Platform for the interdisciplinary study of cardiovascular, metabolic and neurovascular diseases (PICMAN) protocol.

Through extensive multisystem phenotyping, the central aim of Project PICMAN is to correlate metabolic flexibility to measures of cardiometabolic health, including myocardial diastolic dysfunction, coronary and cerebral atherosclerosis, body fat distribution and severity of non-alcoholic fatty liver disease. This cohort will form the basis of larger interventional trials targeting metabolic inflexibility in the prevention of cardiovascular disease. Participants aged 21-72 years with no prior manifest atherosclerotic cardiovascular disease (ASCVD) are being recruited from a preventive cardiology clinic and an existing cohort of non-alcoholic fatty liver disease (NAFLD) in an academic medical centre. A total of 120 patients will be recruited in the pilot phase of this study and followed up for 5 years. Those with 10-year ASCVD risk ≥ 5% as per the QRISK3 calculator are eligible. Those with established diabetes mellitus are excluded. Participants recruited undergo a detailed assessment of health behaviours and physical measurements. Participants also undergo a series of multimodality clinical phenotyping comprising cardiac tests, vascular assessments, metabolic tests, liver and neurovascular testing. Blood samples are also being collected and banked for plasma biomarkers, 'multi-omics analyses' and for generation of induced pluripotent stem cells (iPSC). Extensive evidence points to metabolic dysregulation as an early precursor of cardiovascular disease, particularly in Asia. We hypothesise that quantifiable metabolic inflexibility may be representative of an individual in his/her silent, but high-risk progression towards insulin resistance, diabetes and cardiovascular disease. The platform for interdisciplinary cardiovascular-metabolic-neurovascular diseases (PICMAN) is a pilot, prospective, multi-ethnic cohort study.

Association of face mask use with self-reported cardiovascular symptoms during the COVID-19 pandemic.

Introduction: Countries are mandating the use of face masks to stem the spread of coronavirus disease 2019 (COVID-19). Face mask use has been associated with discomfort due to its effects on thermoregulation, breathing and oxygenation. We evaluated the prevalence and severity of self-reported cardiovascular symptoms before and during face mask use. Methods: This was a cross-sectional study of 1,001 participants residing in Singapore, who participated in a self-administered questionnaire between 25 April 2020 and 4 May 2020. Symptom severity before and during mask use, and health-seeking behaviour information were collected. The study outcome was self-reported worsening of cardiovascular symptoms and its association with the type of mask worn, duration of mask worn per day, and intensity of physical activities during mask use. Results: The most common symptom reported during mask use was dyspnoea. Independent predictors for self-reported cardiovascular symptoms during mask use were moderate-high physical activity during mask use (odds ratio [OR] 1.634, 95% confidence interval [CI] 1.176-2.270, P = 0.003), duration of mask use for ≥3 h (OR 1.672, 95% CI 1.189-2.352, P = 0.003) and type of mask used, after adjusting for age, sex, healthcare-based worker status and presence of comorbidities. N95 mask was associated with worse symptoms when compared to surgical mask. Participants with ≥3 worsening symptoms or worsening dyspnoea, palpitations, fatigue and dizziness were more likely to seek medical help. Conclusion: Face mask use has been proven to be an effective way in curbing COVID-19 transmission. However, participants in this study had concerns regarding its use and these concerns should be urgently addressed to enable mask use policies to be enacted.

Percutaneous coronary intervention in patients aged 80 years old and above: a systematic review and meta-analysis.

Background: Ischaemic heart disease remains the main cause of death in the world. With increasing age, frailty and comorbidities, senior patients aged 80 years old and above who undergo percutaneous coronary intervention (PCI) are at higher risk of mortality and other complications. Aims: We aimed to examine the overall outcomes for this group of patients. Methods: Four databases (PUBMED, EMBASE, SCOPUS and CENTRAL) were searched. Studies with patients aged 80 years old and above who underwent PCI for all indications were included. Pooled outcomes of all-cause death, cardiac death, in-hospital death, subsequent stroke/transient ischaemic attack (TIA), subsequent myocardial infarction (MI), subsequent congestive cardiac failure (CCF), and overall major adverse cardiac events (MACE) were obtained for meta-analysis. Results: From 2,566,004 patients, the pooled cumulative incidence of death was 19.22%, cardiac death was 7.78%, in-hospital death was 7.16%, subsequent stroke/TIA was 1.54%, subsequent MI was 3.58%, subsequent CCF was 4.74%, and MACE was 17.51%. The mortality rate of all patients was high when followed up for 3 years (33.27%). ST-elevation myocardial infarction patients had more outcomes of in-hospital death (14.24% vs 4.89%), stroke/TIA (1.93% vs 0.12%), MI (3.68 vs 1.55%) and 1-year mortality (26.16% vs 13.62%), when compared to non-ST-elevation myocardial infarction patients. Conclusions: There was a high mortality rate at 1 year and 3 years post-PCI in the overall population of senior patients aged 80 years old and above, regardless of indication. This necessitates further studies to explore the implications of these observations.

The Impact of Cognitive Impairment on Clinical Outcomes After Transcatheter Aortic Valve Implantation (from a Systematic Review and Meta-Analysis).

This study sought to investigate the impact of pre-existing cognitive impairment on outcomes after transcatheter aortic valve implantation (TAVI). TAVI has been increasingly used in seniors, and evidence suggests better outcomes than surgical aortic valve replacement. Although frailty has been shown to be associated with poorer outcomes after TAVI, the effect of pre-existing cognitive impairment on patient outcomes after TAVI remains unclear. We searched the Medline, Embase, Scopus and Cochrane databases until May 14, 2022. The risk of bias was assessed using the Newcastle-Ottawa scale. The primary outcome was short-term (6 months to 1 year) mortality, and secondary outcomes included long-term (1 year to 3 years) mortality, in-hospital mortality, and postoperative delirium. A total of 14 studies with 32,746 patients (5,098 patients with cognitive impairment at baseline, 27,648 without) were included in our meta-analysis. Among studies that reported the raw proportion of patients with mortality of postoperative delirium, cognitive impairment significantly increased mortality (risk ratio 2.10, 95% confidence intervals [CIs] 1.43 to 3.08, p = 0.0002) and postoperative delirium (risk ratio 2.27, 95% CI 1.76 to 2.93, p <0.0001). Studies which reported the hazards for mortality (pooled hazards ratio 1.97, 95% CI 1.50 to 2.60, p <0.0001) and odds of postoperative delirium (pooled odds ratio 2.40, 95% CI: 1.51 to 3.80, p = 0.0002) yielded results consistent with the primary meta-analysis. In conclusion, pre-existing cognitive impairment is a significant risk factor for poorer outcomes after TAVI and should be carefully considered in this group of patients. Guidelines and future studies should take cognitive impairment into consideration for preoperative risk stratification.

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.

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.

Long-Term Outcomes of Stroke or Transient Ischemic Attack after Non-Emergency Percutaneous Coronary Intervention.

OBJECTIVES: Non-emergency percutaneous coronary intervention (PCI) has lower risk of stroke than emergency PCI. With increasing elective PCI and increasing risk of stroke after PCI, risk factors for stroke or transient ischaemic attack (TIA) in non-emergency PCI and long-term outcomes needs to be better characterised. We aim to identify risk factors for cerebrovascular accidents in patients undergoing non-emergency PCI and long-term outcomes after stroke or TIA. MATERIALS AND METHODS: A retrospective cohort study was performed on 1724 consecutive patients who underwent non-emergency PCI for non-ST-segment elevation myocardial infarction (NSTEMI), unstable and stable angina. The primary outcomes measured were stroke or TIA, myocardial infarction (MI) and all-cause death. RESULTS: Upon mean follow-up of 3.71 (SD 0.97) years, 70 (4.1%) had subsequent ischaemic stroke or TIA, and they were more likely to present with NSTEMI (50 [71.4%] vs 892 [54.0%], OR 2.13 [1.26-3.62], p = 0.004) and not stable angina (19 [27.1%] vs 648 [39.2%], OR 0.58 [0.34-0.99]). Femoral access was associated with subsequent stroke or TIA compared to radial access (OR 2.10 [1.30-3.39], p < 0.002). Previous stroke/TIA was associated with subsequent stroke/TIA (p < 0.001), death (p < 0.001) and MI (p = 0.002). Furthermore, subsequent stroke/TIA was significantly associated with subsequent MI (p = 0.006), congestive cardiac failure (CCF) (p = 0.008) and death (p < 0.001). CONCLUSIONS: In patients undergoing non-emergency PCI, previous stroke/TIA predicted post-PCI ischaemic stroke/TIA, which was associated with death, MI, CCF.

A new non-invasive index for prognosis evaluation in patients with aortic stenosis.

The global left ventricular (LV) contractility index, dσ*/dtmax measures the maximal rate of change in pressure-normalized LV wall stress. We aim to describe the trend of dσ*/dtmax in differing severity of aortic stenosis (AS) with preserved left ventricular ejection fraction (LVEF) and the association of dσ*/dtmax with clinical outcomes in moderate AS and severe AS. We retrospectively studied a total of 1738 patients with AS (550 mild AS, 738 moderate AS, 450 severe AS) and preserved LVEF ≥ 50% diagnosed from 1st January 2001 to 31st December 2015. dσ*/dtmax worsened with increasing severity of AS despite preserved LVEF (mild AS: 3.69 ± 1.28 s-1, moderate AS: 3.17 ± 1.09 s-1, severe AS: 2.58 ± 0.83 s-1, p < 0.001). Low dσ*/dtmax < 2.8 s-1 was independently associated with a higher composite outcome of aortic valve replacement, congestive cardiac failure admissions and all-cause mortality (adjusted hazard ratio 1.48, 95% CI: 1.25-1.77, p < 0.001). In conclusion, dσ*/dtmax declined with worsening AS despite preserved LVEF. Low dσ*/dtmax < 2.8 s-1 was independently associated with adverse clinical outcomes in moderate AS and severe AS with preserved LVEF.

Transplantation of Endothelial Progenitor Cells in Obese Diabetic Rats Following Myocardial Infarction: Role of Thymosin Beta-4.

Endothelial progenitor cells (EPCs) are bone-marrow derived cells that are critical in the maintenance of endothelial wall integrity and protection of ischemic myocardium through the formation of new blood vessels (vasculogenesis) or proliferation of pre-existing vasculature (angiogenesis). Diabetes mellitus (DM) and the metabolic syndrome are commonly associated with ischemic heart disease through its pathological effects on the endothelium and consequent endothelial dysfunction. Thymosin-ß4 (Tß4) which expressed in the embryonic heart is critical in epicardial and coronary artery formation. In this study, we explored the effects of Tß4 treatment on diabetic EPCs in vitro and intramyocardial injection of Tß4-treated and non-Tß4 treated EPCs following acute myocardial infarction (MI) of diabetic rats in vivo. It was found that 10 ng/mL Tß4 increased migration, tubule formation, and angiogenic factor secretion of diabetic EPCs in vitro. In vivo, although implantation of Tß4 treated diabetic EPCs significantly increased capillary density and attracted more c-Kit positive progenitor cells into the infarcted hearts as compared with implantation of non-Tß4 treated diabetic EPCs, the significantly improved left ventricular ejection fraction was only found in the rats which received non-Tß4 treated EPCs. The data suggests that a low dose Tß4 increases diabetic EPC migration, tubule formation, and angiogenic factor secretion. However, it did not improve the effects of EPCs on left ventricular pump function in diabetic rats with MI.

A myriad of electrocardiographic findings associated with digoxin use.

Digoxin is a commonly prescribed drug in the management of heart failure and atrial fibrillation. Despite its widespread use, most clinicians have little experience with recognising clinical signs and symptoms that might suggest a potentially lethal drug toxicity. We herein describe two cases with specific reference to the electrocardiographic changes induced by digoxin and discuss the predisposing factors for toxicity, recognition of possible toxicity and treatment approaches.