Background Emerging reports raise concerns on the potential association between the COVID-19 vaccines and cardiac manifestations. We sought to evaluate cardiac complications associated with COVID-19 vaccination in a pooled analysis from our institution’s cohort study and systematic review. Methods Consecutive patients admitted in a tertiary hospital in Singapore between 1 January 2021 and 31 March 2021, with onset of cardiac manifestations within 14 days following COVID-19 vaccination were studied. Furthermore, a systematic review was performed, with PubMed, Embase, Research Square, MedRxiv, and LitCovid databases accessed from inception up to 29 June 2021. Relevant manuscripts reporting individual patient data on cardiac complications following COVID-19 vaccination were included. Results Thirty patients were included in the study cohort, with 29 diagnosed with acute myocardial infarction (AMI) and 1 with myocarditis. Five patients developed heart failure, two had cardiogenic shock, three intubated, and one had cardiovascular-related mortality. In the systematic review, 16 studies were included with 41 myocarditis and six AMI cases. In the pooled analysis of the study cohort and the systematic review, 35 patients had AMI and 42 had myocarditis. Majority were men, and myocarditis patients were younger than AMI patients. Myocarditis patients tended to present 72 hours post-vaccination, while AMI patients were older and typically presented 24 hours post-vaccination. Majority with AMI or myocarditis developed symptoms after the first and second vaccination dose respectively. Conclusions This pooled analysis of patients presenting with cardiac manifestations following COVID-19 vaccination highlights the differences between myocarditis and AMI presentations in temporal association with the vaccination.

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BackgroundCurrent guidelines recommend psychological support for patients with pulmonary hypertension suffering from psychological adversity. However, little is known about the prevalence and risk factors of depression and anxiety in patients with pulmonary hypertension (PH).MethodsMedline and Embase were searched from inception to 6 May 2021. Meta-analysis of proportions using the generalized linear mixed model was conducted to analyze the pooled prevalence rates of depression and anxiety in PH patients. Risk factors for depression and anxiety in PH patients were evaluated using meta regression.ResultsA total of 24 studies involving 2,161 PH patients were included. The pooled prevalence of depression in PH was 28.0% (95% CI: 20.5–36.8) and pooled prevalence of anxiety was 37.1% (95% CI: 28.7–46.4). There was a significantly higher prevalence of anxiety (p = 0.0013) amongst PH patients in Asia (61.1%) compared to Europe (40.3%) and North America (22.9%). In terms of risk factors, congenital heart disease-related pulmonary arterial hypertension (PAH-CHD) were significantly associated with both depression (OR: 1.68, 95% CI: 1.27–2.23, p = 0.024) and anxiety (OR: 1.63, 95% CI: 1.45–1.83, p = 0.002). On the other hand, chronic thromboembolic pulmonary hypertension (CTEPH, OR: 1.18, 95% CI: 1.10–1.26, p = 0.004) was significantly associated with depression, whereas worse pulmonary vascular resistance (β: 0.30, 95% CI: 0.09–0.52, p = 0.005) and cardiac index (β: −0.96, 95% CI: −1.58 to −0.35, p = 0.002) were significantly correlated with anxiety.ConclusionThe prevalence of anxiety and depression in PH patients is alarmingly high, with an increased prevalence of anxiety in Asia compared to Europe or North America. Psychological support is warranted for patients with PH, particularly those with underlying congenital heart disease, CTEPH, and severe disease.Systematic Review RegistrationCRD42021251733.

BackgroundAn 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.MethodsWe 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.ResultsStandard 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.ConclusionThere 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.

Background Randomized controlled trials (RCTs) of lipid-lowering therapy (LLT) in which the control groups received placebo without background LLT offer unique insights into the placebo and nocebo effects of lipid-lowering RCTs. Methods and results Embase and Medline were searched for hyperlipidaemia RCTs with placebo-controlled arms. Placebo arms with background LLT were excluded. A single arm meta-analysis of proportions was used to estimate major adverse cardiovascular events (MACE) and adverse events (AE). A meta-analysis of means was used to estimate the pooled mean differences of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoproteins (HDL) and triglycerides (TG). A total of 40 RCTs and 37 668 placebo-treated participants were included. The pooled mean changes for TC, LDL, HDL, and TG were −0.019 mmol/L, −0.028 mmol/L, 0.013 mmol/L, and 0.062 mmol/L respectively among placebo-treated participants, indicating a modest placebo effect. The pooled average nocebo effect among placebo-treated participants was 42.62% for all AEs and 3.38% for musculoskeletal-related AEs, 11.36% for gastrointestinal-related AEs, and 6.62% for headaches. Placebo-treated participants in secondary prevention RCTs had a far higher incidence of these nocebo effects than primary prevention RCTs: any AEs (OR 6.76, 95% CI: 5.56–8.24, P < 0.001), and gastrointestinal-related AE (OR 1.23, 95% CI: 1.00–1.51, P = 0.049). No differences in nocebo effects were found between the placebo arms of statin and non-statin trials. Conclusion Our meta-analysis of placebo-treated participants in RCTs with no background LLT indicate a modest placebo effect but prominent nocebo effect of musculoskeletal, headache, and gastrointestinal symptoms that was greatest among secondary prevention RCTs. These findings may inform the design of future LLT RCTs.

AimsThe cardioprotective effects of glucose-lowering medications in diabetic patients with heart failure (HF) are well known. Several large randomized controlled trials (RCTs) have recently suggested that the cardioprotective effects of glucose-lowering medications extend to HF patients regardless of diabetic status. The aim of this study was to conduct a Bayesian network meta-analysis to evaluate the impact of various glucose-lowering medications on the outcomes of non-diabetic HF patients. Methods and results Medline and Embase were searched for RCTs investigating the use of glucose-lowering medications in non-diabetic HF patients in August 2021. Studies were included in accordance with the inclusion and exclusion criteria, and data were extracted with a pre-defined datasheet. Primary outcomes include serum N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels, left ventricular ejection fraction (LVEF), and maximal oxygen consumption (PVO 2 ). A Bayesian network meta-analysis was performed to compare the effectiveness of different classes of glucose-lowering medications in improving HF outcomes. Risk-of-bias was assessed using Cochrane Risk-of-Bias tool 2.0 for randomized trials (ROB2). Seven RCTs involving 2897 patients were included. Sodium-glucose transporter 2 inhibitor (SGLT2i) was the most favourable in lowering NT-proBNP, with the significant reduction in NT-proBNP when compared with glucagon-like peptide-1 receptor agonists (GLP1-RA) [mean differences (MD): À229.59 pg/mL, 95%-credible intervals (95%-CrI): À238.31 to À220.91], metformin (MD: À237.15 pg/mL, 95%-CrI: À256.19 to À218.14), and placebo (MD: À228.00 pg/mL, 95%-CrI: À233.99 to À221.99). SGLT2i was more effective in improving LVEF for HF with reduced ejection fraction patients relative to GLP1-RA (MD: 8.09%, 95%-CrI: 6.30 to 9.88) and placebo (MD: 6.10%, 95%-CrI: 4.37 to 7.84). SGLT2i and GLP1-RA were more favourable to placebo in improving PVO 2 , with significant increase of PVO 2 at a MD of 1.60 mL/kg/min (95%-CrI: 0.63 to 2.57) and 0.86 mL/kg/min (95%-CrI: 0.66 to 1.06), respectively. All three drugs had comparable safety profiles when compared with placebo. Conclusions This Bayesian network meta-analysis demonstrated that SGLT2i, when compared with GLP1-RA and metformin, was superior in improving LVEF in HF with reduced ejection fraction patients, as well as improving PVO 2 and NT-proBNP in non-diabetic HF patients. Further large-scale prospective studies are needed to confirm these preliminary findings.

Background and AimsData are emerging on 10-year mortality comparing coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) with stenting for multivessel disease (MVD) without left main (LM) involvement. We conducted an updated two-stage meta-analysis using reconstructed individual patient data to compare long-term mortality between CABG and PCI for patients with MVD without significant LM coronary disease.MethodsMedline and Embase databases were searched for articles comparing CABG with PCI for MVD. A two-stage meta-analysis was conducted using reconstructed patient level survival data for all-cause mortality with subgroups by SYNTAX score. The shared-frailty and stratified Cox models were fitted to compare survival endpoints.ResultsWe screened 1,496 studies and included six randomized controlled trials with 7,181 patients. PCI was associated with greater 10-year all-cause mortality risk (HR: 1.282, CI: 1.118–1.469, p < 0.001) compared with CABG. In patients with low SYNTAX score, 10-year all-cause mortality after PCI was comparable to CABG (HR: 1.102, 0.822–1.479, p = 0.516). However, in patients with moderate to high SYNTAX score, 10-year all-cause mortality was significantly higher after PCI compared with CABG (HR: 1.444, 1.122–1.858, p < 0.001; HR: 1.856, 1.380–2.497, p < 0.001, respectively).ConclusionThis updated reconstructed individual patient-data meta-analysis revealed a sustained lower cumulative all-cause mortality of CABG over PCI for multivessel disease without LM involvement.

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