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Background/Objectives: Right ventricular pacing is an effective and safe treatment option for patients experiencing symptomatic bradycardia. However, some individuals may develop left ventricular dysfunction as a consequence. Growth differentiation factor 15 (GDF-15), which is not present in a healthy adult heart, is upregulated in cardiomyocytes in response to various stress stimuli. This study aimed to explore the potential of GDF-15 as a biomarker for chronic right ventricular pacing. Methods: This single-center cross-sectional cohort study analyzed data from 265 consecutive patients (60.4% male) with either single- or dual-chamber pacemakers, all lacking pre-existing heart failure, who attended the outpatient department for routine follow-up. Chronic right ventricular (RV) pacing was defined as pacing exceeding 40% over the past year. Serum samples were collected, and GDF-15 levels were measured using a commercially available immunoassay (R&D Systems Inc., Minneapolis, MN, USA). Student's t -test was utilized to assess group differences, and receiver operating characteristic (ROC) analysis was employed to evaluate diagnostic performance. Results: When stratifying patients by pacing burden, GDF-15 levels were significantly higher in those with pacing over 40% compared to those with 40% or less (789 ± 293 pg/mL vs. 1186 ± 592 pg/mL; p < 0.001). The ROC analysis indicated that GDF-15 serves as a marker for chronic RV pacing, yielding an area under the curve of 0.713 (95% confidence interval 0.650-0.776; p < 0.001). Conclusions: This study suggests that GDF-15 may be a valuable biomarker for chronic right ventricular pacing.

Background/Objectives: Heart failure (HF) remains a major therapeutic and diagnostic challenge nowadays. Albeit, acute decompensated HF is associated with several clinical signs such as dyspnea or edema, it remains a challenge to use easy accessible and suitable tools, such as biomarkers, to distinguish between patients at risk for an acute decompensation of their heart failure and compensated, stable HF patients. Existing biomarkers, such as natriuretic peptides or troponin, are not specific and can be elevated due to several other disease conditions, such as myocardial infarction, atrial fibrillation, or valve diseases. Therefore, the aim of this study was to analyze the predictive potential of four novel cardiovascular biomarkers-the soluble urokinase-type plasminogen activator receptor (suPAR), heart-type fatty acid binding protein (H-FABP), vascular cell adhesion molecule 1 (VCAM-1), and growth/differentiation factor 15 (GDF-15) for the detection of cardiac decompensation in patients with HF. Methods : In this study, 146 patients were prospectively enrolled and the serum biomarker concentrations were analyzed using Enzyme Linked Immunosorbent Assay (ELISA). We correlated the biomarker concentrations with clinical and biochemical parameters of all patients and the predictive value for detection of cardiac decompensation was assessed. Results: A significant increase in the levels of suPAR (1.6-fold-change, p < 0.0001), H-FABP (2.2-fold-change, p = 0.0458), VCAM-1 (1.6-fold-change, p < 0.0001), and GDF-15 (1.7-fold-change, p = 0.0009) was detected in all patients with acute decompensated HF in comparison to patients with compensated HF. Univariate logistic regression analysis revealed a significant association of biomarker plasma concentration with the risk for a cardiac decompensation (suPAR: p < 0.0001; VCAM-1: p < 0.0001, H-FABP: p = 0.0458; GDF-15: p = 0.0009). Conclusion s: In conclusion, the investigated novel cardiovascular biomarkers suPAR, GDF-15, VCAM-1, and H-FABP could be a valuable tool to facilitate therapeutic decisions in patients with heart failure and suspicion of a cardiac decompensation. Parameters such as renal function should be taken into account. Further studies on novel biomarkers are required to find reliable, sensitive, and specific tools that will enable the early detection of patients with acute decompensation.

Background: Increased mortality and occurrence of cardiovascular (CV) outcomes during hospitalization and in short-term follow-up for moderate to severe SARS-CoV-2 infection have been associated with male sex, yet data regarding long-term outcomes by sex and COVID-19 variant (Alpha, Delta, and Omicron) are limited. Methods : This prospective study of 4882 patients examines potential differences by sex in the occurrence of primary combined cardiovascular outcomes (CV death, CV hospitalization, myocardial infarction (MI), stroke, pulmonary embolism) as well as secondary outcomes (CV death, cardiovascular hospitalizations, myocardial infarction, stroke, pulmonary embolism) at 18-month follow-up after urgent hospitalization for SARS-CoV-2-associated pneumonia, as well as evaluating for differences during the three COVID-19 waves. Survival rate was analyzed for the entire cohort by sex and SARS-CoV-2 variant and adjusted for age using the multiple Kaplan-Meier method. To compare survival in groups of men and women for each wave, the Gehan-Wilcoxon test was applied with significance p < 0.05. Univariate Cox proportional hazards models were used to search for potential risk factors of CV death at 18-months follow-up separately for men and women in each COVID-19 wave. Results : Men had significantly higher 18-month CV mortality compared to women in the Delta wave (6.13% men vs. 3.62% women, p = 0.017). Although men had higher percentages of all other CV endpoints (excepting pulmonary embolism) at follow-up during the Delta wave, none were significant compared with women, except for the combined CV endpoint (16.87% men vs. 12.61% women, p = 0.017). No significant differences by sex in CV outcomes were seen during the Alpha and Omicron variants. Discrepancies in CV outcomes in demographical data and concomitant disease between the COVID-19 variants of concern existed. Conclusions: Higher male mortality and higher but non-significant incidences of CV outcomes occurred during the Delta wave of the COVID-19 pandemic, with the lowest incidence of CV outcomes observed during the Omicron variant.

Background: Prediabetes is frequently underdiagnosed and undertreated, yet it poses significant cardiovascular risks. This study investigates the impact of prediabetes on short- and long-term survival outcomes in patients who experienced ST-elevation myocardial infarction (STEMI). Methods: In this retrospective, single-center cohort study, we evaluated 725 STEMI patients stratified into non-diabetic, prediabetic, and diabetic groups based on HbA1c levels at presentation. A Kaplan-Meier survival analysis was employed to compare long-term outcomes over a three-year follow-up period. Cardiovascular risk factors, including hypertension and dyslipidemia, were analyzed across the groups. The discriminatory power of HbA1c for predicting all-cause mortality was assessed using an Area Under the Receiver Operating Characteristic (AUROC) analysis. Results : Of the 725 patients, 407 (56.1%) were non-diabetic, 184 (25.4%) were prediabetic, and 134 (18.5%) were diabetic. Prediabetic patients exhibited significant additional cardiovascular risk factors, such as arterial hypertension (67.4%) and dyslipidemia (78.3%), with prevalence rates between those of non-diabetic and diabetic patients. The Kaplan-Meier analysis revealed that at a three-year follow-up, prediabetic patients faced a survival disadvantage, with a significant decrease in survival rates compared to non-diabetic patients (log-rank p = 0.016); their survival outcomes approached those of diabetic patients ( p = 0.125). The AUROC analysis demonstrated that HbA1c was a significant predictor of short- and long-term mortality, with a cut-off value of 5.75% and an Area Under the Curve (AUC) of 0.580-0.617 (95% CI: 0.458-0.721), indicating a moderate ability to predict survival in patients with STEMI. Conclusions: Prediabetes significantly worsens survival outcomes following STEMI, nearly approaching the risk level of diabetes. Integrating rigorous cardiovascular risk management strategies for prediabetic individuals, including lifestyle interventions and potentially pharmacological treatments, could prevent the progression to diabetes and mitigate associated cardiovascular risks.

Background: Heart failure (HF) remains a challenging healthcare issue necessitating innovative therapies like cardiac resynchronization-defibrillation therapy (CRT-D). However, the definition of a CRT-D response lacks uniformity, impeding effective clinical evaluation. This study explores diverse CRT-D responder definitions encompassing functional, echocardiographic and laboratory criteria. Materials & Methods: A single-center study involving 132 CRT-D patients scrutinized responder criteria including NYHA stage, LVEF increase and proBNP decrease. Statistical analyses such as Kaplan-Meier curves and Cox hazard regression were employed to evaluate responder characteristics and survival outcomes. Results: Responder rates varied across criteria, revealing nuanced patient profiles. CRT-D responders defined by NYHA decrease, LVEF increase or proBNP decrease exhibit improved survival rates after 2 and 3 years ( p < 0.050). Young age, absence of recent myocardial infarction and normal right ventricular echocardiographic parameters emerge as predictors for positive response. In part, drug-based HF therapy correlates with increased responder rates. Cox regression identified LVEF ≥ 5% and proBNP decrease ≥ 25% as independent predictors of extended survival. Conclusions: CRT-D responder definitions exhibit considerable variability, emphasizing the need for a nuanced patient-centered approach. Factors like right ventricular function, drug therapy, atrial fibrillation and renal function influence responses. This study enriches our understanding of CRT-D response and contributes to the foundation for personalized HF management.

Adropin-a multifunctional peptide with tissue-protective capacity that regulates energy homeostasis, sensitivity to insulin and inflammatory response-seems to show an inverse association with the presence of cardiovascular and renal diseases, obesity and diabetes mellitus in the general population. The purpose of the study is to elucidate whether adropin may be a plausible predictive biomarker for clinical outcomes in post-ST elevation of myocardial infarction (STEMI) patients with newly diagnosed prediabetes according to the American Diabetes Association criteria. A total of 1214 post-STEMI patients who received percutaneous coronary intervention were identified in a local database of the private hospital "Vita Center" (Zaporozhye, Ukraine). Between November 2020 and June 2024, we prospectively enrolled 498 patients with prediabetes in this open prospective cohort study and followed them for 3 years. The combined clinical endpoint at follow-up was defined as cardiovascular death due to acute myocardial infarction, heart failure, sudden death due to arrhythmia or cardiac surgery, and/or all-cause death. We identified 126 clinical events and found that serum levels of adropin < 2.15 ng/mL (area under the curve = 0.836; 95% confidence interval = 0.745-0.928; sensitivity = 84.9%; specificity = 72.7%; likelihood ratio = 3.11; p = 0.0001) predicted clinical outcomes. Multivariate logistic regression showed that a Gensini score ≥ 32 (Odds ratio [OR] = 1.07; p = 0.001), adropin ≤ 2.15 ng/mL (OR = 1.18; p = 0.001), use of SGLT2i (OR = 0.94; p = 0.010) and GLP-1 receptor agonist (OR = 0.95; p = 0.040) were independent predictors of clinical outcome. Kaplan-Meier plots showed that patients with lower adropin levels (≤2.15 ng/mL) had worse clinical outcomes compared to patients with higher adropin levels (>2.15 ng/mL). In conclusion, low levels of adropin (≤2.15 ng/mL) independently predicted clinical outcomes in post-STEMI patients with newly detected prediabetes and improved the discriminative ability of the Gensini score for 3-year follow-up events. Future clinical studies are needed to clarify whether adropin is a promising molecule to be incorporated into conventional risk scores for the prediction of MACCEs after STEMI.

The purpose of the study is to elucidate whether irisin is a promising predictive biomarker for kidney-related events in patients with T2DM and concomitant asymptomatic HF. We prospectively enrolled 146 T2DM patients who had either evidence of structural cardiac abnormality or elevated levels of N-terminal brain natriuretic pro-peptide (NT-proBNP) > 125 pmol/mL and followed them for 52 weeks. Structural cardiac abnormalities were used as the minimum from the following criteria: abnormal left ventricular (LV) global longitudinal strain (GLS) < -16%, LV hypertrophy, left atrial volume index > 34 mL/m 2 , abnormal ratio of early transmitral diastolic filling velocity/early mitral annular velocity ≥ 13 units. All the patients underwent echocardiographic and Doppler examinations by two blinded, highly experienced echocardiographers. NT-proBNP, irisin, TNF-alpha, and hs-CRP were quantified in the serum at baseline, at 26 weeks, and at the end of the study. The kidney-related outcomes consisted of an eGFR reduction by 40% from baseline, or end-stage kidney disease, or kidney replacement therapy. We found that levels of irisin at baseline < 4.15 ng/mL and/or its decrease > 20% from baseline in T2DM patients predicted kidney-related events better than baseline levels/dynamic NT-proBNP and the use of SGLT2 inhibitors. In conclusion, we established that a low baseline level of irisin and its 20% decrease correlated with newly kidney-related events in T2DM patients with asymptomatic HFpEF/HFmrEF.

In patients with type 2 diabetes mellitus (T2DM), asymptomatic adverse cardiac remodeling plays a pivotal role in the development of heart failure (HF). Patients with T2DM often have low or near-normal levels of natriuretic peptides, including N-terminal brain natriuretic peptide (NT-proBNP), which have been inconclusive in predicting the transition from asymptomatic adverse cardiac remodeling to HF with preserved ejection fraction (HFpEF). The aim of this study was to elucidate the predictive ability of adropin for HFpEF depending on the circulating levels of NT-proBNP. We prospectively enrolled 561 T2DM patients (glycated hemoglobin < 6.9%) with echocardiographic evidence of structural cardiac abnormalities and left ventricular ejection fractions >50%. All patients underwent B-mode transthoracic echocardiographic and Doppler examinations. Circulating biomarkers, i.e., NT-proBNP and adropin, were assessed at baseline. All individuals were divided into two groups according to the presence of low levels (<125 pmol/mL; n = 162) or elevated levels (≥125 pmol/mL; n = 399) of NT-proBNP. Patients with known asymptomatic adverse cardiac remodeling and elevated NT-proBNP were classified as having asymptomatic HFpEF. A multivariate logistic regression showed that low serum levels of adropin (<3.5 ng/mL), its combination with any level of NT-proBNP, and use of SGLT2 inhibitors were independent predictors of HFpEF. However, low levels of adropin significantly increased the predictive ability of NT-proBNP for asymptomatic HFpEF in patients with T2DM, even though the concentrations of NT-proBNP were low, while adropin added discriminatory value to all concentrations of NT-proBNP. In conclusion, low levels of adropin significantly increase the predictive ability of NT-proBNP for asymptomatic HFpEF in patients with T2DM.

(1) Background : Due to similar clinical presentation and a lack of specific biomarkers, initial differentiation between Takotsubo syndrome (TTS) and non-ST-segment elevation myocardial infarction (NSTEMI) remains challenging in daily practice. Heat Shock Protein 70 (HSP70) is a novel biomarker that is recognized for its potential in the diagnosis and differentiation of cardiovascular conditions. (2) Methods : Data from a total of 156 patients were analyzed (32.1% NSTEMI, 32.7% TTS, and 35.3% controls). Serum concentrations of HSP70 were determined using ELISA and compared between patients and controls. ROC curve analysis, logistic regression analysis and propensity-score-weighted logistic regression were conducted. (3) Results : Concentrations of HSP70 were highest in patients with TTS (median 1727 pg/mL vs. ACS: median 1545 pg/mL vs. controls: median 583 pg/mL, p < 0.0001). HSP70 was predictive for TTS in binary logistic regression analysis (B(SE) = 0.634(0.22), p = 0.004), which even remained significant after correction for possible confounders in propensity-score-weighted analysis. ROC curve analysis also revealed a significant association of HSP70 with TTS (AUC: 0.633, p = 0.008). (4) Conclusions : Based on our findings, HSP70 constitutes a promising biomarker for discrimination between TTS and NSTEMI, especially in combination with established cardiovascular biomarkers like pBNP or high-sensitivity cardiac troponin.

Right heart failure is a major challenge in clinical practice. Soluble Suppression of Tumorigenicity-2 (sST2), a member of the interleukin-1-receptor family, may have clinical prognostic value. The aim of this study was to analyze whether sST2 correlates with signs of acute right heart decompensation. This prospective single-center study included 50 patients admitted for clinical signs of predominant right heart decompensation. Signs of reduced blood supply to other organs (e.g., renal function parameter, troponin T, NT-proBNP), diuretics, and signs of venous congestion (inferior vena cava (IVC) diameter) with fluid retention (weight gain, peripheral edema) resulting from reduced RV function were analyzed. The degree of peripheral edema was defined as none, mild (5-6 mm depressible, regression in 15-60 s) or severe (>7 mm depressible, regression in 2-3 min). sST2 levels were measured at the day of hospitalization. A total of 78.7% showed severe peripheral edema. The median concentration of sST2 was 35.2 ng/mL (25.-75. percentiles 17.2-46.7). sST2 is correlated with the peripheral edema degree (rSpearman = 0.427, p = 0.004) and the diameter of IVC (r = 0.786, p = 0.036), while NT-proBNP (r = 0.114, p = 0.456), troponin T (r = 0.123, p = 0.430), creatinine-based eGFR (r = -0.207, p = 0.195), or cystatin C-based eGFR (r = -0.032, p = 0.839) did not. sST2, but no other established marker, is correlated with peripheral and central fluid status in patients with decompensated right heart failure.

The aim of this retrospective study was to provide real-world data on lipid-lowering therapy (LLT) implementation and low-density lipoprotein cholesterol (LDL-C) target achievement in an ST-segment elevation myocardial infarction (STEMI) population, with a focus on very-high-risk patients according to European guidelines criteria., Methods: Included were all STEMI patients with available LDL-C and total cholesterol treated at a large tertiary center in Salzburg, Austria, 2018-2020 ( n = 910), with stratification into very-high-risk cohorts. Analysis was descriptive, with variables reported as number, percentages, median, and interquartile range., Results: Among patients with prior LLT use, statin monotherapy predominated, 5.3% were using high-intensity statins, 1.2% were using combined ezetimibe therapy, and none were taking PCSK9 inhibitors at the time of STEMI. In very-high-risk secondary prevention cohorts, LLT optimization was alarmingly low: 8-22% of patients were taking high-intensity statins, just 0-6% combined with ezetimibe. Depending on the very-high-risk cohort, 27-45% of secondary prevention patients and 58-73% of primary prevention patients were not taking any LLTs, although 19-60% were actively taking/prescribed medications for hypertension and/or diabetes mellitus. Corresponding LDL-C target achievement in all very-high-risk cohorts was poor: <22% of patients had LDL-C values < 55 mg/dL at the time of STEMI., Conclusion: Severe shortcomings in LLT implementation and optimization, and LDL-C target achievement, were observed in the total STEMI population and across all very-high-risk cohorts, attributable in part to deficits in care delivery.

Atrial fibrillation (AF) is associated with atrial remodeling, cardiac dysfunction, and poor clinical outcomes. External direct current electrical cardioversion is a well-developed urgent treatment strategy for patients presenting with recent-onset AF. However, there is a lack of accurate predictive serum biomarkers to identify the risks of AF relapse after electrical cardioversion. We reviewed the currently available data and interpreted the findings of several studies revealing biomarkers for crucial elements in the pathogenesis of AF and affecting cardiac remodeling, fibrosis, inflammation, endothelial dysfunction, oxidative stress, adipose tissue dysfunction, myopathy, and mitochondrial dysfunction. Although there is ample strong evidence that elevated levels of numerous biomarkers (such as natriuretic peptides, C-reactive protein, galectin-3, soluble suppressor tumorigenicity-2, fibroblast growth factor-23, turn-over collagen biomarkers, growth differential factor-15) are associated with AF occurrence, the data obtained in clinical studies seem to be controversial in terms of their predictive ability for post-cardioversion outcomes. Novel circulating biomarkers are needed to elucidate the modality of this approach compared with conventional predictive tools. Conclusions: Biomarker-based strategies for predicting events after AF treatment require extensive investigation in the future, especially in the presence of different gender and variable comorbidity profiles. Perhaps, a multiple biomarker approach exerts more utilization for patients with different forms of AF than single biomarker use.

The aim of this study was to determine the discriminative value of irisin for acutely decompensated heart failure (ADHF) in type 2 diabetes mellitus (T2DM) patients with chronic HF. We included 480 T2DM patients with any phenotype of HF and followed them for 52 weeks. Hemodynamic performances and the serum levels of biomarkers were detected at the study entry. The primary clinical end-point was ADHF that led to urgent hospitalization. We found that the serum levels of N-terminal natriuretic pro-peptide (NT-proBNP) were higher (1719 [980-2457] pmol/mL vs. 1057 [570-2607] pmol/mL, respectively) and the levels of irisin were lower (4.96 [3.14-6.85] ng/mL vs. 7.95 [5.73-9.16] ng/mL) in ADHF patients than in those without ADHF. The ROC curve analysis showed that the estimated cut-off point for serum irisin levels (ADHF versus non-ADHF) was 7.85 ng/mL (area under curve [AUC] = 0.869 (95% CI = 0.800-0.937), sensitivity = 82.7%, specificity = 73.5%; p = 0.0001). The multivariate logistic regression yielded that the serum levels of irisin < 7.85 ng/mL (OR = 1.20; p = 0.001) and NT-proBNP > 1215 pmol/mL (OR = 1.18; p = 0.001) retained the predictors for ADHF. Kaplan-Meier plots showed a significant difference of clinical end-point accumulations in patients with HF depending on irisin levels (<7.85 ng/mL versus ≥7.85 ng/mL). In conclusion, we established that decreased levels of irisin were associated with ADHF presentation in chronic HF patients with T2DM independently from NT-proBNP.

Adropin is a multifunctional secreted protein, which is involved in the metabolic modulation of the heart-brain-kidney axis in heart failure (HF). The aim of the study was to detect the plausible predictive value of serum levels of adropin for chronic kidney disease (CKD) grades 1-3 in type 2 diabetes mellitus (T2DM) patients with chronic HF. We enrolled 417 T2DM individuals with chronic HF and subdivided them into two groups depending on the presence of CKD. The control group was composed of 25 healthy individuals and 30 T2DM patients without HF and CKD. All eligible patients underwent an ultrasound examination. Adropin was detected by ELISA in blood samples at the study baseline. We found that adropin levels in T2DM patients without HF and CKD were significantly lower than in healthy volunteers, but they were higher than in T2DM patients with known HF. The optimal cut-off point for adropin levels was 2.3 ng/mL (area under the curve [AUC] = 0.86; 95% CI = 0.78-0.95; sensitivity = 81.3%, specificity = 77.4%). The multivariate logistic regression adjusted for albuminuria/proteinuria showed that serum levels of adropin <2.30 ng/mL (OR = 1.55; p = 0.001) independently predicted CKD. Conclusions: Low levels of adropin in T2DM patients with chronic CH seem to be an independent predictor of CKD at stages 1-3.

(1) Background: Cardiac resynchronisation therapy (CRT) is nowadays an indispensable treatment option for heart failure. Although the indication is subject to clear cross-national guidelines by the European Society of Cardiology (ESC), there is immense variation in the number of implantations per 100,000 inhabitants in Europe, especially in German-speaking countries (Germany, Austria and Switzerland). The aim of the present study was to identify possible factors for these differences using a qualitative research approach. (2) Methods: Semi-standardized interviews were conducted with 11 experts in the field of CRT therapy (3 experts from Germany, 4 from Austria and 4 from Switzerland) using a pre-prepared interview template and analysed according to Mayring's qualitative content analysis. (3) Results: The main factors identified were the costs of purchasing the devices and the financing systems of the respective healthcare systems, although cost pressure still seems to play a subordinate role in the German-speaking countries. Moreover, "lack of implementation of ESC guidelines", "insufficient training" and "lack of medical infrastructure" could be excluded as potential reasons. (4) Conclusions: Economic factors, but not a lack of adherence to ESC guidelines, seem to have a major influence on the fluctuating implantation figures in German-speaking countries, according to the unanimous assessment of renowned experts.

Cardiac hepatopathy refers to acute or chronic liver damage caused by cardiac dysfunction in the absence of any other possible causative reasons of liver injury. There is a large number of evidence of the fact that cardiac hepatopathy is associated with poor clinical outcomes in patients with acute or actually decompensated heart failure (HF). However, the currently dominated pathophysiological background does not explain a role of metabolic regulative proteins secreted by hepatocytes in progression of HF, including adverse cardiac remodeling, kidney injury, skeletal muscle dysfunction, osteopenia, sarcopenia and cardiac cachexia. The aim of this narrative review was to accumulate knowledge of hepatokines (adropin; fetuin-A, selenoprotein P, fibroblast growth factor-21, and alpha-1-microglobulin) as adaptive regulators of metabolic homeostasis in patients with HF. It is suggested that hepatokines play a crucial, causative role in inter-organ interactions and mediate tissue protective effects counteracting oxidative stress, inflammation, mitochondrial dysfunction, apoptosis and necrosis. The discriminative potencies of hepatokines for HF and damage of target organs in patients with known HF is under on-going scientific discussion and requires more investigations in the future.

We aimed to identify cardiopulmonary long-term effects after severe COVID-19 disease as well as predictors of Long-COVID in a prospective registry. A total of 150 consecutive, hospitalized patients (February 2020 and April 2021) were included six months post hospital discharge for a clinical follow-up. Among them, 49% experienced fatigue, 38% exertional dyspnea and 75% fulfilled criteria for Long-COVID. Echocardiography detected reduced global longitudinal strain (GLS) in 11% and diastolic dysfunction in 4%. Magnetic resonance imaging revealed traces of pericardial effusion in 18% and signs of former pericarditis or myocarditis in 4%. Pulmonary function was impaired in 11%. Chest computed tomography identified post-infectious residues in 22%. Whereas fatigue did not correlate with cardiopulmonary abnormalities, exertional dyspnea was associated with impaired pulmonary function (OR 3.6 [95% CI: 1.2-11], p = 0.026), reduced GLS (OR 5.2 [95% CI: 1.6-16.7], p = 0.003) and/or left ventricular diastolic dysfunction (OR 4.2 [95% CI: 1.03-17], p = 0.04). Predictors of Long-COVID included length of in-hospital stay (OR: 1.15 [95% CI: 1.05-1.26], p = 0.004), admission to intensive care unit (OR cannot be computed, p = 0.001) and higher NT-proBNP (OR: 1.5 [95% CI: 1.05-2.14], p = 0.026). Even 6 months after discharge, a majority fulfilled criteria for Long-COVID. While no associations between fatigue and cardiopulmonary abnormalities were found, exertional dyspnea correlated with impaired pulmonary function, reduced GLS and/or diastolic dysfunction.

Background: adropin plays a protective role in cardiac remodeling through supporting energy metabolism and water homeostasis and suppressing inflammation. Low circulating levels of adropin were positively associated with the risk of cardiovascular diseases and type 2 diabetes mellitus (T2DM). We hypothesized that sodium-glucose linked transporter 2 (SGLT2) inhibitor dapagliflosin might represent cardiac protective effects in T2DM patients with known chronic HF through the modulation of adropin levels., Methods: we prospectively enrolled 417 patients with T2DM and HF from an entire cohort of 612 T2DM patients. All eligible patients were treated with the recommended guided HF therapy according to their HF phenotypes, including SGLT2 inhibitor dapagliflozin 10 mg, daily, orally. Anthropometry, clinical data, echocardiography/Doppler examinations, and measurements of biomarkers were performed at the baseline and over a 6-month interval of SGLT2 inhibitor administration., Results: in the entire group, dapagliflozin led to an increase in adropin levels by up to 26.6% over 6 months. In the female subgroup, the relative growth (Δ%) of adropin concentrations was sufficiently higher (Δ% = 35.6%) than that in the male subgroup (Δ% = 22.7%). A multivariate linear regression analysis of the entire group showed that the relative changes (Δ) in the left ventricular (LV) ejection fraction (LVEF), left atrial volume index (LAVI), and E/e' were significantly associated with increased adropin levels. In the female subgroup, but not in the male subgroup, ΔLVEF ( p = 0.046), ΔLAVI ( p = 0.001), and ΔE/e' ( p = 0.001) were independent predictive values for adropin changes., Conclusion: the levels of adropin seem to be a predictor for the favorable modification of hemodynamic performances during SGLT2 inhibition, independent ofN-terminal brain natriuretic pro-peptide levels.

Both relevant aortic valve stenosis (AS) and aortic valve insufficiency significantly contribute to structural changes in the ascending aorta (AA) and thus to its dilatation. In patients with severe AS undergoing transcatheter aortic valve replacement (TAVR), survival data regarding aortic changes and laboratory biomarker analyses are scarce., Methods: A total of 179 patients with severe AS and an available computed tomography were included in this retrospective study. AA was measured, and dilatation was defined as a diameter ≥ 40 mm. Thirty-two patients had dilatation of the AA. A further 32 patients from the present population with a normal AA were matched to the aortic dilatation group with respect to gender, age, body mass index and body surface area, and the resulting study groups were compared with each other. In addition to echocardiographic and clinical characteristics, the expression of cardiovascular biomarkers such as brain natriuretic peptide (BNP), soluble suppression of tumorigenicity-2 (sST2), growth/differentiation of factor-15 (GDF-15), heart-type fatty-acid binding protein (H-FABP), insulin-like growth factor binding protein 2 (IGF-BP2) and soluble urokinase-type plasminogen activator receptor (suPAR) was analyzed. Kaplan-Meier curves for short- and long-term survival were obtained, and Pearson's and Spearman's correlations were calculated to identify the predictors between the diameter of the AA and clinical parameters., Results: A total of 19% of the total cohort had dilatation of the AA. The study group with an AA diameter ≥ 40 mm showed a significantly low comorbidity with respect to diabetes mellitus in contrast to the comparison cohort with an AA diameter < 40 mm ( p = 0.010). This result continued in the correlation analyses performed, as the presence of diabetes mellitus correlated negatively not only with the diameter of the AA (r = -0.404; p = 0.001) but also with the presence of aortic dilatation (r = -0.320; p = 0.010). In addition, the presence of AA dilatation after TAVR was shown to have no differences in terms of patient survival at 1, 3 and 5 years. There were no relevant differences in the cardiovascular biomarkers studied between the patients with dilated and normal AAs., Conclusion: The presence of AA dilatation before successful TAVR was not associated with a survival disadvantage at the respective follow-up intervals of 1, 3 and 5 years. Diabetes mellitus in general seemed to have a protective effect against the development of AA dilatation or aneurysm in patients with severe AS.

(1) Background: Currently, echocardiography is the primary non-invasive diagnostic method used to screen patients with severe aortic valve stenosis (AS) for pulmonary hypertension (PH) by estimating systolic pulmonary artery pressure (sPAP). Other radiological methods have been a focus of research in the past couple of years, as it was shown that by determining the pulmonary artery (PA) diameter, prognostic statements concerning overall mortality could be made in these patients. This study compared established and novel cardiovascular biomarkers with the PA/BSA value to detect PH in patients with severe AS. (2) Methods: The study cohort comprised 188 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR), who were then divided into two groups based on PA/BSA values obtained through CT-angiography. The presence of PH was defined as a PA/BSA ≥ 16.6 mm/m2 (n = 81), and absence as a PA/BSA < 16.6 mm/m2 (n = 107). Blood samples were taken before TAVR to assess cardiovascular biomarkers used in this study, namely brain natriuretic peptide (BNP), cardiac troponin I (cTnI), high-sensitive troponin (hsTN), soluble suppression of tumorigenesis-2 (sST2), growth/differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), insulin-like growth factor binding protein 2 (IGF-BP2), and soluble urokinase-type plasminogen activator receptor (suPAR). (3) Results: Patients with a PA/BSA ≥ 16.6 mm/m2 showed significantly higher levels of BNP (p = <0.001), GDF-15 (p = 0.040), and H-FABP (p = 0.007). The other investigated cardiovascular biomarkers did not significantly differ between the two groups. To predict a PA/BSA ≥ 16.6 mm/m2, cut-off values for the biomarkers were calculated. Here, GDF-15 (p = 0.029; cut-off 1172.0 pg/mL) and BNP (p < 0.001; cut-off 2194.0 pg/mL) showed significant results. Consequently, analyses of combined biomarkers were performed, which yielded IGF-BP2 + BNP (AUC = 0.721; 95%CI = 0.585−0.857; p = 0.004) as the best result of the two-way analyses and GDF-15 + IGF-BP2 + BNP (AUC = 0.727; 95%CI = 0.590−0.864; p = 0.004) as the best result of the three-way analyses. No significant difference regarding the 1-year survival between patients with PA/BSA < 16.6 mm/m2 and patients with PA/BSA ≥ 16.6 mm/m2 was found (log-rank test: p = 0.452). (4) Conclusions: Although PA/BSA aims to reduce the bias of the PA value caused by different body compositions and sizes, it is still a controversial parameter for diagnosing PH. Combining the parameter with different cardiovascular biomarkers did not lead to a significant increase in the diagnostic precision for detecting PH in patients with severe AS.

Type 2 diabetes mellitus (T2DM) remains a powerful predictor of progressive heart failure (HF), but it is not clear whether altered glycemic control interferes with HF progression via an impaired profile of circulating myokines. The aim was to investigate plausible effects of glucose control on a myokine signature in T2DM patients affected by chronic HF. We selected 372 T2DM patients from the local database and finally included 314 individuals suffering from chronic HF and subdivided them into two groups according to glycosylated hemoglobin (HbA1c) levels (<6.9% and ≥7.0%). Echocardiography and Doppler examinations along with biomarker measurements were performed at the baseline of the study. The results showed that irisin levels were significantly lower in patients with HbA1c ≥ 7.0% than in those with HbAc1 < 6.9%, whereas concentrations of apelin, myostatin and adropin did not significantly differ between these two groups. We also identified numerous predictors of poor glycemic control, but only N-terminal brain natriuretic propeptide (odds ratio [OR] = 1.07; 95% confidence interval [CI] = 1.02−1.10, p = 0.04) and irisin (OR = 1.09; 95% CI = 1.04−1.17, p = 0.001) remained independent predictors of the dependent variable. In conclusion, we found that decreased levels of irisin were associated with poor glycemic control in T2DM patients with HF regardless of clinical conditions and other biomarkers.

Introduction: COVID-19 survivors reveal an increased long-term risk for cardiovascular disease. Biomarkers like troponins and sST-2 improve stratification of cardiovascular risk. Nevertheless, their prognostic value for identifying long-term cardiovascular risk after having survived COVID-19 has yet to be evaluated. Methods: In this single-center study, admission serum biomarkers of sST-2 and hs-TnI in a single cohort of 251 hospitalized COVID-19 survivors were evaluated. Concentrations were correlated with major cardiovascular events (MACE) defined as cardiovascular death and/or need for cardiovascular hospitalization during follow-up after hospital discharge [FU: 415 days (403; 422)]. Results: MACE was a frequent finding during FU with an incidence of 8.4% (cardiovascular death: 2.8% and/or need for cardiovascular hospitalization: 7.2%). Both biomarkers were reliable indicators of MACE (hs-TnI: sensitivity = 66.7% & specificity = 65.7%; sST-2: sensitivity = 33.3% & specificity = 97.4%). This was confirmed in a multivariate proportional-hazards analysis: besides age (HR = 1.047, 95% CI = 1.012−1.084, p = 0.009), hs-TnI (HR = 4.940, 95% CI = 1.904−12.816, p = 0.001) and sST-2 (HR = 10.901, 95% CI = 4.509−29.271, p < 0.001) were strong predictors of MACE. The predictive value of the model was further improved by combining both biomarkers with the factor age (concordance index hs-TnI + sST2 + age = 0.812). Conclusion: During long-term FU, hospitalized COVID-19 survivors, hs-TnI and sST-2 at admission, were strong predictors of MACE, indicating both proteins to be involved in post-acute sequelae of COVID-19.

Background: Computed tomography (CT) of the aorta and cardiac vessels, which is performed in patients with severe aortic valve stenosis (AS) before transcatheter aortic valve replacement (TAVR), offers the possibility of non-invasive detection of pulmonary hypertension (PH), for example, by determining the diameter of the main pulmonary artery (PA), the right pulmonary artery (RPA) or the left pulmonary artery (LPA). An improvement of the significance of these radiological parameters is often achieved by indexing to the body surface area (BSA). The aim of this study was to compare different echocardiographic systolic pulmonary artery pressure (sPAP) values with radiological data in order to define potential clinical cut-off values for the presence or absence of PH. Methods: A total of 138 patients with severe AS undergoing TAVR underwent pre-interventional transthoracic echocardiography with determination of sPAP values and performance of CT angiography (CTA) of the aorta and femoral arteries. Radiologically, the PA, RPA, LPA, and ascending aorta (AA) diameters were obtained. Vascular diameters were not only indexed to BSA but also ratios were created with AA diameter (for example PA/AA-ratio). From these CT-derived vascular parameters, AUROC curves were obtained regarding the prediction of different sPAP values (sPAP 40−45−50 mmHg) and finally correlation analyses were calculated. Results: The best AUROC and correlation analyses were generally obtained at an sPAP ≥ 40 mmHg. When considering diameters alone, the PA diameter was superior to the RPA and LPA. Indexing to BSA generally increased the diagnostic quality of the parameters, and finally, in a synopsis of all results, PA/BSA had the best AUC 0.741 (95% CI 0.646−0. 836; p < 0.001; YI 0.39; sensitivity 0.87; specificity 0.52) and Spearman’s correlation coefficient (r = 0.408; p < 0.001) at an sPAP of ≥40 mmHg. Conclusions: Features related to pulmonary hypertension are fast and easily measurable on pre-TAVR CT and offer great potential regarding non-invasive detection of pulmonary hypertension in patients with severe AS and can support the echocardiographic diagnosis. In this study, the diameter of the main pulmonary artery with the additionally determined ratios were superior to the values of the right and left pulmonary artery. Additional indexing to body surface area and thus further individualization of the parameters with respect to height and weight can further improve the diagnostic quality.

Background: Transcatheter aortic valve implantation (TAVI) is an established therapeutic option in patients with severe aortic valve stenosis (AS) and a high surgical risk profile. Pulmonary hypertension (PH)—often co-existing with severe AS—is associated with a limited factor for prognosis and survival. The purpose of this study was to evaluate the prevalence of PH in patients undergoing TAVI, classify these patients based on right heart catheter (RHC) measurements in different PH subtypes, and analyze prognostic values on survival after TAVI. Methods: 284 patients with severe AS underwent an RHC examination for hemodynamic assessment prior to TAVI and were categorized into subtypes of PH according to the 2015 European Society of Cardiology (ESC) guidelines. TAVI patients were followed-up with for one year with regard to 30-days and 1-year mortality as primary endpoints. Results: 74 of 284 participants showed a diastolic pressure gradient (DPG) < 7 mmHg and a pulmonary vascular resistance (PVR) > 3 Wood units (WU) and could not be formally allocated to either isolated post-capillary PH (ipc-PH) or combined pre- and post-capillary PH (cpc-PH). Therefore, a new subgroup called “borderline post-capillary PH” (borderlinepc-PH) was introduced. Compared with TAVI patients with pre-capillary PH (prec-PH), ipc-PH patients suffering from borderlinepc-PH (HR 7.114; 95% CI 2.015−25.119; p = 0.002) or cpc-PH (HR 56.459; 95% CI 7.738−411.924; p < 0.001) showed a significantly increased 1-year mortality. Conclusions: Postcapillary PH was expanded to include the so-called “borderlinepc-PH” variant in addition to the ipc-PH and cpc-PH subtypes. The one-year survival after TAVI was significantly different between the subgroups, with the worst prognosis for borderlinepc-PH and cpc-PH.

Background: Patients with severe aortic valve stenosis (AS) often present with heart failure and sarcopenia. Sarcopenia, described as progressive degradation of skeletal muscle mass, has frequently been implicated as a cause of increased mortality, prolonged hospitalization and generalized poor outcome after transcatheter aortic valve replacement (TAVR). At present, sarcopenia is defined by the European Working Group on Sarcopenia in Older People (EWGSOP) based on clinical examination criteria and radiological imaging. The aim of the present study was to compare patients with Computed Tomography (CT)-diagnosed sarcopenia with regard to the expression of cardiovascular biomarkers in order to obtain additional, laboratory-chemical information., Methods: A total of 179 patients with severe AS were included in this retrospective study. Sarcopenia was determined via CT by measurement of the psoas muscle area (PMA), which was indexed to body surface area (PMAi). According to previous studies, the lowest tertile was defined as sarcopenic. Patients with (59/179) and without sarcopenia (120/179) in the overall cohort were compared by gender-specific cut-offs with regard to the expression of cardiovascular biomarkers such as brain natriuretic peptide (BNP), soluble suppression of tumorigenicity-2 (sST2), growth/differentiation of factor-15 (GDF-15), heart-type fatty-acid binding protein (H-FABP), insulin like growth factor binding protein 2 (IGF-BP2) and soluble urokinase-type plasminogen activator receptor (suPAR). Additionally, binary logistic regression analyses were calculated to detect possible predictors of the presence of sarcopenia., Results: No statistical differences regarding one-year survival could be detected between sarcopenic and non-sarcopenic patients in survival curves (log rank test p = 0.179). In the entire cohort, only BNP and hemoglobin (HB) showed a statistically significant difference, with only HB emerging as a relevant predictor for the presence of sarcopenia after binary logistic regression analysis ( p = 0.015). No relevant difference in biomarker expression could be found in the male cohort. Regarding the female cohort, statistically significant differences were found in BNP, HB and hematocrit (HK). In binary logistic regression, however, none of the investigated criteria could be related to sarcopenia., Conclusion: Regardless of gender, patients with imaging-based muscle degradation did not demonstrate significantly different cardiovascular biomarker expression compared to those without it.

Background: Tei index (TI) is a combined myocardial performance index, which was found to be more sensitive for overall cardiac dysfunction than systolic or diastolic parameters alone. Currently, there is only limited evidence for this measure in the context of myocarditis. Thus, TI could add additional benefits to conventional diagnostic workup. Methods: TI of patients with myocarditis (n = 40), acute coronary syndrome (n = 29) and controls (n = 50) was retrospectively analyzed concerning its discriminatory ability for myocarditis. Results: TI was most pathological in patients with myocarditis (median 0.41 vs. 0.35 vs. 0.31, p < 0.0001). Its discriminatory ability was better than that of EF or E/e’ (AUCs: TI: 0.71, p < 0.0001; EF: 0.57, p = 0.112; E/e’: 0.64, p = 0.983), which was also verified in logistic regression analysis (B(SE) = 0.81(0.23), p = 0.0004). The association of TI with myocarditis remained significant even after correction for confounders in propensity score weighted analysis. Conclusions: The TI showed a better discriminatory ability for myocarditis than conventional echocardiographic parameters. Since TI is easily conducted, it might be a helpful adjunctive tool to supplement conventional diagnostic modalities in patients with suspected myocarditis.

Introduction: Takotsubo cardiomyopathy (TTC) and acute coronary syndrome (ACS) are clinically indistinguishable from each other. Although therapeutically redundant, coronary angiography remains indispensable for differential diagnosis. Methods: In our study, we compared hemogram parameters and their ratios in 103 patients presenting with undiagnosed chest pain. Blood was drawn at baseline in 40 patients with TTC, 63 patients with ACS, and 68 healthy controls ((Ctrl) no coronary artery disease or signs of heart failure). Results: Peripheral lymphocyte counts were significantly depressed in TTC and ACS patients when compared to the Ctrl. Consequently, all three investigated hemogram ratios were significantly elevated in patients with ACS or TTC (NLR: TTC: median 3.20 vs. ACS: median 3.82 vs. Ctrl: median 2.10, p < 0.0001; BLR: median 0.02 vs. ACS: median 0.00 vs. Ctrl: median 0.00, p < 0.0001; MLR: median 0.37 vs. ACS: median 0.44 vs. Ctrl: median 0.28, p < 0.0001). Of note, BLR was only significantly elevated in patients with TTC, and not in patients with ACS (ACS vs. Ctrl p = 0.183). Conclusion: Basophil count and BLR are significantly increased in TTC patients when compared to ACS and may, therefore, be helpful in the distinction of TTC from ACS. Whereas NLR might be useful to differentiate ACS from controls. Elevated basophil counts and BLR in TTC patients are interesting findings and may confirm speculations about the partly unexplained pathophysiology.

Introduction: Takotsubo syndrome (TTS) is clinically indistinguishable from an ACS. Despite the implementation of clinical scoring systems and novel biomarkers, coronary angiography currently remains necessary for differential diagnosis., Methods: 93 patients with chest pain and the suspicion of TTS were enrolled in two study centers. Fetuin-A, IGFBP-2, Galectin-3, and TNF α were determined in serum samples, collected within 24 h after the onset of symptoms. Serum levels of biomarkers were analyzed for the differential diagnostic value between TTS and ACS., Results: Compared to TTS, patients with ACS had significantly lower serum levels of Fetuin-A and IGFBP-2. The cut-off value of Fetuin-A for the identification of TTS compared to ACS was 55.74 μg/mL (sensitivity: 100.0%, specificity: 82.6%, PPV: 63.2%, NPV: 100.0%). An optimal cut-off value for IGFBP-2 for the differential diagnosis between TTS and ACS was determined as 171.77 ng/mL (sensitivity: 76.0%, specificity: 82.6%, PPV: 76.4%, NPV 72.7%)., Conclusion: Fetuin-A and IGFBP-2 might facilitate the triage between TTS and ACS and could be therefore of great benefit for the guidance of treatment.

(1) Background: Myocarditis following group A streptococcal pharyngitis and tonsillitis is a relatively rare medical condition. The aim of this systematic review was to identify specific ECG changes, laboratory parameters and signs, and symptoms associated with this disease. (2) Methods: A systematic literature review was performed in concordance with the current PRISMA guidelines, including the databases PubMed/MEDLINE, Web of Science, CDSR, CENTRAL, CCAs, EBM Reviews, and LILACS. Articles were included if they covered myocarditis after streptococcal pharyngitis/tonsillitis in humans. Exclusion criteria were rheumatic, autoimmune, or toxic myocarditis. (3) Results: Patients that developed myocarditis after group A streptococcal throat infection frequently presented with chest pain, elevated cardiac markers, and ST-segment elevations, making it a condition that shows more similarities to acute coronary syndrome than viral myocarditis. (4) Conclusions: Myocarditis after streptococcal pharyngitis and/or tonsillitis is a rather infrequently described disease; however, it is necessary to consider this condition when investigating streptococcal sore throat because it can be associated with severe adverse events for the individual patient.

Background: Pulmonary capillary wedge pressure (PCWP) and left ventricular end-diastolic pressure (LVEDP) are often used as equivalents for determination of pulmonary hypertension (PH). PH is a comorbidity in patients with severe aortic valve stenosis (AS) and associated with limited prognosis. The aim of the study was to examine the role of differentiated classification basis of PCWP and LVEDP in patients planning for transcatheter aortic valve implantation (TAVI)., Methods: 284 patients with severe AS completed a combined left (LHC) and right heart catheterization (RHC) as part of a TAVI planning procedure. Patients were categorized twice into subtypes of PH according to 2015 European Society of Cardiology (ESC) guidelines-on the one hand with PCWP and on the other hand with LVEDP as classification basis. PCWP-LVEDP relationships were figured out using Kaplan-Meier curves, linear regressions and Bland-Altman analysis., Results: Regarding 1-year mortality, Kaplan-Meier analyses showed similar curves in spite of different classification bases of PH subtypes according to PCWP or LVEDP with exception of pre-capillary PH subtype. PCWP-LVEDP association in the overall cohort was barely present (R = 0.210, R 2 = 0.044). When focusing analysis on PH patients only a slightly increased linear regression was noted compared to the overall cohort (R = 0.220, R 2 = 0.048). The strongest regression was observed in patients with creatinine ≥ 132 µmol/L (R = 0.357, R 2 = 0.127) and in patients with mitral regurgitation ≥ II° (R = 0.326, R 2 = 0.106)., Conclusions: In patients with severe AS, there is a weak association between hemodynamic parameters measured by LHC and RHC. RHC measurements alone are not suitable for risk stratification with respect to one-year mortality. If analysis of hemodynamic parameters is necessary in patients with severe AS scheduled for TAVI, measurement results of LHC and RHC should be combined and LVEDP could serve as a helpful indicator for risk assessment.

Background: Gender-specific differences in the outcome of COVID-19 patients requiring intensive care treatment have been reported. However, a potential association with ICU therapy remains elusive., Methods: A total of 224 consecutive patients (63 women) treated for severe COVID-19 disease requiring mechanical ventilation were screened for the study. After propensity score matching for gender, 40 men and 40 women were included in the study. Comparative analysis was conducted for laboratory parameters, ICU therapy and complications (pulmonary embolism, thrombosis, stroke, and ventricular arrhythmias), and outcome (mortality)., Results: Male patients had significantly higher levels of CRP ( p = 0.012), interleukin-6 ( p = 0.020) and creatinine ( p = 0.027), while pH levels ( p = 0.014) were significantly lower compared to females. Male patients had longer intubation times ( p = 0.017), longer ICU stays ( p = 0.022) and higher rates of catecholamine dependence ( p = 0.037). Outcome, complications and ICU therapy did not differ significantly between both groups., Conclusion: The present study represents the first matched comparison of male and female COVID-19 patients requiring intensive care treatment. After propensity matching, male patients still displayed a higher disease severity. This was reflected in higher rates of vasopressors, duration of ICU stay and duration of intubation. In contrast, no significant differences were observed in mortality rates, organ replacement therapy and complications during ICU stay.

Patients with severe aortic valve stenosis and concomitant pulmonary hypertension show a significantly reduced survival prognosis. Right heart catheterization as a preoperative diagnostic tool to determine pulmonary hypertension has been largely abandoned in recent years in favor of echocardiographic criteria. Clinically, determination of echocardiographically estimated systolic pulmonary artery pressure falls far short of invasive right heart catheterization data in terms of accuracy. The aim of the present systematic review was to highlight noninvasive possibilities for the detection of pulmonary hypertension in patients with severe aortic valve stenosis, with a special focus on cardiovascular biomarkers. A total of 525 publications regarding echocardiography, cardiovascular imaging and biomarkers related to severe aortic valve stenosis and pulmonary hypertension were analyzed in a systematic database analysis using PubMed Central ® . Finally, 39 publications were included in the following review. It was shown that the current scientific data situation, especially regarding cardiovascular biomarkers as non-invasive diagnostic tools for the determination of pulmonary hypertension in severe aortic valve stenosis patients, is poor. Thus, there is a great scientific potential to combine different biomarkers (biomarker scores) in a non-invasive way to determine the presence or absence of PH.

Aim: The impact of chronic kidney disease (CKD) on patient-related outcomes in patients with tricuspid regurgitation (TR) is well known. However, the impact of the progression of CKD in patients with TR and potentially modifiable risk factors of progressing CKD is unknown. Methods: 444 consecutive adult patients with TR and CKD stage 1−4 admitted in an inpatient setting between January 2010 and December 2017 were included. During a median follow-up of two years, eGFR and survival status were collected. Independent risk factors for CKD progression and all-cause mortality were determined. Patient survival statuses were grouped according to different combinations of the presence or absence of CKD progression and the TR grade. Results: Progression of CKD (OR 2.38 (95% confidence interval 1.30−4.35), p = 0.005), the grade of TR (OR 2.38 (1.41−4.00), p = 0.001) and mitral regurgitation (OR 1.72 (1.20−2.46), p = 0.003) were independent risk factors for all-cause mortality. Haemoglobin at admission (OR 0.80 (0.65−0.99), p = 0.043) and the presence of type 2 diabetes (OR 1.67 (1.02−2.73), p = 0.042) were independent risk factors for CKD progression. The combination of the status of CKD progression and the TR grade showed a stepwise pattern for all-cause mortality (p < 0.001). Patients with CKD progression and TR grade 1 had comparable all-cause mortality with patients without CKD progression but with TR grade 2 or 3. Even in patients with TR grade 1, the risk for all-cause mortality doubled if CKD progression occurred (OR 2.49 (95% CI 1.38−4.47), p = 0.002). Conclusion: CKD progression appears to be a risk factor for all-cause mortality in patients with TR. Anaemia and diabetes are potential modifiers of CKD progression.

Background: Severe aortic valve stenosis (AS) is associated with pulmonary hypertension (PH) and has been shown to limit patient survival. Soluble suppression of tumorigenicity-2 (sST2) is a cardiovascular biomarker that has proven to be an important prognostic marker for survival in patients undergoing transcatheter aortic valve replacement (TAVR). The aim of this study was to assess the importance of the sST2 biomarker for risk stratification in patients with severe AS in presence or absence of PH., Methods: In 260 patients with severe AS undergoing TAVR procedure, sST2 serum level concentrations were analyzed. Right heart catheter measurements were performed in 152 patients, with no PH detection in 43 patients and with PH detection in 109 patients. Correlation analyses according to Spearman, AUROC analyses and Kaplan-Meier curves were calculated., Results: Patients with severe AS and PH showed significantly higher serum sST2 concentrations ( p = 0.006). The sST2 cut-off value for non-PH patients regarding 1-year survival yielded 5521.15 pg/mL, whereas the cut-off value of PH patients was at a considerably higher level of 10,268.78 pg/mL. A cut-off value of 6990.12 pg/mL was related with a significant probability of PH presence. Survival curves showed that patients with severe AS and PH not only had higher 1-year mortality, but also that increased levels of sST2 plasma concentration were associated with earlier death., Conclusion: sST2 definitely has the potential to provide information about the presence of PH in patients with severe AS, in a noninvasive way.

Introduction : Treatment with betablockers is controversial in Takotsubo syndrome (TTS); however, many physicians intuitively initiate or continue betablocker therapy in these patients. The effect of preadmission betablocker use on adverse cardiovascular events has not been studied in the literature. Methods: To investigate this issue, we evaluated clinical complications, defined by the endpoint of occurrence of hemodynamically relevant arrythmia, cardiac decompensation, and all-cause adverse cardiac events, during hospitalization, in 56 patients hospitalized for TTS between April 2017 and July 2021. We compared the risk of adverse cardiovascular events between patients with preadmission betablocker therapy and those without preadmission betablocker therapy. Pretreatment betablocker therapy was defined as daily betablocker intake for more than a week including day of admission. Results : TTS patients taking preadmission betablockers had a significantly increased risk of all-cause complications relative to patients without betablockers in preadmission medication ((52.0% vs. 19.4%, p = 0.010; OR 4.5 (95% Cl 1.38-14.80)). Furthermore, TTS patients already taking betablockers on admission showed a statistically significant increased risk of cardiac decompensation when compared to patients without pretreatment with betablockers ( p = 0.013). There were no significant differences in patient characteristics in patients who were taking beta blockers as an adjunct therapy prior to admission for TTS relative to those who were not. There is however an increase in comorbidities, hypertension, and atrial fibrillation, in past medical history in patients taking a preadmission betablocker. The difference is related to therapeutic applications for beta blockers and was not significant based on endpoints of our study. Conclusions: Preadmission betablocker treatment was associated with a 4.5 times higher risk of adverse cardiac events. This increased risk of all-cause complications and of cardiac decompensation within the acute phase of TTS is presumably due to the negative inotropic effects of betablockers and upregulation of β-adrenergic receptors in patients with chronic betablocker therapy.

Background: Previous animal studies reported an association of non-steroidal anti-inflammatory drugs (NSAIDs) with adverse outcomes in acute myocarditis, which is why these drugs are currently not recommended in affected patients. In this retrospective case-control study, we sought to investigate the effects of NSAID treatment in patients with acute myocarditis and myopericarditis to complement the available evidence. Method: A total of 114 patients with acute myocarditis were retrospectively enrolled. Demographical, clinical and laboratory data were extracted from hospital records. Patients who received NSAIDs ( n = 39, 34.2%) were compared to controls. Follow-up on all-cause mortality was acquired for two years. Propensity score matching was additionally conducted to account for covariate imbalances between groups. Results: Treatment with NSAIDs was neither associated with a worse outcome ( p = 0.115) nor with significant differences in left ventricular systolic function ( p = 0.228) or in-hospital complications ( p = 0.507). Conclusion: Treatment with NSAIDs was not associated with adverse outcomes in our study cohort. Together with the findings of previous studies, our results indicate that these drugs could be safely administered in patients with myocarditis and myopericarditis.

Introduction: Takotsubo cardiomyopathy (TTC) remains a life-threatening disease with the risk of decompensated heart failure and arrhythmias. Valid markers for the prediction of outcome are unavailable. The novel biomarkers fetuin-A, matrix metalloproteinases-2 (MMP-2), myeloperoxidase (MPO), Syndecan-1 and CD40-L show promising results for risk stratification of cardiovascular patients. Nevertheless, clinical implementation has not been investigated in TTC patients., Methods: To investigate this issue, we evaluated clinical complications in 51 patients hospitalized for TTC and measured the serum levels of fetuin-A, MPO, MMP-2, Syndecan-1 and CD40-L within 24 h after admission., Results: Serum levels of Fetuin-A correlated inversely with the risk of cardiac decompensation and all cause complications within the acute phase of TTC. Fetuin-A levels over 190.1 µg/mL (AUC: 0.738, sensitivity 87.5%, specificity: 52.6%) indicate an acute phase of TTC without cardiac decompensation. Despite lower fetuin-A levels in patients with all cause complications, the combined endpoint remained slightly unmet ( p = 0.058, AUC: 0.655). Patients with fetuin-A levels over 213.3 µg/mL are at risk of experiencing hemodynamic relevant rhythm disorders (AUC: 0.794; sensitivity: 75.0%, specificity: 79.1%). Other biomarkers failed to reveal a prognostic impact. Pro-BNP and hs troponin levels at admission did not predict adverse cardiac events., Conclusion: Fetuin-A is a promising marker in our study and could be of benefit for the prediction of short-term adverse cardiac events in TTC patients. Therefore, fetuin-A might be of value to evaluate an individual's risk for complications within the acute phase of TTC and to individually choose the time of intensive care and hospitalization.

Background: With the advent of implantable cardioverter-defibrillator (ICD) technology in recent decades, patients with inherited or congenital cardiomyopathy have a greater chance of survival into adulthood. Women with ICDs in this group are now more likely to reach reproductive age. However, pregnancy represents a challenge for clinicians, as no guidelines for the treatment of pregnant women with an ICD are currently available., Methods: To analyze this issue, we performed a systematic screening of the literature using the keywords: pregnancy with ICD, lead fracture in pregnancy, lead thrombi in pregnancy, ventricular tachycardia in pregnancy, inappropriate shocks in pregnancy, ICD discharge in pregnancy and ICD shock in pregnancy. Of 1101 publications found, 27 publications were eligible for further analysis (four retrospective trials and 23 case reports)., Results: According to physiological changes in pregnancy, resulting in an increase in heart rate and cardiac output, a vulnerability for malignant arrhythmias and device-related complications in ICD carriers might be suspected. While the literature is limited on this issue, maternal complications including arrhythmia burden with following ICD therapies, thromboembolic events and lead complications as well as inappropriate shock therapy have been reported. According to the limited available studies, associated risk seems not to be more frequent than in the general population and depends on the underlying cardiac pathology. Furthermore, worsening of heart failure and related cardiovascular disease have been reported with associated risk of preterm delivery. These observations are exaggerated by restricted applications of diagnostics and treatment due to the risk of fetal harm in this population., Conclusions: Due to limited data on management of ICDs during pregnancy, further scientific investigations are required. Consequently, careful risk assessment with individual risk evaluation and close follow ups with interdisciplinary treatment are recommended in pregnant ICD carriers.

Assuming that atrial fibrillation (AF) is associated with left atrial remodeling and dysfunction, we hypothesize that left atrial and left atrial appendage ejection fractions (LAEF and LAAEF) are useful and may be more sensitive outcome predictors of pulmonary vein isolation (PVI). Fifty patients who underwent PVI at our institution with available pre-interventional cardiac computed tomography (CT) for procedure planning were included in this retrospective study. The patients were separated into two groups by recurrence and non-recurrence of AF and subgroups of paroxysmal and persistent AF. Semiautomatic volumetric analysis of the left atrium was used to calculate morphological and functional parameters and optimal cut-offs were calculated using the Youden index. LAEF (accuracy 94%, sensitivity 67%) and LAAEF (accuracy 90%, sensitivity 67%) were significantly reduced in patients with AF recurrence (16% vs. 36%, p = 0.00002; 16% vs. 42%, p = 0.000002), and in the subgroup analysis, the functional parameters were independent from AF type (paroxysmal and persistent). With a cut-off of <23% for both LAEF and LAAEF (area under the curve (AUC) 0.94, 95%CI 0.84-0.99 and AUC 0.96, 95%CI 0.86-0.99, respectively), AF recurrence occurred in 77.8%, within a mean follow-up period of 229 days. In conclusion, left atrial function on prior cardiac CT offers useful parameters for predicting AF recurrence after PVI.

Background: Low levels of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) were reported in patients with coronary artery disease, heart failure, chronic kidney disease and diabetes mellitus. Soluble cluster differentiation 163 (sCD163) serum levels are related to M2 macrophages, having anti-inflammatory attributes. As sport is well-known for its anti-inflammatory and cardioprotective effects we aimed to investigate the influence of eight months of physical activity on serum sCD163 and sTWEAK levels., Methods: In total, 109 subjects with at least one cardiovascular risk factor were asked to perform endurance training within the calculated training pulse for eight months. Overall, 98 finished the study. The performance gain was measured/quantified by bicycle stress tests at the beginning and end of the observation period. The cohort was divided into four groups, dependent on their baseline performance and performance gain. sCD163 and sTWEAK were measured at baseline and after two, six and eight months by ELISA., Results: Those participants who had a performance gain of ≤2.9% (mean gain 12%) within eight months showed a significant increase in sTWEAK (group 2: from 133 to 200 pg/mL, p = 0.002 and group 4: from 166 to 212 pg/mL, p = 0.031) and sCD163 levels (group 2: from 255 to 348 ng/mL, p = 0.035 and group 4: from 247 to 288 ng/mL, p = 0.025) in contrast to subjects without performance gain (sTWEAK: group 1: from 161 to 177 pg/mL, p = 0.953 and group 3: from 153 to 176 pg/mL, p = 0.744; sCD163: group 1: from 289 to 256 ng/mL, p = 0.374 and group 4: from 291 to 271 ng/mL, p = 0.913). Baseline sCD163 correlated with erythrocyte count, hematocrit, ASAT and lipoprotein a, the presence of hypertension and a BMI > 30 kg/m 2 ., Conclusion: Regular physical activity leads to a significant increase in sCD163 and sTWEAK levels of up to 37% and 50%, respectively. It is well-known that physical activity prevents or retards the onset and genesis of chronic inflammatory disease. One possible way of how training evolves its beneficial effect might be by modifying the inflammation status using the sTWEAK-sCD163 axis. Brief Summary: Regular physical activity leads to a significant increase in sTWEAK and sCD163 levels. Both factors are diminished in patients with chronic (inflammation-based) diseases, such as coronary artery disease, heart failure, pulmonary artery hypertension, chronic kidney disease and diabetes mellitus. It seems that the amounts of soluble TWEAK and CD163 are essential for a healthy balance and modulation between pro- and anti-inflammatory processes, and regular physical training could use the sCD163-sTWEAK axis to unfold its beneficial effect.

Background: Heart failure with preserved ejection fraction (HFpEF) remains an ongoing therapeutic and diagnostic challenge to date. In this study we aimed for an analysis of the diagnostic potential of four novel cardiovascular biomarkers, GDF-15, H-FABP, sST2, and suPAR in HFpEF patients compared to controls as well as ICM, and DCM., Methods: In total, we included 252 stable outpatients and controls (77 DCM, 62 ICM, 18 HFpEF, and 95 controls) in the present study. All patients were in a non-decompensated state and on a stable treatment regimen. Serum samples were obtained and analyzed for GDF-15 (inflammation, remodeling), H-FABP (ischemia and subclinical ischemia), sST2 (inflammation, remodeling) and suPAR (inflammation, remodeling) by means of ELISA., Results: A significant elevation of GDF-15 was found for all heart failure entities compared to controls ( p < 0.005). Similarly, H-FABP evidenced a significant elevation in all heart failure entities compared to the control group ( p < 0.0001). Levels of sST2 were significantly elevated in ICM and DCM patients compared to the control group and HFpEF patients ( p < 0.0001). Regarding suPAR, a significant elevation in ICM and DCM patients compared to the control group ( p < 0.0001) and HFpEF patients ( p < 0.01) was observed. An AUC analysis identified H-FABP (0.792, 95% CI 0.713-0.870) and GDF-15 (0.787, 95% CI 0.696-0.878) as paramount diagnostic biomarkers for HFpEF patients., Conclusion: Based on their differences in secretion patterns, novel cardiovascular biomarkers might represent a promising diagnostic tool for HFpEF in the future.

Background: Chronic kidney disease (CKD) and cardiovascular diseases (CVD) often occur concomitantly, and CKD is a major risk factor for cardiovascular mortality. Since some of the most commonly used biomarkers in CVD are permanently elevated in patients with CKD, novel biomarkers are warranted for clinical practice. Methods: Plasma concentrations of five cardiovascular biomarkers (soluble suppression of tumorigenicity (sST2), growth differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), insulin-like growth factor-binding protein 2 (IGF-BP2), and soluble urokinase plasminogen activator receptor) were analyzed by means of enzyme-linked immunosorbent assay (ELISA) in 219 patients with CKD enrolled in the German Chronic Kidney Disease (GCKD) study. Results: Except for sST2, all of the investigated biomarkers were significantly elevated in patients with CKD (2.0- to 4.4-fold increase in advanced CKD (estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m² body surface area (BSA)) and showed a significant inverse correlation with eGFR. Moreover, all but H-FABP and sST2 were additionally elevated in patients with micro- and macro-albuminuria. Conclusions: Based on our findings, sST2 appears to be the biomarker whose diagnostic performance is least affected by decreased renal function, thus suggesting potential viability in the management of patients with CVD and concomitant CKD. The predictive potential of sST2 remains to be proven in endpoint studies.

Background: Heart failure (HF) remains one of the leading causes of death to date despite extensive research funding. Various studies are conducted every year in an attempt to improve diagnostic accuracy and therapy monitoring. The small cytoplasmic heart-type fatty acid-binding protein (H-FABP) has been studied in a variety of disease entities. Here, we provide a review of the available literature on H-FABP and its possible applications in HF. Methods: Literature research using PubMed Central was conducted. To select possible studies for inclusion, the authors screened all available studies by title and, if suitable, by abstract. Relevant manuscripts were read in full text., Results: In total, 23 studies regarding H-FABP in HF were included in this review., Conclusion: While, algorithms already exist in the area of risk stratification for acute pulmonary embolism, there is still no consensus for the routine use of H-FABP in daily clinical practice in HF. At present, the strongest evidence exists for risk evaluation of adverse cardiac events. Other future applications of H-FABP may include early detection of ischemia, worsening of renal failure, and long-term treatment planning., Competing Interests: The authors declare no conflict of interest.