Deciphering the Role of microRNAs: Unveiling Clinical Biomarkers and Therapeutic Avenues in Atrial Fibrillation and Associated Stroke-A Systematic Review.

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression by binding to target messenger RNAs (mRNAs). miRNAs have been implicated in a variety of cardiovascular and neurological diseases, such as myocardial infarction, cardiomyopathies of various geneses, rhythmological diseases, neurodegenerative illnesses and strokes. Numerous studies have focused on the expression of miRNA patterns with respect to atrial fibrillation (AF) or acute ischemic stroke (AIS) However, only a few studies have addressed the expression pattern of miRNAs in patients with AF and AIS in order to provide not only preventive information but also to identify therapeutic potentials. Therefore, the aim of this review is to summarize 18 existing manuscripts that have dealt with this combined topic of AF and associated AIS in detail and to shed light on the most frequently mentioned miRNAs-1, -19, -21, -145 and -146 with regard to their molecular mechanisms and targets on both the heart and the brain. From this, possible diagnostic and therapeutic consequences for the future could be derived.

Insulin-like Growth Factor-Binding Protein 2 in Severe Aortic Valve Stenosis and Pulmonary Hypertension: A Gender-Based Perspective.

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.

Tei Index Complements Conventional Echocardiographic Parameters in Diagnostic Workup of Suspected Takotsubo Syndrome.

BACKGROUND: Tei index (TI) is a combined myocardial performance index for overall cardiac function, the sensitivity of which seems to be better than that of systolic and diastolic parameters alone. Evidence for TI in the context of Takotsubo syndrome (TTS) is currently limited, which is why we chose to investigate this parameter in affected patients. SUBJECTS AND METHODS: Patients with TTS (n = 51), acute coronary syndrome (ACS; n = 29), and controls (n = 58) were retrospectively investigated. Laboratory and echocardiographic parameters including TI were analyzed for their ability to discriminate TTS in the total study cohort. RESULTS: TI was the highest, and thus most pathological, in patients with TTS (median 0.516 vs. ACS: 0.355 vs. control: 0.313, p < 0.0001) and showed the best discriminatory ability for TTS (AUC: 0.836, p < 0.0001). A cut-off for diagnosis of TTS was calculated at ≥0.418 (specificity: 83.5% and sensitivity: 74.0%) by means of the Youden index. CONCLUSION: The discriminatory ability of TI was better than that of other echocardiographic parameters such as LV systolic function. Due to the simple, fast, and inexpensive way of calculating TI, diagnostic workup with conventional parameters could be complemented by TI in patients with suspected TTS.

Systolic Pulmonary Artery Pressure and Cardiovascular Biomarkers-New Non-Invasive Ways to Detect Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis Undergoing TAVR?

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 < 40 mmHg in comparison to patients with an sPAP ≥ 40 mmHg. Methods: 179 patients with echocardiographic evidence of severe AS before TAVR procedure were divided into 2 groups based on sPAP. An sPAP of 40 mmHg was considered the cut-off value, with absence of PH defined by an sPAP < 40 mmHg (n = 82) and presence of PH defined by an sPAP ≥ 40 mmHg (n = 97). Directly before TAVR, a blood sample was drawn from each patient, and plasma concentrations of the cardiovascular biomarkers 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), Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR), Brain Natriuretic Peptide (BNP) and Cardiac Troponin I (cTnI) were determined. Results: Patients with an sPAP ≥ 40 mmHg had significantly higher sST2 (p = 0.010), GDF-15 (p = 0.005), IGF-BP2 (p = 0.029), suPAR (p = 0.018), BNP (p < 0.001) and cTnI (p = 0.039) plasma levels. Only for H-FABP (p = 0.069), no significant differences were discernible between the two groups. In addition, cut-off values were calculated to predict an sPAP ≥ 40 mmHg. Significant results were shown with 16045.84 pg/mL for sST2 (p = 0.010), with 1117.54 pg/mL for GDF-15 (p = 0.005), with 107028.43 pg/mL for IGF-BP2 (p = 0.029), with 3782.84 pg/mL for suPAR (p = 0.018), with 2248.00 pg/mL for BNP (p < 0.001) and with 20.50 pg/mL for cTnI (p = 0.002). Conclusions: sPAP as an echocardiographic parameter in combination with supplementary use of cardiovascular biomarkers presented here have the potential to provide more detailed information about the presence or absence of PH in a non-invasive way.

Endothelialization and Inflammatory Reactions After Intracardiac Device Implantation.

BACKGROUND: Due to the advances in catheter-based interventional techniques, a wide range of heart diseases can now be treated with a purely interventional approach. Little is yet known regarding biological effects at the intracardiac implantation site or the effects on endothelialization and vascular inflammation in an in vivo environment. Detailed knowledge of ongoing vascular response, the process of endothelialization, and possible systemic inflammatory reactions after implantation is crucial for the clinical routine, since implants usually remain in the body for a lifetime. METHODS: For this narrative review, we conducted an extensive profound PubMed analysis of the current literature on the endothelialization processes of intracardially implanted devices, such as persistent foramen ovale (PFO) occluders, atrial septal defect (ASD) occluders, left atrial appendage (LAA) occluders, transcatheter aortic valve implantations (TAVIs), and leadless pacemakers. Additionally, the known biological activities of common metallic and synthetic components of intracardiac devices in an "in vivo" setting have been evaluated. RESULTS: Nitinol, an alloy of nickel and titanium, is by far the most commonly used material found in intracardiac devices. Although allergies to both components are known, implantation can be performed safely in the vast majority of patients. Depending on the device used, endothelialization can be expected within a time frame of 3-6 months. For those patients with a known allergy, gold coating may be considered as a viable alternative. CONCLUSION: Based on our analysis, we conclude that the vast majority of devices are made of a material that is both safe to implant and nontoxic in long-term treatment according to the current knowledge. The literature on the respective duration of endothelialization of individual devices however is highly divergent.

Anti-oxidative effect of the tyrosine kinase inhibitor nintedanib: a potential therapy for chronic lung allograft dysfunction?

Background: The long-term survival after lung transplantation (LTx) is often limited by the development of chronic lung allograft dysfunction (CLAD). Increased oxidative stress has been found to occur in chronic lung allograft dysfunction because of several risk factors, e.g. immunological factors or drug related factors. The aim of this study was to investigate the anti-oxidative effect of the receptor tyrosine kinase (RTK) inhibitor nintedanib on immunologically induced oxidative stress and on drug induced oxidative stress.Methods: In-vivo studies were used for investigation of immunologically induced oxidative stress: Immunohistochemistry of transglutaminase-2 (TGM-2) was used to figure out a potential anti-oxidative effect of receptor tyrosine kinase inhibitor nintedanib in a rat model of allogeneic left LTx. In-vitro studies were used for investigation of drug induced oxidative stress: Cell viability assay, 2'7'-dichlorodihydrofluorescein diacetate (DCFDA) and immunofluorescence of transglutaminase-2 were disposed to examine the potential impact of nintedanib on cyclosporin A (CsA) treated lung fibroblasts of the rat.Results: In-vivo studies: Allogeneic transplanted animals without drug interaction showed severe chronic rejection and an excessive expression of TGM-2, whereas the application of nintedanib significantly decreased the number of TGM-2 positive cells. In-vitro studies: Concentrations of CsA ranging from 250 ng/ml to 500 ng/ml demonstrated oxidative stress caused by an increased production of reactive oxygen species (ROS) and an overexpression of TGM-2 without inducing apoptosis in cells. Concentrations of more than 1000 ng/ml led to a considerable decrease of cellularity. 30 min-pre-incubation with nintedanib at a concentration between 25 and 100 nM reduced generation of intracellular ROS and expression of TGM-2.Conclusion: These results demonstrate a downregulation of ROS and TGM-2 by pretreatment with the receptor tyrosine kinase inhibitor nintedanib and present its potential anti-oxidative and immunomodulatory effect in the treatment of chronic lung allograft dysfunction.

The activity of nintedanib in an animal model of allogenic left lung transplantation resembling aspects of allograft rejection.

AIM OF THE STUDY: The prevention and treatment of chronic lung allograft dysfunction (CLAD) after lung transplantation (LTx) remain unsatisfactory. Growth factors may play an important role in the development of CLAD. This study evaluated the effects of nintedanib, a receptor tyrosine kinase inhibitor, in the treatment of CLAD after experimental LTx. MATERIALS AND METHODS: A rat model of left lung allo-transplantation (Fisher 344 to Wistar Kyoto) was used to evaluate the effect of nintedanib (50 mg/kg per day) on the development of CLAD. Therapy with nintedanib began 2 days before LTx and ended on postoperative day (POD) 20 (n = 6) or 60 (n = 6). Nontreated animals who underwent LTx (n = 12) were used as controls, whereas naïve lungs (n = 24) served as reference for physiological healthy organs without transplantation damage or medical effects. Acute and chronic rejection were evaluated on POD 20 and 60, respectively. RESULTS: Immunohistologic analysis showed a decrease in growth factors/receptors on POD 60 (nintedanib-treated vs. nontreated controls: platelet-derived growth factor (PDGF) A: [P ≤ 0.001]; PDGF receptor-α: [P ≤ 0.001]; vascular endothelial growth factor (VEGF) A: [P ≤ 0.001]; VEGF receptor-2: [P ≤ 0.001]). However, no reductions in fibrotic changes were observed in nintedanib-treated allografts compared with nontreated allografts. Although nintedanib treatment started before LTx none of the animals showed impaired wound healing. No dehiscence of the sutures of the bronchus, vessels or skin, or stenosis of the bronchus was found. CONCLUSION: In conclusion, while nintedanib reduced the expression of growth factors/receptors in a rat LTx model, a reduction in fibrotic alterations was not observed at POD 60.

Elevated systolic pulmonary artery pressure is a substantial predictor of increased mortality after transcatheter aortic valve replacement in males, not in females.

BACKGROUND: While pulmonary hypertension (PH) in patients with severe aortic valve stenosis (AS) is associated with increased mortality after transcatheter aortic valve replacement (TAVR), there is limited data on gender differences in the effects on long-term survival. OBJECTIVE: The aim of this retrospective, multicenter study was to investigate the prognostic impact of pre-interventional PH on survival of TAVR patients with respect to gender. METHODS: 303 patients undergoing TAVR underwent echocardiography to detect PH prior to TAVR via measurement of systolic pulmonary artery pressure (sPAP). Different cut-off values were set for the presence of PH. The primary endpoint was all-cause mortality at 1, 3 and 5 years. RESULTS: Kaplan-Meier analysis by gender showed that only males exhibited significant increased mortality at elevated sPAP values during the entire follow-up period of 5 years (sPAP ≥ 40 mmHg: p ≤ 0.001 and sPAP ≥ 50 mmHg: p ≤ 0.001 in 1- to 5-year survival), whereas high sPAP values had no effect on survival in females. In Cox regression analysis based on the selected sPAP thresholds, male gender was an independent risk factor for long-term mortality after TAVR in all time courses. CONCLUSION: Male gender was an isolated risk factor for premature death after TAVR in patients with echocardiographic evidence of PH and severe AS. This could mean that, the indication for TAVR should be discussed more critically in men with severe AS and an elevated sPAP, while in females, PH should not be an exclusion criterion for TAVR.

Cardiac MRI after Sudden Cardiac Arrest: A Systematic Review.

Purpose To perform a systematic review to assess the diagnostic and prognostic value of cardiac MRI after sudden cardiac arrest (SCA). Materials and Methods PubMed and Cochrane Library databases were systematically searched for studies investigating cardiac MRI after SCA in adult patients (≥18 years of age). The time frame of the encompassed studies spans from January 2012 to January 2023. The study protocol was preregistered in OSF Registries (www.osf.io/nxaev), and the systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of the included studies was evaluated using the Newcastle-Ottawa quality assessment scale. Results Fourteen studies involving 1367 individuals, 1257 (91.9%) of whom underwent cardiac MRI, were included. Inconsistent findings were reported on the diagnostic value of cardiac MRI-specific findings. The included studies demonstrated the following main findings: (a) cardiac MRI led to a new or alternative diagnosis in patients with SCA; (b) cardiac MRI identified pathologic or arrhythmogenic substrates; (c) cardiac MRI helped detect myocardial edema (potentially reversible); (d) cardiac MRI provided evidence for the occurrence of adverse events; and (e) functional markers or ventricular dimensions were considered prognostically relevant in a few studies. Relevant challenges in this systematic review were the lack of comparators and reference standards relative to cardiac MRI as the index test and patient selection bias. Conclusion Cardiac MRI following SCA can contribute to the diagnostic process and offer supplementary information essential for treatment planning. Limitations of the review include studies with insufficient comparators and potential bias in patient selection. Systematic review registration link: osf.io/nxaev Keywords: Cardiac MRI, Cardiovascular Disease, Cardiomyopathy, Ischemia, Myocardial Edema, Sudden Cardiac Arrest © RSNA, 2024.

Radiological Parameters for the Detection of Pulmonary Hypertension in Severe Aortic Valve Stenosis and Their Influence on Mortality: Does Sex Matter?

Background: Echocardiography has long been established as the primary noninvasive method for diagnosing pulmonary hypertension (PH) prior to transcatheter aortic valve replacement (TAVR) in patients with severe aortic valve stenosis (AS). In recent years, radiological methods for diagnosing PH have been investigated. Measurements such as the computed tomography angiography (CTA)-derived pulmonary artery (PA) diameter and PA diameter/body surface area (PA/BSA) have shown promising results regarding their diagnostic strength. However, it has yet to be determined if a patient's sex has any impact on the effectiveness of these diagnostic measurements. Methods: In all, 271 patients (51.3% male, mean age 82.6 ± 4.8 years) with severe AS undergoing TAVR were separated into male and female groups. The cut-off values for the diagnosis of PH were calculated for the CTA-derived PA diameter and PA/BSA based on different systolic pulmonal artery pressure values (40-45-50 mmHg). Patients were then subclassified according to measurements above or below these PA diameters and PA/BSA cut-off values. A PA diameter ≥29.5 mm and PA/BSA ≥ 15.7 mm/m2 qualified for PH. The 1-5 year survival rate in these cohorts was further analyzed. Results: Patients with a PA diameter ≥29.5 mm showed a significantly higher 1 year mortality rate (p = 0.014). This observation could only be confirmed for the male sex (p = 0.018) and not for the female sex (p = 0.492). As for the PA/BSA, in patients over the cut-off value, no significant increase in mortality was noted in the overall cohort. However, the male patients showed increased 3 year (p = 0.048) and 5 year mortality rates (p = 0.033). Conclusions: The CTA-obtained PA diameter and PA/BSA are both useful in the diagnosis of PH and mortality risk stratification in patients with severe AS undergoing TAVR, especially in males. Male patients with PA ≥ 29.5 mm or PA/BSA ≥ 15.7 mm/m2 seem to be at a higher risk of death during follow-up after undergoing TAVR. In females, no such correlation was observed.

Beyond the Valve: Incidence, Outcomes, and Modifiable Factors of Acute Kidney Injury in Patients with Infective Endocarditis Undergoing Valve Surgery-A Retrospective, Single-Center Study.

Background/Objectives: Infective endocarditis (IE) often requires surgical intervention, with postoperative acute kidney injury (AKI), posing a significant concern. This retrospective study aimed to investigate AKI incidence, its impact on short-term mortality, and identify modifiable factors in patients with IE scheduled for valve surgery. Methods: This single-center study enrolled 130 consecutive IE patients from 2013 to 2021 undergoing valve surgery. The creatinine levels were monitored pre- and postoperatively, and AKI was defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patient demographics, comorbidities, procedural details, and complications were recorded. Primary outcomes included AKI incidence; the relevance of creatinine levels for AKI detection; and the association of AKI with 30-, 60-, and 180-day mortality. Modifiable factors contributing to AKI were explored as secondary outcomes. Results: Postoperatively, 35.4% developed AKI. The highest creatinine elevation occurred on the second postoperative day. Best predictive value for AKI was a creatinine level of 1.35 mg/dL on the second day (AUC: 0.901; sensitivity: 0.89, specificity: 0.79). Elevated creatinine levels on the second day were robust predictors for short-term mortality at 30, 60, and 180 days postoperatively (AUC ranging from 0.708 to 0.789). CK-MB levels at 24 h postoperatively and minimum hemoglobin during surgery were identified as independent predictors for AKI in logistic regression. Conclusions: This study highlights the crucial role of creatinine levels in predicting short-term mortality in surgical IE patients. A specific threshold (1.35 mg/dL) provides a practical marker for risk stratification, offering insights for refining perioperative strategies and optimizing outcomes in this challenging patient population.

Harmonizing Heartbeats: The Mosaic of Cardiac Resynchronization Therapy Responders-A Comprehensive Exploration of Diverse Criteria and Predictors.

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.

Cardiac Hepatopathy: New Perspectives on Old Problems through a Prism of Endogenous Metabolic Regulations by Hepatokines.

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.

Adropin Predicts Chronic Kidney Disease in Type 2 Diabetes Mellitus Patients with Chronic Heart Failure.

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.

Large Bouncing Mass in the Right Atrium: Metastasis of Malignant Melanoma.

This paper presents a rare case of malignant melanoma metastasizing to the heart, highlighting the diagnostic journey, therapeutic considerations, and clinical implications. Enhanced awareness of atypical metastases aids early recognition and treatment strategies for improved patient care. Comprehensive understanding of cardiac involvement in melanoma contributes to better outcomes and clinical decision making. (Level of Difficulty: Beginner.).

Biomarkers of Atrial Fibrillation Recurrence in Patients with Paroxysmal or Persistent Atrial Fibrillation Following External Direct Current Electrical Cardioversion.

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.

MicroRNA-30d-5p-A Potential New Therapeutic Target for Prevention of Ischemic Cardiomyopathy after Myocardial Infarction.

(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.

Impact of cavotricuspid isthmus ablation for typical atrial flutter and heart failure in the elderly-results of a retrospective multi-center study.

Introduction: While in the CASTLE-AF trial, in patients with atrial fibrillation and heart failure with reduced ejection fraction, interventional therapy using pulmonary vein isolation was associated with outcome improvement, data on cavotricuspid isthmus ablation (CTIA) in atrial flutter (AFL) in the elderly is rare. Methods: We included 96 patients between 60 and 85 years with typical AFL and heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF) treated in two medical centers. 48 patients underwent an electrophysiological study with CTIA, whereas 48 patients received rate or rhythm control and guideline-compliant heart failure therapy. Patients were followed up for 2 years, with emphasis on left ventricular ejection fraction (LVEF) over time. Primary endpoints were cardiovascular mortality and hospitalization for cardiac causes. Results: Patients with CTIA showed a significant increase in LVEF after 1 (p < 0.001) and 2 years (p < 0.001) in contrast to baseline LVEF. Improvement of LVEF in the CTIA group was associated with significantly lower 2-year mortality (p = 0.003). In the multivariate regression analysis, CTIA remained the relevant factor associated with LVEF improvement (HR: 2.845 CI:95% 1.044-7.755; p = 0.041). Elderly patients (≥ 70 years) further benefited from CTIA, since they showed a significantly reduced rehospitalization (p = 0.042) and mortality rate after 2 years (p = 0.013). Conclusions: CTIA in patients with typical AFL and HFrEF/HFmrEF was associated with significant improvement of LVEF and reduced mortality rates after 2 years. Patient age should not be a primary exclusion criterion for CTIA, since patients ≥70 years also seem to benefit from intervention in terms of mortality and hospitalization.

A Story of PA/BSA and Biomarkers to Diagnose Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis-The Rise of IGF-BP2 and GDF-15.

(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.