BACKGROUND:Chronic kidney disease (CKD) is an important risk factor for the progression of coronary artery disease (CAD). OBJECTIVES:The purposes of this study were to quantify the prevalence of CKD in CAD patients from 14 countries from all World Health Organization regions and to evaluate the prognostic value of estimated glomerular filtration rate (eGFR) and urinary albumin/creatinine ratio (UACR). METHODS:A total of 4,548 patients with CAD were included (79.6% were males; age range: 18-80 years). They were assessed for eGFR and UACR 6 to 24 months after the CAD diagnosis. Complete information on kidney function and cardio-renal protective therapy was available for 3,865 patients and follow-up data after a median of 1 year were available for 3,577 (92.5%). RESULTS:CKD according to the Kidney Disease Improving Global Outcomes classification was present in 32% of whom 19.7% were classified as low-moderate, 6.9% as high, and 5.6% as very high risk. Without UACR, 51.3% of them would have been undetected. The primary event, first of cardiovascular death, myocardial infarction, stroke, and hospitalization for heart failure, was observed in 7.9%, with the highest incidence in the Kidney Disease Improving Global Outcomes high-risk group (men: 13.0%; women: 11.8%). This relationship was independent of other risk factors and evident soon after the index examination. Only a minority of the patients received adequate cardio-renal protective therapy. CONCLUSIONS:Early screening for CKD in patients with CAD is important and should preferably include both eGFR and UACR to provide a complete diagnosis. Without UACR, half of those with CKD would remain undetected. Treatment with cardio-renal protective therapy was low, providing great potential for improvement.

BACKGROUND:Preventing frailty is crucial for improving outcomes in aging populations at heightened cardiovascular risk, yet implementation in real-world practice remains challenging. The authors previously reported low use of frailty strategies among cardiologists in Asia. OBJECTIVES:The aim of this study was to explore the barriers to frailty implementation among cardiologists, other physicians, and nurses. METHODS:A multinational web-based survey was conducted targeting health care communities across Asia. RESULTS:Among 238 respondents (median age 34.0 years; IQR: 12 years; 63.4% women), 172 were doctors, 57 nurses, and 8 allied health professionals. Among doctors, 59 were cardiologists representing various subspecialties, including critical care cardiology, interventional cardiology, and general cardiology. Among all respondents, one-quarter lacked confidence in identifying (22.7%) or treating (28.2%) frailty, and many were uncertain of the screening tools (34.9%) and subsequent steps (37.8%). Other barriers include inadequate multidisciplinary support (21%), communication difficulties (45.8%), resource limitations (52.9%), patient and caregiver unreceptiveness (21.8%), and insufficient community care collaborations (39.5%). Compared with other physicians, cardiologists reported being too busy (P = 0.041) and having less awareness of screening selection (P = 0.018) and appropriate assessment tools (P = 0.008). Nurses experienced fewer interdisciplinary communication difficulties (P = 0.003) than cardiologists. There were no significant differences in understanding, support received, and patients' and caregivers' receptiveness toward frailty interventions between nurses and cardiologists. CONCLUSIONS:Distinct barriers to frailty implementation exist at multiple levels, including gaps in provider expertise, insufficient support, and resource constraints that limit adequate frailty care provision. To address the diverse needs of stakeholders, a comprehensive implementation strategy leveraging interdisciplinary cardiogeriatric team resources and involving nurses could improve frailty care in cardiology.

BACKGROUND:The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention. METHODS:This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore. Patients were randomized to receive either cangrelor or placebo initiated before the primary percutaneous coronary intervention procedure on top of oral ticagrelor. The key exclusion criteria included presenting <6 hours of symptom onset; previous MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance. The primary efficacy end point was acute MI size by cardiovascular magnetic resonance within the first week expressed as percentage of the left ventricle mass (%LVmass). Microvascular obstruction was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety end point was Bleeding Academic Research Consortium-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test (reported as median [first quartile-third quartile]), and categorical variables were compared by Fisher exact test. A 2-sided P<0.05 was considered statistically significant. RESULTS:Of 209 recruited patients, 164 patients (78%) completed the acute cardiovascular magnetic resonance scan. There were no significant differences in acute MI size (placebo, 14.9% [7.3-22.6] %LVmass versus cangrelor, 16.3 [9.9-24.4] %LVmass; P=0.40) or the incidence (placebo, 48% versus cangrelor, 47%; P=0.99) and extent of microvascular obstruction (placebo, 1.63 [0.60-4.65] %LVmass versus cangrelor, 1.18 [0.53-3.37] %LVmass; P=0.46) between placebo and cangrelor despite a 2-fold decrease in platelet reactivity with cangrelor. There were no Bleeding Academic Research Consortium-defined major bleeding events in either group in the first 48 hours. CONCLUSIONS:Cangrelor administered at the time of primary percutaneous coronary intervention did not reduce acute MI size or prevent microvascular obstruction in patients with ST-segment-elevation MI given oral ticagrelor despite a significant reduction of platelet reactivity during the percutaneous coronary intervention procedure. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03102723.

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

Importance: Individual variation in statin biotransformation may explain differences in clinical outcomes but remains poorly understood. Objectives: To quantify statin biotransformation phenotypes in cardiology patients and validate predictors of 5-year clinical outcomes in two independent cohorts. Design: SAPhIRE is a multicentre, prospective, observational trial of 1363 general cardiology patients taking atorvastatin or simvastatin. The study was initiated in 2014. Sample collection was completed in 2016, and outcomes of participants were followed-up to June 2020 via the Singapore National Registry of Diseases Office (NRDO). Setting: Participants were enrolled across the National University Hospital of Singapore (NUH) and Singapore General Hospital (SGH). Pharmacologic, genotypic, and mechanistic predictors of 5-year clinical outcomes were determined using clinical data, quantitative mass spectrometry and GWAS. Main Outcome(s): Major Adverse Cardiovascular Events (MACE) via linkage with NRDO. Risk analysis (multivariable Cox hazards modelling, univariable Kaplan Meier) was used to assess association of metabolism, genomics, and co-prescriptions on 5-year outcomes. Results: In both independent cohorts, increased statin lactone production of the upper tertile (ATVLAC≥3.9ng/ml) predicted MACE (HR=2.45, CI=1.60-3.44, P<0.001) and all-cause mortality (HR=3.18, CI=1.96-5.16, P<0.001), independently of LDL and drug dose. UGT1A, a lactone-producing gene, associated with ATVLAC at genome-wide significance. In a candidate gene analysis of UGT1A, UGT1A1*80-associated GOF mutations (rs887829, rs11891311, rs6742078, rs4148324, rs4148325 and rs10929302) predicted 1.34-fold higher ATVLAC compared to major allele homozygotes, and after controlling for clinical variables, exhibited higher rates of MACE (average HR=1.40, p<0.05). Among 51 co-prescriptions, omeprazole was the strongest predictor of increased ATVLAC (1.41-fold, P<10-8) and MACE (HR=1.46, CI=1.06-2.00, P=0.020). Conclusion: A phenotype of low statin lactone production predicts preferential cardiac outcomes in two-thirds of statin takers and is influenced by both UGT1A variation and omeprazole co-prescription.

In the Asia-Pacific region, heart failure (HF) is associated with significant health and socioeconomic burden. Given the differences in the epidemiology of HF, as well as the availability of healthcare resources between Asian and Western countries, an Asian Pacific Society of Cardiology (APSC) working group developed consensus recommendations on the management of chronic HF in the Asia-Pacific region. The APSC expert panel reviewed and appraised the available evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Consensus recommendations were developed and put to an online vote. Consensus was reached when 80% of votes for a given recommendation were either ‘agree’ or ‘neutral’. The resulting statements provide guidance on the diagnosis, assessment and treatment of patients with HF with reduced, mildly reduced or preserved ejection fraction in the Asia-Pacific region.

Conventional dual antiplatelet therapy (DAPT) for patients with acute coronary syndromes undergoing percutaneous coronary intervention comprises aspirin with a potent P2Y purinoceptor 12 (P2Y12) inhibitor (prasugrel or ticagrelor) for 12 months. Although this approach reduces ischaemic risk, patients are exposed to a substantial risk of bleeding. Strategies to reduce bleeding include de-escalation of DAPT intensity (downgrading from potent P2Y12 inhibitor at conventional doses to either clopidogrel or reduced-dose prasugrel) or abbreviation of DAPT duration. Either strategy requires assessment of the ischaemic and bleeding risks of each individual. De-escalation of DAPT intensity can reduce bleeding without increasing ischaemic events and can be guided by platelet function testing or genotyping. Abbreviation of DAPT duration after 1–6 months, followed by monotherapy with aspirin or a P2Y12 inhibitor, reduces bleeding without an increase in ischaemic events in patients at high bleeding risk, particularly those without high ischaemic risk. However, these two strategies have not yet been compared in a head-to-head clinical trial. In this Consensus Statement, we summarize the evidence base for these treatment approaches, provide guidance on the assessment of ischaemic and bleeding risks, and provide consensus statements from an international panel of experts to help clinicians to optimize these DAPT approaches for individual patients to improve outcomes. Dual antiplatelet therapy (DAPT) reduces the risk of ischaemic events but can increase the risk of bleeding in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Gorog and colleagues provide consensus statements on strategies to reduce the risk of bleeding by de-escalating the intensity or abbreviating the duration of DAPT.

Jack WC Tan reports honoraria from AstraZeneca, Bayer, Amgen, Medtronic, Abbott Vascular, Biosensors, Alvimedica, Boehringer Ingelheim, and Pfizer; research and educational grants from Medtronic, Biosensors, Biotronik, Philips, Amgen, AstraZeneca, Roche, Otsuka, Terumo, and Abbott Vascular; and consulting fees from Elixir and CSL Behring. Sidney TH Lo reports lecture honoraria from Bristol-Myers Squibb, Bayer, and Boehringer-Ingelheim; proctorship fees from Abbott, Boston Scientific, and Bioexcel; research funding from Abbot; and is an advisory board member for Abbott and Medtronic. Derek P Chew reports consulting fees from APSC; support for travel to meetings for the study or otherwise from APSC; grants/grants pending from Roche Diagnostics and AstraZeneca; and payment for development of educational presentations including service on speakers' bureaus from AstraZeneca.

Background: There is growing recognition that COVID-19 does cause cardiac sequelae. The underlying mechanisms involved are still poorly understood to date. Viral infections, including COVID-19, have been hypothesized to contribute to autoimmunity, by exposing previously hidden cryptic epitopes on damaged cells to an activated immune system. Given the high incidence of cardiac involvement seen in COVID-19, our aim was to determine the frequency of anti-DSG2 antibodies in a population of post COVID-19 patients. Methods and results: 300 convalescent serum samples were obtained from a group of post COVID-19 infected patients from October 2020 to February 2021. 154 samples were drawn 6 months post-COVID-19 infection and 146 samples were drawn 9 months post COVID infection. 17 samples were obtained from the same patient at the 6-and 9-month mark. An electrochemiluminescent-based immunoassay utilizing the extracellular domain of DSG2 for antibody capture was used. The mean signal intensity of anti-DSG2 antibodies in the post COVID-19 samples was significantly higher than that of a healthy control population (19 +/- 83.2 in the post-COVID-19 sample vs. 2.1 +/- 7.2 (p < 0. 0001) in the negative control healthy population). Of note, 29.3% of the post COVID-19 infection samples demonstrated a signal higher than the 90th percentile of the control population and 8.7% were higher than the median found in ARVC patients. The signal intensity between the 6-month and 9-month samples did not differ significantly. Conclusions: We report for the first time that recovered COVID-19 patients demonstrate significantly higher and sustained levels of anti-DSG2 autoantibodies as compared to a healthy control population, comparable to that of a diagnosed ARVC group.

Background: Statins can cause muscle symptoms resulting in poor adherence to therapy and increased cardiovascular risk. We hypothesize that combinations of potentially functional SNPs (pfSNPs), rather than individual SNPs, better predict myalgia in patients on atorvastatin. This study assesses the value of potentially functional single nucleotide polymorphisms (pfSNPs) and employs six machine learning algorithms to identify the combination of SNPs that best predict myalgia. Methods: Whole genome sequencing of 183 Chinese, Malay and Indian patients from Singapore was conducted to identify genetic variants associated with atorvastatin induced myalgia. To adjust for confounding factors, demographic and clinical characteristics were also examined for their association with myalgia. The top factor, sex, was then used as a covariate in the whole genome association analyses. Variants that were highly associated with myalgia from this and previous studies were extracted, assessed for potential functionality (pfSNPs) and incorporated into six machine learning models. Predictive performance of a combination of different models and inputs were compared using the average cross validation area under ROC curve (AUC). The minimum combination of SNPs to achieve maximum sensitivity and specificity as determined by AUC, that predict atorvastatin-induced myalgia in most, if not all the six machine learning models was determined. Results: Through whole genome association analyses using sex as a covariate, a larger proportion of pfSNPs compared to non-pf SNPs were found to be highly associated with myalgia. Although none of the individual SNPs achieved genome wide significance in univariate analyses, machine learning models identified a combination of 15 SNPs that predict myalgia with good predictive performance (AUC >0.9). SNPs within genes identified in this study significantly outperformed SNPs within genes previously reported to be associated with myalgia. pfSNPs were found to be more robust in predicting myalgia, outperforming non-pf SNPs in the majority of machine learning models tested. Conclusion: Combinations of pfSNPs that were consistently identified by different machine learning models to have high predictive performance have good potential to be clinically useful for predicting atorvastatin-induced myalgia once validated against an independent cohort of patients.

The unique characteristics of patients with acute coronary syndrome in the Asia-Pacific region mean that international guidelines on the use of dual antiplatelet therapy (DAPT) cannot be routinely applied to these populations. Newer generation P2Y12 inhibitors (i.e. ticagrelor and prasugrel) have demonstrated improved clinical outcomes compared with clopidogrel. However, low numbers of Asian patients participated in pivotal studies and few regional studies comparing DAPTs have been conducted. This article aims to summarise current evidence on the use of newer generation P2Y12 inhibitors in Asian patients with acute coronary syndrome and provide recommendations to assist clinicians, especially cardiologists, in selecting a DAPT regimen. Guidance is provided on the management of ischaemic and bleeding risks, including duration of therapy, switching strategies and the management of patients with ST-elevation and non-ST-elevation MI or those requiring surgery. In particular, the need for an individualised DAPT regimen and considerations relating to switching, de-escalating, stopping or continuing DAPT beyond 12 months are discussed.

IMPORTANCE There are few data on remote postdischarge treatment of patients with acute myocardial infarction. OBJECTIVE To compare the safety and efficacy of allied health care practitioner-led remote intensive management (RIM) with cardiologist-led standard care (SC). DESIGN, SETTING, AND PARTICIPANTS This intention-to-treat feasibility trial randomized patients with acute myocardial infarction undergoing early revascularization and with N-terminal-pro-B-type natriuretic peptide concentration more than 300 pg/mL to RIM or SC across 3 hospitals in Singapore from July 8, 2015, to March 29, 2019. RIM participants underwent 6 months of remote consultations that included beta-blocker and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACE-I/ARB) dose adjustment by a centralized nurse practitioner team while SC participants were treated face-to-face by their cardiologists. MAIN OUTCOMES AND MEASURES The primary safety end point was a composite of hypotension, bradycardia, hyperkalemia, or acute kidney injury requiring hospitalization. To assess the efficacy of RIM in dose adjustment of beta-blockers and ACE-I/ARBs compared with SC, dose intensity scores were derived by converting comparable doses of different beta-blockers and ACE-I/ARBs to a scale from 0 to 5. The primary efficacy end point was the 6-month indexed left ventricular end-systolic volume (LVESV) adjusted for baseline LVESV. RESULTS Of 301 participants, 149 (49.5%) were randomized to RIM and 152 (50.5%) to SC. RIM and SC participants had similar mean (SD) age (55.3 [8.5] vs 54.7 [9.1] years), median (interquartile range) N-terminal-pro-B-type natriuretic peptide concentration (807 [524-1360] vs 819 [485-1320] pg/mL), mean (SD) baseline left ventricular ejection fraction (57.4% [11.1%] vs 58.1% [10.3%]), and mean (SD) indexed LVESV (32.4 [14.1] vs 30.6 [11.7] mL/m(2)); 15 patients [5.9%] had a left ventricular ejection fraction <40%. The primary safety end point occurred in 0 RIM vs 2 SC participants (1.4%) (P = .50). The mean beta-blocker and ACE-I/ARB dose intensity score at 6 months was 3.03 vs 2.91 (adjusted mean difference, 0.12 [95% CI, -0.02 to 0.26; P = .10]) and 2.96 vs 2.77 (adjusted mean difference, 0.19 [95% CI, -0.02 to 0.40; P = .07]), respectively. The 6-month indexed LVESV was 28.9 vs 29.7 mL/m(2) (adjusted mean difference, -0.80 mL/m(2) [95% CI, -3.20 to 1.60; P = .51]). CONCLUSIONS AND RELEVANCE Among low-risk patients with revascularization after myocardial infarction, RIM by allied health care professionals was feasible and safe. There were no differences in achieved medication doses or indices of left ventricular remodeling. Further studies of RIM in higher-risk cohorts are warranted.

The disease burden of AF is greater in Asia-Pacific than other areas of the world. Direct oral anticoagulants (DOACs) have emerged as effective alternatives to vitamin K antagonists (VKA) for preventing thromboembolic events in patients with AF. The Asian Pacific Society of Cardiology developed this consensus statement to guide physicians in the management of AF in Asian populations. Statements were developed by an expert consensus panel who reviewed the available data from patients in Asia-Pacific. Consensus statements were developed then put to an online vote. The resulting 17 statements provide guidance on the assessment of stroke risk of AF patients in the region, the appropriate use of DOACs in these patients, as well as the concomitant use of DOACs and antiplatelets, and the transition to DOACs from VKAs and vice versa. The periprocedural management of patients on DOAC therapy and the management of patients with bleeding while on DOACs are also discussed.

This randomized clinical trial compares the safety and efficacy of nurse practitioner–led remote intensive management with cardiologist-led standard care for low-risk patients with acute myocardial infarction.

Level of Evidence: 1 Technical Efficacy: Stage 2

Pivotal trials of beta-blockers (BB) and angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in acute myocardial infarction (AMI) were largely conducted prior to the widespread adoption of early revascularization. A total of 15,073 patients with AMI who underwent inhospital coronary revascularization from January 2007 to December 2013 were analyzed. At 12 months, BB was significantly associated with a lower incidence of major adverse cardiovascular events (MACE, adjusted HR 0.80, 95% CI 0.70–0.93) and all-cause mortality (adjusted HR 0.69, 95% CI 0.55–0.88), while ACEI/ARB was significantly associated with lower all-cause mortality (adjusted HR 0.80, 95% CI 0.66–0.98) and heart failure (HF) hospitalization (adjusted HR 0.80, 95% CI 0.68–0.95). Combined BB and ACEI/ARB use was associated with the lowest incidence of MACE (adjusted HR 0.70, 95% CI 0.57–0.86), all-cause mortality (adjusted HR 0.55, 95% CI 0.40–0.77) and HF hospitalization (adjusted HR 0.64, 95% CI 0.48–0.86). This were consistent for left ventricular ejection fraction < 50% or ≥ 50%. In conclusion, in AMI managed with revascularization, both BB and ACEI/ARB were associated with a lower incidence of 12-month all-cause mortality. Combined BB and ACEI/ARB was associated with the lowest incidence of all-cause mortality and HF hospitalization.

Sex differences in 1-year rehospitalization for heart failure and myocardial infarction 1 after primary percutaneous coronary intervention 2 3 Huili Zheng, MSc; Ling Li Foo, PhD; Huay Cheem Tan, MBBS; A. Mark Richards, PhD; 4 Siew Pang Chan, PhD; Ronald C.H. Lee, MBBS; Adrian F.H. Low, MBBS; Derek J. 5 Hausenloy, PhD; Jack W.C. Tan, MBBS; Anders O. Sahlen, MD; Hee Hwa Ho, 6 MBBS; Siang Chew Chai, MBBS; Khim Leng Tong, MBBS; Doreen S.Y. Tan, BSc; 7 Khung Keong Yeo, MBBS; Terrance S.J. Chua, MBBS; Carolyn S.P. Lam, PhD*; Mark Y. 8 Chan, PhD 9