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Severe aortic valve stenosis (AS) and pulmonary hypertension (PH) are life-threatening cardiovascular conditions, necessitating early detection and intervention. Recent studies have explored the role of Insulin-like Growth Factor-Binding Protein 2 (IGF-BP2) in cardiovascular pathophysiology. Understanding its involvement may offer novel insights into disease mechanisms and therapeutic targets for these conditions. A total of 102 patients (46 female, 56 male) with severe AS undergoing a transcatheter aortic valve replacement (TAVR) in a single-center study were classified using echocardiography tests to determine systolic pulmonary artery pressure (sPAP) and the presence (sPAP ≥ 40 mmHg) or absence (sPAP < 40 mmHg) of PH. Additionally, serial laboratory determinations of IGF-BP2 before, and at 24 h, 96 h, and 3 months after intervention were conducted in all study participants. Considering the entire cohort, patients with PH had significant and continuously higher serum IGF-BP2 concentrations over time than patients without PH. After subdivision by sex, it could be demonstrated that the above-mentioned results were only verifiable in males, but not in females. In the male patients, baseline IGF-BP2 levels before the TAVR was an isolated risk factor for premature death after intervention and at 1, 3, and 5 years post-intervention. The same was valid for the combination of male and echocardiographically established PH patients. The predictive role of IGF-BP2 in severe AS and concurrent PH remains unknown. A more profound comprehension of IGF-BP2 mechanisms, particularly in males, could facilitate the earlier consideration of the TAVR as a more effective and successful treatment strategy.

Introduction: Hypertrophies of the cardiac septum are caused either by aortic valve stenosis (AVS) or by congenital hypertrophic obstructive cardiomyopathy (HOCM). As they induce cardiac remodeling, these cardiac pathologies may promote an arrhythmogenic substrate with associated malignant ventricular arrhythmias and may lead to heart failure. While altered calcium (Ca2+) handling seems to be a key player in the pathogenesis, the role of mitochondrial calcium handling was not investigated in these patients to date.Methods: To investigate this issue, cardiac septal samples were collected from patients undergoing myectomy during cardiac surgery for excessive septal hypertrophy and/or aortic valve replacement, caused by AVS and HOCM. Septal specimens were matched with cardiac tissue obtained from post-mortem controls without cardiac diseases (Ctrl).Results and discussion: Patient characteristics and most of the echocardiographic parameters did not differ between AVS and HOCM. Most notably, the interventricular septum thickness, diastolic (IVSd), was the greatest in HOCM patients. Histological and molecular analyses showed a trend towards higher fibrotic burden in both pathologies, when compared to Ctrl. Most notably, the mitochondrial Ca2+ uniporter (MCU) complex associated proteins were altered in both pathologies of left ventricular hypertrophy (LVH). On the one hand, the expression pattern of the MCU complex subunits MCU and MICU1 were shown to be markedly increased, especially in AVS. On the other hand, PRMT-1, UCP-2, and UCP-3 declined with hypertrophy. These conditions were associated with an increase in the expression patterns of the Ca2+ uptaking ion channel SERCA2a in AVS (p = 0.0013), though not in HOCM, compared to healthy tissue. Our data obtained from human specimen from AVS or HOCM indicates major alterations in the expression of the mitochondrial calcium uniporter complex and associated proteins. Thus, in cardiac septal hypertrophies, besides modifications of cytosolic calcium handling, impaired mitochondrial uptake might be a key player in disease progression.

(1) Background and Objective: MicroRNAs (miRs) are biomarkers for assessing the extent of cardiac remodeling after myocardial infarction (MI) and important predictors of clinical outcome in heart failure. Overexpression of miR-30d-5p appears to have a cardioprotective effect. The aim of the present study was to demonstrate whether miR-30d-5p could be used as a potential therapeutic target to improve post-MI adverse remodeling. (2) Methods and Results: MiR profiling was performed by next-generation sequencing to assess different expression patterns in ischemic vs. healthy myocardium in a rat model of MI. MiR-30d-5p was significantly downregulated (p < 0.001) in ischemic myocardium and was selected as a promising target. A mimic of miR-30d-5p was administered in the treatment group, whereas the control group received non-functional, scrambled siRNA. To measure the effect of miR-30d-5p on infarct area size of the left ventricle, the rats were randomized and treated with miR-30d-5p or scrambled siRNA. Histological planimetry was performed 72 h and 6 weeks after induction of MI. Infarct area was significantly reduced at 72 h and at 6 weeks by using miR-30d-5p (72 h: 22.89 ± 7.66% vs. 35.96 ± 9.27%, p = 0.0136; 6 weeks: 6.93 ± 4.58% vs. 12.48 ± 7.09%, p = 0.0172). To gain insight into infarct healing, scratch assays were used to obtain information on cell migration in human umbilical vein endothelial cells (HUVECs). Gap closure was significantly faster in the mimic-treated cells 20 h post-scratching (12.4% more than the scrambled control after 20 h; p = 0.013). To analyze the anti-apoptotic quality of miR-30d-5p, the ratio between phosphorylated p53 and total p53 was evaluated in human cardiomyocytes using ELISA. Under the influence of the miR-30d-5p mimic, cardiomyocytes demonstrated a decreased pp53/total p53 ratio (0.66 ± 0.08 vs. 0.81 ± 0.17), showing a distinct tendency (p = 0.055) to decrease the apoptosis rate compared to the control group. (3) Conclusion: Using a mimic of miR-30d-5p underlines the cardioprotective effect of miR-30d-5p in MI and could reduce the risk for development of ischemic cardiomyopathy.

Abstract Prognostication after cardiopulmonary resuscitation (CPR) is complex. Novel biomarkers like soluble suppression of tumorigenicity 2 (sST2) may provide an objective approach. A total of 106 post-CPR patients were included in this single-center observational prospective study. Serum sST2 levels were obtained 24 h after admission. Individuals were assigned to two groups: patients below and above the overall cohort’s median sST2 concentration. Primary outcome was a combined endpoint at 6 months (death or Cerebral Performance Category > 2); secondary endpoint 30-day mortality. A uni- and multivariate logistic regression analysis were conducted. Elevated sST2-levels were associated with an increased risk for the primary outcome (OR 1.011, 95% CI 1.004–1.019, p = 0.004), yet no patients with poor neurological outcome were observed at 6 months. The optimal empirical cut-off for sST2 was 46.15 ng/ml (sensitivity 81%, specificity 53%, AUC 0.69). Levels above the median (> 53.42 ng/ml) were associated with higher odds for both endpoints (death or CPC > 2 after 6 months: 21% vs. 49%, OR 3.59, 95% CI 1.53–8.45, p = 0.003; death after 30 days: 17% vs. 43.3%, OR 3.75, 95% CI 1.52–9.21, p = 0.003). A positive correlation of serum sST2 after CPR with mortality at 30 days and 6 months after cardiac arrest could be demonstrated.

Introduction: Among the causes of de novo diagnosed cardiomyopathy, Takotsubo cardiomyopathy (TTC) plays a minor role, with an occurrence of 50,000–100,000 cases per annum in the United States. In clinical practice, a differentiation of a TTC toward an ischemic cardiomyopathy (ICMP) or a dilatative cardiomyopathy (DCMP) appears to be challenging, especially in a subacute setting or in atypical types of TTC.Methods: To investigate this issue, we analyzed serum levels of sST2, GDF-15, suPAR, HFABP, and clinical parameters including echocardiography in 51 patients with TTC, 52 patients with ischemic cardiomyopathy (ICMP) and 65 patients with dilated cardiomyopathy (DCMP).Results: sST-2 seemed to be the most promising biomarker for prediction of a TTC in differential diagnosis to an ICMP (AUC: 0.879, p = < 0.001, Cut off values: 12,140.5 pg/ml) or to a DCMP (AUC: 0.881, p = < 0.001, cut off value: 14521.9 pg/ml). GDF-15 evidenced a slightly lower AUC for prediction of a TTC in differential diagnosis to an ICMP (AUC: 0.626, p = 0.028) and to a DCMP (AUC: 0.653, p = 0.007). A differential diagnostic value was found for H-FABP in the prediction of a DCMP compared to TTC patients (AUC: 0.686, p = < 0.001). In propensity score matching for left ventricular ejection fraction, sex, and cardiovascular risk factors, differences in the plasma levels of sST2 and H-FABP in the matched cohort of TTC vs. DCMP remained statistically significant. In the matched cohort of TTC vs. ICMP, differences in sST2 also remained statistically significantConclusion: As medical therapy, long term prognosis, interval of follow-ups, rehabilitation program and recommendations differ completely between TTC and ICMP/DCMP, biomarkers for differential diagnosis, or rather for confirmation of diagnosis, are warranted in cases of cardiomyopathies with unsure origin. sST-2, GDF-15 and H-FABP might facilitate the classification.

(1) Double-stranded DNA (dsDNA) and deoxyribonuclease (DNase) as surrogate parameters for accumulating inflammatory hazards are insufficiently studied in resuscitation research. (2) Blood samples of 76 individuals after CA were analyzed 24 and 96 h after ICU admission. Plasma levels of dsDNA, interleukin-8, and monocyte chemoattractant protein-1 and activity of DNase were assessed along with baseline characteristics, intensive care measures, and outcome data. DsDNA/DNase ratio was used as main prognostication parameter. After calculating an optimal empirical cut-off for outcome prediction (death or Cerebral Performance Category ≥3 at 6 months), multivariable logistic regression was applied. (3) Using receiver operating characteristic (ROC) analysis, an area under the curve (AUC) of 0.65 (95% CI 0.50–0.79) was found for dsDNA/DNase after 24 h versus 0.83 (95% CI 0.73–0.92) after 96 h (p = 0.03). The empirical cut-off for dsDNA/DNase ratio after 96 h was 149.97 (Youden). DsDNA/DNase ratio was associated with unfavorable outcome at six months (aOR 1.006, 95% CI 1.0017–1.0094, p = 0.005). In multivariable analysis, the association of dsDNA/DNase ratio independently predicted outcome as a continuous variable (aOR 1.004, 95% CI 1.0004–1.0079, p = 0.029) after adjusting for potential confounders. (4) DsDNA/DNase ratio at 96 h demonstrates good predictive performance for estimating outcome after CA.

Background: Patients with severe aortic valve stenosis (AS) frequently present with pulmonary hypertension (PH). The gold standard for detection of pulmonary hypertension is right heart catheterization, which is not routinely performed as a preoperative standard in cardiology centers today, neither before surgical valve replacement nor before transcatheter aortic valve replacement (TAVR) procedure. Echocardiographic determination of systolic pulmonary artery pressure (sPAP) provides an opportunity to assess the presence or absence of PH. The aim of the present study was to investigate the extent to which plasma levels of common cardiovascular biomarkers behave in patients with severe AS and an sPAP

Background: Since right heart catheterization is rarely performed in patients with severe aortic valve stenosis (AS), echocardiography is currently the tool of choice to determine the presence or absence of pulmonary hypertension (PH). The systolic pulmonary artery pressure (sPAP) has established itself as a reliable measurement value for this purpose. The aim of our study was to evaluate the behavior of plasma-level concentrations of novel cardiovascular biomarkers (sST2, GDF-15, H-FABP, IGF-BP2, and suPAR) in patients with severe AS and an sPAP < 40 mmHg in comparison to patients with an sPAP ≥ 40 mmHg before transcatheter aortic valve replacement (TAVR) and after TAVR (24 h, 96 h, 3 months, and 12 months). Methods: We retrospectively separated 85 patients with echocardiographic evidence of severe AS before TAVR procedure into two groups based on sPAP level. An sPAP of 40 mmHg was considered the cut-off value, with the absence of PH defined by an sPAP < 40 mmH (n = 32) and the presence of PH defined by an sPAP ≥ 40 mmHg (n = 53). Blood samples were drawn from each patient one day before TAVR and 24 h, 96 h, 3 months, and 12 months after TAVR. Plasma concentrations of the cardiovascular biomarkers sST2, GDF-15, H-FABP, IGF-BP2, and suPAR were determined and analyzed with univariate and multivariate binary logistic regression and AUROC curves. Results: Patients with severe AS and an sPAP ≥ 40 mmHg had significantly higher plasma concentrations of H-FABP (baseline: p = 0.022; 24 h: p = 0.012; 96 h: p = 0.037; 3 months: p = 0.006; 12 months: p = 0.030) and IGF-BP2 (baseline: p = 0.029; 24 h: p = 0.012; 96 h: p = 0.001; 3 months: p = 0.015; 12 months: p = 0.022) before and continuously up to 12 months after TAVR than did patients with an sPAP < 40 mmHg sST2, with the exception of the 12-month follow-up. We also consistently found significantly higher plasma concentrations in the sPAP ≥ 40 mmHg group (baseline: p = 0.007; 24 h: p = 0.006; 96 h: p = 0.014; 3 months: p ≤ 0.001; 12 months: p = 0.092), whereas suPAR had significantly elevated values at baseline and after 24 h in patients with echocardiographic evidence of PH and significantly decreased values after 3 months (baseline: p = 0.003; 24 h p = 0.041; 96 h: p = 0.127; 3 months: p = 0.006; 12 months: p = 0.477). Plasma concentrations of GDF-15 were only significantly different after 24 h (baseline: p = 0.075; 24 h: p = 0.016; 96 h: p = 0.101; 3 months: p = 0.244; 12 months: p = 0.090). In a multivariate binary logistic regression, atrial fibrillation, tricuspid annular plane systolic excursion (TAPSE), and sST2 at baseline were found to have a significant p-value < 0.050. Conclusion: In this descriptive study, sST2, H-FABP, and IGF-BP2 emerged as the cardiovascular biomarkers with the greatest potential with respect to echocardiographically PH detection in long-term follow-up after TAVR, as patients with an sPAP ≥ 40 mmHg had significantly continuously higher plasma biomarker concentrations than the corresponding cohort did, with an sPAP < 40 mmHg.

(1) Background: Sepsis still represents a major health care challenge, with mortality rates exceeding 25% in the western world. To further improve outcomes in this patient collective, new cardiovascular biomarkers present a promising opportunity as they target the paramount prognostic processes in sepsis: inflammation and ischemia. However, in contrast to cardiovascular diseases, a detailed analysis of novel biomarkers in sepsis is still lacking. (2) Objective: In this project, we aimed to perform a comparative analysis of biomarker levels in ischemic cardiovascular disease and sepsis. Analyzed markers comprised soluble suppression of tumorigenicity 2 (sST2; hemodynamics and inflammation), growth-differentiation factor 15 (GDF-15; injury, remodelling), soluble urokinase-type plasminogen activator receptor (suPAR; inflammation and remodeling) and heart-type fatty acid binding protein (H-FABP; myocardial ischemia). (3) Methods: In total, 311 patients were included in the study: 123 heart-failure (HF) patients, 60 patients with ST-segment elevation myocardial infarction (STEMI) and 53 sepsis patients. A total of 75 patients without coronary artery disease or signs of heart failure served as a control group. Plasma samples were analyzed by use of ELISA after informed consent. (4) Results: Patients with sepsis showed significantly increased plasma levels in all tested biomarkers compared to cardiovascular disease entities (sST2, suPAR, GDF-15: p < 0.001; H-FABP: compared to HF p < 0.001) and controls (sST2: 7.4-fold, suPAR: 3.4-fold, GDF-15: 6.5-fold and H-FABP: 15.3-fold increased plasma levels, p < 0.001). Moreover, in patients with sepsis, serum concentrations of sST2 and suPAR were significantly elevated in patients with HF and patients with STEMI (sST2: HF: 1.6-fold increase and STEMI: 2.5-fold increase, p < 0.001; suPAR: HF: 1.4-fold increase, p < 0.001 and STEMI: 1.4-fold increase, p < 0.01), whereas plasma levels of GDF-15 and H-FABP were markedly elevated in patients with STEMI only (GDF-15: 1.6-fold increase, H-FABP: 6.4-fold increase, p < 0.001). (5) Conclusions: All tested novel cardiac biomarkers showed significantly elevated levels in sepsis patients. Interestingly, a secretion pattern similar to STEMI was observed with regards to sST2 and HFABP. Thus, by providing an assessment tool especially covering the cardiovascular component of the disease, novel biomarkers offer a promising tool in sepsis patients.

Background: Renal sympathetic denervation (RSD) has provided promising data in its ability to treat therapy resistant arterial hypertension. The effect of RSD on sST-2, a promising biomarker for risk stratification in cardiovascular diseases, has so far not been systematically studied. Methods: We evaluated serum levels of sST-2 and clinical parameter including left ventricular mass (LVM) in 54 patients with resistant hypertension (RH) undergoing bilateral RSD at baseline as well as at one and/or three months. Results: After RSD, mean office blood pressure showed a significant decrease after one month (p < 0.001). On echocardiography a reduction of LVM was observed at three months (p < 0.01). This was accompanied by a significant decrease of sST-2 levels at three months (sST-2 baseline: 6310.1 ± 3246.0 pg/mL vs. sST-2 three months: 4703.8 ± 1585.9 pg/mL, p = 0.048). Furthermore, baseline sST-2 levels were positively correlated with systolic blood pressure at one month (r = 0.514, p < 0.01) but not three months, indicating a potential predictive value of sST-2 for early intervention success. Conclusion: In patients with RH, RSD is associated with a significant decrease of sST-2 levels after three months, indicating sST-2 to be involved in remodeling processes after RSD. Furthermore, lower sST-2 levels at baseline might be a potential predictor of early intervention success of RSD.