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Supplemental Digital Content is Available in the Text.Diastolic dysfunction (DD) in heart failure is associated with increased myocardial cytosolic calcium and calcium-efflux through the sodium–calcium exchanger depends on the sodium gradient. Beta-3-adrenoceptor (β3-AR) agonists lower cytosolic sodium and have reversed organ congestion. Accordingly, β3-AR agonists might improve diastolic function, which we aimed to assess. In a first-in-man, randomized, double-blinded trial, we assigned 70 patients with HF with reduced ejection fraction, New York Heart Association II-III, and left ventricular ejection fraction <40% to receive the β3-AR agonist mirabegron (300 mg/day) or placebo for 6 months, in addition to recommended heart failure therapy. We performed echocardiography and cardiac computed tomography and measured N-terminal probrain natriuretic peptide at baseline and follow-up. DD was graded per multiple renowned algorithms. Baseline and follow-up data were available in 57 patients (59 ± 11 years, 88% male, 49% ischemic heart disease). No clinically significant changes in diastolic measurements were found within or between the groups by echocardiography (E/e′ placebo: 13 ± 7 to 13 ± 5, P= 0.21 vs. mirabegron: 12 ± 6 to 13 ± 8, P= 0.74, between-group follow-up difference 0.2 [95% CI, −3 to 4], P= 0.89) or cardiac computed tomography (left atrial volume index: between-group follow-up difference 9 mL/m2[95% CI, −3 to 19], P= 0.15). DD gradings did not change within or between the groups following 2 algorithms (P= 0.72, P= 0.75). N-terminal probrain natriuretic peptide remained unchanged in both the groups (P= 0.74, P= 0.64). In patients with HF with reduced ejection fraction, no changes were identified in diastolic measurements, gradings or biomarker after β3-AR stimulation compared with placebo. The findings add to the previous literature questioning the role of impaired Na+-Ca2+–mediated calcium export as a major culprit in DD. NCT01876433.

Abdominal aortic aneurysm (AAA) is a common disease with substantial heritability. In this study, we performed a genome-wide association meta-analysis from 14 discovery cohorts and uncovered 141 independent associations, including 97 previously unreported loci. A polygenic risk score derived from meta-analysis explained AAA risk beyond clinical risk factors. Genes at AAA risk loci indicate involvement of lipid metabolism, vascular development and remodeling, extracellular matrix dysregulation and inflammation as key mechanisms in AAA pathogenesis. These genes also indicate overlap between the development of AAA and other monogenic aortopathies, particularly via transforming growth factor β signaling. Motivated by the strong evidence for the role of lipid metabolism in AAA, we used Mendelian randomization to establish the central role of nonhigh-density lipoprotein cholesterol in AAA and identified the opportunity for repurposing of proprotein convertase, subtilisin/kexin-type 9 (PCSK9) inhibitors. This was supported by a study demonstrating that PCSK9loss of function prevented the development of AAA in a preclinical mouse model.

AbstractBackground:An interatrial communication is present in most neonates. The majority are considered the “normal” patency of the oval foramen, while a minority are abnormal atrial septal defects. Differentiation between the two with transthoracic echocardiography may be challenging, and no generally accepted method of classification is presently available. We aimed to develop and determine the reliability of a new classification of interatrial communications in newborns.Methods and Results:An algorithm was developed based on echocardiographic criteria from 495 newborns (median age 11[8;13] days, 51.5% females). The algorithm defines three main categories: patency of the oval foramen, atrial septal defect, and no interatrial communication as well as several subtypes. We found an interatrial communication in 414 (83.6%) newborns. Of these, 386 (93.2%) were categorised as patency of the oval foramen and 28 (6.8%) as atrial septal defects.Echocardiograms from another 50 newborns (median age 11[8;13] days, 36.0% female), reviewed by eight experts in paediatric echocardiography, were used to assess the inter- and intraobserver variation of classification of interatrial communications into patency of the oval foramen and atrial septal defect, with and without the use of the algorithm. Review with the algorithm gave a substantial interobserver agreement (kappa = 0.66), and an almost perfect intraobserver agreement (kappa = 0.82). Without the use of the algorithm, the interobserver agreement between experienced paediatric cardiologists was low (kappa = 0.20).Conclusion:A new algorithm for echocardiographic classification of interatrial communications in newborns produced almost perfect intraobserver and substantial interobserver agreement. The algorithm may prove useful in both research and clinical practice.

Despite the success of mRNA-based vaccines against infectious diseases (including COVID-19), safety concerns have been raised relating to the lipid nanoparticles (LNPs) used to deliver the mRNA cargo. Antibodies against the polyethylene glycol (PEG) coating on these non-viral vectors are present in the general population and can in some instances induce allergic reactions. Furthermore, treatment with PEGylated therapeutics may increase the plasma concentration of such anti-PEG antibodies. The widespread use of PEGylated nanoparticles for mRNA vaccines concerns researchers and clinicians about a potential rise in future cases of allergic reactions against mRNA vaccines and cross-reactions with other PEGylated therapeutics. To determine if vaccination with Comirnaty increased the plasma concentration of antibodies against LNPs, we investigated the blood plasma concentration of anti-LNP antibodies in healthy individuals before and after vaccination with the mRNA-based COVID-19 vaccine Comirnaty (BNT162b2). Blood samples were acquired from 21 healthy adults before vaccination, 3–4 weeks after the first vaccination dose but before the second dose, and 2–6 months after the second (booster) dose. The blood plasma concentration of antibodies recognizing the LNPs was analyzed using a microscopy-based assay capable of measuring antibody-binding to individual authentic LNPs. No significant increase in anti-LNP antibodies was observed after two doses of Comirnaty. The LNPs used for intramuscular delivery of mRNA in the vaccine against COVID-19, Comirnaty, do, therefore, not seem to induce the generation of anti-vector antibodies.

We report a genome-wide association study of venous thromboembolism (VTE) incorporating 81,190 cases and 1,419,671 controls sampled from six cohorts. We identify 93 risk loci, of which 62 are previously unreported. Many of the identified risk loci are at genes encoding proteins with functions converging on the coagulation cascade or platelet function. A VTE polygenic risk score (PRS) enabled effective identification of both high- and low-risk individuals. Individuals within the top 0.1% of PRS distribution had a VTE risk similar to homozygous or compound heterozygous carriers of the variants G20210A (c.*97 G > A) in F2and p.R534Q in F5. We also document that F2and F5mutation carriers in the bottom 10% of the PRS distribution had a risk similar to that of the general population. We further show that PRS improved individual risk prediction beyond that of genetic and clinical risk factors. We investigated the extent to which venous and arterial thrombosis share clinical risk factors using Mendelian randomization, finding that some risk factors for arterial thrombosis were directionally concordant with VTE risk (for example, body mass index and smoking) whereas others were discordant (for example, systolic blood pressure and triglyceride levels).

ABSTRACTDoping is claimed to create a negative image of sport, and of professional cycling in particular. Yet few studies have investigated interrelations between doping and sponsorships. Thus, this study aims to answer the question: How do company representatives make sense of sponsoring a sport like cycling with its dubious doping image? Theoretically informed by a sensemaking perspective and the strategy-as-practice approach, this interpretive study draws on sixteen semi-structured interviews with managers who, in the period between 1998 and 2016, were engaged in sponsoring professional Danish cycling. Findings reveal that cycling is more than just a sport with a dubious image as multiple frames such as sporting levels, existing business landscapes, personal interests and sport-for-all practices influence managers’ sensemaking. Furthermore, doping occasionally creates an advantage for sponsors. Accordingly, the study contributes to a research field dominated by quantitative marketing methodologies.

IMPORTANCE: Observational studies have indicated that glasses might protect against contracting COVID-19 through reduced airborne and contact transmission. OBJECTIVE: To investigate the association between wearing one’s own glasses with contracting COVID-19 when adjusting for relevant confounders. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted during the first wave of the COVID-19 pandemic (June to August 2020) in Denmark and Sweden, where personal protective equipment was not recommended for the general population at the time. Employees at Falck, an international rescue corps with different job functions (ambulance, health care, office, and field staff, firefighters, and roadside assistance) participated in the study. EXPOSURES: The main exposure was wearing glasses (also including contact lenses and reading glasses), which was assessed in a questionnaire. Persons wearing glasses were compared with those who did not wear glasses (ie, nonusers). To adjust for potential confounders, information on age, sex, job function, and number of workday contacts were included. MAIN OUTCOMES AND MEASURES: The outcome was COVID-19 infection before (positive polymerase chain reaction test) or during the study period (biweekly voluntary tests with a rapid test). The investigated hypothesis was formulated after collecting the data. RESULTS: A total of 1279 employees in Denmark and 841 in Sweden were included (839 [39.6%] female and 1281 [60.4%] male; 20.5% were aged &lt;40 years; 57.0%, 40-60 years, and 22.5%, >60 years). Of these, 829 individuals (64.8%) in Denmark and 619 (73.6%) in Sweden wore glasses. Wearing glasses was inversely associated with COVID-19 infection in the Swedish cohort (odds ratio [OR], 0.61 [95% CI, 0.37-0.99]; P = .047; seroprevalence, 9.3%) but not in the Danish cohort (OR, 1.14 [95% CI, 0.53-2.45]; P = .73; seroprevalence, 2.4%). Adjusting for age, sex, job function, and number of workday contacts in Sweden, wearing glasses no longer was associated with COVID-19 infection (OR, 0.64 [95% CI, 0.37-1.11]; P = .11). When stratifying by job function, a large difference was observed among office staff (OR, 0.20 [95% CI, 0.06-0.70]; P = .01) but not ambulance staff (OR, 0.83 [95% CI, 0.41-1.67]; P = .60) nor health care staff (OR, 0.89 [95% CI, 0.35-2.30]; P = .81). CONCLUSIONS AND RELEVANCE: While wearing one’s glasses was inversely associated with COVID-19 in Sweden in an unadjusted analysis, an association no longer was identified when adjusting for confounders. These results provide inconclusive findings regarding whether wearing one’s own glasses is associated with a decreased risk of COVID-19 infections.

ObjectiveTo assess the prevalence and severity of anaemia in patients with left-sided infective endocarditis (IE) and association with mortality.MethodsIn the Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis trial, 400 patients with IE were randomised to conventional or partial oral antibiotic treatment after stabilisation of infection, showing non-inferiority. Haemoglobin (Hgb) levels were measured at randomisation. Primary outcomes were all-cause mortality after 6 months and 3 years. Patients who underwent valve surgery were excluded due to competing reasons for anaemia.ResultsOut of 400 patients with IE, 248 (mean age 70.6 years (SD 11.1), 62 women (25.0%)) were medically managed; 37 (14.9%) patients had no anaemia, 139 (56.1%) had mild anaemia (Hgb <8.1 mmol/L in men and Hgb <7.5 mmol/L in women and Hgb ≥6.2 mmol/L) and 72 (29.0%) had moderate to severe anaemia (Hgb <6.2 mmol/L). Mortality rates in patients with no anaemia, mild anaemia and moderate to severe anaemia were 2.7%, 3.6% and 15.3% at 6-month follow-up and 13.5%, 20.1% and 34.7% at 3-year follow-up, respectively. Moderate to severe anaemia was associated with higher mortality after 6 months (HR 4.81, 95% CI 1.78 to 13.0, p=0.002) and after 3 years (HR 2.14, 95% CI 1.27 to 3.60, p=0.004) and remained significant after multivariable adjustment.ConclusionModerate to severe anaemia was present in 29% of patients with medically treated IE after stabilisation of infection and was independently associated with higher mortality within the following 3 years. Further investigations are warranted to determine whether intensified treatment of anaemia in patients with IE might improve outcome.

Glucagon and glucagon-like peptide-1 (GLP-1) originate from the common precursor, proglucagon, and their plasma concentrations have been reported to be increased during inflammatory conditions. Increased blood glucose levels are frequently observed in septic patients, and therefore we hypothesized that glucagon, but not GLP-1, is increased in individuals with inflammation.Prospective longitudinal cohort study.We measured glucagon and GLP-1 in plasma sampled consecutively in three cohorts consisting of patients with infective endocarditis (n= 16), urosepsis (n= 28) and post-operative inflammation following percutaneous aortic valve implantation or thoracic endovascular aortic repair (n= 5). Correlations between C-reactive protein (CRP), a marker of systemic inflammation, and glucagon and GLP-1 concentrations were investigated. Additionally, glucagon and GLP-1 concentrations were measured after a bolus infusion of lipopolysaccharide (LPS, 1 ng/kg) in nine healthy young males.Glucagon and CRP were positively and significantly correlated (r = 0.27; P= 0.0003), whereas no significant association between GLP-1 and CRP was found (r = 0.08, P= 0.30). LPS infusion resulted in acute systemic inflammation reflected by increased temperature, pulse, tumor necrosis factor-α (TNFα), interleukin-6 (IL-6) and concomitantly increased concentrations of glucagon (P< 0.05) but not GLP-1.Systemic inflammation caused by bacterial infections or developed as a non-infected condition is associated with increased plasma concentration of glucagon, but not GLP-1. Hyperglucagonemia may contribute to the impaired glucose control in patients with systemic inflammatory diseases.

Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to support clinical diagnosis and epidemiological investigations. Recently, assays for large-scale detection of total antibodies (Ab), immunoglobulin G (IgG), and IgM against SARS-CoV-2 antigens have been developed, but there are limited data on the diagnostic accuracy of these assays.

AbstractBackground:Amino-terminal-pro-B-type-natriuretic-peptide (NT-proBNP) is a diagnostic biomarker for heart failure (HF), but plasma concentrations are influenced by numerous factors. Mid-regional-pro-atrial-natriuretic-peptide (MR-proANP) have comparable diagnostic value in acute HF. However, data are lacking in the non-acute setting. This study sought to assess the diagnostic utility of MR-proANP in outpatients with a high risk of HF.Methods:This prospective study included 399 outpatients. Inclusion criteria were: age ≥ 60 years, ≥1 risk factor for HF (diabetes, chronic kidney disease, vascular disease, atrial fibrillation, hypertension), without known or suspected HF. Unrecognized HF was diagnosed based on clinical signs, patient-reported symptoms and echocardiography. Plasma concentrations of MR-proANP and NT-proBNP were analysed.Results:In total, 65 patients were diagnosed with HF or asymptomatic left ventricular systolic dysfunction (N = 12 LVEF ≤ 40%, N = 7 LVEF > 40% to ≤50%, N = 46 LVEF > 50%). Both MR-proANP (odds-ratio: 1.77; 95% CI:1.16–2.72; p = 0.009) and NT-proBNP (odds-ratio: 1.49; 95% CI:1.22–1.82; p < 0.001) were associated with HF. Area under receiver-operator characteristics curve (AUC) for the diagnosis of HF or asymptomatic left ventricular systolic dysfunction was higher for MR-proANP (AUC = 0.886; p < 0.001) and NT-proBNP (AUC = 0.910; p < 0.001) compared to patient-reported symptoms of HF (AUC = 0.830), but NT-proBNP added more diagnostic information compared to MR-proANP (p = 0.022).Conclusions:Both NT-proBNP and MR-proANP are useful biomarkers in the diagnosis of HF or asymptomatic left ventricular systolic dysfunction in a non-acute setting. However, NT-proBNP added more diagnostic information compared to MR-proANP.

Fibroblast growth factor 23 (FGF23) is known to cause left ventricular hypertrophy (LVH), but controversy exists concerning its effect in dialysis. This study evaluated associations between FGF23 levels, echocardiography and prognosis in patients on hemodialysis (HD).

Fibroblast growth factor 23 (FGF23) is known to cause left ventricular hypertrophy (LVH), but controversy exists concerning its effect in dialysis. This study evaluated associations between FGF23 levels, echocardiography and prognosis in patients on hemodialysis (HD).

ObjectiveTo compare the Danish Emergency Process Triage (DEPT) with a quick clinical assessment (Eyeball triage) as predictors of short-term mortality in patients in the emergency department (ED).MethodsThe investigation was designed as a prospective cohort study conducted at North Zealand University Hospital. All patient visits to the ED from September 2013 to December 2013 except minor injuries were included. DEPT was performed by nurses. Eyeball triage was a quick non-systematic clinical assessment based on patient appearance performed by phlebotomists. Both triage methods categorised patients as green (not urgent), yellow, orange or red (most urgent). Primary analysis assessed the association between triage level and 30-day mortality for each triage method. Secondary analyses investigated the relation between triage level and 48-hour mortality as well as the agreement between DEPT and Eyeball triage.ResultsA total of 6383 patient visits were included. DEPT was performed for 6290 (98.5%) and Eyeball triage for 6382 (~100%) of the patient visits. Only patients with both triage assessments were included. The hazard ratio (HR) for 48-hour mortality for patients categorised as yellow was 0.9 (95% CI 0.4 to 1.9) for DEPT compared with 4.2 (95% CI 1.2 to 14.6) for Eyeball triage (green is reference). For orange the HR for DEPT was 2.2 (95% CI 1.1 to 4.4) and 17.1 (95% CI 5.1 to 57.1) for Eyeball triage. For red the HR was 30.9 (95% CI 12.3 to 77.4) for DEPT and 128.7 (95% CI 37.9 to 436.8) for Eyeball triage. For 30-day mortality the HR for patients categorised as yellow was 1.7 (95% CI 1.2 to 2.4) for DEPT and 2.4 (95% CI 1.6 to 3.5) for Eyeball triage. For orange the HR was 2.6 (95% CI 1.8 to 3.6) for DEPT and 7.6 (95% CI 5.1 to 11.2) for Eyeball triage, and for red the HR was 19.1 (95% CI 10.4 to 35.2) for DEPT and 27.1 (95% CI 16.9 to 43.5) for Eyeball triage. Agreement between the two systems was poor (kappa 0.05).ConclusionAgreement between formalised triage and clinical assessment is poor. A simple clinical assessment by phlebotomists is superior to a formalised triage system to predict short-term mortality in ED patients.

AbstractPurpose:This study aimed to determine serum YKL-40 in patients with end-stage renal disease (ESRD) on haemodialysis (HD) and to evaluate the prognostic value of serum YKL-40.Methods:Patients >18 years on maintenance HD were included. Serum YKL-40 was measured using ELISA before and after a single HD treatment.Results:A total of 306 patients were included. Median serum YKL-40 concentration was 238 µgL−1(IQR: 193–291 µgL−1) before HD treatment and 198 µgL−1(IQR: 147–258 µgL−1) after HD treatment, which corresponded to age-corrected 93th percentile in healthy subjects. All-cause mortality after 2.8 years was 35.9%. Patients with serum YKL-40 in the highest quartile compared with the lowest quartile had a univariate HR of 4.0 (95% CI: 2.2–7.3, p < 0.001) for all-cause mortality which decreased to 2.4 (95% CI: 1.1–4.5, p = 0.01) in multivariate analysis. Time-dependent receiver operating characteristic curves showed that serum YKL-40 after HD treatment had significant higher area under the curves from 90 d (p = 0.004) and throughout the rest of the follow-up period when compared to serum YKL-40 before HD treatment.Conclusion:YKL-40 was highly elevated in patients with ESRD on HD, and dialysis reduced serum YKL-40 concentrations approximately one-sixth. YKL-40 measured after dialysis was independently associated with mortality in HD patients.

AbstractBackground:Cardiac-specific troponin T (cTnT) and troponin I (cTnI) are considered diagnostically equal in patients with acute coronary syndrome (ACS). The aim of this systematic review was to compare the prevalence and prognostic strength of elevations of cTnT and cTnI in patients with other conditions than ACS.Methods:A systemic review was conducted in concordance with the PRISMA guidelines. The studies were identified by searching PubMed, EMBASE and Cochrane Central Register, from May to August 2016. Studies measuring both cTnT and cTnI in populations without ACS were eligible.Results:Twenty-nine studies were included (n = 25,859). Seventeen studies reported on prognostic information with follow-up time ranging for 30 d–5 years. Elevation above the 99th percentile (reference value for a healthy population) in non-ACS population was reported to be 0–39% for cTnI and 40–100% for cTnT. Elevation of cTnT tends to be a superior predictor for all-cause mortality and elevation of cTnI tends to be a superior predictor for cardiovascular related mortality.Discussion:In the absence of ACS, elevation of cTnT is more frequent than elevation of cTnI.Conclusion:Both cTnT and cTnI elevations have important prognostic information regarding morbidity, cardiac mortality and all-cause mortality.

Introduction:Preeclampsia is a multifactorial disease and a cause of maternal and neonatal morbidity and mortality. Women with preeclampsia have increased risk of cardiovascular diseases in later life. The impact on the offspring is, however, still uncertain. Lipid traits in newborns are considered to reflect the child’s own production.Hypothesis:We assessed the hypothesis that preeclampsia increases risk of future cardiovascular disease in both mother and offspring.Methods:For this purpose, we used the Copenhagen General Population Study comprising 59,571 women of which 1,365 had a diagnosis of preeclampsia to investigate the association between preeclampsia and risk of cardiovascular diseases. Further, we used the Copenhagen Baby Heart Study comprising more than 13,000 umbilical cord blood samples and assessed the impact of preeclampsia on atherogenic lipid traits in cord blood.Results:Age adjusted hazard ratios for preeclampsia versus no preeclampsia (95% CI) were 1.48 (1.13-1.94) for ischemic heart disease, 1.50 (1.07-2.12) for ischemic cerebrovascular disease, and 1.53 (1.22-1.91) for composite vascular disease. Corresponding multivariable adjusted hazard ratios (95% CI) were 1.31 (1.00-1.72), 1.44 (1.02-2.02), and 1.39 (1.11-1.74). Concentrations of non-HDL cholesterol, total cholesterol, LDL cholesterol, apolipoprotein B, and triglycerides in cord blood increased stepwise from no preeclampsia (n=11,221) to mild/moderate preeclampsia (n=253) to severe preeclampsia (n=104) (p for trends <0.0001 for non-HDL cholesterol, total cholesterol and LDL cholesterol; p for trend=0.0002 for apolipoprotein B; p for trend=0.003 for triglycerides). Multivariable adjusted odds ratios (95% CI) for preeclampsia versus no preeclampsia (reference) for cord blood concentrations above the 80thpercentile were 2.09 (1.67-2.61) for non-HDL cholesterol, 1.58 (1.25-2.01) for total cholesterol, 1.72 (1.37-2.16) for LDL cholesterol, 1.38 (1.07-1.78) for apolipoprotein B, and 2.64 (2.07-3.35) for triglycerides.Conclusion:Women with preeclampsia had increased risk of future cardiovascular disease and lipid traits in umbilical cord blood of their offspring were elevated. This indicates that preeclampsia affects lipid metabolism during fetal life and potentially contributes to an increased risk of future cardiovascular disease in offspring of mothers with preeclampsia.

Purpose: ß2-Agonists are widely used for relief of respiratory symptoms. Studies so far have reported conflicting results regarding use of ß2-agonists and risk of myocardial infarction (MI). Yet, coronary angiographical data and longitudinal outcomes data are sparse and could help explain if there is an association between use of ß2-agonists and MI.Methods: Using a novel data-linkage of the Eastern Danish Heart Registry and nationwide administrative registries we identified a cohort of patients referred for acute coronary angiography due to ST-elevation MI (STEMI). Clinical and angiographical findings were compared between ß2-agonist users and non-users.Results: Among 66,234 patients undergoing coronary angiography, 9857 patients had STEMI. Of these, 933 (9%) patients used ß2-agonists. ß2-Agonist users were more often without significant coronary stenosis (15% in ß2-agonist users vs 9% in non-users; p<0.0001), odds ratio (OR) 1.68 (95% confidence interval (CI) 1.37–2.07; p<0.0001). The association was correlated to the number of filled prescriptions. One prescription: OR=1.00 (CI 95% 0.66–1.50; p=1.00)), 2–5 prescriptions: OR= 2.02 (CI 95% 1.47–2.78; p<0.0001), more than five prescriptions: OR=2.30 (CI 95% 1.69–3.12; p<0.0001). All-cause mortality during up to 14 years of follow-up was significantly higher among the ß2-agonist-user group compared to the non-user group (34% vs 23%; p<0.0001), hazard ratio 1.36, 95% CI 1.18–1.56; p<0.0001).Conclusion: Among patients referred to urgent coronary angiography for STEMI, use of ß2-agonists was associated with a lower frequency of significant coronary stenosis and a higher mortality compared with non-users.

No medical treatment has been reliably shown to halt or reverse disease progression in hypertrophic cardiomyopathy, but the results of several pilot studies have suggested beneficial effects of angiotensin II receptor blockers on left ventricular hypertrophy and fibrosis, which are predictive of an adverse outcome. We aimed to assess the effect of the angiotensin II receptor blocker losartan on left ventricular hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy.

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AbstractObjective: The aim was to assess serial measurements of high-sensitivity cardiac troponin T (hs-cTNT) post-exercise in patients with stable coronary artery disease (CAD).Methods: Twelve patients with positive coronary angiograms (CAD positives) and 12 controls performed an exercise stress test.Results: CAD positive had higher baseline and peak concentrations of hs-cTNT than controls. Significant increases in hs-cTNT were seen in both groups after exercise. In two-third of patients the peak in hs-cTNT was above the 99th percentile.Conclusion: hs-cTNT is higher in patients with stable coronary disease than in controls and exceeds the diagnostic cut-off value for myocardial infarction in a majority of patients with CAD after exercise.

The clinical benefit of Early Warning Scores (EWSs) is undocumented. Nursing staff's clinical assessment might improve the prediction of outcome and allow more efficient use of resources. We aimed to investigate whether the combination of clinical assessment and EWS would reduce the number of routine measurements without increasing mortality.

Objective:The interpretation of the neonatal electrocardiogram (ECG) is challenging and reflects the underlying developing physiology. The possible effects of gestational age (GA) on the ECG has never been evaluated in a large general population study. We aimed at investigating the effect of GA on neonatal electrocardiographic parameters and create GA-specific reference values.Methods:The Copenhagen Baby Heart Study is a prospective, general population study that offered cardiac evaluation of neonates. ECGs and echocardiograms were obtained and systematically analyzed. GA, weight, height, and other baseline variables were registered.Results:We included 16,462 neonates (52% boys) with normal echocardiograms. Median postnatal age was 11 days (range 0-30 days) and median GA was 281 days (range 238-301 days). Analyzing the ECG parameters as a function of GA we found a significant effect of GA on heart rate (HR), PR-, QRS-, and QT intervals, QRS axis, and maximum amplitudes of R-waves in V1/V6 and maximum S-wave in V6 (all p<0.01). The largest percentual effect of GA was on HR, QRS axis, and R-wave in V1. Boys had longer PR- and QRS intervals and more right-shifted QRS axis within multiple GA-intervals (all p<0.01, Figure: Box plots of ECG parameters subdivided by gestational age intervals and sex). The effect of GA generally persisted after adjustment for HR, weight, postnatal age, and sex. In addition, when comparing HR, PR interval, QRS axis, QRS duration, uncorrected QT interval, and QTcBazett subdivided into postnatal age intervals, we found a significant effect of gestational age on most ECG parameters within these postnatal age intervals.Conclusion:Gestational age was associated with significant differences in multiple neonatal ECG parameters and the effect generally persisted after multifactorial adjustment. Our results indicate a direct effect of GA on the developing neonatal cardiac conduction system. Use of GA-specific reference values may be useful.

Introduction:Left ventricular non-compaction (LVNC) is characterized by excessive trabeculations of the left ventricular wall and may be associated with reduced systolic function. It is debated whether LVNC is congenital or may develop later as part of other cardiomyopathies. The clinical importance and heredity of LVNC with normal systolic function is unclear.We aimed to describe the cardiac development in children with LVNC from birth to 2-4 years of age, compared to matched controls. Additionally, we aimed to describe the prevalence of LVNC in first-degree relatives.Methods:A follow-up transthoracic echocardiography was performed in children at 2-4 years of age diagnosed with LVNC at birth (<30 days) in the Copenhagen Baby Heart Study. Cases were matched to controls on mothers age at delivery, parity, and age of child at follow-up. First-degree relatives (parents, siblings and half-siblings) were also included. LVNC was defined as a non-compact to compact ratio of myocardium of ≥2 in at least one left ventricular segment, measured in 24 segments in end-diastole perpendicular to the left ventricular cavity as previously suggested.Results:Of the 16 children diagnosed with LVNC at birth, 10 have been reevaluated (age 3.5 (interquartile range (IQR) 3, 4) years, 80% male) together with 20 matched controls (age 4 (IQR 3, 4) years, 70% male), 29 first-degree relatives in case group (age 29 (IQR 4, 35) years, 45% male) and 55 first-degree relatives in control group (age 32 (IQR 11, 36) years, 51% male). In probands, the extent of trabeculation (13% vs. 12%, p=0.97) and fractional shortening (FS) (29% vs. 31%, p=0.24) were unchanged from birth to follow-up. At follow-up, the median left ventricular FS was significantly lower in probands compared to matched controls (31% vs. 33%, p=0.03). Ten (35%) first-degree relatives to probands fulfilled criteria for LVNC compared to 0 (0%) of first-degree relatives to controls (p<0.001).Conclusions:Children with LVNC diagnosed neonatally as part of a population study had no further progression of left ventricular dysfunction or extent of trabeculation at the age of 2-4 years, but systolic function was reduced compared to matched controls. One third of first-degree relatives to children with LVNC fulfilled criteria for LVNC.