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Abstract Epstein–Barr virus (EBV) reactivation may be involved in long-COVID symptoms, but reactivation of other viruses as a factor has received less attention. Here we evaluated the reactivation of parvovirus-B19 and several members of the Herpesviridae family (DNA viruses) in patients with long-COVID syndrome. We hypothesized that monovalent COVID-19 vaccines inhibit viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome, thereby reducing clinical symptoms. Clinical and laboratory data for 252 consecutive patients with PCR-verified past SARS-CoV-2 infection and long-COVID syndrome (155 vaccinated and 97 non-vaccinated) were recorded during April 2021–May 2022 (median 243 days post-COVID-19 infection). DNA virus–related IgG and IgM titers were compared between vaccinated and non-vaccinated long-COVID patients and with age- and sex-matched non-infected, unvaccinated (pan-negative for spike-antibody) controls. Vaccination with monovalent COVID-19 vaccines was associated with significantly less frequent fatigue and multiorgan symptoms (p

Abstract Aims Left ventricular ejection fraction (LVEF) ≤ 40% is a well‐established risk factor for mortality after acute coronary syndromes (ACS). However, the long‐term prognostic impact of mildly reduced ejection fraction (EF) (LVEF 41–49%) after ACS remains less clear. Methods and results This was a retrospective study enrolling patients admitted with ACS included in a single‐centre databank. LVEF was assessed by echocardiography during index hospitalization. Patients were divided in the following categories according to LVEF: normal (LVEF ≥ 50%), mildly reduced (LVEF 41–49%), and reduced (LVEF ≤ 40%). The endpoint of interest was all‐cause death after hospital discharge. A multivariable Cox model was used to adjust for confounders. A total of 3200 patients were included (1952 with normal EF, 375 with mildly reduced EF, and 873 with reduced EF). The estimated cumulative incidence rates of mortality at 10 years for patients with normal, mildly reduced, and reduced EF were 24.8%, 33.5%, and 41.3%, respectively. After adjustments, the presence of reduced EF was associated with higher mortality compared with normal EF [adjusted hazard ratio (HR) 1.64; 95% confidence interval (CI) 1.36–1.96; P

Abstract Aims We aim to explore the relationship of heart failure (HF) and diabetes with cardiovascular (CV) death or hospitalization for HF (HHF) and to study the clinical utility of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) in an unselected patient population with atrial fibrillation (AF). Methods and results Patients with AF admitted to a tertiary academic center between January 2005 and July 2019 were identified through a search of electronic health records. We used Cox regression models adjusted for age, sex, estimated glomerular filtration rate, diabetes, HF, body mass index, prior myocardial infarction, coronary artery disease, hypertension, smoking, C‐reactive protein, and low‐density lipoprotein cholesterol. To select the most informative variables, we performed a least absolute shrinkage and selection operator Cox regression with 10‐fold cross‐validation. In total, 7412 patients (median age 70 years, 39.7% female) were included in this analysis and followed over a median of 4.5 years. Both diabetes [adjusted (Adj.) HR 1.87, 95% CI 1.55–2.25] and HF (Adj. HR 2.57, 95% CI 2.22–2.98) were significantly associated with CV death/HHF after multivariable adjustment. Compared with patients with diabetes, HF patients had a higher risk of HHF but a similar risk of CV and all‐cause death. NT‐proBNP showed good discriminatory performance (area under the curve 0.78, 95% CI 0.77–0.80) and the addition of NT‐proBNP to the covariates used for adjustment resulted in a significant area under the curve improvement (Δ = 0.04, P

Background Fibroblast growth factor 23 (FGF‐23) is crucial in regulating phosphate and vitamin D metabolism and is moreover associated with an increased cardiovascular risk. The specific objective of this study was to investigate the influence of FGF‐23 on cardiovascular outcomes, including hospitalization for heart failure (HHF), postoperative atrial fibrillation, and cardiovascular death, in an unselected patient population after cardiac surgery. Methods and Results Patients undergoing elective coronary artery bypass graft and/or cardiac valve surgery were prospectively enrolled. FGF‐23 blood plasma concentrations were assessed before surgery. A composite of cardiovascular death/HHF was chosen as primary end point. A total of 451 patients (median age 70 years; 28.8% female) were included in the present analysis and followed over a median of 3.9 years. Individuals with higher FGF‐23 quartiles showed elevated incidence rates of the composite of cardiovascular death/HHF (quartile 1, 7.1%; quartile 2, 8.6%; quartile 3, 15.1%; and quartile 4, 34.3%). After multivariable adjustment, FGF‐23 modeled as a continuous variable (adjusted hazard ratio for a 1‐unit increase in standardized log‐transformed biomarker, 1.82 [95% CI, 1.34–2.46]) as well as using predefined risk groups and quartiles remained independently associated with the risk of cardiovascular death/HHF and the secondary outcomes, including postoperative atrial fibrillation. Reclassification analysis indicated that the addition of FGF‐23 to N‐terminal pro‐B‐type natriuretic peptide provides a significant improvement in risk discrimination (net reclassification improvement at the event rate, 0.58 [95% CI, 0.34–0.81]; P

Soluble (s)ST2 has been proposed as a useful biomarker for heart failure (HF) patient management. Myocardial damage or mechanical stress stimulate sST2 release. ST2 competes with a membrane bound receptor (ST2 ligand, or ST2L) for interleukin-33 (IL-33) binding, inhibiting the effects induced by the ST2L/IL-33 interaction so that excessive sST2 may contribute to myocardial fibrosis and ventricular remodeling. Compared to natriuretic peptides (NPs), sST2 concentration is not substantially affected by age, sex, body mass index, kidney function, atrial fibrillation, anemia, or HF etiology, and has low intra-individual variation. Its prognostic role as an independent marker is well reported in the literature. However, there is a gap on its use in combination with NPs, currently the only biomarkers recommended by European and American guidelines for HF management. Reflecting the activation of two distinct biological systems, a benefit from the use of sST2 and NP in combination is advocated. The aim of this review is to report the current scientific knowledge on sST2 in the acute and chronic HF settings with a particular attention to its additive role to natriuretic peptides (NPs).

Objectives This study aimed to estimate and compare the prevalence of the virus-specific antibodies against the SARS-CoV-2 nucleoprotein antigen (anti-SARS-CoV-2 N) in healthcare workers and an all-comer paediatric and adult patient population.Design, setting and participants A longitudinal study enrolling healthcare professionals and concurrent serial cross-sectional studies of unselected all-comer patients were conducted at an Austrian academic medical centre. Healthcare workers were tested at enrolment and after 1, 2, 3, 6 and 12 months. The cross-sectional studies in patients were conducted at three time periods, which roughly coincided with the times after the first, second and third wave of SARS-CoV-2 in Austria (ie, 24 August–7 September 2020; 8–22 February 2021 and 9–23 November 2021). Anti-SARS-CoV-2 N antibodies were measured using a sandwich electrochemiluminescence assay (Roche).Results In total, 2735 and 9275 samples were measured in 812 healthcare workers (median age: 40 years, 78% female) and 8451 patients (median age: 55 years, 52% female), respectively. Over the entire study period, anti-SARS-CoV-2 N antibodies were detected in 98 of 812 healthcare workers, resulting in a seroprevalence of 12.1% (95% CI 10.0% to 14.5%), which did not differ significantly (p=0.63) from that of the all-comer patient population at the end of the study period (407/3184; 12.8%, 95% CI 11.7% to 14.0%). The seroprevalence between healthcare workers and patients did not differ significantly at any time and was 1.5-fold to 2-fold higher than the number of confirmed cases in Austria throughout the pandemic. In particular, there was no significant difference in the seroprevalence between paediatric and adult patients at any of the tested time periods.Conclusion Throughout the pandemic, healthcare staff and an adult and paediatric all-comer patient population had similar exposure to SARS-CoV-2.Trial registration number ClinicalTrials.gov Identifier: NCT04407429.

Abstract Biomarkers that reflect hemodynamic stress, inflammation, extracellular matrix remodeling, angiogenesis, and endothelial dysfunction may improve risk stratification and add valuable pathobiological insight in patients with out-of-hospital cardiac arrest (OHCA). In total, 120 patients with OHCA who survived at least 48 h after return of spontaneous circulation were consecutively included in the present analysis. Concentrations of 30 biomarkers were measured simultaneously using a multi-panel biomarker assay. Cox regression models were adjusted for age, sex, estimated glomerular filtration rate, lactate concentration, bystander resuscitation, initial cardiac rhythm, and type of targeted temperature management. Overall, 57 patients (47.5%) had a favorable neurological outcome (Cerebral Performance Category ≤ 2) at 30 days, while palliative care was initiated in 49 patients (40.8%), and 52 patients (43.3%) died. After correction for multiple testing with Bonferroni-Holm, 8 biomarkers (including Angiopoietin-2, Procalcitonin, Resistin, IL-4Rα, MMP-8, TNFα, Renin, and IL-1α) were significantly associated with all-cause death. After multivariable adjustment, only angiopoietin-2 (Adjusted (Adj) hazard ratio (HR) per 1-unit increase in standardized biomarker concentrations 1.52 (95% CI 1.16–1.99)) and renin (Adj HR 1.32 (95% CI 1.06–1.65) remained independently associated with an increased risk of death. The discriminatory performance indicated good performance for angiopoietin-2 (area under the curve (AUC): 0.75 (95% CI 0.66–0.75) and was significantly higher (P = 0.011) as compared with renin (AUC: 0.60, 95% CI 0.50–0.60). In conclusion, angiopoietin-2 was significantly associated with all-cause mortality in patients with OHCA who survived the first 48 h and may prove to be useful for risk stratification of these patients.

Patients with type 2 diabetes are at increased risk of developing heart failure, cardiovascular death and renal failure. The recent results of three large sodium-glucose cotransporter 2 inhibitor cardiovascular outcomes trials have demonstrated a reduction in heart failure hospitalisation and progressive renal failure. One trial also showed a fall in cardiovascular and total death. A broad spectrum of patients with diabetes benefit from these salutary effects in cardiac and renal function and so these trials have important implications for the management of patients with type 2 diabetes. Selected glucagon-like peptide 1 receptor agonists have also been shown to reduce adverse cardiovascular outcomes.

Background Plasma omega‐3 polyunsaturated fatty acids (ω3‐PUFAs) have been shown to be inversely correlated with the risk of cardiovascular death in primary prevention. The risk relationship in the setting of an acute coronary syndrome is less well established. Methods and Results Baseline plasma ω3‐PUFA composition (α‐linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) was assessed through gas chromatography with flame ionization detection in a case‐cohort study involving 203 patients with cardiovascular death, 325 with myocardial infarction, 271 with ventricular tachycardia, and 161 with atrial fibrillation, and a random sample of 1612 event‐free subjects as controls from MERLIN‐TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST‐Elevation‐Acute Coronary Syndrome–Thrombolysis in Myocardial Infarction 36), a trial of patients hospitalized with non–ST‐segment–elevation ‐acute coronary syndrome. After inverse‐probability‐weighted multivariable adjustment including all traditional risk factors, a higher relative proportion of long‐chain ω3‐PUFAs (eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid) were associated with 18% lower odds of cardiovascular death (adjusted [adj] odds ratio [OR] per 1 SD, 0.82; 95% CI, 0.68–0.98) that was primarily driven by 27% lower odds of sudden cardiac death (adj OR per 1 SD, 0.73; 95% CI, 0.55–0.97). Long‐chain ω3‐PUFA levels in the top quartile were associated with 51% lower odds of cardiovascular death (adj OR 0.49; 95% CI, 0.27–0.86) and 63% lower odds of sudden cardiac death (adj OR, 0.37; 95% CI, 0.16–0.56). An attenuated relationship was seen for α‐linolenic acid and subsequent odds of cardiovascular (adj OR, 0.92; 95% CI, 0.74–1.14) and sudden cardiac death (adj OR, 0.91; 95% CI, 0.67–1.25). No significant relationship was observed between any ω3‐PUFAs and the odds of cardiovascular death unrelated to sudden cardiac death, myocardial infarction, atrial fibrillation, or early post‐acute coronary syndrome ventricular tachycardia. Conclusions In patients after non–ST‐segment–elevation‐acute coronary syndrome, plasma long‐chain ω3‐PUFAs are inversely associated with lower odds of sudden cardiac death, independent of traditional risk factors and lipids. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00099788.

Background: This study explores the application of CardioSecur® (CS-ECG), a hand-held 4-electrode/22-lead ECG-device, in comparison with conventional 12-lead electrocardiogram (c12L-ECG) in patients with acute chest pain in the prehospital emergency setting.Methods: CS-ECG systems were provided for two physician-staffed emergency ambulances and parallel recordings of c12L-ECG and CS-ECG were obtained from all patients with acute chest pain. Treating emergency physicians were asked to evaluate the CS-ECG system with a standardized questionnaire. Following study completion, acquired ECGs were analyzed separately by two independent cardiologists blinded to all other medical records.Results: Over a period of 20 months a total of 203 patients were included in our study. According to a standardized questionnaire, 79% of emergency medical professionals preferred application of CS-ECG, with 87% of teams judging CS-ECG to be beneficial for patients. Morover, 79% of physicians reported a reduction in time to definitive diagnosis with implementation of CS-ECG. The majority of professional users attested user-friendliness and feasibility of CS-ECG in terms of easy general handling (94%), application (93%), and placement of electrodes (98%). During prehospital triage, both c12L-ECG and CS-ECG correctly identified 31 (91%) patients with ST-elevation myocardial infarction (STEMI).Conclusion: In this first pilot study, implementation of the CardioSecur®-ECG system in the prehospital emergency setting demonstrated feasibility and user-friendliness so that emergency teams generally preferred CS-ECG to c12L-ECG. Diagnostic yield of CS-ECG was similar to c12L-ECG recordings.

Background Small studies have suggested an association between markers of collagen turnover and adverse outcomes in heart failure (HF). We examined C‐terminal telopeptide (beta‐CTx) and the risk of cardiovascular death or new or worsening HF in non–ST‐elevation acute coronary syndrome. Methods and Results We measured baseline serum beta‐CTx, NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), hsTnT (high‐sensitivity cardiac troponin T) and hsCRP (high‐sensitivity C‐reactive protein) (Roche Diagnostics) in a nested biomarker analysis (n=4094) from a study of patients with non–ST‐elevation acute coronary syndrome. The relationship between quartiles of beta‐CTx and cardiovascular death or HF over a median follow‐up time of 12 months was analyzed using adjusted Cox models. Higher beta‐CTx levels identified a significantly higher risk of cardiovascular death/HF (Q4 10.9% versus Q1 3.8%, Logrank P