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Aims/hypothesis: Type 2 diabetes is a complex and heterogeneous disease and the aetiological components underlying the heterogeneity remain unclear in the Chinese and East Asian population. Therefore, we aimed to investigate whether specific pathophysiological pathways drive the clinical heterogeneity in type 2 diabetes., Methods: We employed newly developed type 2 diabetes hard-clustering and soft-clustering pathway-specific polygenic risk scores (psPRSs) to characterise individual genetic susceptibility to pathophysiological pathways implicated in type 2 diabetes in 18,217 Chinese patients from Hong Kong. The 'total' type 2 diabetes polygenic risk score (PRS) was summed by genome-wide significant type 2 diabetes signals (n=1289). We examined the associations between psPRSs and cardiometabolic profile, age of onset, two glycaemic deterioration outcomes (clinical requirement of insulin treatment, defined by two consecutive HbA 1c values ≥69 mmol/mol [8.5%] more than 3 months apart during treatment with two or more oral glucose-lowering drugs, and insulin initiation), three renal (albuminuria, end-stage renal disease and chronic kidney disease) outcomes and five cardiovascular outcomes., Results: Although most psPRSs and total type 2 diabetes PRS were associated with an earlier and younger onset of type 2 diabetes, the psPRSs showed distinct associations with clinical outcomes. In particular, individuals with normal weight showed higher psPRSs for beta cell dysfunction and lipodystrophy than those who were overweight. The psPRSs for obesity were associated with faster progression to clinical requirement of insulin treatment (adjusted HR [95% CI] 1.09 [1.05, 1.13], p<0.0001), end-stage renal disease (1.10 [1.04, 1.16], p=0.0007) and CVD (1.10 [1.05, 1.16], p<0.0001) while the psPRSs for beta cell dysfunction were associated with reduced incident end-stage renal disease (0.90 [0.85, 0.95], p=0.0001) and heart failure (0.83 [0.73, 0.93], p=0.0011). Major findings remained significant after adjusting for a set of clinical variables., Conclusions/interpretation: Beta cell dysfunction and lipodystrophy could be the driving pathological pathways in type 2 diabetes in individuals with normal weight. Genetic risks of beta cell dysfunction and obesity represent two major genetic drivers of type 2 diabetes heterogeneity in disease progression and diabetic complications, which are shared across ancestry groups. Type 2 diabetes psPRSs may help inform patient stratification according to aetiology and guide precision diabetes care., Competing Interests: Acknowledgements The authors thank all the participants and investigators of the HKDR and HKDB for their contributions, and the medical and nursing staff of the respective hospitals for their professional input and support. The full lists of team members of the Hong Kong Diabetes Biobank Study Group and the TRANSCEND Consortium are included in the ESM additional information section. Data availability The list of SNPs used to calculate hard- and soft-clustering psPRSs can be found in ESM Tables 6 and 7. HKDR and HKDB data are not publicly available but may be made available upon reasonable request to the corresponding author. Funding This work was supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region (CU R4012-18), Research Grants Council Theme-based Research Scheme (T12-402/13N), the University Grants Matching Scheme, a CUHK Direct Grant and the Focused Innovation Scheme. RCWM acknowledges support from a Croucher Foundation Senior Medical Research Fellowship, the Research Committee Postdoctoral Fellowship Scheme, the CUHK Internationalisation Faculty Mobility Scheme and the Provost’s Scheme for PhD scholarship of the Chinese University of Hong Kong. JCNC acknowledges support from the Hong Kong Government Health and Medical Research Fund (CFS-CUHK2), Hong Kong Genome Institute, Chinese University of Hong Kong Research Committee Postdoctoral Fellowship Scheme and Innovation and Technology Commission Research Talent Hub. RAO has a research grant from Randox Ltd on autoimmune disease genetic risk score diagnostics and the University of Exeter licenses know-how to Randox and receives royalties for a type 1 diabetes GRS biochip. Authors’ relationships and activities JCNC received consultancy fees from Astra Zeneca, Bayer, Boehringer Ingelheim, Celltrion, MSD, Pfizer, Servier and Viatris Pharmaceutical; speaker fees from Astra Zeneca, Bayer, Boehringer Ingelheim, MSD, Merck, Sanofi and Servier; and research grants through her institutions from Applied Therapeutics, Astra Zeneca, Hua Medicine, Lee Powder, Lilly, Merck and Servier. APSK received research grants from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli-Lilly, Kyowa Kirin and Merck Serono and honoraria for consultancy or giving lectures from Nestle, Novo Nordisk, Pfizer and Sanofi. EYKNC received speaker fees from Sanofi and Novartis and institutional research funding from Sanofi, Medtronic Diabetes and Powder Pharmaceuticals Inc. RCWM has received research funding from Bayer, Boehringer Ingelheim, Novo Nordisk, Roche Diagnostics and Tricida Inc. for carrying out clinical trials or studies; and from AstraZeneca, Bayer, Boehringer Ingelheim, Diachii Sankyo, Kyowa Kirin and Merck for speaker honoraria or consultancy in advisory boards. All proceeds have been donated to the Chinese University of Hong Kong to support diabetes research. JCNC, CKPL, RCWM and W-yS are co-founders of GemVCare, a biotech start-up supported by the Technology Start-up Support Scheme for Universities of the Hong Kong Government Innovation and Technology Commission. RCWM is an advisory board member of the editorial board of Diabetologia. RAO has performed consulting for Janssen, Provention Bio and Sanofi.The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work. Contribution statement GY, CHTT, CKPL, MNW, RAO and RCWM conceptualised and designed the study. CHTT, CKPL, ESHL, RO, H-mL, ACWN, YH, BF, CH, HW, AY, HMC, KFL, SCS, GH, CCT, KPL, JYYL, EYNC, MWT, GK, ITL, JKYL, VTFY, EL, SL, SF, YLC, CCS, EC, APSK, WHT, AOYL, W-yS, JCNC and RCWM contributed to data acquisition. GY, CHTT, ESHL conducted statistical analysis. GY, CHTT, CKPL, MS, ESHL, BF, WHT, MNW, RAO, JCNC and RCWM were involved in data interpretation. GY, RAO and RCWM drafted the manuscript. All authors contributed to the editing, review and critical revision of the manuscript. WHT, W-yS, JCNC, RAO and RCWM contributed to funding acquisition for the study. All authors read and approved the final version to be published. RCWM is the guarantor of this work., (© 2024. The Author(s).)

Objective: To investigate fetal/neonatal and obstetric events in pregnancies with both maternal and fetal heart disease., Study Design: From the CARPREG database, singleton pregnancies (>24 weeks) in patients with structural heart disease that underwent fetal/neonatal echocardiograms were selected and separated in two groups: maternal heart disease only (M-HD) and maternal and fetal heart disease (MF-HD). Differences in adverse fetal/neonatal (death, preterm birth, and small for gestational age) and obstetric (preeclampsia/eclampsia) outcomes between groups were analyzed., Results: From 1011 pregnancies, 93 had MF-HD. Fetal/neonatal events (38.7% vs 25.3%, p = 0.006) and spontaneous preterm birth (10.8% vs 4.9%, p = 0.021) were more frequent in MF-HD compared to M-HD, with no difference in obstetric events. MF-HD remained as a significant predictor of fetal/neonatal events after adjustment (OR:1.883; 95% CI:1.182-3.000; p = 0.008)., Conclusions: Pregnancies with MF-HD are at risk of adverse fetal/neonatal events and spontaneous preterm birth. Larger studies are needed to determine their association with preeclampsia., (© 2024. The Author(s).)

Background: Non-diabetics and diabetics might have different oral health problems and impacts on their oral health-related quality of life (OHRQoL). Comparison of oral health status and coping strategies between these patients, and evaluation of factors associated with OHRQoL might facilitate better treatment planning for improved patient-centred outcome., Methods: One hundred and eleven non-diabetics and 107 diabetics attending a public hospital were clinically examined and evaluated for coping strategies (abbreviated coping orientation to problems experienced) and OHRQoL [short-form oral health impact profile (OHIP-14S)]. Factors associated with OHRQoL were analysed through correlation/partial correlation. Minimally important differences (MID) of OHIP-14S were calculated to confirm associations between attachment loss, caries, and tooth loss with OHRQoL., Results: Non-diabetics had worse periodontal status. Diabetics had more missing teeth. Non-diabetics and diabetics employed maladaptive coping to manage oral health problems. Overall, non-diabetics reported worse OHRQoL. Determination of MID showed that non-diabetics with high-severe attachment loss and <20 teeth experienced poorer OHRQoL. Diabetics with caries, high-severe attachment loss, and <25 teeth experienced poorer OHRQoL., Conclusion: Different factors were associated with OHRQoL of non-diabetics and diabetics. Delivery of treatment aimed at maintaining teeth in a periodontally healthy and caries free state, and provision of more chewing units might help improve OHRQoL of diabetics. © 2024 Australian Dental Association., (© 2024 The Authors. Australian Dental Journal published by John Wiley & Sons Australia, Ltd on behalf of Australian Dental Association.)

Background: Atrial fibrillation (AF) may increase the risk of adverse maternal and fetal outcomes among pregnant with rheumatic valvular lesions (RHD). We aimed to assess the rate of occurrence of AF in pregnant with RHD and its impact on cardiac and maternal-fetal outcomes compared to those without it., Methods: The study group consisted of pregnant women with RHD and AF (cases) and a matched comparison group of pregnant women with RHD but without AF (controls) was derived from the database of pregnant women with RHD receiving care at our center between 2011 and 2021. Incidence of composite adverse outcomes(maternal death, heart failure, or thrombo-embolic events) and pregnancy outcomes were compared between them., Results: Seventy-one (5.1%; 95%CI 4.1%-6.4%) pregnant women with RHD had AF during pregnancy and childbirth, most occurring in the late second or early third trimester. New-onset AF was diagnosed in 34 (47.9%) of them. After matching, the incidence of composite outcome was higher in women with AF (77.5% (95%CI 66.3%-85.7%) compared to women without AF (17.3%(95%CI 13.3%-22.1%), P < .001), with seven (9.9%) maternal deaths among cases and two (0.7%) in controls. Heart failure was the most common adverse cardiac event (26.7% vs. 4.2%, P < .001, cases vs controls). Those with AF had higher odds (adjusted OR 56.6 (14.1-226.8)) of adverse cardiac outcomes after adjusting for other risk factors. The frequency of most non-cardiac pregnancy complications was similar in both groups. However, there was a trend towards a higher rate of miscarriage (16.9% vs. 9.9%), small-for-gestational-age babies(16.3 vs. 9.0%), and cesarean rates(31.9% vs. 18.3%) women with AF compared to those who did not experience AF., Conclusions: Atrial fibrillation in pregnancy among women with RHD was associated with an increased risk of maternal morbidity and mortality, with a trend towards an increase in some non-cardiac pregnancy complications compared to those pregnant women without AF. Our study results provide background data for developing and implementing a pregnancy-specific management strategy tailored to middle-income settings., Competing Interests: Conflict of interest All authors declare no conflict of interest in relation to this publication., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims/hypothesis: The aim of this study was to describe the metabolome in diabetic kidney disease (DKD) and its association with incident CVD in type 2 diabetes, and identify prognostic biomarkers., Methods: From a prospective cohort of individuals with type 2 diabetes, baseline sera (N=1991) were quantified for 170 metabolites using NMR spectroscopy with median 5.2 years of follow-up. Associations of chronic kidney disease (CKD, eGFR<60 ml/min per 1.73 m 2 ) or severely increased albuminuria with each metabolite were examined using linear regression, adjusted for confounders and multiplicity. Associations between DKD (CKD or severely increased albuminuria)-related metabolites and incident CVD were examined using Cox regressions. Metabolomic biomarkers were identified and assessed for CVD prediction and replicated in two independent cohorts., Results: At false discovery rate (FDR)<0.05, 156 metabolites were associated with DKD (151 for CKD and 128 for severely increased albuminuria), including apolipoprotein B-containing lipoproteins, HDL, fatty acids, phenylalanine, tyrosine, albumin and glycoprotein acetyls. Over 5.2 years of follow-up, 75 metabolites were associated with incident CVD at FDR<0.05. A model comprising age, sex and three metabolites (albumin, triglycerides in large HDL and phospholipids in small LDL) performed comparably to conventional risk factors (C statistic 0.765 vs 0.762, p=0.893) and adding the three metabolites further improved CVD prediction (C statistic from 0.762 to 0.797, p=0.014) and improved discrimination and reclassification. The 3-metabolite score was validated in independent Chinese and Dutch cohorts., Conclusions/interpretation: Altered metabolomic signatures in DKD are associated with incident CVD and improve CVD risk stratification., (© 2024. The Author(s).)

Background: The increasing and potentially preventable cardiac events in pregnant patients have led to calls to enhance multidisciplinary cardio-obstetrics education. To design a multidisciplinary cardio-obstetrics curriculum for general cardiology and obstetrics and gynecology (OBGYN) residents, we need to define educational needs from the perspectives of both cardiology and OBGYN residents. Our study characterizes the educational needs of Canadian cardiology and OBGYN residents., Methods: Canadian cardiology and OBGYN residents were surveyed on clinical exposures, perceived needs for topics, unperceived needs for topics (multiple-choice questions) and preferences for educational formats. High priorities were defined as ≥ 50% of responses indicating a perceived need or ≥ 50% indicating an unperceived need., Results: A total of 154 residents participated (cardiology n = 44, OBGYN n = 110). Residents reported insufficient clinical exposure to nearly all cardiac disorders, with 33% of exposures occurring in multidisciplinary contexts. All topics aside from gestational hypertension were rated as high priority on perceived needs by both specialties. High-priority unperceived needs were congenital heart disease (both specialties), pre-existing acquired heart disease (both specialties), medication safety (OBGYN), peripartum management (OBGYN), and pregnancy-related heart disease (OBGYN). Cardiology and OBGYN residents shared preferences for in-person simulation, virtual simulation, and online modules., Conclusions: Residents in both specialties reported low clinical exposure to most cardiac disorders during pregnancy, identified high-priority perceived needs in multiple topics, and shared 2 high-priority unperceived needs. OBGYN residents identified 3 additional high-priority unperceived needs. These data can inform design of multidisciplinary cardio-obstetrics curricula for general cardiology and OBGYN residents., (© 2023 The Authors.)

Background: Most risk stratification tools for pregnant patients with heart disease were developed in high-income countries and in populations with predominantly congenital heart disease, and therefore, may not be generalizable to those with valvular heart disease (VHD)., Objectives: The purpose of this study was to validate and establish the clinical utility of 2 risk stratification tools-DEVI (VHD-specific tool) and CARPREG-II-for predicting adverse cardiac events in pregnant patients with VHD., Methods: We conducted a cohort study involving consecutive pregnancies complicated with VHD admitted to a tertiary center in a middle-income setting from January 2019 to April 2022. Individual risk for adverse composite cardiac events was calculated using DEVI and CARPREG-II models. Performance was assessed through discrimination and calibration characteristics. Clinical utility was evaluated with Decision Curve Analysis., Results: Of 577 eligible pregnancies, 69 (12.1%) experienced a component of the composite outcome. A majority (94.7%) had rheumatic etiology, with mitral regurgitation as the predominant lesion (48.2%). The area under the receiver-operating characteristic curve was 0.884 (95% CI: 0.844-0.923) for the DEVI and 0.808 (95% CI: 0.753-0.863) for the CARPREG-II models. Calibration plots suggested that DEVI score overestimates risk at higher probabilities, whereas CARPREG-II score overestimates risk at both extremes and underestimates risk at middle probabilities. Decision curve analysis demonstrated that both models were useful across predicted probability thresholds between 10% and 50%., Conclusions: In pregnant patients with VHD, DEVI and CARPREG-II scores showed good discriminative ability and clinical utility across a range of probabilities. The DEVI score showed better agreement between predicted probabilities and observed events., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: In this study we aim to unravel genetic determinants of coronary heart disease (CHD) in type 2 diabetes (T2D) and explore their applications., Research Design and Methods: We performed a two-stage genome-wide association study for CHD in Chinese patients with T2D (3,596 case and 8,898 control subjects), followed by replications in European patients with T2D (764 case and 4,276 control subjects) and general populations (n = 51,442-547,261). Each identified variant was examined for its association with a wide range of phenotypes and its interactions with glycemic, blood pressure (BP), and lipid controls in incident cardiovascular diseases., Results: We identified a novel variant (rs10171703) for CHD (odds ratio 1.21 [95% CI 1.13-1.30]; P = 2.4 × 10-8) and BP (β ± SE 0.130 ± 0.017; P = 4.1 × 10-14) at PDE1A in Chinese T2D patients but found only a modest association with CHD in general populations. This variant modulated the effects of BP goal attainment (130/80 mmHg) on CHD (Pinteraction = 0.0155) and myocardial infarction (MI) (Pinteraction = 5.1 × 10-4). Patients with CC genotype of rs10171703 had >40% reduction in either cardiovascular events in response to BP control (2.9 × 10-8 < P < 3.6 × 10-5), those with CT genotype had no difference (0.0726 < P < 0.2614), and those with TT genotype had a threefold increase in MI risk (P = 6.7 × 10-3)., Conclusions: We discovered a novel CHD- and BP-related variant at PDE1A that interacted with BP goal attainment with divergent effects on CHD risk in Chinese patients with T2D. Incorporating this information may facilitate individualized treatment strategies for precision care in diabetes, only when our findings are validated., (© 2023 by the American Diabetes Association.)

Background After pregnancy, patients with preexisting heart disease are at high risk for cardiovascular complications. The primary objective was to compare the incidence of new hypertension after pregnancy in patients with and without heart disease. Methods and Results This was a retrospective matched-cohort study comparing the incidence of new hypertension after pregnancy in 832 patients who are pregnant with congenital or acquired heart disease to a comparison group of 1664 patients who are pregnant without heart disease; matching was by demographics and baseline risk for hypertension at the time of the index pregnancy. We also examined whether new hypertension was associated with subsequent death or cardiovascular events. The 20-year cumulative incidence of hypertension was 24% in patients with heart disease, compared with 14% in patients without heart disease (hazard ratio [HR], 1.81 [95% CI, 1.44-2.27]). The median follow-up time at hypertension diagnosis in the heart disease group was 8.1 years (interquartile range, 4.2-11.9 years). The elevated rate of new hypertension was observed not only in patients with ischemic heart disease, but also in those with left-sided valve disease, cardiomyopathy, and congenital heart disease. Pregnancy risk prediction methods can further stratify risk of new hypertension. New hypertension was associated with an increased rate of subsequent death or cardiovascular events (HR, 1.54 [95% CI, 1.05-2.25]). Conclusions Patients with heart disease are at higher risk for developing hypertension in the decades after pregnancy when compared with those without heart disease. New hypertension in this young cohort is associated with adverse cardiovascular events highlighting the importance of systematic and lifelong surveillance.

Objective: High-density lipoproteins (HDL) comprise particles of different size, density and composition and their vasoprotective functions may differ. Diabetes modifies the composition and function of HDL. We assessed associations of HDL size-based subclasses with incident cardiovascular disease (CVD) and mortality and their prognostic utility., Research Design and Methods: HDL subclasses by nuclear magnetic resonance spectroscopy were determined in sera from 1991 fasted adults with type 2 diabetes (T2D) consecutively recruited from March 2014 to February 2015 in Hong Kong. HDL was divided into small, medium, large and very large subclasses. Associations (per SD increment) with outcomes were evaluated using multivariate Cox proportional hazards models. C-statistic, integrated discrimination index (IDI), and categorial and continuous net reclassification improvement (NRI) were used to assess predictive value., Results: Over median (IQR) 5.2 (5.0-5.4) years, 125 participants developed incident CVD and 90 participants died. Small HDL particles (HDL-P) were inversely associated with incident CVD [hazard ratio (HR) 0.65 (95% CI 0.52, 0.81)] and all-cause mortality [0.47 (0.38, 0.59)] (false discovery rate < 0.05). Very large HDL-P were positively associated with all-cause mortality [1.75 (1.19, 2.58)]. Small HDL-P improved prediction of mortality [C-statistic 0.034 (0.013, 0.055), IDI 0.052 (0.014, 0.103), categorical NRI 0.156 (0.006, 0.252), and continuous NRI 0.571 (0.246, 0.851)] and CVD [IDI 0.017 (0.003, 0.038) and continuous NRI 0.282 (0.088, 0.486)] over the RECODe model., Conclusion: Small HDL-P were inversely associated with incident CVD and all-cause mortality and improved risk stratification for adverse outcomes in people with T2D. HDL-P may be used as markers for residual risk in people with T2D., (© 2022. The Author(s).)

Background: Although pregnancy outcomes in women with normally functioning bioprosthetic valves (BPVs) are often good, structural valve dysfunction (SVD) may adversely affect pregnancy outcomes, but this has not been studied., Objectives: The aim of this study was to examine outcomes in pregnant women with BPVs and the association with SVD., Methods: Pregnancy outcomes in women with BPVs were prospectively collected. Adverse maternal cardiac events (CEs) included cardiac death or arrest, sustained arrhythmia, heart failure, thromboembolism, and stroke. Adverse fetal events were also studied. Determinants of adverse events were examined using logistic regression., Results: Overall, 125 pregnancies in women with BPVs were included, 27% with left-sided and 73% with right-sided BPV. SVD was present in 27% of the pregnancies (44% with left-sided BPVs vs 21% with right-sided BPVs; P = 0.009). CEs occurred in 13% of pregnancies and were more frequent in women with SVD compared with those with normally functioning BPVs (26% vs 8%; P = 0.005). CEs were more common in women with left-sided BPVs with SVD vs normally functioning BPVs (47% vs 5%; P = 0.01) but not in women with right-sided BPVs (11% in those with SVD vs 8% in those without SVD; P = 0.67). Left-sided SVD (P = 0.007), maternal age >35 years (P = 0.001), and a composite variable of "high-risk" features (P = 0.006) were predictors of CEs. Fetal events occurred in 28% of pregnancies., Conclusions: In this cohort of young women with BPVs, SVD was present in 27% at the first antenatal visit and negatively affected pregnancy outcomes. In particular, SVD of left-sided BPVs was associated with high rates of adverse outcomes., Competing Interests: Funding Support and Author Disclosures This study was supported by a grant from the Allan E. Tiffin Trust (Toronto General and Western Hospital Foundation). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: Nonalbuminuric diabetic kidney disease (DKD) has become the prevailing DKD phenotype. We compared the risks of adverse outcomes among patients with this phenotype compared with other DKD phenotypes., Study Design: Multicenter prospective cohort study., Settings & Participants: 19,025 Chinese adults with type 2 diabetes enrolled in the Hong Kong Diabetes Biobank., Exposures: DKD phenotypes defined by baseline estimated glomerular filtration rate (eGFR) and albuminuria: no DKD (no decreased eGFR or albuminuria), albuminuria without decreased eGFR, decreased eGFR without albuminuria, and albuminuria with decreased eGFR., Outcomes: All-cause mortality, cardiovascular disease (CVD) events, hospitalization for heart failure (HF), and chronic kidney disease (CKD) progression (incident kidney failure or sustained eGFR reduction ≥40%)., Analytical Approach: Multivariable Cox proportional or cause-specific hazards models to estimate the relative risks of death, CVD, hospitalization for HF, and CKD progression. Multiple imputation was used for missing covariates., Results: Mean participant age was 61.1 years, 58.3% were male, and mean diabetes duration was 11.1 years. During 54,260 person-years of follow-up, 438 deaths, 1,076 CVD events, 298 hospitalizations for HF, and 1,161 episodes of CKD progression occurred. Compared with the no-DKD subgroup, the subgroup with decreased eGFR without albuminuria had higher risks of all-cause mortality (hazard ratio [HR], 1.59 [95% CI, 1.04-2.44]), hospitalization for HF (HR, 3.08 [95% CI, 1.82-5.21]), and CKD progression (HR, 2.37 [95% CI, 1.63-3.43]), but the risk of CVD was not significantly greater (HR, 1.14 [95% CI, 0.88-1.48]). The risks of death, CVD, hospitalization for HF, and CKD progression were higher in the setting of albuminuria with or without decreased eGFR. A sensitivity analysis that excluded participants with baseline eGFR <30 mL/min/1.73 m 2 yielded similar findings., Limitations: Potential misclassification because of drug use., Conclusions: Nonalbuminuric DKD was associated with higher risks of hospitalization for HF and of CKD progression than no DKD, regardless of baseline eGFR., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

We aim to assess the long-term impact of acute kidney injury (AKI) on progression of diabetic kidney disease (DKD) and all-cause mortality and investigate determinants of AKI in Chinese patients with type 2 diabetes (T2D). A consecutive cohort of 9,096 Chinese patients with T2D from the Hong Kong Diabetes Register was followed for 12 years (mean ± SD age 57 ± 13.2 years; 46.9% men; median duration of diabetes 5 years). AKI was defined based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria using serum creatinine. Estimated glomerular filtration rate measurements were used to identify the first episode with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Polygenic risk score (PRS) composed of 27 single nucleotide polymorphisms (SNPs) known to be associated with serum uric acid (SUA) in European populations was used to examine the role of SUA in pathogenesis of AKI, CKD, and ESRD. Validation was sought in an independent cohort including 6,007 patients (age 61.2 ± 10.9 years; 59.5% men; median duration of diabetes 10 years). Patients with AKI had a higher risk for developing incident CKD (hazard ratio 14.3 [95% CI 12.69-16.11]), for developing ESRD (12.1 [10.74-13.62]), and for all-cause death (7.99 [7.31-8.74]) compared with those without AKI. Incidence rate for ESRD among patients with no episodes of AKI and one, two, and three or more episodes of AKI was 7.1, 24.4, 32.4, and 37.3 per 1,000 person-years, respectively. Baseline SUA was a strong independent predictor for AKI. A PRS composed of 27 SUA-related SNPs was associated with AKI and CKD in both discovery and replication cohorts but not ESRD. Elevated SUA may increase the risk of DKD through increasing AKI. The identification of SUA as a modifiable risk factor and PRS as a nonmodifiable risk factor may facilitate the identification of individuals at high risk to prevent AKI and its long-term impact in T2D., (© 2022 by the American Diabetes Association.)

There has been an increase in maternal deaths from cardiovascular disease in many countries. In high-income countries, cardiovascular deaths secondary to cardiomyopathies, ischemic heart disease, sudden arrhythmic deaths, aortic dissection, and valve disease are responsible for up to one-third of all pregnancy-related maternal deaths. In low- and middle-income countries, rheumatic heart disease is a much more common cause of cardiac death during pregnancy. Although deaths occur in women with known heart conditions or cardiovascular risk factors such as hypertension, many women present for the first time in pregnancy with unrecognised heart disease or with de novo cardiovascular conditions such as preeclampsia, peripartum cardiomyopathy, spontaneous coronary artery dissection. Not only has maternal cardiovascular mortality increased, but serious cardiac morbidity, or "near misses," during pregnancy also have increased in frequency. Although maternal morbidity and mortality are often preventable, many health professionals remain unaware of the impact of cardiovascular disease in this population, and the lack of awareness contributes to inappropriate care and preventable deaths. In this review, we discuss the maternal mortality from cardiovascular causes in both high- and low- and middle-income countries and strategies to improve outcomes., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: One of the most common fetal complications in pregnant women with cardiovascular disease is a small for gestational age (SGA) neonate, which is associated with a higher risk of perinatal morbidity/mortality and poor long-term health outcomes. The objective of this study was to identify cardiac determinants and derive a risk score for clinically relevant SGA < 5th percentile (SGA-5th)., Methods: A prospective cohort of 1812 pregnancies in women with heart disease were studied. SGA-5th was the outcome of interest, defined as birth weight < 5th percentile for gestational age and sex. Multivariable logistic regression analysis was used to identify predictors for SGA-5th. Based on the regression coefficients, a weighted risk score was created., Results: SGA-5th complicated 10% of pregnancies, 11 predictors of SGA-5th were identified, and each was assigned a weighted score: maternal cyanosis (8), Fontan palliation (7), smoking (3), moderate or severe valvular regurgitation (3), β-blocker use throughout pregnancy (4) or only in the 2nd and 3rd trimesters (2), high baseline β-blocker dose (4), body mass index < 18.5 kg/m 2 (3) or 18.5-24.9 kg/m 2 (1), Asian/other ethnicity (2), and significant outflow tract obstruction (1). In the absence of these identified risk factors, the risk of SGA-5th was approximately 4%. Pregnancies with risk scores of 1 had a rate of 5%; 2, 7%; 3, 9%; 4, 12%; 5, 14%; 6, 18%; 7, 23%; 8, 28%; and ≥ 9, 34%., Conclusions: There are a number of cardiac predictors that are associated with increased risk of SGA-5th. This is a prognostically important outcome, and consideration should be given to routinely predicting and modifying the risk whenever possible., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

The number of women of childbearing age with cardiovascular disease (CVD) is growing because of increased survival of children with congenital heart disease. More women are also becoming pregnant at an older age, which is associated with increased rates of comorbidities including hypertension, diabetes, and acquired CVD. Over the past decade the field of cardio-obstetrics has significantly advanced with the development of multidisciplinary cardio-obstetric programs (COPs) to address the increasing burden of CVD in pregnancy. With the introduction of formal COPs, pregnancy outcomes in women with heart disease have improved. COPs provide preconception counselling, antenatal and postpartum cardiac surveillance, and labor and delivery planning. Prepregnancy counselling in a COP should be offered to women with suspected CVD who are of childbearing age. In women who present while pregnant, counselling should be performed in a COP as early as possible in pregnancy. The purpose of counselling is to reduce the risk of pregnancy to the mother and fetus whenever possible. This is done through accurate maternal and fetal risk stratification, optimizing cardiac lesions, reviewing safety of medications in pregnancy, and making a detailed plan for the pregnancy, labor, and delivery. This Clinical Practice Update highlights the COP approach to prepregnancy counselling, risk stratification, and management of commonly encountered cardiac conditions through pregnancy. We highlight "red flags" that should trigger a more timely assessment in a COP. We also describe the approach to some of the cardiac emergencies that the care provider might encounter in a pregnant woman., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Cardiovascular disease is now the leading cause of maternal mortality in the industrialised nations. This public health crisis is driven by a variety of factors, including advancing maternal age, increasing prevalence of diabetes and hypertension and the growing number of adults with congenital heart disease. To meet the needs of this complex and diverse population, the subspecialty of cardio-obstetrics has developed. By its very nature, cardio-obstetrics is a team endeavour and requires contributions from multiple disciplines to deliver optimal care. In this article, we argue that cardio-obstetrics is not a niche issue. The magnitude of the current health challenges makes it imperative that all physicians who care for women of childbearing age have a basic knowledge of how cardiovascular disease can impart risk to women during and beyond pregnancy. We address how to increase awareness within the general medical community so that health care workers are able to recognise potential issues and are aware of how to refer to appropriate specialists. We discuss how to incorporate this within cardiology training so that general cardiologists consider the implications that pregnancy has on their patients. And we reflect on the training of the obstetric cardiologists of tomorrow as this field continues to evolve., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Existing predictive outcomes models for type 2 diabetes developed and validated in historical European populations may not be applicable for East Asian populations due to differences in the epidemiology and complications. Despite the continuum of risk across the spectrum of risk factor values, existing models are typically limited to diabetes alone and ignore the progression from prediabetes to diabetes. The objective of this study is to develop and externally validate a patient-level simulation model for prediabetes and type 2 diabetes in the East Asian population for predicting lifetime health outcomes., Methods and Findings: We developed a health outcomes model from a population-based cohort of individuals with prediabetes or type 2 diabetes: Hong Kong Clinical Management System (CMS, 97,628 participants) from 2006 to 2017. The Chinese Hong Kong Integrated Modeling and Evaluation (CHIME) simulation model comprises of 13 risk equations to predict mortality, micro- and macrovascular complications, and development of diabetes. Risk equations were derived using parametric proportional hazard models. External validation of the CHIME model was assessed in the China Health and Retirement Longitudinal Study (CHARLS, 4,567 participants) from 2011 to 2018 for mortality, ischemic heart disease, cerebrovascular disease, renal failure, cataract, and development of diabetes; and against 80 observed endpoints from 9 published trials using 100,000 simulated individuals per trial. The CHIME model was compared to United Kingdom Prospective Diabetes Study Outcomes Model 2 (UKPDS-OM2) and Risk Equations for Complications Of type 2 Diabetes (RECODe) by assessing model discrimination (C-statistics), calibration slope/intercept, root mean square percentage error (RMSPE), and R2. CHIME risk equations had C-statistics for discrimination from 0.636 to 0.813 internally and 0.702 to 0.770 externally for diabetes participants. Calibration slopes between deciles of expected and observed risk in CMS ranged from 0.680 to 1.333 for mortality, myocardial infarction, ischemic heart disease, retinopathy, neuropathy, ulcer of the skin, cataract, renal failure, and heart failure; 0.591 for peripheral vascular disease; 1.599 for cerebrovascular disease; and 2.247 for amputation; and in CHARLS outcomes from 0.709 to 1.035. CHIME had better discrimination and calibration than UKPDS-OM2 in CMS (C-statistics 0.548 to 0.772, slopes 0.130 to 3.846) and CHARLS (C-statistics 0.514 to 0.750, slopes -0.589 to 11.411); and small improvements in discrimination and better calibration than RECODe in CMS (C-statistics 0.615 to 0.793, slopes 0.138 to 1.514). Predictive error was smaller for CHIME in CMS (RSMPE 3.53% versus 10.82% for UKPDS-OM2 and 11.16% for RECODe) and CHARLS (RSMPE 4.49% versus 14.80% for UKPDS-OM2). Calibration performance of CHIME was generally better for trials with Asian participants (RMSPE 0.48% to 3.66%) than for non-Asian trials (RMPSE 0.81% to 8.50%). Main limitations include the limited number of outcomes recorded in the CHARLS cohort, and the generalizability of simulated cohorts derived from trial participants., Conclusions: Our study shows that the CHIME model is a new validated tool for predicting progression of diabetes and its outcomes, particularly among Chinese and East Asian populations that has been lacking thus far. The CHIME model can be used by health service planners and policy makers to develop population-level strategies, for example, setting HbA1c and lipid targets, to optimize health outcomes., Competing Interests: The authors have declared that no competing interests exist.

Background: Pregnancies in women with regurgitant valve lesions are generally considered low risk, but this has not been well studied., Objectives: This study determined the frequency of adverse cardiac events (CEs) in pregnant women with moderate or severe regurgitant valve lesions., Methods: Maternal and fetal outcomes in women with moderate or severe chronic valve regurgitation enrolled in a prospective multicenter study on pregnancy outcomes were examined. Adverse CEs included heart failure, sustained arrhythmias, cardiac arrest, or death. A multivariate logistic regression model was used to identify determinants of CEs in women at the highest risk., Results: Outcomes of 430 pregnancies in women with moderate or severe regurgitant lesions were examined: 145 with mitral regurgitation (MR), 101 with pulmonary regurgitation (PR), 71 with multivalve disease, 73 with tricuspid regurgitation (TR), and 40 with aortic regurgitation (AR). Most women had associated congenital or acquired heart disease. Adverse CEs occurred in 13% of pregnancies: 27% of pregnancies with multivalve disease; 15% with MR; 15% with TR; 5% with AR; and 3% with PR. Maternal mortality was rare. In women with MR, TR, or multivalve disease (n = 289), left ventricular systolic dysfunction (p = 0.001), pulmonary hypertension (p = 0.005), and cardiac events before pregnancy (p < 0.001) were important determinants of CEs during pregnancy., Conclusions: Women with AR and PR are at low risk for cardiac complications during pregnancy. While many women with MR, TR, and multivalve regurgitation do well during pregnancy, additional clinical variables help stratify those at highest risk. This new information will enhance the quality and precision of preconception counseling and pregnancy planning., Competing Interests: Funding Support and Author Disclosures This study was supported by a grant from the Allan E. Tiffin Trust (Toronto General, and Western Hospital Foundation). Dr. Silversides was supported by the Miles Nadal Chair in Pregnancy and Heart Disease (Mount Sinai Hospital Foundation). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background Women with heart disease are at risk for pregnancy complications, but their long-term cardiovascular outcomes after pregnancy are not known. Methods and Results We examined long-term cardiovascular outcomes after pregnancy in 1014 consecutive women with heart disease and a matched group of 2028 women without heart disease. The primary outcome was a composite of mortality, heart failure, atrial fibrillation, stroke, myocardial infarction, or arrhythmia. Secondary outcomes included cardiac procedures and new hypertension or diabetes mellitus. We compared the rates of these outcomes between women with and without heart disease and adjusted for maternal and pregnancy characteristics. We also determined if pregnancy risk prediction tools (CARPREG [Canadian Cardiac Disease in Pregnancy] and World Health Organization) could stratify long-term risks. At 20-year follow-up, a primary outcome occurred in 33.1% of women with heart disease, compared with 2.1% of women without heart disease. Thirty-one percent of women with heart disease required a cardiac procedure. The primary outcome (adjusted hazard ratio, 19.6; 95% CI, 13.8-29.0; P <0.0001) and new hypertension or diabetes mellitus (adjusted hazard ratio, 1.6; 95% CI, 1.4-2.0; P <0.0001) were more frequent in women with heart disease compared with those without. Pregnancy risk prediction tools further stratified the late cardiovascular risks in women with heart disease, a primary outcome occurring in up to 54% of women in the highest pregnancy risk category. Conclusions Following pregnancy, women with heart disease are at high risk for adverse long-term cardiovascular outcomes. Current pregnancy risk prediction tools can identify women at highest risk for long-term cardiovascular events.

Background: Women with heart disease are at risk for complications during pregnancy. This study sought to examine the effect of maternal obesity on pregnancy complications in women with heart disease., Objectives: The objective was to determine the incidence of adverse cardiac events (CE) in pregnant women with heart disease and obesity., Methods: Adverse CE during pregnancy were examined in a prospective cohort of women with heart disease. CE were a composite of the following: cardiac death/arrest, arrhythmias, heart failure, myocardial infarction, stroke, aortic dissection, and thromboembolic events. Pre-eclampsia and post-partum hemorrhage were also studied. Outcomes were examined according to body mass index (BMI). To identify additional predictors of CE, a baseline risk score (CARPREG [Canadian Cardiac Disease in Pregnancy Study] II score) for predicting cardiac complications was calculated for all pregnancies and included in a multivariable logistic regression model., Results: Of 790 pregnancies, 19% occurred in women with BMI ≥30 kg/m 2 (obesity), 25% in women with BMI 25 to 29.9 kg/m 2 (overweight), 53% in women with BMI 18.5 to 24.9 kg/m 2 (normal weight), and 3% in women with BMI <18.5 kg/m 2 (underweight). Women with obesity were at higher risk of CE when compared with women with normal weight (23% vs. 14%; p = 0.006). In a multivariable model, obesity (odds ratio: 1.7; 95% confidence interval: 1.0 to 2.7) and higher CARPREG II risk scores (odds ratio: 1.7; 95% confidence interval: 1.5 to 1.9) predicted CE. Pre-eclampsia was more frequent in women with obesity compared with those with normal weight (8% vs. 2%; p = 0.001)., Conclusions: Obesity increases the risk of maternal cardiovascular complications in pregnant women with heart disease. This modifiable risk factor should be addressed at the time of preconception counseling., Competing Interests: Funding Support and Author Disclosures This study was supported by a grant from the Allan E. Tiffin Trust, Toronto General and Western Hospital Foundation. This study was also supported by a generous donation provided by Mrs. Josephine Rogers, Toronto General Hospital. Dr. Silversides is supported by the Miles Nadal Chair in Pregnancy and Heart Disease. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021. Published by Elsevier Inc.)

Background: The clinical utility of personal genomic information in identifying individuals at increased risks for dyslipidemia and cardiovascular diseases remains unclear., Methods: We used data from Biobank Japan (n = 70,657-128,305) and developed novel East Asian-specific genome-wide polygenic risk scores (PRSs) for four lipid traits. We validated (n = 4271) and subsequently tested associations of these scores with 3-year lipid changes in adolescents (n = 620), carotid intima-media thickness (cIMT) in adult women (n = 781), dyslipidemia (n = 7723), and coronary heart disease (CHD) (n = 2374 cases and 6246 controls) in type 2 diabetes (T2D) patients., Results: Our PRSs aggregating 84-549 genetic variants (0.251 < correlation coefficients (r) < 0.272) had comparably stronger association with lipid variations than the typical PRSs derived based on the genome-wide significant variants (0.089 < r < 0.240). Our PRSs were robustly associated with their corresponding lipid levels (7.5 × 10 - 103  < P < 1.3 × 10 - 75 ) and 3-year lipid changes (1.4 × 10 - 6  < P < 0.0130) which started to emerge in childhood and adolescence. With the adjustments for principal components (PCs), sex, age, and body mass index, there was an elevation of 5.3% in TC (β ± SE = 0.052 ± 0.002), 11.7% in TG (β ± SE = 0.111 ± 0.006), 5.8% in HDL-C (β ± SE = 0.057 ± 0.003), and 8.4% in LDL-C (β ± SE = 0.081 ± 0.004) per one standard deviation increase in the corresponding PRS. However, their predictive power was attenuated in T2D patients (0.183 < r < 0.231). When we included each PRS (for TC, TG, and LDL-C) in addition to the clinical factors and PCs, the AUC for dyslipidemia was significantly increased by 0.032-0.057 in the general population (7.5 × 10 - 3  < P < 0.0400) and 0.029-0.069 in T2D patients (2.1 × 10 - 10  < P < 0.0428). Moreover, the quintile of TC-related PRS was moderately associated with cIMT in adult women (β ± SE = 0.011 ± 0.005, P trend  = 0.0182). Independent of conventional risk factors, the quintile of PRSs for TC [OR (95% CI) = 1.07 (1.03-1.11)], TG [OR (95% CI) = 1.05 (1.01-1.09)], and LDL-C [OR (95% CI) = 1.05 (1.01-1.09)] were significantly associated with increased risk of CHD in T2D patients (4.8 × 10 - 4  < P < 0.0197). Further adjustment for baseline lipid drug use notably attenuated the CHD association., Conclusions: The PRSs derived and validated here highlight the potential for early genomic screening and personalized risk assessment for cardiovascular disease.

Women with heart disease are at increased risk for maternal and fetal complications in pregnancy. Therefore, all women with heart disease should undergo evaluation and counseling, ideally before conception, or as early in pregnancy as possible. In this article we will review the role of risk assessment, the history of development of the cardiac risk prediction tools, and the role of current cardiac risk prediction tools.

Background: Women with a prosthetic heart valve are perceived to be at higher risk for adverse outcomes, but their absolute and relative risk of experiencing maternal morbidity and cardiac complications is largely unknown., Objective: The objective of the study was to determine the risk of maternal morbidity and cardiac complications in women with a prior heart valve replacement, compared with matched counterparts without known cardiac disease., Study Design: A retrospective population-based matched cohort study was completed in the province of Ontario, Canada, where there is universal health care. Included were all women of child-bearing age who had bioprosthetic or mechanical replacement of the mitral or aortic valve, April 1994 to March 2016 (valve replacement group). Those in the valve replacement group, and who had at least 1 birth, were 1:4 matched to a community comparison group without heart disease and who also had at least 1 birth. Matching was by maternal age at cohort entry, year of cohort entry, geographic area, income level, and age at first birth. Maternal outcomes included severe maternal morbidity, all-cause mortality, and cardiac morbidity as well as a prolonged hospital length of stay >7 days. Relative risks and 95% confidence intervals were further adjusted for age at birth and immigration status., Results: There were 90 live births among the 64 women in the valve replacement group and 404 live births among the 253 women in the matched community comparison group. There were no stillbirths. Severe maternal morbidity occurred in 13 pregnancies (14.4%) in the valve replacement group and 6 (1.5%) in the community comparison group (adjusted relative risk, 9.73, 95% confidence interval, 3.70-25.59); there were no maternal deaths. The corresponding rates of prolonged hospital length of stay were 37.8% and 18.8% (adjusted relative risk, 2.33, 95% confidence interval, 1.48-3.67)., Conclusion: Pregnant women who had aortic or mitral valve replacement were more likely to experience severe maternal morbidity, as well as prolonged hospital length of stay, than matched counterparts without heart disease. This information can enhance shared decision making about the timing of valve replacement and pregnancy planning in young and middle-aged women. To determine the absolute and relative risk of maternal morbidity and cardiac complications in women with prior heart valve replacement, a retrospective population-based matched cohort study was completed in the province of Ontario, Canada, where there is universal health care. Included were all women of child-bearing age who had bioprosthetic or mechanical replacement of the mitral or aortic valve, April 1994 to March 2016 (valve replacement group). Those in the valve replacement group, and who had at least one birth, were 1:4 matched to a community comparison group without heart disease and who also had at least 1 birth. There were 90 live births among the 64 women in the valve replacement group and 404 live births among the 253 women in the matched community comparison group. Severe maternal morbidity occurred in 13 pregnancies (14.4%) in the valve replacement group and 6 (1.5%) in the community comparison group (adjusted relative risk, 9.73); there were no maternal deaths. The corresponding rates of prolonged hospital length of stay were 37.8% and 18.8% (adjusted relative risk, 2.33). In summary, pregnant women who had an aortic or mitral valve replacement were more likely to experience severe maternal morbidity, as well as prolonged hospital length of stay, than matched counterparts without heart disease., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Type 2 diabetes (T2D) is a progressive disease whereby there is often deterioration in glucose control despite escalation in treatment. There is significant heterogeneity to this progression of glycemia after onset of diabetes, yet the factors that influence glycemic progression are not well understood. Given the tremendous burden of diabetes in the Chinese population, and limited knowledge on factors that influence glycemia, we aim to identify the clinical and genetic predictors for glycemic progression in Chinese patients with T2D., Methods and Findings: In 1995-2007, 7,091 insulin-naïve Chinese patients (mean age 56.8 ± 13.3 [SD] years; mean age of T2D onset 51.1 ± 12.7 years; 47% men; 28.4% current or ex-smokers; median duration of diabetes 4 [IQR: 1-9] years; mean HbA1c 7.4% ± 1.7%; mean body mass index [BMI] 25.3 ± 4.0 kg/m2) were followed prospectively in the Hong Kong Diabetes Register. We examined associations of BMI and other clinical and genetic factors with glycemic progression defined as requirement of continuous insulin treatment, or 2 consecutive HbA1c ≥8.5% while on ≥2 oral glucose-lowering drugs (OGLDs), with validation in another multicenter cohort of Hong Kong Diabetes Biobank. During a median follow-up period of 8.8 (IQR: 4.8-13.3) years, incidence of glycemic progression was 48.0 (95% confidence interval [CI] 46.3-49.8) per 1,000 person-years with 2,519 patients started on insulin. Among the latter, 33.2% had a lag period of 1.3 years before insulin was initiated. Risk of progression was associated with extremes of BMI and high HbA1c. On multivariate Cox analysis, early age at diagnosis, microvascular complications, high triglyceride levels, and tobacco use were additional independent predictors for glycemic progression. A polygenic risk score (PRS) including 123 known risk variants for T2D also predicted rapid progression to insulin therapy (hazard ratio [HR]: 1.07 [95% CI 1.03-1.12] per SD; P = 0.001), with validation in the replication cohort (HR: 1.24 [95% CI 1.06-1.46] per SD; P = 0.008). A PRS using 63 BMI-related variants predicted BMI (beta [SE] = 0.312 [0.057] per SD; P = 5.84 × 10-8) but not glycemic progression (HR: 1.01 [95% CI 0.96-1.05] per SD; P = 0.747). Limitations of this study include potential misdiagnosis of T2D and lack of detailed data of drug use during follow-up in the replication cohort., Conclusions: Our results show that approximately 5% of patients with T2D failed OGLDs annually in this clinic-based cohort. The independent associations of modifiable and genetic risk factors allow more precise identification of high-risk patients for early intensive control of multiple risk factors to prevent glycemic progression., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: RCWM acknowledges receiving research support (outside of this work) from AstraZeneca, Bayer, and Pfizer and honoraria or consultancy fees from AstraZeneca and Boehringer Ingelheim, all of which have been donated to the Chinese University of Hong Kong to support diabetes research. CKPL, WYS, JCNC, and RCWM are cofounders of GemVCare, a diabetes genetic testing laboratory, which was established through support from the Technology Start-up Support Scheme for Universities (TSSSU) from the Hong Kong Government Innovation and Technology Commission (ITC). RCWM is a member of the editorial board of PLOS Medicine. JCNC has received research grants and/or honoraria for consultancy or giving lectures, from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Eli-Lilly, GlaxoSmithKline, Merck Serono, Merck Sharp & Dohme, Novo Nordisk, Pfizer, and Sanofi. APSK has received research grants and/or speaker honoraria from Abbott, AstraZeneca, Eli-Lilly, Merck Serono, Nestle, Sanofi, and Novo Nordisk. AOL has served as an advisory committee member for AstraZeneca, Boehringer Ingelheim, Sanofi, and Amgen and has received research grants and travel grants from AstraZeneca, Boehringer Ingelheim, MSD, Novartis, Novo Nordisk, Sanofi, and Amgen.

Pregnancy, which is associated with profound cardiovascular changes and higher risk of thrombosis, increases the risk of cardiovascular complications in women with pre-existing heart disease. A comprehensive history and physical examination, 12-lead electrocardiogram, and transthoracic echocardiogram remain the foundation of assessing cardiac risk during pregnancy in women with heart disease. These are often combined to generate risk scores, which are statistically derived. Several statistically derived risk and 1 lesion-specific classification system are currently available. A suggested clinical approach to risk stratification is first to identify pregnancies in women with cardiac lesions at risk for serious or life-threatening maternal cardiac complications and for the remainder to use the Cardiac Disease in Pregnancy II (CARPREG II) risk score, integrating additional lesion-specific and patient-specific information. Conversely, clinicians can use the modified World Health Organization (mWHO) risk classification system and integrate general risk predictors and patient-specific information. Importantly, cardiac-risk assessment should always incorporate clinical judgement in addition to the use of risk scores or risk-classification systems. As pregnant women with heart disease are also at risk for obstetric and fetoneonatal complications, risk assessment should be performed by a multidisciplinary team, preferably before conception, or as soon as conception is confirmed, and repeated at regular intervals during the course of pregnancy., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Pregnancy can lead to complications in women with heart disease, and these complications can be life threatening. Understanding serious complications and how they can be prevented is important., Objectives: The primary objectives were to determine the incidence of serious cardiac events (SCEs) in pregnant women with heart disease, whether they were preventable, and their impact on fetal and neonatal outcomes. Serious obstetric events were also examined., Methods: A prospectively assembled cohort of 1,315 pregnancies in women with heart disease was studied. SCEs included cardiac death or arrest, ventricular arrhythmias, congestive heart failure or arrhythmias requiring admission to an intensive care unit, myocardial infarction, stroke, aortic dissection, valve thrombosis, endocarditis, and urgent cardiac intervention. The Harvard Medical Study criteria were used to adjudicate preventability., Results: Overall, 3.6% of pregnancies (47 of 1,315) were complicated by SCEs. The most frequent SCEs were cardiac death or arrest, heart failure, arrhythmias, and urgent interventions. Most SCEs (66%) occurred in the antepartum period. Almost one-half of SCEs (49%) were preventable; the majority of preventable SCEs (74%) were secondary to provider management factors. Adverse fetal and neonatal events were more common in pregnancies with SCEs compared with those without cardiac events (62% vs. 29%; p < 0.001). Serious obstetric events were less common (1.7%) and were primarily due to pre-eclampsia with severe features., Conclusions: Pregnant women with heart disease are at risk for serious cardiac complications, and approximately one-half of all SCEs are preventable. Strategies to prevent serious cardiac complications in this high-risk cohort of women need to be developed., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Context: Risk scores for cardiovascular and mortality outcomes have not been commonly applied in Chinese populations., Objective: To develop and externally validate a set of parsimonious risk scores [University of Hong Kong-Singapore (HKU-SG)] to predict the risk of mortality, cerebrovascular disease, and ischemic heart disease among Chinese people with type 2 diabetes and compare HKU-SG risk scores to other existing ones., Design: Retrospective population-based cohorts drawn from Hong Kong Hospital Authority health records from 2006 to 2014 for development and Singapore Ministry of Health records from 2008 to 2016 for validation. Separate five-year risk scores were derived using Cox proportional hazards models for each outcome., Setting: Study participants were adults with type 2 diabetes aged 20 years or over, consisting of 678,750 participants from Hong Kong and 386,425 participants from Singapore., Main Outcome Measures: Performance was evaluated by discrimination (Harrell C-index), and calibration plots comparing predicted against observed risks., Results: All models had fair external discrimination. Among the risk scores for the diabetes population, ethnic-specific risk scores (HKU-SG and Joint Asia Diabetes Evaluation) performed better than UK Prospective Diabetes Study and Risk Equations for Complications Of type 2 Diabetes models. External validation of the HKU-SG risk scores for mortality, cerebrovascular disease, and ischemic heart disease had corresponding C-indices of 0.778, 0.695, and 0.644. The HKU-SG models appeared well calibrated on visual plots, with predicted risks closely matching observed risks., Conclusions: The HKU-SG risk scores were developed and externally validated in two large Chinese population-based cohorts. The parsimonious use of clinical predictors compared with previous risk scores could allow wider implementation of risk estimation in diverse Chinese settings., (Copyright © 2019 Endocrine Society.)

Background: Women with prosthetic heart valves are at higher risk for adverse outcomes during pregnancy. The rates of achieved pregnancy, regardless of the pregnancy outcome, are largely unknown in this group of women., Objective: To determine the rate of pregnancy in women with prior heart valve replacement, and compare that to women without known heart disease., Study Design: A retrospective matched population-based cohort study was done between April 1994 and March 2017, in Ontario, Canada, where universal health care is available. Administrative healthcare databases were used to identify study participants, exposures and outcomes. Each woman of child-bearing age who had a bioprosthetic or mechanical mitral or aortic valve replacement (valve replacement group) was matched to four women without heart disease (community comparison group) -- by age, year of cohort entry, any recent prior pregnancy, geographic area of residence and income level. Starting after the date of cohort entry (defined as the date valve replacement date in the valve replacement group), participants were assessed for a recognized pregnancy, namely, a livebirth, stillbirth, miscarriage or induced abortion. Hazard ratios (HR) and 95% confidence intervals (CI) were further adjusted for age, immigrant status and comorbid medical conditions., Results: 1596 women with a valve replacement were matched with 6378 women in the community comparison group. After a median (interquartile range, IQR) duration of follow-up of 3.1 (1.0-5.6) and 2.7 (1.0-6.0) years, respectively, 98 women in the valve replacement group achieved a recognized pregnancy (0.63 per 100 person-years), compared to 607 women in the community comparison group (0.88 per 100 person-years) - an adjusted HR of 0.72 (95% CI 0.57-0.89). Within the valve replacement group, those with a mechanical valve were less likely to achieve a recognized pregnancy than those with a bioprosthetic valve (adjusted HR 0.57, 95% CI 0.38-0.87)., Conclusion: Women who undergo aortic or mitral valve replacement are less likely to achieve a pregnancy than matched counterparts without heart disease. This information, and the reasons for why this is so, can inform decisions about the timing of valve replacement and pregnancy planning., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: An observational post-randomized controlled trial (RCT) design was adopted to evaluate the long-term sustainability and maintenance of improved glycemic control, lipid profile, reduced progression to diabetes at 3-year following a 2-year short messaging service (SMS). We performed a naturalistic follow-up to the 104 participants of SMS intervention, a 2-year randomized controlled trial comparing the SMS to non-SMS for pre-diabetes. All participants were arranged screening for diabetes at 5-year assessment. Primary outcome of this post-RCT study was cumulative incidence of diabetes whereas secondary outcomes were the change in biometric data over a 5-year period., Results: After a mean 57-month follow-up, 19 (18.3%) were lost to follow-up after the RCT period. Progression to diabetes occurred in 20 and 16 patients among the intervention and control group respectively, with no significant between-group difference (8.06 and 7.31 cases per 100 person years, respectively; Hazard Ratio in the intervention group, 1.184; 95% confidence interval, 0.612 to 2.288; p-value = 0.616). No significant effect of SMS on reduction in diabetes was observed in overall and pre-defined subgroups. The SMS intervention preserved the clinical benefits within the trial period but failed to transform from treatment efficacy to long-term effectiveness beyond 2 years after intervention. Trail registration ClinicalTrials.gov Identifier NCT01556880, retrospectively registered on March 16, 2012.

Bicuspid aortic valve disease is a common congenital cardiac disorder, being present in 1% to 2% of the general population. Associated aortopathy is a common finding in patients with bicuspid aortic valve disease, with thoracic aortic dilation noted in approximately 40% of patients in referral centers. Several previous consensus statements and guidelines have addressed the management of bicuspid aortic valve-associated aortopathy, but none focused entirely on this disease process. The current document is an executive summary of "The American Association for Thoracic Surgery Guidelines on Bicuspid Aortic Valve-Related Aortopathy." All major aspects of bicuspid aortic valve aortopathy, including natural history, phenotypic expression, histology and molecular pathomechanisms, imaging, indications for surgery, surveillance, and follow-up, and recommendations for future research are contained within these guidelines. The current executive summary serves as a condensed version of the guidelines to provide clinicians with a current and comprehensive review of bicuspid aortic valve aortopathy and to guide the daily management of these complex patients., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Bicuspid aortic valve disease is the most common congenital cardiac disorder, being present in 1% to 2% of the general population. Associated aortopathy is a common finding in patients with bicuspid aortic valve disease, with thoracic aortic dilation noted in approximately 40% of patients in referral centers. Several previous consensus statements and guidelines have addressed the management of bicuspid aortic valve-associated aortopathy, but none focused entirely on this disease process. The current guidelines cover all major aspects of bicuspid aortic valve aortopathy, including natural history, phenotypic expression, histology and molecular pathomechanisms, imaging, indications for surgery, surveillance, and follow-up, and recommendations for future research. It is intended to provide clinicians with a current and comprehensive review of bicuspid aortic valve aortopathy and to guide the daily management of these complex patients., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Identifying women at high risk is an important aspect of care for women with heart disease., Objectives: This study sought to: 1) examine cardiac complications during pregnancy and their temporal trends; and 2) derive a risk stratification index., Methods: We prospectively enrolled consecutive pregnant women with heart disease and determined their cardiac outcomes during pregnancy. Temporal trends in complications were examined. A multivariate analysis was performed to identify predictors of cardiac complications and these were incorporated into a new risk index., Results: In total, 1,938 pregnancies were included. Cardiac complications occurred in 16% of pregnancies and were primarily related to arrhythmias and heart failure. Although the overall rates of cardiac complications during pregnancy did not change over the years, the frequency of pulmonary edema decreased (8% from 1994 to 2001 vs. 4% from 2001 to 2014; p value = 0.012). Ten predictors of maternal cardiac complications were identified: 5 general predictors (prior cardiac events or arrhythmias, poor functional class or cyanosis, high-risk valve disease/left ventricular outflow tract obstruction, systemic ventricular dysfunction, no prior cardiac interventions); 4 lesion-specific predictors (mechanical valves, high-risk aortopathies, pulmonary hypertension, coronary artery disease); and 1 delivery of care predictor (late pregnancy assessment). These 10 predictors were incorporated into a new risk index (CARPREG II [Cardiac Disease in Pregnancy Study])., Conclusions: Pregnancy in women with heart disease continues to be associated with significant morbidity, although mortality is rare. Prediction of maternal cardiac complications in women with heart disease is enhanced by integration of general, lesion-specific, and delivery of care variables., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Pregnancy in women with repaired truncus arteriosus (TA) is rare. We report the outcomes of 8 pregnancies in 4 women with surgically repaired TA. None of the women had adverse cardiac events during pregnancy. Two pregnancies, both in the same woman, were complicated by hypertensive disorders of pregnancy. The birth weight was less than the 10th percentile for gestational age in 3 pregnancies. Although women with repaired TA can do well during pregnancy, they require careful preconception assessment and surveillance., (Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objectives: Individuals with childhood-onset coronary artery anomalies are at increased risk of lifelong complications. Although pregnancy is thought to confer additional risk, a few data are available regarding outcomes in this group of women. We sought to define outcomes of pregnancy in this unique population., Methods: We performed a retrospective survey of women with paediatric-onset coronary anomalies and pregnancy in our institution, combined with a systematic review of published cases. We defined paediatric-onset coronary artery anomalies as congenital coronary anomalies and inflammatory arteriopathies of childhood that cause coronary aneurysms. Major cardiovascular events were defined as pulmonary oedema, sustained arrhythmia requiring treatment, stroke, myocardial infarction, cardiac arrest, or death., Results: A total of 25 surveys were mailed, and 20 were returned (80% response rate). We included 46 articles from the literature, which described cardiovascular outcomes in 82 women (138 pregnancies). These data were amalgamated for a total of 102 women and 194 pregnancies; 59% of women were known to have paediatric-onset coronary artery anomalies before pregnancy. In 23%, the anomaly was unmasked during or shortly after pregnancy. The remainder, 18%, was diagnosed later in life. Major cardiovascular events occurred in 14 women (14%) and included heart failure (n=5, 5%), myocardial infarction (n=7, 7%), maternal death (n=2, 2%), cardiac arrest secondary to ventricular fibrillation (n=1, 1%), and stroke (n=1, 1%). The majority of maternal events (13/14, 93%) occurred in women with no previous diagnosis of coronary disease., Conclusions: Women with paediatric-onset coronary artery anomalies have a 14% risk of adverse cardiovascular events in pregnancy, indicating the need for careful assessment and close follow-up. Prospective, multicentre studies are required to better define risk and predictors of complications during pregnancy.

Aims: To estimate recent secular changes in the incidence and prevalence of diabetes and pre-diabetes among Hong Kong Chinese adults, and thus show possible future trends for developing mainland China., Methods: Based on a complete census of the public sector health records of 6.4 million people from 2006 to 2014, diabetes cases were ascertained using different methods including the World Health Organization (WHO) 2011 guidelines (HbA 1c , fasting plasma glucose and glucose tolerance test), American Diabetes Association (ADA) 2015 guidelines (plus random plasma glucose), and additionally recorded diagnosis codes and medication dispensation. Pre-diabetes was defined using ADA 2015 guidelines., Results: We identified 697 201 people with diabetes (54.2% were incident cases); and 1 229 731 people with diabetes or pre-diabetes. In 2014, the overall incidence of diabetes was 9.46 per 1000 person-years [95% confidence interval (CI): 9.38 to 9.54], and overall prevalence was 10.29% (95% CI: 10.27% to 10.32%). Incidence of diabetes decreased significantly from 2007 to 2014 (quadratic trend, P < 0.001). From 2006 to 2014, the prevalence of diabetes increased significantly in both sexes and across all age groups (quadratic trend, P < 0.001). The overall incidence of pre-diabetes in 2014 was 18.88 per 1000 person-years (95% CI: 18.76 to 18.99), and the overall prevalence of pre-diabetes was 8.90% (95% CI: 8.87% to 8.92%)., Conclusions: Similar to other developed western and Asian populations, diabetes (and pre-diabetes) incidence in Hong Kong Chinese appeared to have stabilized and there have been small declines during the period of observation. Ageing and survivorship will likely drive a continued increase in the prevalence of diabetes and pre-diabetes, albeit with a decelerating growth rate if past trends persist., (© 2016 Diabetes UK.)

Objective: Nationwide studies on secular trends of diabetes complications are not available in Asia. We examined changes in risk factor control and incidence of complications from diabetes and death in a large longitudinal cohort of Chinese adults with type 2 diabetes in Hong Kong., Research Design and Methods: Between 1 January 2000 and 31 December 2012, 338,908 Chinese adults with type 2 diabetes underwent metabolic and complication assessment in 16 diabetes centers operated by Hong Kong Hospital Authority that provided care to a large majority of diagnosed patients. Patients were followed for incident acute myocardial infarction (AMI), stroke, end-stage renal disease (ESRD), and death until 31 December 2012. Risk factor levels between enrollment periods were compared. Incidence of clinical events, stratified by diabetes duration, was examined over time., Results: Incidence of complications from diabetes and death declined over the observation period in patients at varying disease duration. Among the high-risk group with diabetes for at least 15 years, crude incidence of AMI decreased from 8.7 to 5.8, stroke from 13.5 to 10.1, ESRD from 25.8 to 22.5, and death from 29.0 to 26.6 per 1,000 person-year between the periods 2000 to 2002 and 2010 to 2012. Improvements in levels of metabolic risk factors were detected. Proportion of patients achieving HbA 1c <7.0% (53 mmol/mol) was increased from 32.9 to 50.0%, blood pressure ≤130/80 mmHg from 24.7 to 30.7%, and LDL cholesterol <2.6 mmol/L from 25.8 to 38.1%., Conclusions: From this territory-wide Hong Kong Diabetes Database, we observed decreases in incidence of cardiovascular-renal complications and death and corresponding improvements in risk factor control over a 13-year period., (© 2017 by the American Diabetes Association.)

Background: The knowledge on the type and influence of visuospatial ability on sonography performance relevant for ultrasound-guided regional anaesthesia remains incomplete. The aim of this study was to determine whether four different factors of visuospatial ability are important in determining proficiency and procedure time of novices performing brachial plexus sonography. These factors were spatial visualisation, flexibility of closure, spatial relations and speed of closure., Methods: Thirty-three ultrasound novices were recruited in this prospective, observational trial. Five cognitive tests, from a standardised battery that assesses all four visuospatial factors, were administered to each participant at the start of the study. Each novice then performed brachial plexus sonography on a human model at baseline and final exams, separated by a discovery learning session. Novices were examined in their sonography performance by blinded assessors who scored proficiency, technique, image quality, and time taken to perform at both baseline and final scans., Results: Novices with intermediate and high visuospatial ability in spatial visualisation, spatial relations and speed of closure were significantly more proficient and efficient compared with their peers stratified into low-ability cohorts (P < 0.02). The Matrix Reasoning and the Mental Rotations Test-A were both correlated with sonography final exam scores (Spearman rank correlation ρ = 0.38 and 0.36, P = 0.03 and 0.04, respectively)., Conclusions: Spatial visualisation, spatial relations and speed of closure, but not flexibility of closure, influence sonography performance. Visuospatial ability testing can identify novices who will require extra assistance in learning ultrasound relevant for regional anaesthesia. (, Trial Registration: Australian and New Zealand Clinical Trials Registry 12614000819628)., (© 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Thioamides antithyroid-drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD-induced agranulocytosis is important for clinical management. We performed a genome-wide association study (GWAS) involving 20 patients with ATD-induced agranulocytosis and 775 healthy controls. The top finding was further replicated. A single-nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD-induced agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8-103.7; P = 1.3 × 10(-24)) and replication (OR = 37; 95% CI = 3.7-367.4; P = 9.6 × 10(-7)). HLA-B*38:02:01 was in complete linkage disequilibrium with rs185386680. High-resolution HLA typing confirmed that HLA-B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)-induced agranulocytosis (OR = 265.5; 95% CI = 27.9-2528.0; P = 2.5 × 10(-14)), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA-B*38:02:01 in predicting CMZ/MMI-induced agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing agranulocytosis in populations in which the frequency of the risk allele is high., (© 2015, The American Society for Clinical Pharmacology and Therapeutics.)

Background: The aim of the present study was to develop a simple nomogram that can be used to predict the risk of diabetes mellitus (DM) in the asymptomatic non-diabetic subjects based on non-laboratory- and laboratory-based risk algorithms., Methods: Anthropometric data, plasma fasting glucose, full lipid profile, exercise habits, and family history of DM were collected from Chinese non-diabetic subjects aged 18-70 years. Logistic regression analysis was performed on a random sample of 2518 subjects to construct non-laboratory- and laboratory-based risk assessment algorithms for detection of undiagnosed DM; both algorithms were validated on data of the remaining sample (n = 839). The Hosmer-Lemeshow test and area under the receiver operating characteristic (ROC) curve (AUC) were used to assess the calibration and discrimination of the DM risk algorithms., Results: Of 3357 subjects recruited, 271 (8.1%) had undiagnosed DM defined by fasting glucose ≥7.0 mmol/L or 2-h post-load plasma glucose ≥11.1 mmol/L after an oral glucose tolerance test. The non-laboratory-based risk algorithm, with scores ranging from 0 to 33, included age, body mass index, family history of DM, regular exercise, and uncontrolled blood pressure; the laboratory-based risk algorithm, with scores ranging from 0 to 37, added triglyceride level to the risk factors. Both algorithms demonstrated acceptable calibration (Hosmer-Lemeshow test: P = 0.229 and P = 0.483) and discrimination (AUC 0.709 and 0.711) for detection of undiagnosed DM., Conclusion: A simple-to-use nomogram for detecting undiagnosed DM has been developed using validated non-laboratory-based and laboratory-based risk algorithms., (© 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Background: Women with transposition of the great arteries (TGA) following atrial redirection surgery are at risk of pregnancy-associated arrhythmia and heart failure. The cardiovascular magnetic resonance imaging (CMR) characteristics of these women and the relationship of CMR findings to pregnancy outcomes have not been described., Methods: We included 17 women with atrial redirection surgery and CMR within 2 years of delivery., Results: All women were asymptomatic at baseline (New York Heart Association Class 1). CMR studies were completed pre-pregnancy in 3, antepartum/peripartum in 2, and postpartum in 12 women. Three women (3/17, 18%) experienced major cardiovascular events related to pregnancy: cardiac arrest (n = 1) and symptomatic atrial arrhythmia (n = 2). Median gestational age at delivery was 38 weeks (24-39 weeks) and birth weight was 2770 g (2195-3720 g). Complications were seen in 3 offspring (3/17, 18%): death (n = 1) and prematurity (n = 2). CMR characteristics included median right ventricular end diastolic volume 119 mL/m 2 (range 85-214 mL/m 2 ) and median right ventricular ejection fraction (RVEF) 37% (range 30-51%). All women with cardiovascular complications had an RVEF < 35% (range 32-34%). The association between RVEF < 35% and cardiovascular complications trended towards statistical significance (p = 0.05). No statistically significant differences in CMR measurements were found between those with and without neonatal complications., Conclusions: While the majority of women in this cohort had successful outcomes following pregnancy, important cardiovascular complications were seen in a significant minority, all of whom had an RVEF < 35%. The preliminary findings of our study provide impetus for a larger prospective study to evaluate the prognostic role of CMR in pregnant women with atrial redirection surgery.

Aims. To investigate the costs and cost-effectiveness of a short message service (SMS) intervention to prevent the onset of type 2 diabetes mellitus (T2DM) in subjects with impaired glucose tolerance (IGT). Methods. A Markov model was developed to simulate the cost and effectiveness outcomes of the SMS intervention and usual clinical practice from the health provider's perspective. The direct programme costs and the two-year SMS intervention costs were evaluated in subjects with IGT. All costs were expressed in 2011 US dollars. The incremental cost-effectiveness ratio was calculated as cost per T2DM onset prevented, cost per life year gained, and cost per quality adjusted life year (QALY) gained. Results. Within the two-year trial period, the net intervention cost of the SMS group was $42.03 per subject. The SMS intervention managed to reduce 5.05% onset of diabetes, resulting in saving $118.39 per subject over two years. In the lifetime model, the SMS intervention dominated the control by gaining an additional 0.071 QALY and saving $1020.35 per person. The SMS intervention remained dominant in all sensitivity analyses. Conclusions. The SMS intervention for IGT subjects had the superiority of lower monetary cost and a considerable improvement in preventing or delaying the T2DM onset. This trial is registered with ClinicalTrials.gov NCT01556880.

Background: The mechanistic basis of the proposed relationship between maternal cardiac output and neonatal complications in pregnant women with heart disease has not been well elucidated., Methods and Results: Pregnant women with cardiac disease and healthy pregnant women (controls) were prospectively followed with maternal echocardiography and obstetrical ultrasound scans at baseline, third trimester, and postpartum. Fetal/neonatal complications (death, small-for-gestational-age or low birthweight, prematurity, respiratory distress syndrome, or intraventricular hemorrhage) comprised the primary study outcome. One hundred and twenty-seven women with cardiac disease and 45 healthy controls were enrolled. Neonatal events occurred in 28 pregnancies and were more frequent in the heart disease group as compared with controls (n=26/127 or 21% versus n=2/45 or 4%; P=0.01). Multiple complications in an infant were counted as a single outcome event. Neonatal complications in the heart disease group were small-for-gestational-age/low birthweight (n=18), prematurity (n=14), and intraventricular hemorrhage/respiratory distress syndrome (n=5). Preexisting obstetric risk factors (P=0.003), maternal cardiac output decline from baseline to third trimester (P=0.017), and third trimester umbilical artery Doppler abnormalities (P<0.001) independently predicted neonatal complications and were incorporated into a novel risk index in which 0, 1, and >1 predictor corresponded to expected complication rates of 5%, 30%, and 76%, respectively., Conclusions: Decline in maternal cardiac output during pregnancy and abnormal umbilical artery Doppler flows independently predict neonatal complications. These findings will enhance the identification of higher risk pregnancies that would benefit from close antenatal surveillance., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Objective: The objective of this study was to determine outcomes in pregnant women with pre-existing coronary artery disease (CAD) or following an acute coronary syndrome (ACS) including myocardial infarction (MI)., Background: The physiological changes of pregnancy can contribute to myocardial ischaemia. The pregnancy risk for women with pre-established CAD or a history of ACS/MI is not well studied., Methods: This was a retrospective multicentre study. Adverse maternal cardiac, obstetric and fetal/neonatal events were examined. The primary outcome was a composite endpoint of cardiac arrest, ACS/MI, ventricular arrhythmia or congestive heart failure. The prevalence of new or progressive angina during pregnancy was also examined., Results: Fifty pregnancies in 43 women (mean age 35±5 years) were included. Coronary atherosclerosis (40%) and coronary thrombus (36%) were the most common underlying diagnoses. The primary outcome occurred in 10% (5/50) of pregnancies and included one maternal death secondary to cardiac arrest. Other events included ACS/MI (3/50) and heart failure (1/50). New or progressive angina occurred in 18% of pregnancies. Ischaemic complications of any type (new or progressive angina, ACS/MI, ventricular arrhythmia, cardiac arrest) occurred more commonly in women with coronary atherosclerosis compared with those without (50% vs 10%, p=0.003). A high rate of adverse obstetric (16%) and fetal/neonatal (30%) events was observed., Conclusions: Pregnant women with pre-existing CAD or ACS/MI before pregnancy are at increased risk of adverse events during pregnancy. Those with coronary atherosclerosis are at highest risk of adverse maternal cardiac events due to myocardial ischaemia during pregnancy., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Rigid chromatography resins, such as controlled pore glass based adsorbents, offer the advantage of high permeability and a linear pressure-flow relationship irrespective of column diameter which improves process time and maximizes productivity. However, the rigidity and irregularly shaped nature of these resins often present challenges in achieving consistent and uniform packed beds as formation of bridges between resin particles can hinder bed consolidation. The standard flow-pack method when applied to irregularly shaped particles does not yield well-consolidated packed beds, resulting in formation of a head space and increased band broadening during operation. Vibration packing methods requiring the use of pneumatically driven vibrators are recommended to achieve full packed bed consolidation but limitations in manufacturing facilities and equipment may prevent the implementation of such devices. The stop-flow packing method was developed as an improvement over the flow-pack method to overcome these limitations and to improve bed consolidation without the use of vibrating devices. Transition analysis of large-scale columns packed using the stop-flow method over multiple cycles has shown a two- to three-fold reduction of change in bed integrity values as compared to a flow-packed bed demonstrating an improvement in packed bed stability in terms of the height equivalent to a theoretical plate (HETP) and peak asymmetry (As )., (© 2014 American Institute of Chemical Engineers.)