To explore the incidence and potential mechanisms of oligosymptomatic myocardial injury following COVID-19 mRNA booster vaccination.
Hospital employees scheduled to undergo mRNA-1273 booster ...vaccination were assessed for mRNA-1273 vaccination-associated myocardial injury, defined as acute dynamic increase in high-sensitivity cardiac troponin T (hs-cTnT) concentration above the sex-specific upper limit of normal on day 3 (48-96 h) after vaccination without evidence of an alternative cause. To explore possible mechanisms, antibodies against interleukin-1 receptor antagonist (IL-1RA), the SARS-CoV-2-nucleoprotein (NP) and -spike (S1) proteins and an array of 14 inflammatory cytokines were quantified. Among 777 participants (median age 37 years, 69.5% women), 40 participants (5.1%; 95% confidence interval CI 3.7-7.0%) had elevated hs-cTnT concentration on day 3 and mRNA-1273 vaccine-associated myocardial injury was adjudicated in 22 participants (2.8% 95% CI 1.7-4.3%). Twenty cases occurred in women (3.7% 95% CI 2.3-5.7%), two in men (0.8% 95% CI 0.1-3.0%). Hs-cTnT elevations were mild and only temporary. No patient had electrocardiographic changes, and none developed major adverse cardiac events within 30 days (0% 95% CI 0-0.4%). In the overall booster cohort, hs-cTnT concentrations (day 3; median 5, interquartile range IQR 4-6 ng/L) were significantly higher compared to matched controls (n = 777, median 3 IQR 3-5 ng/L, p < 0.001). Cases had comparable systemic reactogenicity, concentrations of anti-IL-1RA, anti-NP, anti-S1, and markers quantifying systemic inflammation, but lower concentrations of interferon (IFN)-λ1 (IL-29) and granulocyte-macrophage colony-stimulating factor (GM-CSF) versus persons without vaccine-associated myocardial injury.
mRNA-1273 vaccine-associated myocardial injury was more common than previously thought, being mild and transient, and more frequent in women versus men. The possible protective role of IFN-λ1 (IL-29) and GM-CSF warrant further studies.
Aims
Systemic inflammation may be central in the pathophysiology of acute heart failure (AHF). We aimed to assess the possible role of systemic inflammation in the pathophysiology, phenotyping, and ...risk stratification of patients with AHF.
Methods and results
Using a novel Interleukin‐6 immunoassay with unprecedented sensitivity (limit of detection 0.01 ng/L), we quantified systemic inflammation in unselected patients presenting with acute dyspnoea to the emergency department in a multicentre study. One‐year mortality was the primary prognostic endpoint. Among 2042 patients, 1026 (50.2%) had an adjudicated diagnosis of AHF, 83.7% of whom had elevated interleukin‐6 concentrations (>4.45 ng/L). Interleukin‐6 was significantly higher in AHF patients compared to patients with other causes of dyspnoea (11.2 6.1–26.5 ng/L vs. 9.0 3.2–32.3 ng/L, p < 0.0005). Elevated interleukin‐6 concentrations were independently predicted by increasing N‐terminal pro‐B‐type natriuretic peptide and high‐sensitivity cardiac troponin T, as well as the clinical diagnosis of infection. Among the different AHF phenotypes, interleukin‐6 concentrations were highest in patients with cardiogenic shock (25.7 14.0–164.2 ng/L) and lowest in patients with hypertensive AHF (9.3 4.8–21.6 ng/L, p = 0.001). Inflammation as quantified by interleukin‐6 was a strong and independent predictor of 1‐year mortality both in all AHF patients, as well as those without clinically overt infection at presentation (adjusted hazard ratio 95% confidence interval 1.45 1.15–1.83 vs. 1.48 1.09–2.00). The addition of interleukin‐6 significantly improved the discrimination of the BIOSTAT‐CHF risk score.
Conclusion
An unexpectedly high percentage of patients with AHF have subclinical systemic inflammation as quantified by interleukin‐6, which seems to contribute to AHF phenotype and to the risk of death.
An unexpectedly high percentage of acute heart failure (AHF) patients have subclinical systemic inflammation, which can be quantified by interleukin‐6. This novel biomarker seems to contribute to AHF phenotype (left: median interleukin‐6 concentrations among different AHF phenotypes) and to the risk of death (right: Kaplan–Meier curves displaying 1‐year all‐cause mortality). ACS, acute coronary syndrome; HF, heart failure; URL, upper reference limit.
The determinants and prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) among patients with a systemic right ventricle are largely unknown.
Ninety-eight patients from the randomized ...controlled SERVE (Effect of Phosphodiesterase-5 Inhibition With Tadalafil on Systemic Right Ventricular Size and Function) trial were included. The correlation between baseline hs-cTnT concentrations and biventricular volumes and function quantified by cardiac magnetic resonance or cardiac multirow detector computed tomography was assessed by adjusted linear regression models. The prognostic value of hs-cTnT was assessed by adjusted Cox proportional hazards models, survival analysis, and concordance statistics. The primary outcome was time to the composite of clinically relevant arrhythmia, hospitalization for heart failure, or all-cause death. Median age was 39 (interquartile range, 32-48) years, and 32% were women. Median hs-cTnT concentration was 7 (interquartile range, 4-11) ng/L. Coefficients of determination for the relationship between hs-cTnT concentrations and right ventricular end-systolic volume index and right ventricular ejection fraction (RVEF) were +0.368 (
=0.046) and -0.381 (
=0.018), respectively. The sex- and age-adjusted hazard ratio for the primary outcome of hs-cTnT at 2 and 4 times the reference level (5 ng/L) were 2.89 (95% CI, 1.14-7.29) and 4.42 (95% CI, 1.21-16.15), respectively. The prognostic performance quantified by the concordance statistics for age- and sex-adjusted models based on hs-cTnT, right ventricular ejection fraction, and peak oxygen uptake predicted were comparable: 0.71% (95% CI, 0.61-0.82), 0.72% (95% CI, 0.59-0.84), and 0.71% (95% CI, 0.59-0.83), respectively.
Hs-cTnT concentration was significantly correlated with right ventricular ejection fraction and right ventricular end-systolic volume index in patients with a systemic right ventricle. The prognostic accuracy of hs-cTnT was comparable to that of right ventricular ejection fraction and peak oxygen uptake predicted.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03049540.
•H-ficolin at rest, at peak exercise, and 2 h after exercise did not demonstrate diagnostic ability in distinguishing between patients with fCAD versus patients without fCAD.•H-ficolin was not a ...predictor of cardiovascular death and non-fatal myocardial infarction in the overall cohort.•H-ficolin slightly increased during bicycle exercise stress, and decreased to baseline levels 2 h after bicycle stress. Similarly, H-ficolin slightly decreased during pharmacological (adenosine) or combined stress, and returned to baseline levels at 2 h.•H-ficolin was weakly correlated with systolic and diastolic blood pressure.
We aimed to test the diagnostic and prognostic ability of H-ficolin, an initiator of the lectin pathway of the complement system, for functionally relevant coronary artery disease (fCAD), and explore its determinants.
The presence of fCAD was adjudicated using myocardial perfusion imaging single-photon emission tomography and coronary angiography. H-ficolin levels were measured by a sandwich-type immunoassay at rest, peak stress-test, and 2 h after stress-test. Cardiovascular death and non-fatal myocardial infarction were assessed during 5-year follow-up.
Among 1,571 patients (32.3 % women), fCAD was detected in 462 patients (29.4 %). H-ficolin concentration at rest was 18.6 (15.3–21.8) µg/ml in patients with fCAD versus 17.8 (15.4–21.5) µg/ml, p = 0.33, in patients without fCAD, resulting in an AUC of 0.53 (95 %CI 0.48–0.56). During follow-up, 107 patients (6.8 %) had non-fatal myocardial infarction and 99 patients (6.3 %) experienced cardiovascular death. In Cox regression analysis, H-ficolin was not a predictor of events in the overall cohort. Subgroup analysis suggested a potential link between H-ficolin and non-fatal myocardial infarction in patients without fCAD (adjusted HR 1.03, 95 % CI 1.02–1.15, p = 0.005). H-ficolin concentration showed a weak positive correlation with systolic (r = 0.069, p < 0.001) and diastolic blood pressure (r = 0.111, p < 0.001).
H-ficolin concentration did not have diagnostic and/or prognostic value in patients referred for fCAD work-up.
The European Society of Cardiology (ESC) recommends the 0/1-h algorithm for rapid triage of patients with suspected non–ST-segment elevation myocardial infarction (MI). However, its impact on patient ...management and safety when routinely applied is unknown.
This study sought to determine these important real-world outcome data.
In a prospective international study enrolling patients presenting with acute chest discomfort to the emergency department (ED), the authors assessed the real-world performance of the ESC 0/1-h algorithm using high-sensitivity cardiac troponin T embedded in routine clinical care and its associated 30-day rates of major adverse cardiac events (MACE) (the composite of cardiovascular death and MI).
Among 2,296 patients, non–ST-segment elevation MI prevalence was 9.8%. In median, 1-h blood samples were collected 65 min after the 0-h blood draw. Overall, 94% of patients were managed without protocol violations, and 98% of patients triaged toward rule-out did not require additional cardiac investigations including high-sensitivity cardiac troponin T measurements at later time points or coronary computed tomography angiography in the ED. Median ED stay was 2 h and 30 min. The ESC 0/1-h algorithm triaged 62% of patients toward rule-out, and 71% of all patients underwent outpatient management. Proportion of patients with 30-day MACE were 0.2% (95% confidence interval: 03% to 0.5%) in the rule-out group and 0.1% (95% confidence interval: 0% to 0.2%) in outpatients. Very low MACE rates were confirmed in multiple subgroups, including early presenters.
These real-world data document the excellent applicability, short time to ED discharge, and low rate of 30-day MACE associated with the routine clinical use of the ESC 0/1-h algorithm for the management of patients presenting with acute chest discomfort to the ED.
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The study of stool microbiota has taken great relevance in the last years, given its role in the maintenance of the intestinal metabolic, physiological, and immunological homeostasis, as well as, its ...effect over HIV biomarkers levels such as CD4/CD8 ratio, high sensitivity C-Reactive Protein (hs-CRP), related to poor outcomes (rapid progression to AIDS). Several efforts have been made to characterize the gut microbiome. In HIV infection, most of the studies report the presence of a dysbiotic pattern; however, few of them have made an approach in elderly HIV-positive subjects despite the fact that nowadays this subgroup is rising. In this study, we compared the composition of faecal microbiota, Short Chain Fatty Acids (SCFAs), and systemic biomarkers between elderly HIV-positive and HIV-negative subjects.
A cross-sectional study with 18 HIV-negative controls and 20 HIV-positive patients. The quantification of Bacteroidetes, Firmicutes, Proteobacteria, Actinobacteria, Lactobacillus, Enterobacteriaceae, Bifidobacterium, Escherichia coli, Clostridium leptum, Clostridium coccoides was performed in faecal samples by qPCR. The analysis was performed by calculating the ΔCq of each microorganism using 16S rDNA as a reference gene. Faecal SCFAs were measured by HPLC. The hs-CRP and sCD14 were performed by ELISA.
An increase in the Firmicutes/Bacteroidetes ratio, coupled with a significant increase in the proteobacteria phylum was detected in HIV-positive subjects. In contrast, a decrease in the Clostridium leptum group was observed. Nevertheless, these elderly HIV-positive patients showed higher levels of total SCFAs mainly by an augmented propionic acid values, compared to HIV-negative subjects. Whereas high levels of hs-CRP were positively correlated with sCD14 in the HIV-positive group.
Alterations in bacterial communities reveals a dysbiotic state related to an unbalance of faecal SCFAs. Therefore, these intestinal conditions might drive an increase of poor prognostic biomarkers in elderly HIV-positive subjects.
Aims
Cardiac myosin‐binding protein C (cMyC) seems to be even more sensitive in the quantification of cardiomyocyte injury vs. high‐sensitivity cardiac troponin, and may therefore have diagnostic and ...prognostic utility.
Methods and results
In a prospective multicentre diagnostic study, cMyC, high‐sensitivity cardiac troponin T (hs‐cTnT), and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) plasma concentrations were measured in blinded fashion in patients presenting to the emergency department with acute dyspnoea. Two independent cardiologists centrally adjudicated the final diagnosis. Diagnostic accuracy for acute heart failure (AHF) was quantified by the area under the receiver operating characteristic curve (AUC). All‐cause mortality within 360 days was the prognostic endpoint. Among 1083 patients eligible for diagnostic analysis, 51% had AHF. cMyC concentrations at presentation were higher among AHF patients vs. patients with other final diagnoses 72 (interquartile range, IQR 39–156) vs. 22 ng/L (IQR 12–42), P < 0.001). cMyC's AUC was high 0.81, 95% confidence interval (CI) 0.78–0.83, higher than hs‐cTnT's (0.79, 95% CI 0.76–0.82, P = 0.081) and lower than NT‐proBNP's (0.91, 95% CI 0.89–0.93, P < 0.001). Among 794 AHF patients eligible for prognostic analysis, 28% died within 360 days; cMyC plasma concentrations above the median indicated increased risk of death (hazard ratio 2.19, 95% CI 1.66–2.89; P < 0.001). cMyC's prognostic accuracy was comparable with NT‐proBNP's and hs‐cTnT's. cMyC did not independently predict all‐cause mortality when used in validated multivariable regression models. In novel multivariable regression models including medication, age, left ventricular ejection fraction, and discharge creatinine, cMyC remained an independent predictor of death and had no interactions with medical therapies at discharge.
Conclusion
Cardiac myosin‐binding protein C may aid physicians in the rapid triage of patients with suspected AHF.
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