NT-proBNP), HF-hospitalization and cardiovascular admission (MR-proANP only), and all-cause mortality (NT-proBNP only) (P < 0.05). The discriminative value of MR-proANP was superior to BNP/NT-proBNP (HF-hospitalization) and BNP (primary outcome) (P < 0.05). CONCLUSIONS: MR-proANP was not inappropriately low relative to concurrent BNP/NT-proBNP values. Proportional increments in MR-proANP were more pronounced than for B-peptides for given decrements in cardiac structure/function. MR-proANP offered greater independent predictive power overall.

Validity and feasibility of using the Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F) in primary care clinics in Singapore.

LAY ABSTRACT: Systematic screening for autism in early childhood has been suggested to improve eventual outcomes by facilitating earlier diagnosis and access to intervention. However, clinical implementation of screening has to take into account effectiveness and feasibility of use within a healthcare setting for accurate diagnosis of autism. In Singapore, autism screening using a structured screening tool is not currently employed as a part of routine well-child visits for children in primary care clinics. In this study, 5336 children (aged 17-20 months) were screened for autism using the Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F) during their 18-month well-child visit in seven primary care clinics. Screening and follow-up interviews were administered by nursing staff at each clinic. Children screened positive and a portion of those screened negative then underwent diagnostic assessments to determine whether they met the diagnostic criteria for autism. In total, 113 (2.1%) were screened positive, of which 54 (1.0%) met the criteria for autism. Children who screened positive and received a diagnosis accessed autism-specific intervention at an average age of 22 months. Nurses and physicians rated the acceptability and practicality of the M-CHAT-R/F highly. Therefore, the M-CHAT-R/F questionnaire was an effective and feasible tool for autism screening among 18-month-old children in this study. Future studies will be designed to determine the optimal age of screening and role of repeated screening in Singapore, as well as to better understand any potential improved outcomes nationwide compared with pre-implementation of autism screening.

Temporal trends in out-of-hospital cardiac arrest with an initial non-shockable rhythm in Singapore.

Aim: Out-of-hospital cardiac arrest (OHCA) with an initial non-shockable rhythm is the predominant form of OHCA in adults. We evaluated its 10-year trends in epidemiology and management in Singapore. Methods: Using the national OHCA registry we studied the trends of 20,844 Emergency Medical Services-attended adult OHCA from April 2010 to December 2019. Survival to hospital discharge was the primary outcome. Trends and outcomes were analyzed using linear and logistic regression, respectively. Results: Incidence rates of adult OHCAs increased during the study period, driven by non-shockable OHCA. Compared to shockable OHCA, non-shockable OHCAs were significantly older, had more co-morbidities, unwitnessed and residential arrests, longer no-flow time, and received less bystander cardiopulmonary resuscitation (CPR) and in-hospital interventions (p < 0.001). Amongst non-shockable OHCA, age, co-morbidities, residential arrests, no-flow time, time to patient, bystander CPR and epinephrine administration increased during the study period, while presumed cardiac etiology decreased (p < 0.05). Unlike shockable OHCA, survival for non-shockable OHCA did not improve (p < 0.001 for trend difference). The likelihood of survival for non-shockable OHCA significantly increased with witnessed arrest (adjusted odds ratio (aOR) 2.02) and bystander CPR (aOR 3.25), but decreased with presumed cardiac etiology (aOR 0.65), epinephrine administration (aOR 0.66), time to patient (aOR 0.93) and age (aOR 0.98). Significant two-way interactions were observed for no-flow time and residential arrest with bystander CPR (aOR 0.96 and 0.40 respectively). Conclusion: The incidence of non-shockable OHCA increased between 2010 and 2019. Despite increased interventions, survival did not improve for non-shockable OHCA, in contrast to the improved survival for shockable OHCA.

Comparison of Pacing Performance and Clinical Outcomes Between Left Bundle Branch and His Bundle Pacing.

BACKGROUND: Left bundle branch (LBBP) and His-bundle pacing (HBP) provide physiological ventricular activation. OBJECTIVES: This study investigated differences in feasibility, device performance, and clinical outcomes between LBBP and HBP. METHODS: Consecutive patients with LBBP and HBP from 2018 to 2021 in 2 centers were prospectively studied. The primary endpoint was optimal device performance during follow-up, defined as the presence of pacing thresholds <2.5 V, R-wave amplitude ≥5 V, and absence of conduction system pacing (CSP)-related complications. The secondary endpoint was the composite of heart failure hospitalizations or all-cause mortality. RESULTS: Among 338 patients, 282 underwent successful CSP (119 HBP, 163 LBBP). Success rates, CSP-related complications, and need for reoperations did not differ between LBBP and HBP (P > 0.05). Pacing thresholds were lower, whereas R-wave amplitudes and lead impedance were higher in LBBP (P < 0.05). The primary endpoint was more frequent in LBBP than HBP (79% vs 34%; P < 0.001), with LBBP independently associated with 9-fold increased odds of optimal device performance (adjusted OR: 9.31; 95% CI: 5.14-16.86). LBBP was less likely to have increased pacing thresholds by >1 V (1% vs 19% HBP, P < 0.001). The secondary outcome was less frequent in LBBP than HBP (9% vs 24%, P = 0.001), with LBBP trending towards higher event-free survival (HR: 0.62; 95% CI: 0.31-1.23). The secondary outcome was independent of pacing burden or pacing indication. CONCLUSIONS: Despite similar feasibility and safety profiles, LBBP confers additional benefits in pacing performance and reliability, shows trends towards improved survival compared to HBP, and should be the preferred first-line CSP modality of choice.

Regional Handling and Prognostic Performance of Circulating Insulin-Like Growth Factor Binding Protein-7 in Heart Failure.

BACKGROUND: Regional handling and the prognostic performance of insulin-like growth factor binding protein (IGFBP)-7, in contrast or in combination with other candidate biomarkers, in chronic heart failure (CHF) remain uncertain. OBJECTIVES: The authors investigated the regional handling of plasma IGFBP-7 and its association with long-term outcomes in CHF in comparison with selected circulating biomarkers. METHODS: Plasma concentrations of IGFBP-7, N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin-T, growth differentiation factor-15, and high-sensitivity C-reactive protein were measured prospectively in a cohort with CHF (n = 863). The primary outcome was the composite of heart failure (HF) hospitalization or all-cause mortality. In a separate non-HF cohort (n = 66) undergoing cardiac catheterization, transorgan gradients of plasma IGFBP-7 concentrations were evaluated. RESULTS: Among 863 patients (age 69 ± 14 years, 30% female, 36% HF with preserved ejection fraction), IGFBP-7 (median: 121 [IQR: 99-156] ng/mL) related inversely to left ventricular volumes but directly to diastolic function. Above the optimal cutoff, IGFBP-7 ≥110 ng/mL was independently associated with 32% increased hazard of the primary outcome: 1.32 (95% CI: 1.06-1.64). Among the 5 markers, IGFBP-7 had the highest hazard for a proportional increment in plasma concentrations independent of HF phenotype in single- and double-biomarker models, and provided incremental prognostic value beyond clinical predictors plus NT-proBNP, high-sensitivity troponin-T, and high-sensitivity C-reactive protein (P < 0.05). Assessment of regional concentrations indicated renal secretion of IGFBP-7 in contrast to renal extraction of NT-proBNP, possible cardiac extraction of IGFBP-7 in contrast to secretion of NT-proBNP, and common hepatic extraction of both peptides. CONCLUSIONS: Transorgan regulation of IGFBP-7 is distinct from NT-proBNP. Circulating IGFBP-7 independently predicts adverse outcomes in CHF with a strong prognostic performance when compared with other well-recognized cardiac-specific or noncardiac prognostic markers.

Predicting late aortic complications after acute type A dissection surgery with volumetric measurements in a Singapore cohort.

Introduction: This study was conducted to evaluate the efficacy of postoperative computed tomography (CT) measurements of aortic lumen volumes in predicting aortic-related complications following acute type A aortic dissection (ATAAD) repair. Methods: We conducted a single-institution retrospective aortic volumetric analysis of patients after ascending aorta replacement performed during 2001-2015. The volumetric measurements of total lumen (total-L), true lumen (TL), false lumen (FL), as well as the TL:FL ratio from the first and second postoperative computer angiograms were obtained. A generalised structural equation model was created to analyse the predictive utility of TL:FL ratio. Results: One hundred and twenty-five patients underwent surgical intervention, of whom 97 patients were eventually discharged and analysed for postoperative complications. A total of 19 patients were included in the final analysis. Patients with late postoperative aortic complications had a significantly higher FL volume and total-L volume on the first (FL volume P = 0.041, total-L volume P = 0.05) and second (FL volume P = 0.01, total-L volume P = 0.007) postoperative scans. The odds of having aortic complications were raised by 1% with a 1 cm3 increase in total-L volume and by 2% with a 1 cm3 increase in FL volume. The TL:FL ratio was significantly lower in patients who developed complications. Conclusion: Postoperative CT volumetric measurements in patients who developed complications are characterised by a significant increase in the FL volume and total-L volume from the first postoperative scans. Patients with disproportionately expanded FL presenting with TL:FL ratios less than 1 were associated with aortic complications. Hence, the TL:FL ratio may be a reliable and useful parameter to monitor postoperative disease progression and to evaluate the risk of late complications in ATAAD patients.

Mandibular advancement device versus CPAP in lowering 24-hour blood pressure in patients with obstructive sleep apnoea and hypertension: the CRESCENT trial protocol.

INTRODUCTION: Although 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 ANALYSIS: This 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 <60 years old), body mass index (25 vs <25 kg/m2) and apnoea-hypopnoea index (30 vs <30 events/hour), an adaptive randomisation scheme with permuted blocks constructed in real-time is implemented to restrict imbalance. The overall study duration is 12 months. The primary endpoint is the 24-hour mean arterial BP difference between baseline and 6-month follow-up. The secondary endpoints include other measures of ambulatory BP monitoring, arrhythmia based on a 4-day electrocardiographic monitoring, biomarker and proteomic analysis, cardiovascular magnetic resonance-derived myocardial fibrosis and remodelling and quality-of-life questionnaires. Recruitment began in October 2019 and ended in December 2022. Comparison between MAD and CPAP will be performed using covariance (ANCOVA) analysis of the changes in 24-hour mean arterial BP while adjusting for the baseline 24-hour mean arterial BP. We will compare the 95% CIs around the treatment difference point estimate with the prespecified non-inferiority margin (1.5 mm Hg). If the upper limit of the 95% CI is <1.5 mm Hg and crosses 0, non-inferiority of the MAD relative to CPAP will be established. ETHICS AND DISSEMINATION: The 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 NUMBER: NCT04119999.

The Belun sleep platform to diagnose obstructive sleep apnea in patients with hypertension and high cardiovascular risk.

STUDY OBJECTIVE: Current hypertension guidelines recommend that at-risk individuals be screened for obstructive sleep apnea (OSA). The Belun Ring is a wearable OSA diagnostic device worn on the palmar side of the proximal phalanx of the index finger. METHODS: We recruited 129 participants (age: 60 ±â€Š8 years, male sex: 88%, BMI: 27 ±â€Š4 kg/m 2 ) with hypertension and high cardiovascular risk for a simultaneous polysomnography and Belun Ring monitoring for one night. Epworth Sleepiness Scale score more than 10 was detected in 27 (21.0%) participants. RESULTS: In the 127 participants who completed the study, the apnea-hypopnea index (AHI) derived from polysomnography was 18.1 (interquartile range: 33.0) events/h and that derived from the Belun Ring was 19.5 (interquartile range: 23.3) events/h [intraclass correlation coefficient: 0.882, 95% confidence interval (95% CI): 0.837-0.916]. A Bland-Altman plot showed the difference between the Belun Ring and polysomnography AHIs to be -1.3 ±â€Š10.4 events/h. Area under the receiver operating characteristic for the Belun Ring AHI was 0.961 (95% CI: 0.932-0.990, P  < 0.001). When the Belun Ring AHI of at least 15 events/h was used to diagnose OSA, the sensitivity, specificity, positive predictive value, and negative predictive value were 95.7, 77.6, 85.3, and 93.8%, respectively. The overall accuracy was 87.4%. The Cohen's kappa agreement was 0.74 ±â€Š0.09 ( P  < 0.001). Similar results were obtained when the oxygen desaturation index was used to diagnose OSA. CONCLUSION: A high prevalence of OSA was detected in patients with hypertension and high cardiovascular risk. The Belun Ring is a reliable device for OSA diagnosis similar to polysomnography.