Ferritin Levels on Hospital Admission Predict Hypoxic-Ischemic Encephalopathy in Patients After Out-of-Hospital Cardiac Arrest: A Prospective Observational Single-Center Study.

AIM: Out-of-hospital cardiac arrest (OHCA) is a major health concern in Western societies. Poor outcome after OHCA is determined by the extent of hypoxic-ischemic encephalopathy (HIE). Dysregulation of iron metabolism has prognostic relevance in patients with ischemic stroke and sepsis. The aim of this study was to determine whether serum iron parameters help to estimate outcomes after OHCA. METHODS: In this prospective single-center study, 70 adult OHCA patients were analyzed. Serum ferritin, iron, transferrin (TRF), and TRF saturation (TRFS) were measured in blood samples drawn on day 0 (admission), day 2, day 4, and 6 months after the return of spontaneous circulation (ROSC). The association of 4 iron parameters with in-hospital mortality, neurological outcome (cerebral performance category [CPC]), and HIE was investigated by receiver operating characteristics and multivariate regression analyses. RESULTS: OHCA subjects displayed significantly increased serum ferritin levels on day 0 and lowered iron, TRF, and TRFS on days 2 and 4 after ROSC, as compared to concentrations measured at a 6-month follow-up. Iron parameters were not associated with in-hospital mortality or neurological outcomes according to the CPC. Ferritin on admission was an independent predictor of features of HIE on cranial computed tomography and death due to HIE. CONCLUSION: OHCA is associated with alterations in iron metabolism that persist for several days after ROSC. Ferritin on admission can help to predict HIE.

Incidence of ablation-induced esophageal lesions and gastroparesis in patients undergoing ablation index guided high power short duration atrial fibrillation ablation.

INTRODUCTION: Aim of this study was to evaluate the incidence of ablation-induced endoscopically detected esophageal lesions (EDEL) and gastroparesis in patients undergoing high-power short-duration (HPSD) atrial fibrillation (AF) ablation using different target ablation index (AI) values. METHODS AND RESULTS: Consecutive patients undergoing AF ablation were included. Radiofrequency (RF) ablation was performed using HPSD ablation (50 W, target AI of 320 and 350 (group 1) and 380 (group 2) at posterior wall). Postablation endoscopy was performed in all patients. In total, 233 patients (66.8 ± 10 years; 52% male) were included consecutively (n = 137 patients in group 1 and n = 96 patients in group 2). Mean AI values und RF time at posterior wall was significantly higher and longer in group 2 compared to group 1 patients (413 ± 9 vs. 392 ± 19 AI, p < 0.01; 9.0 ± 0.8 s vs. 7.8 ± 0.7 s, p < 0.01). Esophageal endoscopy revealed esophageal lesions or gastroparesis in 43 of 233 patients (18.5%) in the total cohort (13.1% in group 1 and 26.0% in group 2; p = 0.02). Incidence of EDEL was 8.0% and 13.5% in group 1 and group 2, respectively. According to logistic analysis incidence of EDEL and/or gastroparesis was significantly lower in patients with a higher body mass index and higher in group 2 patients compared to group 1 patients. CONCLUSION: The incidence of EDEL or gastroparesis in patients undergoing HPSD AF ablation was 18.5% in the total cohort. The risk of EDEL and gastroparesis was associated with a higher AI target value of 380 compared to 320 and 350 at posterior wall and was reversely associated with body mass index.

Proof of SARS-CoV-2 genomes in endomyocardial biopsy with latency after acute infection.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has reached pandemic levels. Cardiovascular complications in COVID-19 have been reported frequently, however evidence for a causal relationship has not been established. This report describes the detection of SARS-CoV-2 viral genomes in a patient with symptoms of heart failure, in whom endomyocardial biopsy was investigated following a latency period of 4 weeks after the onset of pulmonary symptoms. The viral infection was accompanied by myocardial inflammation indicating an infection of the heart muscle.

Detection of viral SARS-CoV-2 genomes and histopathological changes in endomyocardial biopsies.

AIMS: Since December 2019, the novel coronavirus SARS-CoV-2 has spread rapidly throughout China and keeps the world in suspense. Cardiovascular complications with myocarditis and embolism due to COVID-19 have been reported. SARS-CoV-2 genome detection in the heart muscle has not been demonstrated so far, and the underlying pathophysiological mechanisms remain to be investigated. METHODS AND RESULTS: Endomyocardial biopsies (EMBs) of 104 patients (mean age: 57.90 ± 16.37 years; left ventricular ejection fraction: 33.7 ± 14.6%, sex: n = 79 male/25 female) with suspected myocarditis or unexplained heart failure were analysed. EMB analysis included histology, immunohistochemistry, and detection of SARS-CoV-2 genomes by real-time reverse transcription polymerase chain reaction in the IKDT Berlin, Germany. Among 104 EMBs investigated, five were confirmed with SARS-CoV-2 infected by reverse real-time transcriptase polymerase chain reaction. We describe patients of different history of symptoms and time duration. Additionally, we investigated histopathological changes in myocardial tissue showing that the inflammatory process in EMBs seemed to permeate vascular wall leading to small arterial obliteration and damage. CONCLUSIONS: This is the first report that established the evidence of SARS-CoV-2 genomes detection in EMBs. In these patients, myocardial injury ischaemia may play a role, which could explain the ubiquitous troponin increases. EMB-based identification of the cause of myocardial injury may contribute to explain the different evolution of complicated SARS-CoV-2-infection and to design future specific and personalized treatment strategies.

Genetic polymorphism of the type A human natriuretic peptide receptor (NPR-A) gene contributes to the interindividual variability in the BNP system.

AIMS: To analyse the contribution of recently described genetic polymorphisms in the human natriuretic peptide receptor (NPR-A) to the interindividual variability in the BNP system. METHODS AND RESULTS: We evaluated NT-proBNP in 402 subjects, including healthy controls (n=93), patients with acute coronary syndrome (n=194) and heart failure (n=115). Three polymorphic sites encoding six common haplotypes of the NPR-A receptor gene, including three haplotypes in the 5' region (CT11, CT10 and CT6) and three haplotypes in the 3' region (3-plus, 4-minus and 4-plus), were studied. The frequency of the identified "4-minus" haplotype was higher in control subjects with high NT-proBNP (>75th percentile) levels as compared to those with low NT-proBNP levels (15.2% vs. 5.7%, p<0.05). In the control subjects, carriers of the "4-plus/4-minus" genotype had about 2-fold higher median NT-proBNP levels than individuals with other genetic variants (142 pg/ml (88-371 pg/ml) vs. 71 pg/ml (35-111 pg/ml, p=0.011). In contrast, in patients with cardiovascular disorders no relation between NT-proBNP and the described polymorphisms was observed. CONCLUSION: The "4-minus" haplotype of the NPR-A receptor gene is associated with high NT-proBNP values and is a genetic determinant of the interindividual variability in the BNP system in healthy individuals but probably not in patients with cardiovascular disorders.

Image quality on dual-source computed-tomographic coronary angiography.

Multi-detector CT reliably permits visualization of coronary arteries, but due to the occurrence of motion artefacts at heart rates >65 bpm caused by a temporal resolution of 165 ms, its utilisation has so far been limited to patients with a preferably low heart rate. We investigated the assessment of image quality on computed tomography of coronary arteries in a large series of patients without additional heart rate control using dual-source computed tomography (DSCT). DSCT (Siemens Somatom Definition, 83-ms temporal resolution) was performed in 165 consecutive patients (mean age 64 +/- 11.4 years) after injection of 60-80 ml of contrast. Data sets were reconstructed in 5% intervals of the cardiac cycle and evaluated by two readers in consensus concerning evaluability of the coronary arteries and presence of motion and beam-hardening artefacts using the AHA 16-segment coronary model. Mean heart rate during CT was 65 +/- 10.5 bpm; visualisation without artefacts was possible in 98.7% of 2,541 coronary segments. Only two segments were considered unevaluable due to cardiac motion; 30 segments were unassessable due to poor signal-to-noise ratio or coronary calcifications (both n = 15). Data reconstruction at 65-70% of the cardiac cycle provided for the best image quality. For heart rates >85 bpm, a systolic reconstruction at 45% revealed satisfactory results. Compared with earlier CT generations, DSCT provides for non-invasive coronary angiography with diagnostic image quality even at heart rates >65 bpm and thus may broaden the spectrum of patients that can be investigated non-invasively.

Diagnostic and prognostic value of N-terminal pro B-type natriuretic peptide (NT-proBNP) in patients with chronic aortic regurgitation.

BACKGROUND: BNP and its N-terminal fragment NT-proBNP have proven to be of diagnostic and prognostic value in patients with valvular aortic stenosis. Data regarding those biomarkers in patients with chronic aortic regurgitation (AR) are sparse. Thus it was the aim of the present study to evaluate the diagnostic and the long term prognostic value of NT-proBNP in patients presenting with AR. METHODS AND RESULTS: This study included 60 patients with isolated AR of varying severity (AR I mild, AR II moderate and AR III severe) and preserved left ventricular function. Patients were followed over a median period of 824 (770-921) days. NT-proBNP at baseline was related to disease severity and to functional status (161 (70-456) pg/ml in AR I, 226 (100-666) pg/ml in AR II and 1268 (522-5446) pg/ml in AR III (p=0.003)). Patients (n=6) experiencing an adverse event had higher NT-proBNP values at baseline as event free survivors (1271 (613-2992) pg/ml vs. 215 (92-534) pg/ml; p=0.034). The AUC of the ROC curve for NT-proBNP as a predictor for an adverse event was 0.76 (p<0.036) with an optimised cut-off value of 602 pg/ml. Consequently, in Kaplan-Meier analysis NT-proBNP values dichotomised at this cut-off were able to discriminate patients with an adverse outcome in the entire study group (Log rank 9.98, p=0.0016) and even better in the conservative group (Log rank 26.92, p<0.001). CONCLUSION: NT-proBNP is linked to disease severity in patients with chronic aortic regurgitation reflecting hemodynamic stress due to volume overload. It provides prognostic information for the clinical outcome and thus might be a useful biomarker for risk stratification.

Influence of sample type and storage conditions on soluble CD40 ligand assessment.

BACKGROUND: Several studies have consistently shown that soluble CD40 ligand (sCD40L) concentrations are increased in patients with acute coronary syndromes and can serve as a biomarker for risk stratification. However, few data are available on preanalytic conditions that impact sCD40L values. Thus, the aim of our prospective study was to evaluate the impact of sampling techniques and storage conditions on sCD40L concentrations. METHODS: We included a total of 30 patients with no, stable, or unstable coronary heart disease. Blood samples were collected in gel-filled tubes without additives, in EDTA-filled tubes, and in citrate-filled tubes and were kept at various storage conditions. RESULTS: Median (interquartile range) sCD40L values at baseline were higher in serum samples [5.29 (3.89-6.33) microg/L] than in either EDTA plasma [0.78 (0.39-1.12) microg/L; P <0.001] or citrate plasma [0.37 (0.22-0.51) microg/L; P <0.001]. Serum values increased with delayed processing [7.94 (5.97-9.62) microg/L after 1.5 h (P <0.001) vs baseline; 10.55 (7.58-11.55) microg/L after 3 h (P <0.001) vs baseline]. However, after centrifugation, sCD40L values remained stable for all 3 sample types. CONCLUSION: Plasma, but not serum, samples are appropriate for sCD40L measurements. In general, preanalytic conditions are critical in the assessment of sCD40L concentrations and thus should be carefully considered for future studies.

Diagnostic utility of new immunoassays for the cardiac markers cTnI, myoglobin and CK-MB mass.

OBJECTIVES: We investigated the diagnostic value of a new system, the Innotrac Aio! immunoassays for troponin, myoglobin and CK-MB, in 270 samples from patients with ACS, after bypass surgery (CABG) or with stable heart failure in comparison to the respective Roche assays. RESULTS: The values of the cardiac markers assessed by the respective assays correlated (cTnT/cTnI Rho = 0.94, myoglobin Rho = 0.87, CK-MB Rho = 0.84). If values were dichotomised, we found a high concordance of test positive and negative classified patients by troponins with the respective assays. CONCLUSION: There is strong evidence that the Innotrac Aio! system for cTnI measurement can be used reliably.

Relation of N-terminal pro B-type natriuretic peptide to progression of aortic valve disease.

AIMS: Recently an elevation of B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) in patients with aortic stenosis (AS) and aortic regurgitation (AR) has been described. The objective of this study was to evaluate the relation of NT-proBNP values to the progression of aortic valve disease. METHODS AND RESULTS: One hundred and sixty-eight patients were included. NT-proBNP was elevated in patients with AS (n=109) and AR (n=37) linked to disease severity. Values for NT-proBNP, pressure gradient, and left ventricular mass were identical in patients (n=22) after previous valve replacement and in those patients with mild AS. NT-proBNP levels decreased in 86 patients after valve replacement (2292+/-353 vs. 785+/-101 pg/ml; P<0.01) but increased in 82 patients who were treated conservatively (616+/-120 vs. 1155+/-432 pg/mL; P=0.029), related to the progression of disease. CONCLUSION: NT-proBNP is elevated in patients with aortic valve disease linked to disease severity and decreases after successful surgical therapy but increases in conservatively treated patients. These data underline the consistent relation of NT-proBNP to severity of aortic valve disease. Therefore, NT-proBNP should be considered as a biomarker for the monitoring of disease during follow-up, but further studies are warranted.