Migraine and atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Patients with migraines, particularly those with auras, may present with stroke. Atrial fibrillation is a known risk factor for stroke. With common pathophysiological factors between migraines and atrial fibrillation, we aimed to clarify the association between migraine and atrial fibrillation in this systematic review and meta-analysis. METHODS: A literature search was conducted in EMBASE, PubMed, Scopus and Cochrane electronic bibliographic databases from inception to 5 September 2022 with the following inclusion criteria: (a) cohort or cross-sectional studies; (b) studies that included only patients aged ≥18 years; and (c) studies that examined the association between atrial fibrillation and migraines. Exclusion criteria were case-control studies and the studies that included patients with previous diagnosis of atrial fibrillation or nonmigrainous headache. The Newcastle-Ottawa Scale was used to assess the quality of studies. RESULTS: Six studies were included, demonstrating a pooled prevalence of atrial fibrillation of 1.61% (95% confidence interval [CI] 0.51, 3.29) in migraine with aura and 1.32% (95% CI 0.17, 3.41) in migraine without aura. The overall prevalence of atrial fibrillation in migraine was 1.39% (95% CI 0.24, 3.46). CONCLUSION: In this systematic review and meta-analysis, the overall prevalence of atrial fibrillation in patients with migraine was low. Further studies are needed to clarify this relationship.

Association of body mass index, metabolic health status and clinical outcomes in acute myocardial infarction patients: a national registry-based study.

Introduction: Obesity is an important risk factor for acute myocardial infarction (AMI), but the interplay between metabolic health and obesity on AMI mortality has been controversial. In this study, we aimed to elucidate the risk of short- and long-term all-cause mortality by obesity and metabolic health in AMI patients using data from a multi-ethnic national AMI registry. Methods: A total of 73,382 AMI patients from the national Singapore Myocardial Infarction Registry (SMIR) were included. These patients were classified into four groups based on the presence or absence of metabolic diseases, diabetes mellitus, hyperlipidaemia, and hypertension, and obesity: (1) metabolically-healthy-normal-weight (MHN); (2) metabolically-healthy-obese (MHO); (3) metabolically-unhealthy-normal-weight (MUN); and (4) metabolically-unhealthy-obese (MUO). Results: MHO patients had reduced unadjusted risk of all-cause in-hospital, 30-day, 1-year, 2-year, and 5-year mortality following the initial MI event. However, after adjusting for potential confounders, the protective effect from MHO on post-AMI mortality was lost. Furthermore, there was no reduced risk of recurrent MI or stroke within 1-year from onset of AMI by the MHO status. However, the risk of 1-year mortality was higher in female and Malay AMI patients with MHO compared to MHN even after adjusting for confounders. Conclusion: In AMI patients with or without metabolic diseases, the presence of obesity did not affect mortality. The exception to this finding were female and Malay MHO who had worse long-term AMI mortality outcomes when compared to MHN suggesting that the presence of obesity in female and Malay patients may confer worsened outcomes.

Long-Term Prognosis of Patients With Coexisting Obesity and Malnutrition After Acute Myocardial Infarction: A Cohort Study.

BACKGROUND: The double burden of malnutrition, described as the coexistence of malnutrition and obesity, is a growing global health issue. This study examines the combined effects of obesity and malnutrition on patients with acute myocardial infarction (AMI). METHODS: Patients presenting with AMI to a percutaneous coronary intervention-capable hospital in Singapore between January 2014 and March 2021 were retrospectively studied. Patients were stratified into the following: (1) nourished nonobese, (2) malnourished nonobese, (3) nourished obese, and (4) malnourished obese. Obesity and malnutrition were defined according to the World Health Organization definition (body mass index ≥27.5 kg/m2) and Controlling Nutritional Status score, respectively. The primary outcome was all-cause mortality. The association between combined obesity and nutritional status with mortality was examined using Cox regression, adjusted for age, sex, AMI type, previous AMI, ejection fraction, and chronic kidney disease. Kaplan-Meier curves for all-cause mortality were constructed. RESULTS: The study included 1829 AMI patients, of which 75.7% were male and mean age was 66 years. Over 75% of patients were malnourished. Majority were malnourished nonobese (57.7%), followed by malnourished obese (18.8%), nourished nonobese (16.9%), and nourished obese (6.6%). Malnourished nonobese had highest all-cause mortality (38.6%), followed by the malnourished obese (35.8%), nourished nonobese (21.4%), and nourished obese (9.9%, P<0.001). Kaplan-Meier curves demonstrated least favorable survival in malnourished nonobese group, followed by malnourished obese, nourished nonobese, and nourished obese. With nourished nonobese group as the reference, malnourished nonobese had higher all-cause mortality (hazard ratio, 1.46 [95% CI, 1.10-1.96], P=0.010), but only a nonsignificant increase in mortality was observed in the malnourished obese (hazard ratio, 1.31 [95% CI, 0.94-1.83], P=0.112). CONCLUSIONS: Among AMI patients, malnutrition is prevalent even in the obese. Compared to nourished patients, malnourished AMI patients have a more unfavorable prognosis especially in those with severe malnutrition regardless of obesity status, but long-term survival is the most favorable among nourished obese patients.

Hepatic steatosis and advanced hepatic fibrosis are independent predictors of long-term mortality in acute myocardial infarction.

AIM: To examine the prevalence and prognosis of hepatic steatosis and fibrosis in post-acute myocardial infarction (AMI) patients. METHODS: Patients presenting with AMI to a tertiary hospital were examined from 2014 to 2021. Hepatic steatosis and advanced hepatic fibrosis were determined using the Hepatic Steatosis Index and fibrosis-4 index, respectively. The primary outcome was all-cause mortality. Cox regression models identified determinants of mortality after adjustments and Kaplan-Meier curves were constructed for all-cause mortality, stratified by hepatic steatosis and advanced fibrosis. RESULTS: Of 5765 patients included, 24.8% had hepatic steatosis, of whom 41.7% were diagnosed with advanced fibrosis. The median follow-up duration was 2.7 years. Patients with hepatic steatosis tended to be younger, female, with elevated body mass index and an increased metabolic burden of diabetes, hypertension and hyperlipidaemia. Patients with hepatic steatosis (24.6% vs. 20.9% mortality, P < .001) and advanced fibrosis (45.6% vs. 32.9% mortality, P < .001) had higher all-cause mortality rates compared with their respective counterparts. Hepatic steatosis (adjusted hazard ratio 1.364, 95% CI 1.145-1.625, P = .001) was associated with all-cause mortality after adjustment for confounders. Survival curves showed excess mortality in patients with hepatic steatosis compared with those without (P = .002). CONCLUSIONS: Hepatic steatosis and advanced fibrosis have a substantial prevalence among patients with AMI. Both are associated with mortality, with an incrementally higher risk when advanced fibrosis ensues. Hepatic steatosis and fibrosis could help risk stratification of AMI patients beyond conventional risk factors.

Coronary CT Angiography-based Morphologic Index for Predicting Hemodynamically Significant Coronary Stenosis.

Purpose To develop a new coronary CT angiography (CCTA)-based index, α×LL/MLD4, that considers lesion entrance angle (α) in addition to lesion length (LL) and minimal lumen diameter (MLD) and to evaluate its efficacy in predicting hemodynamically significant coronary stenosis compared with invasive coronary angiography (ICA)-derived fractional flow reserve (FFR). Materials and Methods This prospective study enrolled participants (September 2016-March 2020) from two centers who underwent CCTA followed by ICA (ClinicalTrials.gov identifier: NCT03054324). CCTA images were processed semiautomatically to measure LL, MLD, and α for calculating α×LL/MLD4. Diagnostic performance and accuracy of α×LL/MLD4 and LL/MLD4 in detecting hemodynamically significant coronary stenosis were compared against the reference standard (invasive FFR ≤ 0.80). Results In total, 133 participants (mean age, 63 years ± 9 [SD]; 99 [74%] men) with 210 stenosed coronary arteries were analyzed. Median α×LL/MLD4 was 54.0 degree/mm3 (IQR, 25.3-128.7) in participants with invasive FFR of 0.80 or less and 6.7 degree/mm3 (IQR, 3.3-12.8) in participants with invasive FFR of more than 0.80 (P < .001). The per-vessel accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for discriminating ischemic lesions were 86.2%, 83.1%, 88.4%, 84.1%, and 87.7% for α×LL/MLD4 and 80.5%, 66.3%, 90.9%, 84.3%, and 78.6% for LL/MLD4, respectively. Area under the receiver operating characteristic curve for discriminating hemodynamically significant stenosis was 0.93 for α×LL/MLD4, which was significantly greater than the values of 0.84 for LL/MLD4 and 0.63 for diameter stenosis (both P < .001). Conclusion The new morphologic index, α×LL/MLD4, incorporating lesion entrance angle achieved higher diagnostic performance in detecting hemodynamically significant lesions compared with diameter stenosis and LL/MLD4. Keywords: CT Angiography, Cardiac, Coronary Arteries, Ischemia, Infarction, Technology Assessment Clinical trial registration no. NCT03054324 Supplemental material is available for this article. © RSNA, 2023 See also the commentary by Fairbairn and Nørgaard in this issue.

Trans-interaction of risk loci 6p24.1 and 10q11.21 is associated with endothelial damage in coronary artery disease.

BACKGROUND AND AIMS: Single nucleotide polymorphism rs6903956 has been identified as one of the genetic risk factors for coronary artery disease (CAD). However, rs6903956 lies in a non-coding locus on chromosome 6p24.1. We aim to interrogate the molecular basis of 6p24.1 containing rs6903956 risk alleles in endothelial disease biology. METHODS AND RESULTS: We generated induced pluripotent stem cells (iPSCs) from CAD patients (AA risk genotype at rs6903956) and non-CAD subjects (GG non-risk genotype at rs6903956). CRISPR-Cas9-based deletions (Δ63-89bp) on 6p24.1, including both rs6903956 and a short tandem repeat variant rs140361069 in linkage disequilibrium, were performed to generate isogenic iPSC-derived endothelial cells. Edited CAD endothelial cells, with removal of 'A' risk alleles, exhibited a global transcriptional downregulation of pathways relating to abnormal vascular physiology and activated endothelial processes. A CXC chemokine ligand on chromosome 10q11.21, CXCL12, was uncovered as a potential effector gene in CAD endothelial cells. Underlying this effect was the preferential inter-chromosomal interaction of 6p24.1 risk locus to a weak promoter of CXCL12, confirmed by chromatin conformation capture assays on our iPSC-derived endothelial cells. Functionally, risk genotypes AA/AG at rs6903956 were associated significantly with elevated levels of circulating damaged endothelial cells in CAD patients. Circulating endothelial cells isolated from patients with risk genotypes AA/AG were also found to have 10 folds higher CXCL12 transcript copies/cell than those with non-risk genotype GG. CONCLUSIONS: Our study reveals the trans-acting impact of 6p24.1 with another CAD locus on 10q11.21 and is associated with intensified endothelial injury.

Symptomatic intracerebral hemorrhage after non-emergency percutaneous coronary intervention: Incidence, risk factors, and association with cardiovascular outcomes.

Objective: To investigate the incidence, risk factors, and association with cardiovascular outcomes of patients who developed symptomatic intracerebral hemorrhage (ICH) after non-emergency percutaneous coronary intervention (PCI). Methods: We conducted a single-institution retrospective study of patients who developed symptomatic ICH after non-emergency PCI. To identify associations between clinical variables and outcomes, Cox-proportional hazards regression models were constructed. Outcomes analyzed include (1) all-cause mortality, (2) acute ischemic stroke (AIS) or transient ischemic attack (TIA), and (3) major adverse cardiovascular events (MACE). Results: A total of 1,732 patients were included in the analysis. The mean (±SD) age was 61.1 (±11.3) years, and 1,396 patients (80.6%) were male. The cumulative incidence of symptomatic ICH after non-emergency PCI was 1.3% (22 patients). Age, chronic kidney disease, and prior coronary artery bypass graft surgery were independently associated with a higher risk of ICH after PCI, while hyperlipidemia was independently associated with a lower risk of ICH after PCI. ICH after PCI was independently associated with a higher risk of all-cause mortality and AIS or TIA after PCI. Conclusion: Patients who are older, who have chronic kidney disease, and who have had prior coronary artery bypass graft surgery should be monitored for symptomatic ICH after non-emergency PCI.

Prevalence and incidence of stroke, white matter hyperintensities, and silent brain infarcts in patients with chronic heart failure: A systematic review, meta-analysis, and meta-regression.

Introduction: Heart failure (HF) is associated with ischemic stroke (IS). However, there are limited studies on the prevalence of IS, white matter hyperintensities (WMHs), and silent brain infarcts (SBIs). Furthermore, interaction with ejection fraction (EF) is unclear. Methods: We searched three databases (viz., PubMed, Embase, and Cochrane) for studies reporting the incidence or prevalence of IS, WMHs, and SBIs in HF. A total of two authors independently selected included studies. We used random-effects models, and heterogeneity was evaluated with I2 statistic. Meta-regression was used for subgroup analysis. Results: In total, 41 articles involving 870,002 patients were retrieved from 15,267 records. Among patients with HF, the pooled proportion of IS was 4.06% (95% CI: 2.94-5.59), and that of WMHs and SBIs was higher at 15.67% (95% CI: 4.11-44.63) and 23.45% (95% CI: 14.53-35.58), respectively. Subgroup analysis of HFpEF and HFrEF revealed a pooled prevalence of 2.97% (95% CI: 2.01-4.39) and 3.69% (95% CI: 2.34-5.77), respectively. Subgroup analysis of WMH Fazekas scores 1, 2, and 3 revealed a decreasing trend from 60.57 % (95% CI: 35.13-81.33) to 11.57% (95% CI: 10.40-12.85) to 3.07% (95% CI: 0.95-9.47). The relative risk and hazard ratio of patients with HF developing IS were 2.29 (95% CI: 1.43-3.68) and 1.63 (95% CI: 1.22-2.18), respectively. Meta-regression showed IS prevalence was positively correlated with decreasing anticoagulant usage. Conclusion: We obtained estimates for the prevalence of IS, WMH, and SBI in HF from systematic review of the literature. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=255126, PROSPERO [CRD42021255126].

Long-term outcomes in acute coronary syndrome patients without standard modifiable risk factors: a multi-ethnic retrospective cohort study Of 5400 asian patients.

A sizeable number of patients without standard modifiable cardiovascular risk factors (SMuRFs), such as hypertension, diabetes, hypercholesterolemia and smoking, suffer from acute coronary syndrome (ACS). These SMuRF-less patients have high short-term morbidity and mortality. We compared both short- and long-term outcomes of SMuRF-less and SMuRF ACS patients in a multi-ethnic Asian cohort.This was a retrospective study of patients with first ACS from 2011 to 2017. The primary outcome was long-term all-cause mortality. Secondary outcomes were 30-day all-cause mortality, cardiac-mortality, unplanned cardiac readmission, cardiogenic shock, heart failure, and stroke. Subgroup analysis was carried out by sex and ACS type.Of 5400 patients, 8.6% were SMuRF-less. The median follow-up time was 6.3 years (interquartile range [IQR] 4.2-8.2 years). SMuRF-less patients were younger and tended to present with ST-segment elevation myocardial infarction (STEMI). They were more likely to require inotropic support, intubation, and have cardiac arrest. At 30 days, SMuRF-less patients had higher rates of all-cause mortality, cardiac-related mortality and cardiogenic shock, but lower rates of heart failure. At 6 years, all-cause mortality was similar in both groups (18.0% versus 17.1% respectively, p = 0.631). Kaplan-Meier curves showed increased early mortality in the SMuRF-less group, but the divergence in survival curves was no longer present in the long-term. The absence of SMuRF was an independent predictor of mortality, regardless of sex or ACS type.In a multi-ethnic cohort of patients with ACS, SMuRF-less patients were observed to have higher mortality than SMuRF patients during the early stages which was attenuated over time.

A systematic review and meta-analysis of non-vitamin K antagonist oral anticoagulants vs vitamin K antagonists after transcatheter aortic valve replacement in patients with atrial fibrillation.

PURPOSE: Transcatheter aortic valve replacement (TAVR) is increasingly carried out in patients with aortic valvular conditions. Atrial fibrillation (AF) is a common comorbidity among patients undergoing TAVR. Despite this, there remains a paucity of data and established guidelines regarding anticoagulation use post-TAVR in patients with AF. METHODS: Four databases were searched from inception until 12 October 2021. A title and abstract sieve, full-text review and data extraction were conducted by independent authors, and articles including patients without AF were excluded. The Review Manager (Version 5.4) was utilised in data analysis. RESULTS: A total of 25,199 post-TAVR patients with AF were included from seven articles, with 9764 patients on non-vitamin K antagonist oral anticoagulants (NOAC) and 15,435 patients on vitamin K antagonists (VKA). In this analysis, there was a significantly lower risk of all-cause mortality at 1 year (RR: 0.75, CI: 0.58-0.97, p = 0.04, I2 = 56%), and bleeding at 1 year (RR: 0.73, CI: 0.68-0.79, p = < 0.00001, I2 = 0%), between patients on NOAC and VKA. There were no detectable differences between patients on NOAC and VKA for all-cause mortality at 2 years, stroke within 30 days, stroke within 1 year, ischaemic stroke at 1 year and life-threatening bleeding at 30 days. CONCLUSION: While the results of this analysis reveal NOAC as a potential alternate treatment modality to VKA in post-TAVR patients with AF, further research is needed to determine the full safety and efficacy profile of NOAC (PROSPERO: CRD42021283548).

Comparison of the modified Singapore myocardial infarction registry risk score with GRACE 2.0 in predicting 1-year acute myocardial infarction outcomes.

Risk stratification plays a key role in identifying acute myocardial infarction (AMI) patients at higher risk of mortality. However, current AMI risk scores such as the Global Registry of Acute Coronary Events (GRACE) score were derived from predominantly Caucasian populations and may not be applicable to Asian populations. We previously developed an AMI risk score from the national-level Singapore Myocardial Infarction Registry (SMIR) confined to ST-segment elevation myocardial infarction (STEMI) patients and did not include non-STEMI (NSTEMI) patients. Here, we derived a modified SMIR risk score for both STEMI and NSTEMI patients and compared its performance to the GRACE 2.0 score for predicting 1-year all-cause mortality in our multi-ethnic population. The most significant predictor of 1-year all-cause mortality in our population using the GRACE 2.0 score was cardiopulmonary resuscitation on admission (adjusted hazards ratio [HR] 6.50), while the most significant predictor using the SMIR score was age 80-89 years (adjusted HR 7.78). Although the variables used in the GRACE 2.0 score and SMIR score were not exactly the same, the c-statistics for 1-year all-cause mortality were similar between the two scores (GRACE 2.0 0.841 and SMIR 0.865). In conclusion, we have shown that in a multi-ethnic Asian AMI population undergoing PCI, the SMIR score performed as well as the GRACE 2.0 score.

A Factor XIa Inhibitor Engineered from Banded Krait Venom Toxin: Efficacy and Safety in Rodent Models of Arterial and Venous Thrombosis.

Activated factor XI (FXIa) is an important antithrombotic drug target. Clinical and pre-clinical data have demonstrated that its inhibition attenuates thrombosis with minimal risk of excessive bleeding. We isolated Fasxiator from the venom of banded krait Bungarus fasciatus and subsequently engineered FasxiatorN17R,L19E, with improved affinity (Ki = 0.9 nM) and selectivity towards FXIa. Here, we assess the in vivo efficacy and bleeding risk of rFasxiatorN17R, L19E in pre-clinical animal models. Rats injected intravenously (i.v.) with bolus rFasxiatorN17R, L19E showed the specific in vivo attenuation of the intrinsic coagulation pathway, lasting for at least 60 min. We performed the in vivo dose-ranging experiments for rFasxiatorN17R, L19E as follows: FeCl3-induced carotid artery occlusion in rats (arterial thrombosis); inferior vena cava ligation in mice (venous thrombosis); tail bleeding time in both rats and mice (bleeding risk). Head-to-head comparisons were made using therapeutic dosages of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) for arterial and venous thrombosis, respectively. In the arterial thrombosis model, 2 mg/kg i.v. rFasxiatorN17R,L19E achieved a similar antithrombotic efficacy to that of UFH, with >3-fold lower bleeding time. In the venous thrombosis model, the 10 mg/kg subcutaneous (s.c.) injection of rFasxiatorN17R,L19E achieved similar efficacy and bleeding levels to those of LMWH enoxaparin. Overall, rFasxiatorN17R,L19E represents a promising molecule for the development of FXIa-targeting anticoagulants.

Effects of Sodium/Glucose Cotransporter 2 (SGLT2) Inhibitors on Cardiac Imaging Parameters: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Recent studies have shown that sodium/glucose cotransporter 2 (SGLT2) inhibitors might exert favourable changes on cardiac parameters as observed on cardiovascular imaging. We conducted a systematic review and meta-analysis to determine the effects of SGLT2 inhibitors on cardiac imaging parameters. Four electronic databases (PubMed, Embase, Cochrane, Scopus) were searched for studies in which the effects of SGLT2 inhibitors on cardiac imaging parameters were examined. Studies in which a population was administered SGLT2 inhibitors and analysed by echocardiography and/or cardiac magnetic resonance (CMR) imaging were included. Random-effects pair-wise meta-analysis models were utilized to summarize the studies. A total of 11 randomized controlled trials was included with a combined cohort of 910 patients. Comparing patients receiving SGLT2 inhibitors with subjects receiving placebo, the mean change in CMR-measured left ventricular mass (LVM) was -3.87 g (95% confidence interval [CI], -7.77 to 0.04), that in left ventricular end-systolic volume (LVESV) was -5.96 mL (95% CI, -10.52 to -1.41) for combined LVESV outcomes, that in left atrial volume index (LAVi) was -1.78 mL/m² (95% CI, -3.01 to -0.55) for combined LAVi outcomes, and that in echocardiography-measured E/e' was -0.73 (95% CI, -1.43 to -0.03). Between-group differences were not observed in LVM and LVESV after indexation. The only between-group difference that persisted was for LAVi. Treatment with SGLT2 inhibitors resulted in reduction in LAVi and E/e' on imaging, indicating they might have an effect on outcomes associated with LV diastolic function.

Comparison of Mortality Outcomes in Acute Myocardial Infarction Patients With or Without Standard Modifiable Cardiovascular Risk Factors.

Background: Acute myocardial infarction (AMI) cases have decreased in part due to the advent of targeted therapies for standard modifiable cardiovascular disease risk factors (SMuRF). Recent studies have reported that ST-elevation myocardial infarction (STEMI) patients without SMuRF (termed "SMuRF-less") may be increasing in prevalence and have worse outcomes than "SMuRF-positive" patients. As these studies have been limited to STEMI and comprised mainly Caucasian cohorts, we investigated the changes in the prevalence and mortality of both SMuRF-less STEMI and non-STEMI (NSTEMI) patients in a multiethnic Asian population. Methods: We evaluated 23,922 STEMI and 62,631 NSTEMI patients from a national multiethnic registry. Short-term cardiovascular and all-cause mortalities in SMuRF-less patients were compared to SMuRF-positive patients. Results: The proportions of SMuRF-less STEMI but not of NSTEMI have increased over the years. In hospitals, all-cause and cardiovascular mortality and 1-year cardiovascular mortality were significantly higher in SMuRF-less STEMI after adjustment for age, creatinine, and hemoglobin. However, this difference did not remain after adjusting for anterior infarction, cardiopulmonary resuscitation (CPR), and Killip class. There were no differences in mortality in SMuRF-less NSTEMI. In contrast to Chinese and Malay patients, SMuRF-less patients of South Asian descent had a two-fold higher risk of in-hospital all-cause mortality even after adjusting for features of increased disease severity. Conclusion: SMuRF-less patients had an increased risk of mortality with STEMI, suggesting that there may be unidentified nonstandard risk factors predisposing SMuRF-less patients to a worse prognosis. This group of patients may benefit from more intensive secondary prevention strategies to improve clinical outcomes.

Prognostic Outcomes in Acute Myocardial Infarction Patients Without Standard Modifiable Risk Factors: A Multiethnic Study of 8,680 Asian Patients.

Background: An increasing proportion of patients with acute myocardial infarction (AMI) are presenting without standard modifiable risk factors (SMuRFs) of hypertension, hypercholesterolemia, diabetes, and smoking, but with an unexpectedly increased mortality. This study examined the SMuRF-less patients presenting with AMI in a multiethnic Asian population. Methods: We recruited patients presenting with AMI from 2011 to 2021 and compared the prevalence, clinical characteristics, and outcomes of SMuRF-less and SMuRF patients. Multivariable analysis was used to compare the outcomes of 30-day cardiovascular mortality, all-cause mortality, readmission, cardiogenic shock, stroke, and heart failure. Kaplan-Meier curves were constructed for 30-day cardiovascular mortality, with stratification by ethnicity, gender and AMI type, and 10-year all-cause mortality. Results: Standard modifiable risk factor-less patients, who made up 8.6% of 8,680 patients, were significantly younger with fewer comorbidities that include stroke and chronic kidney disease, but higher rates of ventricular arrhythmias and inotropic or invasive ventilation requirement. Multivariable analysis showed higher rates of cardiovascular mortality (HR 1.48, 95% CI: 1.09-1.86, p = 0.048), cardiogenic shock (RR: 1.31, 95% CI: 1.09-1.52, p = 0.015), and stroke (RR: 2.51, 95% CI: 1.67-3.34, p = 0.030) among SMuRF-less patients. A 30-day cardiovascular mortality was raised in the SMuRF-less group, with similar trends in men, patients with ST-segment elevation myocardial infarction (STEMI), and the three Asian ethnicities. All-cause mortality remains increased in the SMuRF-less group for up to 5 years. Conclusion: There is a significant proportion of patients with AMI without standard risk factors in Asia, who have worse short-term mortality. This calls for greater focus on the management of this unexpectedly high-risk subgroup of patients.

Clinical Characteristics and Long-Term Outcomes of Patients With Differing Haemoglobin Levels Undergoing Semi-Urgent and Elective Percutaneous Coronary Intervention in an Asian Population.

Introduction: This study aimed to investigate the impact of anaemia on long-term clinical outcomes in patients who underwent semi-urgent and elective percutaneous coronary intervention (PCI) in an Asian population. Although the effects of anaemia on outcomes in Asian patients are well studied for acute coronary syndrome, its impact on Asian patients undergoing semi-urgent and elective PCI is unclear. Methods: This was a retrospective cohort study of patients who underwent semi-urgent and elective PCI from January 1, 2014, to December 31, 2015, at a tertiary academic centre. A total of 1,685 patients were included. They were stratified into three groups: normal (≥12 g/dL), intermediate (10-11.9 g/dL), and low (<10 g/dL) haemoglobin levels. Demographics, risk factors, and end-points including the 5-point major adverse cardiac and cerebrovascular events (MACCE) (all-cause death, subsequent stroke, myocardial infarction, congestive cardiac failure, and target lesion revascularisation), cardiovascular death, and bleeding events were analysed. Results: Patients in intermediate and low haemoglobin level groups were older with more comorbidities. Compared to the normal haemoglobin level group, low haemoglobin level group patients were associated with an increased risk of composite endpoints of all-cause death, subsequent stroke, myocardial infarction, congestive cardiac failure, and target lesion revascularisation [adjusted hazard ratio (aHR) 1.89, 95% confidence interval (CI):1.22, 2.92; p = 0.004]. This was driven by the increased risk of target lesions revascularisation observed in the low haemoglobin level group compared to the normal haemoglobin level group (aHR 17.74, 95% CI: 1.74, 180.80; p = 0.015). The patients in the low haemoglobin level group were also associated with a higher risk of bleeding events compared to the normal haemoglobin level group (aHR 7.18, 95% CI: 1.13, 45.40; p = 0.036). Conclusion: In our Asian cohort, patients with anaemia undergoing PCI were associated with a higher comorbid burden. Despite adjustments for comorbidities, these patients had higher mortality and worse cardiovascular outcomes following contemporary PCI.

Cardiac remodelling - Part 2: Clinical, imaging and laboratory findings. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology.

In patients with heart failure, the beneficial effects of drug and device therapies counteract to some extent ongoing cardiac damage. According to the net balance between these two factors, cardiac geometry and function may improve (reverse remodelling, RR) and even completely normalize (remission), or vice versa progressively deteriorate (adverse remodelling, AR). RR or remission predict a better prognosis, while AR has been associated with worsening clinical status and outcomes. The remodelling process ultimately involves all cardiac chambers, but has been traditionally evaluated in terms of left ventricular volumes and ejection fraction. This is the second part of a review paper by the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology dedicated to ventricular remodelling. This document examines the proposed criteria to diagnose RR and AR, their prevalence and prognostic value, and the variables predicting remodelling in patients managed according to current guidelines. Much attention will be devoted to RR in patients with heart failure with reduced ejection fraction because most studies on cardiac remodelling focused on this setting.

Effects of Sodium/Glucose Cotransporter 2 (SGLT2) Inhibitors and Combined SGLT1/2 Inhibitors on Cardiovascular, Metabolic, Renal, and Safety Outcomes in Patients with Diabetes: A Network Meta-Analysis of 111 Randomized Controlled Trials.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of anti-hyperglycemic drugs that has been steadily increasing in popularity due to its cardiovascular and renal benefits. Dual SGLT1/SGLT2 (SGLT1/2) inhibitors have potentially augmented anti-hyperglycemic action due to additional SGLT1 inhibition. This network meta-analysis aimed to compare the treatment effect across various outcomes between pure SGLT2 inhibitors and combined SGLT1/2 inhibitors in patients with diabetes. METHODOLOGY: Four electronic databases (PubMed, Embase, Cochrane, and Scopus) were searched for randomized controlled trials published from inception to 15th January 2022. Frequentist network meta-analysis was conducted to summarize the treatment effects reported in individual trials, stratified by type 1 (T1DM) and type 2 diabetes mellitus (T2DM). This meta-analysis was registered on PROSPERO (CRD42020222031). RESULTS: Our meta-analysis included 111 articles, comprising a combined cohort of 103,922 patients. SGLT2 inhibitors (dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, ertugliflozin, and luseogliflozin) and SGLT1/2 inhibitors (licogliflozin and sotagliflozin) were compared. Frequentist network meta-analysis demonstrated that in T2DM patients, SGLT1/2 inhibitors led to a decreased hazard rate of myocardial infarction (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.56-0.98) and stroke (HR 0.65, 95% CI 0.47-0.92) compared with SGLT2 inhibitors. SGLT2 inhibitors achieved a greater hemoglobin A1c (HbA1c) reduction than SGLT1/2 inhibitors (0.16%, 95% CI 0.06-0.26). In patients with T2DM, the risk of diarrhea (risk ratio [RR] 1.42, 95% CI 1.07-1.88) and severe hypoglycemia (RR 5.89, 95% CI 1.41-24.57) were found to be higher with SGLT1/2 inhibitor use compared with SGLT2 inhibitor use. No differences were observed for cardiovascular, metabolic, and safety outcomes between SGLT1/2 inhibitors and SGLT2 inhibitors in patients with T1DM. CONCLUSIONS: In patients with T2DM, compared with pure SGLT2 inhibitors, combined SGLT1/2 inhibitors demonstrated a lower risk of myocardial infarction and of stroke, but were associated with a higher risk of diarrhea and severe hypoglycemia.

A polygenic risk score improves risk stratification of coronary artery disease: a large-scale prospective Chinese cohort study.

AIMS: To construct a polygenic risk score (PRS) for coronary artery disease (CAD) and comprehensively evaluate its potential in clinical utility for primary prevention in Chinese populations. METHODS AND RESULTS: Using meta-analytic approach and large genome-wide association results for CAD and CAD-related traits in East Asians, a PRS comprising 540 genetic variants was developed in a training set of 2800 patients with CAD and 2055 controls, and was further assessed for risk stratification for CAD integrating with the guideline-recommended clinical risk score in large prospective cohorts comprising 41 271 individuals. During a mean follow-up of 13.0 years, 1303 incident CAD cases were identified. Individuals with high PRS (the highest 20%) had about three-fold higher risk of CAD than the lowest 20% (hazard ratio 2.91, 95% confidence interval 2.43-3.49), with the lifetime risk of 15.9 and 5.8%, respectively. The addition of PRS to the clinical risk score yielded a modest yet significant improvement in C-statistic (1%) and net reclassification improvement (3.5%). We observed significant gradients in both 10-year and lifetime risk of CAD according to the PRS within each clinical risk strata. Particularly, when integrating high PRS, intermediate clinical risk individuals with uncertain clinical decision for intervention would reach the risk levels (10-year of 4.6 vs. 4.8%, lifetime of 17.9 vs. 16.6%) of high clinical risk individuals with intermediate (20-80%) PRS. CONCLUSION: The PRS could stratify individuals into different trajectories of CAD risk, and further refine risk stratification for CAD within each clinical risk strata, demonstrating a great potential to identify high-risk individuals for targeted intervention in clinical utility.