Comparison of diagnostic algorithms in clinically suspected viral myocarditis: agreement between cardiac magnetic resonance, endomyocardial biopsy and troponin T.

AIMS: Myocardial inflammation is increasingly detected non-invasively by tissue mapping with cardiovascular magnetic resonance (CMR). Intraindividual agreement with endomyocardial biopsy (EMB) or marker of myocardial injury, high-sensitive troponin (hs-cTnT) in patients with clinically suspected viral myocarditis not understood. METHODS AND RESULTS: Prospective multicentre study of consecutive patients with clinically suspected myocarditis who underwent blood testing for hs-cTnT, CMR and EMB as a part of diagnostic work-up. EMB was considered positive based on immunohistological criteria in line with the ESC definitions. CMR diagnoses employed tissue mapping using sequence-specific cut-off for native T1 and T2 mapping; active inflammation was defined as T1≥2SD and T2≥2SD above the mean of normal range. Hs-cTnT of greater than 13.9ng/1 was considered significant. A total of 114 patients (age (mean±SD) 54±16, 65% males) were included, of which 79(69%) had positive EMB-criteria, 64(56%) CMR criteria, and a total of 58 (51%) positive troponin. Agreement between EMB and CMR diagnostic criteria was poor (CMR vs. ESC: AUCs: 0.51 (0.39-0.62)). The agreement between the significant hs-cTnT rise and CMR-based diagnosis of myocarditis was good (AUC: 0.84 (0.68-0.92); p<0.001), but poor for EMB (0.50 (0.40-0.61). Hs-cTnT was significantly associated with native T1 and T2, hs-CRP and NT-pro BNP (r=0.37, r=0.35, r=0.30, r=0.25 p<0.001), but not immunohistochemical criteria or viral presence. CONCLUSIONS: In clinically suspected viral myocarditis, all diagnostic approaches reflect the pathophysiological elements of myocardial inflammation, however the differing underlying drivers only partially overlap. The EMB and CMR diagnostic algorithms are neither interchangeable in terms of interpretation of myocardial inflammation nor in their relationship with myocardial injury.

Reweighting and validation of the hospital frailty risk score using electronic health records in Germany: a retrospective observational study.

BACKGROUND: In the hospital setting, frailty is a significant risk factor, but difficult to measure in clinical practice. We propose a reweighting of an existing diagnoses-based frailty score using routine data from a tertiary care teaching hospital in southern Germany. METHODS: The dataset includes patient characteristics such as sex, age, primary and secondary diagnoses and in-hospital mortality. Based on this information, we recalculate the existing Hospital Frailty Risk Score. The cohort includes patients aged ≥ 75 and was divided into a development cohort (admission year 2011 to 2013, N = 30,525) and a validation cohort (2014, N = 11,202). A limited external validation is also conducted in a second validation cohort containing inpatient cases aged ≥ 75 in 2022 throughout Germany (N = 491,251). In the development cohort, LASSO regression analysis was used to select the most relevant variables and to generate a reweighted Frailty Score for the German setting. Discrimination is assessed using the area under the receiver operating characteristic curve (AUC). Visualization of calibration curves and decision curve analysis were carried out. Applicability of the reweighted Frailty Score in a non-elderly population was assessed using logistic regression models. RESULTS: Reweighting of the Frailty Score included only 53 out of the 109 frailty-related diagnoses and resulted in substantially better discrimination than the initial weighting of the score (AUC = 0.89 vs. AUC = 0.80, p < 0.001 in the validation cohort). Calibration curves show a good agreement between score-based predictions and actual observed mortality. Additional external validation using inpatient cases aged ≥ 75 in 2022 throughout Germany (N = 491,251) confirms the results regarding discrimination and calibration and underlines the geographic and temporal validity of the reweighted Frailty Score. Decision curve analysis indicates that the clinical usefulness of the reweighted score as a general decision support tool is superior to the initial version of the score. Assessment of the applicability of the reweighted Frailty Score in a non-elderly population (N = 198,819) shows that discrimination is superior to the initial version of the score (AUC = 0.92 vs. AUC = 0.87, p < 0.001). In addition, we observe a fairly age-stable influence of the reweighted Frailty Score on in-hospital mortality, which does not differ substantially for women and men. CONCLUSIONS: Our data indicate that the reweighted Frailty Score is superior to the original Frailty Score for identification of older, frail patients at risk for in-hospital mortality. Hence, we recommend using the reweighted Frailty Score in the German in-hospital setting.

Regional extracellular volume within late gadolinium enhancement-positive myocardium to differentiate cardiac sarcoidosis from myocarditis of other etiology: a cardiovascular magnetic resonance study.

BACKGROUND: Cardiovascular magnetic resonance (CMR) plays a pivotal role in diagnosing myocardial inflammation. In addition to late gadolinium enhancement (LGE), native T1 and T2 mapping as well as extracellular volume (ECV) are essential tools for tissue characterization. However, the differentiation of cardiac sarcoidosis (CS) from myocarditis of other etiology can be challenging. Positron-emission tomography-computed tomography (PET-CT) regularly shows the highest Fluordesoxyglucose (FDG) uptake in LGE positive regions. It was therefore the aim of this study to investigate, whether native T1, T2, and ECV measurements within LGE regions can improve the differentiation of CS and myocarditis compared with using global native T1, T2, and ECV values alone. METHODS: PET/CT confirmed CS patients and myocarditis patients (both acute and chronic) from a prospective registry were compared with respect to regional native T1, T2, and ECV. Acute and chronic myocarditis were defined based on the 2013 European Society of Cardiology position paper on myocarditis. All parametric measures and ECV were acquired in standard fashion on three short-axis slices according to the ConSept study for global values and within PET-CT positive regions of LGE. RESULTS: Between 2017 and 2020, 33 patients with CS and 73 chronic and 35 acute myocarditis patients were identified. The mean ECV (± SD) in LGE regions of CS patients was higher than in myocarditis patients (CS vs. acute and chronic, respectively: 0.65 ± 0.12 vs. 0.45 ± 0.13 and 0.47 ± 0.1; p < 0.001). Acute and chronic myocarditis patients had higher global native T1 values (1157 ± 54 ms vs. 1196 ± 63 ms vs. 1215 ± 74 ms; p = 0.001). There was no difference in global T2 and ECV values between CS and acute or chronic myocarditis patients. CONCLUSION: This is the first study to show that the calculation of regional ECV within LGE-positive regions may help to differentiate CS from myocarditis. Further studies are warranted to corroborate these findings.

Application of High-Sensitivity Troponin in Suspected Myocardial Infarction.

BACKGROUND: Data regarding high-sensitivity troponin concentrations in patients presenting to the emergency department with symptoms suggestive of myocardial infarction may be useful in determining the probability of myocardial infarction and subsequent 30-day outcomes. METHODS: In 15 international cohorts of patients presenting to the emergency department with symptoms suggestive of myocardial infarction, we determined the concentrations of high-sensitivity troponin I or high-sensitivity troponin T at presentation and after early or late serial sampling. The diagnostic and prognostic performance of multiple high-sensitivity troponin cutoff combinations was assessed with the use of a derivation-validation design. A risk-assessment tool that was based on these data was developed to estimate the risk of index myocardial infarction and of subsequent myocardial infarction or death at 30 days. RESULTS: Among 22,651 patients (9604 in the derivation data set and 13,047 in the validation data set), the prevalence of myocardial infarction was 15.3%. Lower high-sensitivity troponin concentrations at presentation and smaller absolute changes during serial sampling were associated with a lower likelihood of myocardial infarction and a lower short-term risk of cardiovascular events. For example, high-sensitivity troponin I concentrations of less than 6 ng per liter and an absolute change of less than 4 ng per liter after 45 to 120 minutes (early serial sampling) resulted in a negative predictive value of 99.5% for myocardial infarction, with an associated 30-day risk of subsequent myocardial infarction or death of 0.2%; a total of 56.5% of the patients would be classified as being at low risk. These findings were confirmed in an external validation data set. CONCLUSIONS: A risk-assessment tool, which we developed to integrate the high-sensitivity troponin I or troponin T concentration at emergency department presentation, its dynamic change during serial sampling, and the time between the obtaining of samples, was used to estimate the probability of myocardial infarction on emergency department presentation and 30-day outcomes. (Funded by the German Center for Cardiovascular Research [DZHK]; ClinicalTrials.gov numbers, NCT00470587, NCT02355457, NCT01852123, NCT01994577, and NCT03227159; and Australian New Zealand Clinical Trials Registry numbers, ACTRN12611001069943, ACTRN12610000766011, ACTRN12613000745741, and ACTRN12611000206921.).

CILP1 as a biomarker for right ventricular maladaptation in pulmonary hypertension.

The aim of our study was to analyse the protein expression of cartilage intermediate layer protein (CILP)1 in a mouse model of right ventricular (RV) pressure overload and to evaluate CILP1 as a biomarker of cardiac remodelling and maladaptive RV function in patients with pulmonary hypertension (PH).Pulmonary artery banding was performed in 14 mice; another nine mice underwent sham surgery. CILP1 protein expression was analysed in all hearts using Western blotting and immunostaining. CILP1 serum concentrations were measured in 161 patients (97 with adaptive and maladaptive RV pressure overload caused by PH; 25 with left ventricular (LV) hypertrophy; 20 with dilative cardiomyopathy (DCM); 19 controls without LV or RV abnormalities)In mice, the amount of RV CILP1 was markedly higher after banding than after sham. Control patients had lower CILP1 serum levels than all other groups (p<0.001). CILP1 concentrations were higher in PH patients with maladaptive RV function than those with adaptive RV function (p<0.001), LV pressure overload (p<0.001) and DCM (p=0.003). CILP1 showed good predictive power for maladaptive RV in receiver operating characteristic analysis (area under the curve (AUC) 0.79). There was no significant difference between the AUCs of CILP1 and N-terminal pro-brain natriuretic peptide (NT-proBNP) (AUC 0.82). High CILP1 (cut-off value for maladaptive RV of ≥4373 pg·mL-1) was associated with lower tricuspid annular plane excursion/pulmonary artery systolic pressure ratios (p<0.001) and higher NT-proBNP levels (p<0.001).CILP1 is a novel biomarker of RV and LV pathological remodelling that is associated with RV maladaptation and ventriculoarterial uncoupling in patients with PH.

Detecting myocardial scar using electrocardiogram data and deep neural networks.

Ischaemic heart disease is among the most frequent causes of death. Early detection of myocardial pathologies can increase the benefit of therapy and reduce the number of lethal cases. Presence of myocardial scar is an indicator for developing ischaemic heart disease and can be detected with high diagnostic precision by magnetic resonance imaging. However, magnetic resonance imaging scanners are expensive and of limited availability. It is known that presence of myocardial scar has an impact on the well-established, reasonably low cost, and almost ubiquitously available electrocardiogram. However, this impact is non-specific and often hard to detect by a physician. We present an artificial intelligence based approach - namely a deep learning model - for the prediction of myocardial scar based on an electrocardiogram and additional clinical parameters. The model was trained and evaluated by applying 6-fold cross-validation to a dataset of 12-lead electrocardiogram time series together with clinical parameters. The proposed model for predicting the presence of scar tissue achieved an area under the curve score, sensitivity, specificity, and accuracy of 0.89, 70.0, 84.3, and 78.0%, respectively. This promisingly high diagnostic precision of our electrocardiogram-based deep learning models for myocardial scar detection may support a novel, comprehensible screening method.

Definition of acute kidney injury impacts prevalence and prognosis in ACS patients undergoing coronary angiography.

BACKGROUND: Development of acute kidney injury (AKI) in invasively managed patients with acute coronary syndrome (ACS) is associated with a markedly increased mortality risk. Different definitions of AKI are in use, leading to varying prevalence and outcome measurements. The aim of the present study is to analyze an ACS population undergoing coronary angiography for differences in AKI prevalence and outcome using four established AKI definitions. METHODS: 944 patients (30% female) were enrolled in a prospective registry between 2003 and 2005 with 6-month all-cause mortality as outcome measure. Four established AKI definitions were used: an increase in serum creatinine (sCR) ≥ 1.5 fold, ≥ 0.3 mg/dl, and ≥ 0.5 mg/dl and a decrease in eGFR > 25% from baseline (AKIN 1, AKIN 2, CIN, and RIFLE definition groups, respectively). RESULTS: AKI rates varied widely between the different groups. Using the CIN definition, AKI frequency was lowest (4.4%), whereas it was highest if the RIFLE definition was applied (13.2%). AKIN 2 displayed a twofold higher AKI prevalence compared with AKIN 1 (10.2% vs. 5.3% (p < 0.001)). AKI was a strong risk factor for mid-term mortality, with distinctive variability between the definitions. The lowest mortality risk was found in the RIFLE group (HR 6.0; 95% CI 3.7-10.0; p < 0.001), whereas CIN revealed the highest risk (HR 16.7; 95% CI 9.9-28.1; p < 0.001). CONCLUSION: Prevalence and outcome in ACS patients varied considerably depending on the AKI definition applied. To define patients with highest renal function-associated mortality risk, use of the CIN definition seems to have the highest prognostic relevance.

[Heart failure protection by SGLT2 inhibitors in patients with type 2 diabetes mellitus: evidence and possible mechanisms : A systematic review]. / Herzinsuffizienzprotektion bei Patienten mit Diabetes mellitus Typ 2 durch SGLT2-Inhibitoren ­ Evidenzlage und mögliche Mechanismen : Systematische Übersicht.

BACKGROUND: Renal sodium-glucose cotransporter­2 (SGLT2) inhibitors seem to have a cardioprotective effect beyond the antidiabetic effect. The underlying mechanisms are unclear. METHODS: Selective search in PubMed with a focus on heart failure endpoints and possible mechanisms of action. RESULTS: During treatment with three of the substances analyzed, there were fewer hospitalizations for heart failure compared with placebo; however, the numbers needed to treat within the primary analyses were relatively high (72-117). We found that loss of weight and lowering of blood pressure were more pronounced during treatment with verum than with placebo and an association of the preventive effect with more severely impaired renal function. CONCLUSION: The SGLT2 inhibitors show a moderate heart failure protective effect in diabetic patients. It is likely that a nephroprotective effect with modulation of the cardiorenal interaction is an important part of the mechanism of action but this must be substantiated in further investigations.

Precursor proadrenomedullin influences cardiomyocyte survival and local inflammation related to myocardial infarction.

Increased adrenomedullin (ADM) levels are associated with various cardiac diseases such as myocardial infarction (MI). ADM is cleaved off from the full-length precursor protein proadrenomedullin (ProADM) during its posttranslational processing. To date, no biological effect of ProADM is reported, while ADM infusion leads to antiapoptotic effects and improved cardiac function. Using an MI mouse model, we found an induction of ProADM gene as well as protein expression during the early phase of MI. This was accompanied by apoptosis and increasing inflammation, which substantially influence the post-MI remodeling processes. Simulating ischemia in vitro, we demonstrate that ProADM expression was increased in cardiomyocytes and cardiac fibroblasts. Subsequently, we treated ischemic cardiomyocytes with either ProADM or ADM and found that both proteins increased survival. This effect was diminishable by blocking the ADM1 receptor. To investigate whether ProADM and ADM play a role in the regulation of cardiac inflammation, we analyzed chemokine expression after treatment of cells with both proteins. While ProADM induced an expression of proinflammatory cytokines, thus promoting inflammation, ADM reduced chemokine expression. On leukocytes, both proteins repressed chemokine expression, revealing antiinflammatory effects. However, ProADM but not ADM dampened concurrent activation of leukocytes. Our data show that the full-length precursor ProADM is biologically active by reducing apoptosis to a similar extent as ADM. We further assume that ProADM induces local inflammation in affected cardiac tissue but attenuates exaggerated inflammation, whereas ADM has low impact. Our data suggest that both proteins are beneficial during MI by influencing apoptosis and inflammation.

The adipokine fatty-acid binding protein 4 and cardiac remodeling.

BACKGROUND: Previous publications about the association between fatty-acid binding protein 4 (FABP4) and cardiac remodeling have reported different, both beneficial and harmful, associations. Aim of the present investigation was to evaluate the association of FABP4 with parameters of myocardial remodeling defined by cardiac magnetic resonance imaging (CMR). METHODS: We investigated plasma FABP4 levels in 331 patients (71% men, mean age 63±13 years) with preserved left ventricular ejection fraction (LVEF ≥ 55%) who underwent a CMR examination. We used linear cox regression to investigate associations between FABP4 and left ventricular end-diastolic diameter (LVEDD), right ventricular end-diastolic diameter (RVEDD), relative wall thickness (RWT), left ventricular mass index (LVMI), and LVEF (unadjusted and adjusted for age, sex, body mass index, cardiac biomarkers, and comorbidities). RESULTS: FABP4 levels were associated with lower LVMI and higher NT-proBNP levels in an adjusted model. The inverse association between FABP4 and LVMI was more pronounced in lower FABP4 levels, whereas the positive association between FABP4 and NT-proBNP was more pronounced in relatively high NT-proBNP levels. CONCLUSIONS: Possible beneficial and harmful associations between FABP4 and left ventricular size have been reported. Our results suggest a beneficial association with LVMI (more pronounced in lower FABP4 levels) but a harmful association with NT-proBNP (more pronounced in higher FABP4 levels). Therefore, our results might indicate a potential dose-dependent association of FABP4, but this observation needs further investigation in larger study samples.

Pregnancy-associated plasma protein A - a new indicator of pulmonary vascular remodeling in chronic thromboembolic pulmonary hypertension?

BACKGROUND: In chronic thromboembolic pulmonary hypertension (CTEPH) impaired pulmonary hemodynamics lead to right heart failure. Natriuretic peptides reflect hemodynamic disease severity. Pregnancy-associated plasma protein-A (PAPP-A) might address another aspect of CTEPH - chronic tissue injury and inflammation. This study assessed dynamics of PAPP-A in CTEPH patients who undergo therapy with pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA). METHODS: The study included a total of 125 CTEPH patients scheduled for treatment (55 PEA/ 70 BPA) and a control group of 58 patients with pulmonary hypertension other than CTEPH. Biomarker measurement was performed at baseline and follow-up in the CTEPH cohort, prior to each BPA in the BPA cohort and once in the control group. RESULTS: The median PAPP-A level was slightly higher (p = 0.05) in CTEPH patients [13.8 (11.0-18.6) mU/L], than in the control group [12.6 (8.6-16.5) mU/L], without a difference between the BPA and PEA group (p = 0.437) and without a correlation to mean pulmonary artery pressure (p = 0.188), pulmonary vascular resistance (p = 0.893), cardiac index (p = 0.821) and right atrial pressure (p = 0.596). PEA and BPA therapy decreased the mean pulmonary artery pressure (p < 0.001) and pulmonary vascular resistance (p < 0.001) and improved the WHO-functional-class (baseline: I:0/II:25/III:80/IV:20 vs. follow-up: I:55/II:58/III:10/IV:2). PAPP-A levels decreased after PEA [13.5 (9.5-17.5) vs. 11.3 (9.8-13.6) mU/L; p = 0.003) and BPA treatment [14.3 (11.2-18.9) vs. 11.1 (9.7-13.3) mU/L; p < 0.001). The decrease of PAPP-A levels is delayed in comparison to N-terminal pro-B-type natriuretic peptide. CONCLUSION: PAPP-A is overexpressed in CTEPH and decrease significantly after surgical or interventional therapy, however without association to hemodynamics. Further investigation is needed to define the underlying mechanism of PAPP-A expression and changes after therapy in CTEPH.

Galectin-3, GDF-15, and sST2 for the assessment of disease severity and therapy response in patients suffering from inoperable chronic thromboembolic pulmonary hypertension.

PURPOSE: This study examined sST2, GDF-15, and galectin-3 as indicators of disease severity and therapy response in chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: This study included 57 inoperable CTEPH patients who underwent balloon pulmonary angioplasty and 25 controls without cardiovascular disease. Biomarker levels were examined in relation to advanced hemodynamic impairment [tertile with worst right atrial pressure (RAP) and cardiac index], hemodynamic therapy response [normalized hemodynamics (meanPAP ≤25 mmHg, PVR ≤3 WU and RAP ≤6 mmHg) or a reduction of meanPAP ≥25%; PVR ≥ 35%, RAP ≥25%]. RESULTS: GDF-15 [820 (556-1315) pg/ml vs. 370 (314-516) pg/ml; p < 0.001] and sST2 [53.7 (45.3-74.1) ng/ml vs. 48.7 (35.5-57.0) ng/ml; p = 0.02] were higher in CTEPH patients than in controls. At baseline, a GDF-15 level ≥1443 pg/ml (AUC 0.88; OR 31.4) and a sST2 level ≥65 ng/ml (AUC 0.80; OR 10.9) were associated with advanced hemodynamic impairment. At follow-up GDF-15 ≤ 958 pg/ml (AUC = 0.74, OR 18) identified patients with optimal hemodynamic therapy response and ≤760 pg/ml (AUC = 0.79, OR 14). CONCLUSION: GDF-15 and sST2 levels are higher in CTEPH and identified patients with advanced hemodynamic impairment. Further, decreased GDF-15 levels at follow-up were associated with hemodynamic therapy response. The diagnostic strength was not superior to NT-proBNP.

SPARCL1 as a biomarker of maladaptive right ventricular remodelling in pulmonary hypertension.

Aim: This study assessed the utility of SPARC-like protein 1 (SPARCL1) as a biomarker of maladaptive right ventricular (RV) function in patients with pulmonary hypertension (PH).Methods: In this prospective study, we examined SPARCL1 levels in 105 patients with adaptive (n = 34) and maladaptive RV (n = 32) pressure overload caused by PH, dilated cardiomyopathy (DCM, n = 18) with LVEF < 35% and preserved RV function and controls without LV or RV abnormalities (n = 21).Results: The median SPARCL1 concentration in patients with maladaptive RV function was higher than in those with adaptive RV function (p < 0.01), DCM (p < 0.001) or controls (p < 0.001). Patients with adaptive RV function had higher SPARCL1 concentrations than controls (p < 0.05), whereas there was no difference between adaptive RV and DCM. SPARCL1 showed good predictive power for maladaptive RV (AUC 0.77, p < 0.001) with an optimal cut-off value of 9.66 ng/ml. The TAPSE/PASP ratio was the only independent predictor of SPARCL1 ≥ 9.66 ng/ml in multivariable logistic regression analysis.Conclusion: SPARCL1 shows potential as novel biomarker of RV pathological remodelling and is associated with RV maladaptation and ventriculoarterial uncoupling in PH.

Fractional flow reserve and frequency of PCI in patients with coronary artery disease.

BACKGROUND: Fractional flow reserve (FFR) guided percutaneous coronary intervention (PCI) has been validated in patients with stable coronary artery disease (CAD) but has not yet been verified under specific conditions such as heart failure or microvascular dysfunction. The aim of the present study was to examine the influence of specific patient comorbidities on FFR values and thus the frequency of PCI in patients with intermediate coronary stenosis. METHODS: A total of 652 patients with CAD and intermediate coronary stenosis who were assessed for FFR were included in this retrospective study. In a subgroup analysis, specific comorbidities such as heart failure with non-ST-segment-elevated acute coronary syndrome (NSTE-ACS), heart failure, diabetes mellitus, atrial fibrillation (AF), and left ventricular hypertrophy (LVH) were considered. RESULTS: In all lesions with an FFR ≤ 0.80 (n = 227/808, 28.1%), PCI was performed using drug-eluting stents. Pathological FFR values (FFR ≤ 0.80) before PCI were most frequently observed in the left anterior descending artery (LAD; n = 168/418, 39.9%) followed by the right coronary artery (RCA; n = 37/178, 20.7%) and the left circumflex artery (LCX; 22/223, 9.8%). The comorbidities NSTE-ACS (p = 0.28), heart failure with reduced ejection fraction (HFrEF; p = 0.63), heart failure with preserved ejection fraction (HFpEF; p = 0.3719), diabetes mellitus (p = 0.177), or LVH (p = 0.407) had no major impact on the occurrence of pathological FFR values; there was also no association between FFR and the occurrence of lesions in the different target vessels. CONCLUSION: The occurrence of pathological FFR values, most frequently documented in the LAD, was the same in patients with or without HFrEF, HFpEF, diabetes mellitus, AF, and LVH, demonstrating that these comorbidities did not influence FFR values and, thus, the indication for PCI.

Identification and regulation of the long non-coding RNA Heat2 in heart failure.

AIMS: Circulating immune cells have a significant impact on progression and outcome of heart failure. Long non-coding RNAs (lncRNAs) comprise novel epigenetic regulators which control cardiovascular diseases and inflammatory disorders. We aimed to identify lncRNAs regulated in circulating immune cells of the blood of heart failure patients. METHODS AND RESULTS: Next-generation sequencing revealed 110 potentially non-coding RNA transcripts differentially expressed in peripheral blood mononuclear cells of heart failure patients with reduced ejection fraction. The up-regulated lncRNA Heat2 was further functionally characterized. Heat2 expression was detected in whole blood, PBMNCs, eosinophil and basophil granulocytes. Heat2 regulates cell division, invasion, transmigration and immune cell adhesion on endothelial cells. CONCLUSION: Heat2 is an immune cell enriched lncRNA that is elevated in the blood of heart failure patients and controls cellular functions.

Identification of acute myocardial infarction in elderly patients using optimized highly sensitive troponin I thresholds.

Purpose: Established diagnostic thresholds for high-sensitivity cardiac troponins (hs-cTn) might not apply for elderly patients as they are elevated irrespective of the presence of an acute myocardial infarction (AMI). Aim of the present study was to investigate hs-cTnI in elderly patients with suspected AMI and to calculate optimized diagnostic cutoffs. Material and methods: Data from a prospective multi-centre study and from a second independent prospective single-centre cohort study were analysed. A number of 2903 patients were eligible for further analysis. Patients > 70 years were classified as elderly. hs-cTnI was measured upon admission. Results: Around 34.7% of 2903 patients were classified as elderly. Around 22.5% of elderly patients were finally diagnosed with AMI. Elderly patients had higher hs-cTnI levels at admission irrespective of the final diagnosis (p < 0.001). According to the AUROC, hs-cTnI was a strong marker for detection of AMI in elderly patients. Application of the 99th percentile cutoffs showed a substantially lower specificity in elderly. By using optimized thresholds, specificity was improved to levels as in younger patients in both cohorts but accompanied with a decrease in sensitivity. Conclusions: hs-cTnI levels have a lower specificity for detecting AMI in elderly patients. This lower specificity can be improved by using hs-cTnI thresholds optimized for elderly patients.

Predictive value of preprocedural procalcitonin for short- and long-term mortality after transfemoral transcatheter aortic valve implantation.

Current risk scores used for patients undergoing transcatheter aortic valve implantation (TAVI) do not reliably predict adverse events after TAVI. Procalcitonin (PCT) is associated with increased atherosclerotic burden and adverse outcomes in patients with cardiovascular disease. The aim of our study is to assess the predictive value of preprocedural serum PCT levels in comparison with established risk scores in TAVI patients. A total of 243 patients undergoing transfemoral TAVI at our institution were included prospectively in the study and 230 of these patients participated in the follow-up 1 year after TAVI. The primary endpoints were mortality at 30 days and 1 year. Multivariable analysis revealed that preprocedural PCT was the only independent predictor of 30-day mortality (HR 2.84; 95% CI 1.59-5.06; p < 0.001) and 1-year mortality (HR 1.90; 95% CI 1.17-3.11; p = 0.01), whereas high-sensitivity C-reactive protein showed no association with procedural outcomes. The results of ROC analysis showed good predictive power of PCT for both outcomes (AUC 0.75; p = 0.0003 for 30-day mortality and AUC 0.71; p < 0.0001 for 1-year mortality). An optimal cut-off value for PCT of 0.06 ng/ml for short- and long-term mortality was determined with the Youden index. A significantly higher mortality rate was observed in the high-PCT group (≥ 0.06 ng/ml) based on Kaplan-Meier analysis (log rank = 12.1; p = 0.001 at 30 days and log rank = 14.2; p = 0.0002 at 1 year). Patients in the high-PCT group also had a considerably worse clinical pro6file. In conclusion, preprocedural PCT is an independent predictor of 30-day and 1-year mortality after TAVI. In particular, a cut-off value of 0.06 ng/ml discriminates patients at higher risk of mortality within 30 days and 1 year of TAVI.

Development of renal function during staged balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension.

Balloon pulmonary angioplasty (BPA), for chronic thromboembolic pulmonary hypertension, improves pulmonary and systemic hemodynamics. The kidney might benefit from this effect. However, staged BPA therapy comes along with repetitive administration of contrast agent. This study examined the overall effect of BPA therapy on renal function. This study included consecutive patients who underwent BPA treatment and completed a 6-month follow-up between March 2014 and March 2017. Biomarker-based evaluation of renal function was performed at baseline, consecutively prior to and after each BPA and at 6-month follow-up. The 51 patients underwent an average of 5 (±2) BPA sessions. In this course, patients received 133 (±48; 21-300) mL of contrast agent per session and 691 (±24; 240-1410) mL during the whole sequence. Acute kidney injury occurred after 6 (2.3%) procedures. The creatinine [80.1 (IQR 67.8-96.8) µmol/L vs. 77.4 (IQR 66.9-91.5) µmol/L, p = .02] and urea level [13.7 (IQR10.7-16.6) mmol/L vs. 12.5 (IQR 10.0-15.5) mmol/L, p = .02] decreased from baseline to the 6-month follow-up. The estimated glomerular filtration rate (eGFR) [79 (IQR 59-94) mL/min/m2 vs. 79.6 (IQR 67.1-95.0) mL/min/m2, p = .11] did not change. The Chronic kidney disease (CKD) stages at baseline were: G1:15; G2:23; G3a:10; G3b:2; G4:1; G5:0. Among patients with a CKD-stage ≥2, analysis revealed an increase of eGFR, decrease of creatinine and urea from baseline to 6-month follow-up. Among those patients, the baseline-CKD-stage improved in 14 (41.2%) patients. BPA therapy improves pulmonary and systemic hemodynamics, with positive effects on renal function. Repetitive administration of contrast agent seems not to be harmful regarding renal function.

Prognostic Value of High-Sensitivity Versus Conventional Cardiac Troponin T Assays Among Patients With Type 2 Diabetes Mellitus Undergoing Maintenance Hemodialysis.

BACKGROUND: Mortality is high among patients undergoing hemodialysis for whom cardiac troponin concentration is a strong predictor of outcome. Modern troponin assays allow measurement of very low concentrations. STUDY DESIGN: Using data from a randomized controlled trial, a cohort analysis to evaluate the prognostic value of very low cardiac troponin T (TnT) concentrations. SETTING & PARTICIPANTS: 1,255 patients with end-stage renal disease and type 2 diabetes mellitus undergoing maintenance hemodialysis from the German Diabetes and Dialysis Study (4D) who had a median follow-up of 4 years. INDEX TEST, REFERENCE TEST, AND OUTCOME: Cardiac TnT was measured using a high-sensitivity assay (hs-TnT) and a conventional assay (conventional TnT) in a subpopulation (n=1,034) with valid measurements for both assays. Outcome measures were all-cause mortality and a composite cardiovascular end point including cardiac death, myocardial infarction, or stroke. RESULTS: Among the 1,034 study participants, 505 died and 377 had a cardiovascular event. Both hs-TnT and conventional TnT concentrations were associated with mortality and cardiovascular events in models adjusted for cardiovascular risk factors and dialysis-associated variables. 455 (44%) patients with very low TnT concentrations (hs-TNT < 50ng/L) would have been classified as normal by the conventional TnT assay. Among these patients, hs-TnT concentrations were also associated with mortality. LIMITATIONS: The study of patients with type 2 diabetes may limit generalizability. These findings have not been externally validated. CONCLUSIONS: In patients with type 2 diabetes mellitus receiving hemodialysis, cardiac TnT is associated with long-term mortality and cardiovascular outcomes. Concentrations of TnT not measurable with acceptable precision using a conventional TnT assay were associated with a poor prognosis when measured using a high-sensitivity assay.

Immediate Rule-Out of Acute Myocardial Infarction Using Electrocardiogram and Baseline High-Sensitivity Troponin I.

AIMS: Serial measurements of high-sensitivity troponin are used to rule out acute myocardial infarction (AMI) with an assay specific cutoff at the 99th percentile. Here, we evaluated the performance of a single admission troponin with a lower cutoff combined with a low risk electrocardiogram (ECG) to rule out AMI. METHODS: Troponin I measured with a high-sensitivity assay (hs-TnI) was determined at admission in 1040 patients presenting with suspected AMI (BACC study). To rule out AMI we calculated the negative predictive value (NPV) utilizing the optimal hs-TnI cutoff combined with a low risk ECG. The results were validated in 3566 patients with suspected AMI [2-h Accelerated Diagnostic Protocol to Assess Patients With Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarker (ADAPT) studies]. Patients were followed for 6 or 12 months. RESULTS: 184 of all patients were diagnosed with AMI. An hs-TnI cutoff of 3 ng/L resulted in a NPV of 99.3% (CI 97.3-100.0), ruling out 35% of all non-AMI patients. Adding the information of a low risk ECG resulted in a 100% (CI 97.5-100.0) NPV (28% ruled out). The 2 validation cohorts replicated the high NPV of this approach. The follow-up mortality in the ruled out population was low (0 deaths in BACC and Stenocardia, 1 death in ADAPT). CONCLUSIONS: A single hs-TnI measurement on admission combined with a low risk ECG appears to rule out AMI safely without need for serial troponin testing. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02355457).