To Örebro University

BACKGROUND: COVID-19 increases cardiovascular risk, and vaccination reduces adverse outcomes and mortality. We analysed national hospital-based sentinel surveillance data from Bangladesh, and the aim of the study was to identify factors associated with all-cause mortality among patients with cardiovascular complications.

METHODS: We included patients from coronary care units in nine tertiary-hospitals between February 2021 and December 2024 with severe acute respiratory infections (SARI). Nasopharyngeal and oropharyngeal swabs were tested for SARS-CoV-2 and influenza viruses by multiplex rRT-PCR. Patients were followed up from hospital admission to 30 days post-discharge. Survival was assessed with Kaplan-Meier estimates stratified by vaccination status and compared using log-rank test. Risk factors for all-cause mortality were analysed using multivariable Cox proportional hazards regression, stratified by hospital type.

FINDINGS: We enrolled 396 patients (median age 60, IQR: 48-65 years), and 70.5% (279/396) were male. The Median follow-up time was 33 days (IQR: 32-34 days). There were 13.9% (55/396) deaths, 41.2% (163/396) had acute myocardial infarction (AMI) and 71.2% (286/396) were COVID-19 vaccinated patients. SARS-CoV-2 and influenza viruses were detected among 6.8% (27/396) and 4.8% (19/396) patients, respectively. At follow-up, the survival rate was 89.6% in COVID-19 vaccinated patients compared to 81.4% in unvaccinated patients (P-value = 0.041). AMI was associated with higher mortality [HR = 1.74, (95% CI: 1.01-3.02), P-value = 0.048] while COVID-19 vaccination was protective [HR = 0.55, (95% CI: 0.32-0.96), P-value = 0.037].

INTERPRETATION: COVID-19 vaccination was associated with reduced all-cause deaths among SARI patients with cardiovascular complications. FUNDING: Centres for Disease Control and Prevention (CDC), Atlanta, Georgia, USA (U01GH002259). ZA is supported by UNSW by a UIPA PhD scholarship.

BACKGROUND: Microvascular injury (MVI) increases the risk of heart failure and mortality in patients with ST-elevation myocardial infarction (STEMI). Therefore, it is important to detect these patients at an early stage for additional (experimental) therapies to improve outcomes. Currently, there are no methods to diagnose MVI in STEMI patients before reperfusion. The objective of this study was to assess the invasively measured infarct-related absolute myocardial resistance (Rinfarction) to predict MVI before reperfusion. Cardiac magnetic resonance imaging (CMR) characterizes MVI, in the forms of microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH) with IMH being at the "extreme" end of the injury spectrum.

METHODS: In this substudy of the EURO-ICE trial, Rinfarction was calculated as the change in distal coronary pressure during saline infusion in the occluded culprit artery, divided by the flow rate of the infused saline. The primary endpoint was to assess the diagnostic performance of Rinfarction to predict MVO on CMR performed at 2-7 days. The secondary endpoint was a composite of all-cause mortality or hospitalization for heart failure up to 5 years.

RESULTS: A total of 82 patients were included. The area under the Receiver-Operating Characteristic curve of Rinfarction to predict MVO and IMH was 0.84 and 0.78, respectively. The optimal cut-off value for both MVO and IMH was 1000 Wood units (WU). The composite endpoint of all-cause mortality or hospitalization for heart failure occurred in 15.6% and 2.3% in the Rinfarction ≥ 1000 WU and Rinfarction < 1000 WU groups, respectively (p = 0.06).

CONCLUSIONS: Rinfarction is able to predict MVI in STEMI before reperfusion and may serve as a tool in future trials to select patients that might benefit most from experimental therapies.

BACKGROUND: Cardiogenic shock remains the leading cause of in-hospital death in patients with acute myocardial infarction (MI). The intra-aortic balloon pump (IABP), once widely used, was downgraded in European guidelines after a major randomized trial showed no mortality benefit. This prospective observational study evaluated the impact of IABP on 30-day mortality and in-hospital complications in real-world patients with MI complicated by cardiogenic shock.

METHODS: Data were obtained from the Swedish Coronary Angiography and Angioplasty Registry, including all percutaneous coronary intervention procedures performed across 31 hospitals in Sweden between 2005 and 2018. A total of 2991 patients with cardiogenic shock were included, of whom 737 (25%) received IABP. To account for baseline differences, instrumental variable analysis was applied using hospital treatment preference as the instrument.

RESULTS: At 30 days, 52% of patients had died, and by 1 year, mortality reached 63.2%. In-hospital complications occurred in 13.4% of patients. IABP treatment was not associated with reduced mortality at 30 days [risk reduction: -1.1%, 95% confidence interval (CI): -15.7 to 13.5; P = 0.881] or at 1 year (risk reduction: -0.8%, 95% CI: -23.2 to 0.06; P = 0.258). However, IABP use was associated with a significantly higher risk of in-hospital complications (increase of 26.1%, 95% CI: 15.2-36.8; P < 0.001).

CONCLUSION: IABP did not improve short- or long-term survival in patients with MI-related cardiogenic shock but was linked to increased complications, supporting current guideline recommendations against its routine use.

Influenza infection is a well-established trigger of acute cardiovascular events, particularly myocardial infarction, mediated by systemic inflammation, endothelial dysfunction, and thrombosis. In this review, we examine the evidence supporting influenza vaccination as a preventive strategy in cardiovascular disease. Observational studies and randomized trials consistently show reduced cardiovascular event rates among vaccinated individuals, with the most pronounced benefit seen after myocardial infarction. Emerging data suggest that the effects of vaccination extend beyond infection prevention, involving immunomodulatory effects, including regulatory T cell activity, features of trained innate immunity, and mechanisms promoting resolution of inflammation. Unlike conventional anti-inflammatory therapies, vaccination appears to rebalance immune responses without compromising host defence. We also consider an evolutionary perspective, proposing that historical influenza exposure may have contributed to the genetic architecture of atherosclerosis. Taken together, current evidence positions influenza vaccination as a safe, low-cost, and biologically plausible intervention in the prevention of cardiovascular events. However, important questions remain. Whether revaccination during hospitalization provides added benefit in previously immunized individuals, and the potential of high-dose or next-generation vaccine platforms such as mRNA, warrant further study. Dedicated outcome trials conducted outside the influenza season are especially needed to clarify nonspecific cardiovascular benefits. Cardiologists and other stakeholders share a responsibility to implement existing guidelines with the same commitment given to statins and platelet inhibitors.

Background: Win statistics offer an alternative approach to clinical trials that use survival analysis to analyze composite endpoints. Our objective was to re-analyze data from previously published registry-based randomized controlled trials that produced hazard ratios using win statistics to evaluate the correspondence between them. Good correspondence was defined as both results being positive, negative, or neutral. Win statistics were calculated for these trials to encourage transparency, scientific rigor, and possibly validate results.

Methods: The win ratio ordered events hierarchically by clinical importance for each trial, with all-cause death regarded as most severe, followed by acute myocardial infarction. Further components, i.e., other endpoints, were added subsequently to the hierarchy. Each patient in the treatment group was compared with each patient in the control arm in hierarchical order. The total number of wins for each category in the treatment group was added and divided by the total number of wins in the control group. Win odds were calculated as an extension, which incorporate ties into the calculation.

Results: The results using win statistics showed good correspondence to the previously reported hazard ratios with their composite endpoints: for the TASTE trial, the results were neutral for both the hazard ratio and win odds. The hazard ratio was 0.86 (0.67-1.10), and the win odds were 1.02 (0.99-1.04). Similar results were found for the iFR-SWEDEHEART, DETO2X-AMI, and VALIDATE trials. The IAMI trial showed better results for the vaccinated group compared to the placebo for both the hazard ratio and win odds.

Conclusions: Win statistics offer an alternative approach to traditional survival analysis by harnessing multiple events hierarchically by clinical importance. Win statistics also offer the potential to evaluate a broader range of clinical endpoints, providing a more rounded perspective of treatment efficacy, an important consideration when designing future randomized controlled trials. This is the first multi-registry-based controlled trial reanalysis using win statistics.

BACKGROUND: Physiologically guided revascularization improves clinical outcomes. The cutoff values for deferral with fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are the same across all coronary arteries, despite differences in coronary flow patterns. The objective was to compare deferral rates using either FFR or iFR in the right coronary artery (RCA), left anterior descending artery (LAD), and left circumflex artery (LCx), and compare clinical outcomes in deferred lesions in the RCA, LAD, and LCx.

METHODS: Right coronary artery, LAD, and LCx lesions in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry that were evaluated using either FFR or iFR were included. The composite of major adverse cardiac events (MACE) within 5 years and the individual components of cardiovascular death, noncardiovascular death, myocardial infarction, target segment revascularization, and target vessel revascularization were analyzed.

RESULTS: In total, 33,241 lesions were included in the final analysis (RCA, 17.8%; LAD, 62.3%; and LCx, 19.9%). The median follow-up time was 3.4 years. The median age was 69 years, and 73.5% of patients were men. The deferral rates with iFR were 10.6% higher (P < .001) in all coronary arteries combined, 18.7% higher (P < .001) in the RCA, 9.5% higher in the LAD (P < .001), and 5.3% higher in the LCx (P = .007). No significant differences were observed in the MACE rate or its individual components at 5 years between the deferred FFR and iFR groups in any of the investigated vessels.

CONCLUSIONS: Instantaneous wave-free ratio demonstrated a higher deferral rate across all coronary arteries than those examined with FFR, which was especially pronounced in the RCA, without any associated increased risk of MACE.

Background: Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are effective in the long-term treatment of individuals with myocardial infarction (MI) and reduced left ventricular ejection fraction. However, there is a lack of randomised trials assessing these agents in those with preserved ejection fraction (≥50%). One approach is to use observational data to emulate a hypothetical pragmatic trial ("target trial") that one would conduct.

Methods: We emulated a target trial of ACEis/ARBs versus no ACEis/ARBs in individuals under the age of 75 years with MI and left ventricular ejection fraction ≥50% between September 2010 and June 2021 for the prevention of a composite outcome (death, myocardial infarction, or heart failure) and its individual components. We used the Sweden-wide SWEDEHEART quality registry with linkage to other national registers, enabling complete coverage of hospital care and dispensed drugs. We estimated observational analogues of the intention-to-treat effect and the per-protocol effect with confounding adjustment via inverse probability weighting.

Results: The 10,697 individuals in the ACEi/ARB group were on average older (median 61 vs 60 years), more likely to be male (80.2% vs 75.3% male) and more likely to present with STEMI (45.4% vs 27.9%) compared with the 4,730 individuals in the no ACEi/ARB group. In an intention-to-treat analysis, the estimated five-year risk of the composite outcome was 7.8% (95% confidence interval 7.1%, 8.5%) in the ACEi/ARB group and 8.1% (7.0%, 9.3%) in the non-ACEi/ARB group; risk difference -0.3% (-1.6%, 1.0%) (Figure 1). In a per protocol analysis, the risk of the composite outcome was 6.5% (5.9%, 7.2%) in the ACEi/ARB group and 6.7% (5.6%, 8.1%) in the no ACEi/ARB group; risk difference -0.2% (-1.7%, 1.0%) (Figure 2).

Conclusions: The estimated risk of a composite of death, myocardial infarction or heart failure was similar in recipients and non-recipients of ACEi/ARB. Our estimates suggest that ACEi/ARB treatment in patients with myocardial infarction and preserved left ventricular ejection fraction does not confer a benefit.

BACKGROUND: Hemodynamically obstructive coronary plaques may contain more vulnerable plaque characteristics than nonobstructive lesions. OBJECTIVES: The authors aimed to assess whether pressure-wire-based physiologic indices in nonculprit lesions are associated with vulnerable plaque characteristics.

METHODS: In the PROSPECT II study, patients with recent myocardial infarction underwent coronary angiography and culprit lesion percutaneous coronary intervention plus combined near-infrared spectroscopy and intravascular ultrasound assessment of all 3 coronary arteries. Instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements were performed in intermediate lesions with angiographic stenosis >40%.

RESULTS: Among 898 patients, 319 angiographically intermediate lesions in 275 patients had matched intravascular ultrasound/near-infrared spectroscopy and FFR/iFR measurements; 96 (30.1%) lesions were physiologically significant (FFR ≤0.80 or iFR ≤0.89) and 223 (69.9%) were not. Physiologically significant lesions, compared with those that were not, more likely had a minimal lumen area ≤4.0 mm2 (96.9% vs 83.9%), plaque burden ≥70% (92.7% vs 71.3%) and maximum lipid core burden index in any 4 mm segment of the lesion ≥324.7 (57.0% vs 45.4%). By multivariable analysis, lesion location in the left anterior descending artery, small minimal lumen area, and larger plaque burden were independently associated with physiologic significance, whereas maximum lipid core burden index in any 4 mm segment of the lesion was not.

CONCLUSIONS: In patients with recent myocardial infarction, angiographically intermediate but physiologically significant coronary lesions were more likely to have high-risk vulnerable plaque features compared with nonphysiologically significant stenoses. However, coronary lesions without physiological significance also had a moderate-to-high prevalence of high-risk plaque characteristics, which may explain the residual risk associated with conservative noninterventional management of these lesions. (Providing Regional Observations to Study Predictors of Events in the Coronary Tree II [PROSPECT II]; NCT02171065).