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.

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.

Conundrum of Classifying Subtypes of Pulmonary Hypertension-Introducing a Novel Approach to Classify "Borderline" Patients in a Population with Severe Aortic Stenosis Undergoing TAVI.

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 AS­is 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.

Gender-Specific Differences in the Intensive Care Treatment of COVID-19 Patients.

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.

Pretreatment with Betablockers, a Potential Predictor of Adverse Cardiovascular Events in Takotsubo Syndrome.

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 ß-adrenergic receptors in patients with chronic betablocker therapy.