Endothelial progenitor cells (EPC) may influence the integrity and stability of the vascular endothelium. The association of an altered total EPC number and function with cardiovascular diseases (CVD) and risk factors (CVF) was discussed; however, their role and applicability as biomarkers for clinical purposes have not yet been defined. Endothelial dysfunction is one of the key mechanisms in CVD. The assessment of endothelial dysfunction in vivo remains a major challenge, especially for a clinical evaluation of the need for therapeutic interventions or for primary prevention of CVD. One of the main challenges is the heterogeneity of this particular cell population. Endothelial cells (EC) can become senescent, and the majority of circulating endothelial cells (CEC) show evidence of apoptosis or necrosis. There are a few viable CECs that have properties similar to those of an endothelial progenitor cell. To use EPC levels as a biomarker for vascular function and cumulative cardiovascular risk, a correct definition of their phenotype, as well as an update on the clinical application and practicability of current isolation methods, are an urgent priority.

A hallmark of thoracic aortic aneurysms (TAA) is the degenerative remodeling of aortic wall, which leads to progressive aortic dilatation and resulting in an increased risk for aortic dissection or rupture. Telocytes (TCs), a distinct type of interstitial cells described in many tissues and organs, were recently observed in the aortic wall, and studies showed the potential regulation of smooth muscle cell (SMC) homeostasis by TC-released shed vesicles. The purpose of the present work was to study the functions of TCs in medial degeneration of TAA. During aneurysmal formation an increase of aortic TCs was identified in human surgical specimens of TAA-patients, compared to healthy thoracic aortic (HTA)-tissue. We found the presence of epithelial progenitor cells in the adventitial layer, which showed increased infiltration in TAA samples. For functional analysis, HTA- and TAA-telocytes were isolated, characterized, and compared by their protein levels, mRNA- and miRNA-expression profiles. We detected TC and TC-released exosomes near SMCs. TAA-TC-exosomes showed a significant increase of the SMC-related dedifferentiation markers KLF-4-, VEGF-A-, and PDGF-A-protein levels, as well as miRNA-expression levels of miR-146a, miR-221 and miR-222. SMCs treated with TAA-TC-exosomes developed a dedifferentiation-phenotype. In conclusion, the study shows for the first time that TCs are involved in development of TAA and could play a crucial role in SMC phenotype switching by release of extracellular vesicles.

The frozen elephant trunk (FET) technique is an established therapeutic option in the treatment of complex aortic diseases. We report our long-term clinical outcomes after FET repair. A total of 187 consecutive patients underwent FET repair at our department between 8/2005 and 3/2023. Indications included acute and chronic aortic dissections and thoracic aneurysms. Endpoints included operative morbidity and mortality, long-term survival, and the need for reinterventions. Operative mortality, spinal cord injury and permanent stroke rates were: 9.6%, 2.7% and 10.2%, respectively. At five years, overall survival was 69.9 ± 3.9% and freedom from aortic-related death was 82.5 ± 3.0%, whereas at ten years, overall survival was 53.0 ± 5.5% and freedom from aortic-related death was 75.8 ± 4.8%. Sixty-one reinterventions on the thoracic aorta were necessary. Freedom from secondary interventions at ten years was 44.7 ± 6.4% overall (63.1 ± 10.0% for acute dissections, 40.8 ± 10.3% for chronic dissections and 28.9 ± 13.1% for aneurysms, respectively). The high reintervention rate for chronic dissections and for aneurysms is related to the pre-existing aortic pathology. Late aortic growth of untreated segments with potentially fatal outcome occurs even after ten years, so careful annual follow-up is mandatory in this patient cohort.

Transcatheter aortic valve replacement (TAVR) offers a novel treatment option for patients with severe symptomatic aortic valve stenosis, particularly for patients who are unsuitable candidates for surgical intervention. However, high therapeutical costs, socio-economic considerations, and numerous comorbidities make it necessary to target and allocate available resources efficiently. In the present study, we aimed to identify risk factors associated with futile treatment following transfemoral (TF) and transapical (TA) TAVR. Five hundred and thirty-two consecutive patients (82 ± 9 years, female 63%) who underwent TAVR between June 2009 and December 2016 at the Vienna Heart Center Hietzing were retrospectively analyzed to identify predictors of futility, defined as all-cause mortality at one year following the procedure for the overall patient cohort, as well as the TF and TA cohort. Out of 532 patients, 91 (17%) did not survive the first year after TAVR. A multivariate logistic model identified cerebrovascular disease, home oxygen dependency, wheelchair dependency, periinterventional myocardial infarction, and postinterventional renal replacement therapy as the factors independently associated with an increased one-year mortality. Our findings underscore the significance of a precise preinterventional evaluation, as well as illustrating the subtle differences in baseline characteristics in the TF and TA cohort and their impact on one-year mortality.

Thoracic aortic aneurysm (TAA) is an age-related and life-threatening vascular disease. Telomere shortening is a predictor of age-related diseases, and its progression is associated with premature vascular disease. The aim of the present work was to investigate the impacts of chronic hypoxia and telomeric DNA damage on cellular homeostasis and vascular degeneration of TAA. We analyzed healthy and aortic aneurysm specimens (215 samples) for telomere length (TL), chronic DNA damage, and resulting changes in cellular homeostasis, focusing on senescence and apoptosis. Compared with healthy thoracic aorta (HTA), patients with tricuspid aortic valve (TAV) showed telomere shortening with increasing TAA size, in contrast to genetically predisposed bicuspid aortic valve (BAV). In addition, TL was associated with chronic hypoxia and telomeric DNA damage and with the induction of senescence-associated secretory phenotype (SASP). TAA-TAV specimens showed a significant difference in SASP-marker expression of IL-6, NF-κB, mTOR, and cell-cycle regulators (γH2AX, Rb, p53, p21), compared to HTA and TAA-BAV. Furthermore, we observed an increase in CD163⁺ macrophages and a correlation between hypoxic DNA damage and the number of aortic telocytes. We conclude that chronic hypoxia is associated with telomeric DNA damage and the induction of SASP in a diseased aortic wall, promising a new therapeutic target.

Background: The timing of treatment for chronic aortic valve regurgitation (AR), especially in asymptomatic patients, is gaining attention since less invasive strategies have become available. The aim of the present study was to evaluate left ventricular reverse remodeling after aortic valve replacement (AVR) for severe AR. Methods: Patients (n = 25) who underwent surgical AVR for severe AR with left ventricular ejection fraction (LVEF) less than 55% were included in this study. Preprocedural and follow-up clinical and echocardiographic measurements of LVEF and left ventricular (LV) diameters were retrospectively analyzed. Results: Mean LVEF increased significantly following surgical AVR (p < 0.0001). LV diameters showed a clear regression (p = 0.0088). Younger patients and those receiving a mechanical valve tended to have less improved LVEF on follow-up than patients over 60 years or the ones who were implanted with a biological prosthesis (p = 0.0239 and p = 0.069, respectively). Gender had no effect on the degree of LVEF improvement (p = 0.4908). Conclusions: We demonstrated significant LV reverse remodeling following AVR for AR. However, more data are needed on LV functional and geometrical improvement comparing the different types of valve prostheses to provide an optimal treatment strategy.