Native T2 Predicts Myocardial Inflammation Irrespective of a Patient's Volume Status.

Myocardial inflammation and edema are major pathological features in myocarditis. Myocardial tissue water content and myocardial edema can be quantified via T2 mapping. Thus, cardiac magnetic resonance (CMR) is the noninvasive gold standard for diagnosing myocarditis. Several studies showed an impact of short-term volume changes on T2 relaxation time. Plasma volume status (PVS) is a good surrogate parameter to quantify a patient's volume status, and it is simple to use. The aim of this study was to determine the effect of PVS on the diagnostic value of T2 relaxation time in myocardial inflammation. Between April 2017 and December 2022, patients who were indicated for cardiac CMR were included in our prospective clinical registry. Patients with myocardial inflammation and those with unremarkable findings were analyzed in the present study. A blood sample was drawn, and PVS was calculated. Patients were separated into PVS tertiles to explore a possible nonlinear dose-response relationship. Logistic regression analysis was used to determine whether T2 is an independent predictor of myocardial inflammation. A total of 700 patients (47.43% female) were eligible for analysis. Of these, 551 patients were healthy (78.7%), while 149 (21.3%) showed signs of myocardial inflammation. The T2 relaxation time was elevated in patients with myocardial inflammation (40 ms [IQR 37-42 ms] vs. 38.0 ms [IQR 36-39 ms], p < 0.001). PVS showed no difference between the groups (-12.94 [IQR -18.4--7.28] vs.-12.19 [IQR -18.93--5.87], p = 0.384). T2 showed a clear dose-response relationship with PVS, with increasing T2 values along the PVS tertiles. In spite of this, T2 was found to be an independent marker of myocardial inflammation in logistic regression (OR T2 1.3 [95% CI 1.21-1.39], p < 0.001), even after adjusting for PVS (OR T2 [adj. PVS] 1.31 [95% CI 1.22-1.40], p < 0.001). Despite a dose-response relationship between T2 and the volume status, T2 was found to be an independent indicator of myocardial inflammation.

Native T1 is predictive of cardiovascular death/heart failure events and all-cause mortality irrespective of the patient's volume status.

Background: Native T1 has become a pivotal parameter of tissue composition that is assessed by cardiac magnetic resonance (CMR). It characterizes diseased myocardium and can be used for prognosis estimation. Recent publications have shown that native T1 is influenced by short-term fluctuations of volume status due to hydration or hemodialysis. Methods: Patients from a prospective BioCVI all-comers clinical CMR registry were included, and native T1 and plasma volume status (PVS) were determined according to Hakim's formula as surrogate markers of patient volume status. The primary endpoint was defined as combined endpoint of cardiovascular death or hospitalization for heart failure events, the secondary endpoint was defined as all-cause mortality. Results: A total of 2,047 patients were included since April 2017 [median (IQR); age 63 (52-72) years, 33% female]. There was a significant although weak influence of PVS on native T1 (ß = 0.11, p < 0.0001). Patients with volume expansion (PVS > -13%) showed significantly higher values for tissue markers than non-volume-overloaded patients [PVS ≤ -13%; median (IQR); native T1 1,130 (1,095-1,170) vs. 1,123 (1,086-1,166) ms, p < 0.003; and T2 39 (37-40) vs. 38 (36-40) ms, p < 0.0001]. In Cox regression analysis both native T1 and PVS were independently predictive of the primary endpoint and all-cause mortality. Conclusion: Despite a weak effect of PVS on native T1, its predictive power was not affected in a large, all-comers cohort.

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.

Right Ventricular Strain by Magnetic Resonance Feature Tracking Is Largely Afterload-Dependent and Does Not Reflect Contractility: Validation by Combined Volumetry and Invasive Pressure Tracings.

Cardiac magnetic resonance (CMR) is currently the gold standard for evaluating right ventricular (RV) function, which is critical in patients with pulmonary hypertension. CMR feature-tracking (FT) strain analysis has emerged as a technique to detect subtle changes. However, the dependence of RV strain on load is still a matter of debate. The aim of this study was to measure the afterload dependence of RV strain and to correlate it with surrogate markers of contractility in a cohort of patients with chronic thromboembolic pulmonary hypertension (CTEPH) under two different loading conditions before and after pulmonary endarterectomy (PEA). Between 2009 and 2022, 496 patients with 601 CMR examinations were retrospectively identified from our CTEPH cohort, and the results of 194 examinations with right heart catheterization within 24 h were available. The CMR FT strain (longitudinal (GLS) and circumferential (GCS)) was computed on steady-state free precession (SSFP) cine CMR sequences. The effective pulmonary arterial elastance (Ea) and RV chamber elastance (Ees) were approximated by dividing mean pulmonary arterial pressure by the indexed stroke volume or end-systolic volume, respectively. GLS and GCS correlated significantly with Ea and Ees/Ea in the overall cohort and individually before and after PEA. There was no general correlation with Ees; however, under high afterload, before PEA, Ees correlated significantly. The results show that RV GLS and GCS are highly afterload-dependent and reflect ventriculoarterial coupling. Ees was significantly correlated with strain only under high loading conditions, which probably reflects contractile adaptation to pulsatile load rather than contractility in general.

Cardiac biomarkers as indicators of right ventricular dysfunction and recovery in chronic thromboembolic pulmonary hypertension patients after balloon pulmonary angioplasty therapy - a cardiac magnetic resonance imaging cohort study.

BACKGROUND: In chronic thromboembolic pulmonary hypertension, right heart failure determines outcome. Balloon pulmonary angioplasty therapy allows right heart recovery, which can be monitored by cardiac magnetic resonance imaging. This study evaluates whether cardiac biomarkers (NT-proBNP, MR-proANP, sST2, and PAPP-A) are associated with cardiac magnetic resonance imaging findings prior to and after balloon pulmonary angioplasty therapy. METHODS: This observational cohort study enrolled 22 chronic thromboembolic pulmonary hypertension patients who underwent balloon pulmonary angioplasty therapy and completed a six-month follow-up including cardiac magnetic resonance imaging. Biomarker levels were compared with findings for right heart morphology and function derived from cardiac magnetic resonance imaging. RESULTS: Pulmonary hemodynamics improved after balloon pulmonary angioplasty therapy [pulmonary vascular resistance: 7.7 (6.0-9.0) vs. 4.7 (3.5-5.5) wood units, p < 0.001; mean pulmonary artery pressure 41 (38-47) vs. 32 (28-37) mmHg, p < 0.001]. Cardiac magnetic resonance imaging findings indicated right heart maladaptation at baseline and recovery after therapy [right ventricular end-diastolic volume 192 (141-229) ml vs. 143 (128-172) ml, p = 0.002; right ventricular end-systolic volume 131 (73-157) ml vs. 77 (61-99) ml (p < 0.001); right ventricular ejection fraction (RVEF) 34 (28-41) % vs. 52 (41-54) %; p < 0.001]. Biomarker level cut-offs [NT-proBNP 347 ng/L (area under the curve (AUC) 0.91), MR-proANP 230 pg/L (AUC 0.78), PAPP-A 14.5 mU/L (AUC 0.81), and sST2 48.0 ng/ml (AUC 0.88)] indicated a RVEF ≤ 35% at baseline. The dynamics of NT-proBNP (rs = -0.79; p < 0.001), MR-proANP (rs = -0.80; p < 0.001), and sST2 (rs = -0.49; p = 0.02) correlated inversely with the improvement in RVEF after therapy. A relative decrease of NT-proBNP < 53% (AUC 0.86) and MR-proANP < 24% (AUC 0.82) indicated a limited RVEF response. CONCLUSIONS: In chronic thromboembolic pulmonary hypertension patients, cardiac magnetic resonance imaging findings illustrate right heart failure and recovery after balloon pulmonary angioplasty therapy. Cardiac biomarker levels correlate with right heart parameters at baseline and their dynamics after therapy.

Application and Validation of the Tricuspid Annular Plane Systolic Excursion/Systolic Pulmonary Artery Pressure Ratio in Patients with Ischemic and Non-Ischemic Cardiomyopathy.

The main aim of this study was to assess the prognostic utility of TAPSE/PASP as an echocardiographic parameter of maladaptive RV remodeling in cardiomyopathy patients using cardiac magnetic resonance (CMR) imaging. Furthermore, we sought to compare TAPSE/PASP to TAPSE. The association of the echocardiographic parameters TAPSE/PASP and TAPSE with CMR parameters of RV and LV remodeling was evaluated in 111 patients with ischemic and non-ischemic cardiomyopathy and cut-off values for maladaptive RV remodeling were defined. In a second step, the prognostic value of TAPSE/PASP and its cut-off value were analyzed regarding mortality in a validation cohort consisting of 221 patients with ischemic and non-ischemic cardiomyopathy. A low TAPSE/PASP (<0.38 mm/mmHg) and TAPSE (<16 mm) were associated with a lower RVEF and a long-axis RV global longitudinal strain (GLS) as well as higher RVESVI, RVEDVI and NT-proBNP. A low TAPSE/PASP, but not TAPSE, was associated with a lower LVEF and long-axis LV GLS, and a higher LVESVI, LVEDVI and T1 relaxation time at the interventricular septum and the RV insertion points. Furthermore, in the validation cohort, low TAPSE/PASP was associated with a higher mortality and TAPSE/PASP was an independent predictor of mortality. TAPSE/PASP is a predictor of maladaptive RV and LV remodeling associated with poor outcomes in cardiomyopathy patients.

Circulating Monocyte Subsets Are Associated With Extent of Myocardial Injury but Not With Type of Myocardial Infarction.

Inflammation is a hallmark of the period after a myocardial infarction (MI) that is either promoted or resolved by distinct subtypes of circulating inflammatory cells. The three main monocyte subpopulations play different roles inflammation. This study examined whether the type of MI (type 1 or type 2) or the extent of myocardial injury is associated with differences in monocyte subpopulations. For this purpose, peripheral whole blood from patients with a suspected MI was used for flow cytometric measurements of the monocyte subpopulations, and myocardial injury was classified by cardiac troponin levels in serum. In patients with acute coronary syndrome (n = 82, 62.2% male) similar proportions of the monocyte subsets were associated with the two types of MI, whereas total monocyte counts were increased in patients with substantial myocardial injury vs. those with minor injury (p = 0.045). This was accompanied by a higher proportion of intermediate (p = 0.045) and classical monocytes (p = 0.059); no difference was found for non-classical monocytes (p = 0.772). In patients with chronic coronary syndrome (n = 144, 66.5% male), an independent association with myocardial injury was also observed for classical monocytes (p = 0.01) and intermediate monocytes (p = 0.08). In conclusion, changes in monocyte subpopulation counts, particularly for classical and intermediate monocytes, were related to the extent of myocardial injury in acute and stable coronary artery disease but not to the type of MI.

CMR-derived myocardial strain analysis differentiates ischemic and dilated cardiomyopathy-a propensity score-matched study.

Left ventricular (LV) longitudinal, circumferential, and radial motion can be measured using feature tracking of cardiac magnetic resonance (CMR) images. The aim of our study was to detect differences in LV mechanics between patients with dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) who were matched using a propensity score-based model. Between April 2017 and October 2019, 1224 patients were included in our CMR registry, among them 141 with ICM and 77 with DCM. Propensity score matching was used to pair patients based on their indexed end-diastolic volume (EDVi), ejection fraction (EF), and septal T1 relaxation time (psmatch2 module L Feature tracking provided six parameters for global longitudinal, circumferential, and radial strain with corresponding strain rates in each group. Strain parameters were compared between matched pairs of ICM and DCM patients using paired t tests. Propensity score matching yielded 72 patients in each group (DCM mean age 58.6 ± 11.6 years, 15 females; ICM mean age 62.6 ± 13.2 years, 11 females, p = 0.084 and 0.44 respectively; LV-EF 32.2 ± 13.5% vs. 33.8 ± 12.1%, p = 0.356; EDVi 127.2 ± 30.7 ml/m2 vs. 121.1 ± 41.8 ml/m2, p = 0.251; native T1 values 1165 ± 58 ms vs. 1167 ± 70 ms, p = 0.862). There was no difference in global longitudinal strain between DCM and ICM patients (- 10.9 ± 5.5% vs. - 11.2 ± 4.7%, p = 0.72), whereas in DCM patients there was a significant reduction in global circumferential strain (- 10.0 ± 4.5% vs. - 12.2 ± 4.7%, p = 0.002) and radial strain (17.1 ± 8.51 vs. 21.2 ± 9.7%, p = 0.039). Our data suggest that ICM and DCM patients have inherently different myocardial mechanics, even if phenotypes are similar. Our data show that GCS is significantly more impaired in DCM patients. This feature may help in more thoroughly characterizing cardiomyopathy patients.

Safety and efficacy of coronary sinus narrowing in chronic refractory angina: Insights from the RESOURCE study.

INTRODUCTION: Refractory angina (RA) is considered the end-stage of coronary artery disease, and often has no interventional treatment options. Coronary sinus Reducer (CSR) is a recent addition to the therapeutic arsenal, but its efficacy has only been evaluated on small populations. The RESOURCE registry provides further insights into this therapy. METHODS: The RESOURCE is an observational, retrospective registry that includes 658 patients with RA from 20 centers in Europe, United Kingdom and Israel. Prespecified endpoints were the amelioration of anginal symptoms evaluated with the Canadian Cardiovascular Society (CCS) score, the rates of procedural success and complications, and MACEs as composite of all-cause mortality, acute coronary syndromes, and stroke. RESULTS: At a median follow-up of 502 days (IQR 225-1091) after CSR implantation, 39.7% of patients improved by ≥2 CCS classes (primary endpoint), and 76% by ≥1 class. Procedural success was achieved in 96.7% of attempts, with 3% of procedures aborted mostly for unsuitable coronary sinus anatomy. Any complication occurred in 5.7% of procedures, but never required bailout surgery nor resulted in intra- or periprocedural death or myocardial infarction. One patient developed periprocedural stroke after inadvertent carotid artery puncture. At the last available follow-up, overall mortality and MACE were 10.4% and 14.6% respectively. At one, three and five years, mortality rate at Kaplan-Meier analysis was 4%, 13.7%, and 23.4% respectively. CONCLUSIONS: CSR implantation is safe and reduces angina in patients with refractory angina.

Puff-Resolved Analysis and Selected Quantification of Chemicals in the Gas Phase of E-Cigarettes, Heat-Not-Burn Devices, and Conventional Cigarettes Using Single-Photon Ionization Time-of-Flight Mass Spectrometry (SPI-TOFMS): A Comparative Study.

INTRODUCTION: A wide array of alternative nicotine delivery devices (ANDD) has been developed and they are often described as less harmful than combustible cigarettes. This work compares the chemical emissions of three ANDD in comparison to cigarette smoke. All the tested ANDD are characterized by not involving combustion of tobacco. AIMS AND METHODS: Single-photon ionization time-of-flight mass spectrometry (SPI-TOFMS) is coupled to a linear smoking machine, which allows a comprehensive, online analysis of the gaseous phase of the ANDD aerosol and the conventional cigarette (CC) smoke. The following devices were investigated in this study: a tobacco cigarette with a glowing piece of coal as a heating source, an electric device for heating tobacco, and a first-generation electronic cigarette. Data obtained from a standard 2R4F research cigarette are taken as a reference. RESULTS: The puff-by-puff profile of all products was recorded. The ANDD show a substantial reduction or complete absence of known harmful and potentially harmful substances compared with the CC. In addition, tar substances (i.e. semivolatile and low volatile aromatic and phenolic compounds) are formed to a much lower extent. Nicotine, however, is supplied in comparable amounts except for the investigated electronic cigarette. CONCLUSIONS: The data show that consumers switching from CC to ANDD are exposed to lower concentrations of harmful and potentially harmful substances. However, toxicological and epidemiological studies must deliver conclusive results if these reduced exposures are beneficial for users. IMPLICATIONS: The comparison of puff-resolved profiles of emissions from different tobacco products, traditional and alternative, may help users switch to lower emission products. Puff-resolved comparison overcomes technical changes, use modes between products and may help in their regulation.

[Comments on the German consensus statement on prehospital treatment of acute coronary syndrome in patients under long-term treatment with novel oral anticoagulants (NOAC)]. / Kommentar zum Konsensuspapier zur prähospitalen Behandlung des akuten Koronarsyndroms bei Patienten unter Dauertherapie mit neuen oralen Antikoagulanzien (NOAK).

Despite an increasing number of patients suffering from an acute coronary syndrome under novel oral anticoagulant therapy, specific treatment recommendations for anticoagulation are still lacking. For this reason, the German Society of Cardiology and the German Association of Interdisciplinary Intensive Care and Emergency Medicine developed a consensus statement for the treatment of these patients with the aim to summarize the current evidence and to increase the safety of this special patient group.

Prospective validation of an acoustic-based system for the detection of obstructive coronary artery disease in a high-prevalence population.

Recent guidelines recommend a risk-adjusted, non-invasive work-up in patients presenting with chest discomfort to exclude coronary artery disease (CAD). However, a risk-adjusted diagnostic approach remains challenging in clinical practice. An acoustic detection device for analyzing micro-bruits induced by stenosis-generated turbulence in the coronary circulation has shown potential for ruling out CAD in patients with low-to-intermediate likelihood. We examined the diagnostic value of this acoustic detection system in a high-prevalence cohort. In total, 226 patients scheduled for clinically indicated invasive coronary angiography (ICA) were prospectively enrolled at two centers and examined using a portable, acoustic detection system. The acoustic analysis was performed in double-blinded fashion prior to quantitative ICA and following percutaneous coronary intervention (PCI). An acoustic detection result (CAD score) was obtained in 94% of all patients. The mean baseline CAD score was 41.2 ± 11.9 in patients with obstructive CAD and 33.8 ± 13.4 in patients without obstructive CAD (p < 0.001). ROC analysis revealed an AUC of 0.661 (95% CI 0.584-0.737). Sensitivity was 97.6% (95% confidence interval (CI) 91.5-99.7%), specificity was 14.5% (CI 9.0-21.7%), negative predictive value was 90.5% (CI 69.6-98.8%), and positive predictive value was 41.7% (CI 34.6-49.0%). Following PCI, the mean CAD score decreased from 40.5 ± 11.2 to 38.3 ± 13.7 (p = 0.039). Using an acoustic detection device identified individuals with CAD in a high-prevalence cohort with high sensitivity but relatively low specificity. The negative predictive value was within the predicted range and may be of value for a fast rule-out of obstructive CAD even in a high-prevalence population.

Natural history of pulmonary atresia with intact ventricular septum (PAIVS) and critical pulmonary stenosis (CPS) and prediction of outcome.

OBJECTIVES: To analyse prenatal parameters predicting biventricular (BV) outcome in pulmonary atresia with intact ventricular septum/critical pulmonary stenosis (PAIVS/CPS). METHODS: We evaluated 82 foetuses from 01/08 to 10/18 in 3 centres in intervals 1 (< 24 weeks), 2 (24-30 weeks) and 3 (> 30 weeks). RESULTS: 61/82 (74.4%) were livebirths, 5 (8.2%) lost for follow-up, 3 (4.9%) had compassionate care leaving 53 (64.6% of the whole cohort and 86.9% of livebirths) with intention to treat. 9 died, 44/53 (83.0%) survived. 24/38 (63.2%) with information on postnatal outcome had BV outcome, 14 (36.8%) non-BV outcome (2 × 1.5 circulation). One with BV outcome had prenatal valvuloplasty. Best single parameter for BV outcome was tricuspid/mitral valve (TV/MV) ratio (AUC 0.93) in intervals 2 and 3 (AUC 0.92). Ventriculo-coronary-arterial communications (VCAC) were present in 11 (78.6%) in non-BV outcome group vs. 2 (8.3%) in BV outcome group (p < 0.001). Tricuspid insufficiency (TI)-Vmax > 2.5 m/s was present in BV outcome group in75.0% (18/24) vs. 14.3% (2/14) in non-BV outcome group. Including the most predictive markers (VCAC presence, TI- Vmax < 2.5 m/s, TV/MV ratio < cutoff) to a score, non-BV outcome was correctly predicted when > 1 criterion was fulfilled in all cases. After recently published criteria for foetal intervention, only 4/9 (44.4%) and 5/14 (35.7%) in our interval 2 + 3 with predicted non-BV outcome would have been candidates for intervention. Two (1 × intrauterine intervention) in interval 2, two in interval 3 reached BV outcome and one 1.5 circulation without intervention. CONCLUSION: TV/MV ratio as simple parameter has high predictive value. After our score, non-BV outcome was correctly predicted in all cases. Criteria for foetal intervention must further be evaluated.

Mid-regional pro-atrial natriuretic peptide and copeptin as indicators of disease severity and therapy response in CTEPH.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) leads to right heart failure. Pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) restore pulmonary haemodynamics and allow cardiac recovery. This study examined the relationship of copeptin and mid-regional pro-atrial natriuretic peptide (MR-proANP) levels to disease severity and therapy response. METHODS: This observational cohort study included 125 patients (55 PEA/70 BPA) who underwent treatment and completed a 6-/12-month follow-up. Biomarkers, measured at baseline, prior to every BPA and at follow-up, were compared to 1) severe disease at baseline (right atrial pressure (RAP) ≥8 mmHg and cardiac index ≤2.4 L·min-1·m-2) and 2) optimal therapy response (no persistent pulmonary hypertension combined with a normalised RAP (mean PAP ≤25 mmHg, pulmonary vascular resistance (PVR) ≤3 WU and RAP ≤6 mmHg) or a reduction in mean PAP ≥25%, PVR ≥35% and RAP ≥25%). RESULTS: Severely diseased patients had higher levels of MR-proANP (320 (246-527) pmol·L-1 versus 133 (82-215) pmol·L-1; p=0.001) and copeptin (12.7 (7.3-20.6) pmol·L-1 versus 6.8 (4.4-12.8) pmol·L-1; p=0.015) at baseline than the rest of the cohort. At baseline, MR-proANP (area under the curve (AUC) 0.91; cut-off value 227 pmol·L-1; OR 56, 95% CI 6.9-454.3) and copeptin (AUC 0.70; cut-off value 10.9 pmol·L-1; OR 1.5, 95% CI 1.2-1.9) identified severely diseased patients. After PEA/BPA, levels of MR-proANP (99 (58-145) pmol·L-1; p<0.001) and copeptin (6.3 (3.7-12.6) pmol·L-1; p=0.009) decreased and indicated optimal therapy response (MR-proANP <123 pmol·L-1 (AUC 0.70) and copeptin <10.1 pmol·L-1 (AUC 0.58)). CONCLUSION: MR-proANP and copeptin levels are affected in CTEPH and decrease after therapy. MR-proANP identifies a severe disease status and optimal therapy response.

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.

Myeloid-related protein 8/14 and high-sensitivity cardiac troponin I to differentiate type 2 myocardial infarction.

Myocardial infarction (MI) not only defines acute MI with obstructed coronary arteries (T1MI) but also myocardial necrosis caused by myocardial oxygen supply/demand mismatch as type 2 MI (T2MI); only T1MI patients benefit from an early invasive management. Myeloid-related protein(MRP)-8/14 is a biomarker described in various inflammatory diseases and in MI patients. Here we evaluate the potential of MRP-8/14 and high-sensitivity troponin I (hs-cTnI) to differentiate T2MI from T1MI. Patients with final diagnosis NSTEMI (n = 254; 33.1% female) enrolled in a prospective biomarker registry between 08/2011 and 10/2016 were analysed. Median baseline MRP-8/14 levels were higher in T2MI (n = 55; 3.37(1.88-6.48)µg/mL) than in T1MI (n = 199; 2.4 [1.4-3.79]µg/mL) (p = .013) patients, in contrast to hs-cTnI (T2MI:52[11.65-321.4]ng/L vs. T1MI:436.5 [61.25-1973.8]ng/L; p < .001). To detect the strength of this association odds ratios(OR) were calculated with MRP-8/14 yielding 2.13(1.16-3.92; p = .015) to predict T2MI and 0.47(0.26-0.87; p = .015) for T1MI. As expected, hs-cTnI yielded an OR of to predict T2MI 0.34(0.17-0.65; p = .001) and 2.98(1.53-5.81; p = .001) for T1MI. Both markers show comparable and independent results if adjust to hs-cTnI/MRP-8/14, TIMI risk score and CRP. T2MI is associated with higher MRP-8/14 and lower hs-cTnI concentrations than T1MI. Our data suggest that MRP-8/14 as a marker of inflammation might provide usable discriminatory information complementing hs-cTnI in a diagnostic procedure evaluating the type of MI directly upon hospital admission.

Cm(III) retention by calcium silicate hydrate (C-S-H) gel and secondary alteration phases in carbonate solutions with high ionic strength: A site-selective TRLFS study.

We studied the Cm(III) retention by calcium silicate hydrate (C-S-H), portlandite (Ca(OH)2) and their alteration products calcite, vaterite, and aragonite in high ionic strength carbonate-containing solutions representing specific formation waters. For this, we synthesized C-S-H gels with calcium to silicon (C/S) ratios of 1.0 and 2.0 in the absence and presence of Cm(III), resulting in Cm(III)-free and Cm(III) doped C-S-H gel, respectively. For phase identification purposes we applied X-ray diffraction (XRD) while for the identification of the Cm(III)/C-S-H binding mode we applied site-selective time-resolved laser-induced luminescence spectroscopy (TRLFS). The stability of Cm(III) doped phases under repository-relevant conditions was evaluated by studying the time-dependent release of Cm(III) from the Cm(III) doped C-S-H gel into leaching solutions containing 0.02 M NaHCO3 or 2.5 M NaCl/0.02 M NaHCO3 over 60 d. Speciation changes of Cm(III) due to leaching were followed with TRLFS while C-S-H structure alterations and secondary phase formation were monitored with XRD. From the results it could be concluded that Cm(III) is not mobilized by aqueous carbonate but either remains incorporated in the C-S-H structure and portlandite or becomes partially re-immobilized into secondary CaCO3 phases. The presence of NaCl led to an accelerated conversion of metastable secondary CaCO3 phases into calcite.

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.