Alterations in Coronary Resistance Artery Network Geometry in Diabetes and the Role of Tenascin C.

Background: Geometrical alterations in the coronary resistance artery network and the potential involvement of Tenascin C (TNC) extracellular matrix protein were investigated in diabetic and control mice. Methods: Diabetes was induced by streptozotocin (STZ) injections (n = 7-11 animals in each group) in Tenascin C KO (TNC KO) mice and their Wild type (A/J) littermates. After 16-18 weeks the heart was removed and the whole subsurface network of the left coronary artery was prepared (down to branches of 40 µ m outer diameter), in situ pressure-perfused and studied using video-microscopy. Outer and inner diameters, wall thicknesses and bifurcation angles were measured on whole network pictures reconstructed into collages at 1.7 µ m pixel resolutions. Results: Diabetes induced abnormal morphological alterations including trifurcations, sharp bends of larger branches, and branches directed retrogradely (p < 0.001 by the χ 2 test). Networks of TNC KO mice tended to form early divisions producing parallelly running larger branches (p < 0.001 by the χ 2 probe). Networks of coronary resistance arteries were substantially more abundant in 100-180 µ m components, appearing in 2-5 mm flow distance from orifice in diabetes. This was accompanied by thickening of the wall of larger arterioles ( > 220 µ m) and thinning of the wall of smaller (100-140 µ m) arterioles (p < 0.001). Blood flow should cover larger distances in diabetic networks, but interestingly STZ-induced diabetes did not generate further geometrical changes in TNC KO mice. Conclusions: Diabetes promotes hypertrophic and hypotrophic vascular remodeling and induces vasculogenesis at well defined, specific positions of the coronary vasculature. TNC plays a pivotal role in the formation of coronary network geometry, and TNC deletion causes parallel fragmentation preventing diabetes-induced abnormal vascular morphologies.

Specific Graft Treatment Solution Enhances Vascular Endothelial Function.

Background: Saline is still the most widely used storage and rinsing solution for vessel grafts during cardiac surgery despite knowing evidence of its negative influence on the human endothelial cell function. Aim of this study was to assess the effect of DuraGraft©, an intraoperative graft treatment solution, on human saphenous vein segments and further elaborate the vasoprotective effect on rat aortic segments in comparison to saline. Methods: Human Saphenous vein (HSV) graft segments from patients undergoing aortocoronary bypass surgery (n = 15), were randomized to DuraGraft© (n = 15) or saline (n = 15) solution before intraoperative storage. Each segment was divided into two subsegmental parts for evaluation. These segments as well as rat aortic segments stored in DuraGraft© underwent assessment of vascular function in a multichamber isometric myograph system in comparison to Krebs-Henseleit solution (KHS), a physiologic organ buffer solution. Results: Potassium-Chloride (KCL)-induced contraction depicted a tendency towards increase when treated with DuraGraft© compared to saline preservation of HSV segments (23.02 ± 14.77 vs 14.44 ± 9.13 mN, p = 0.0571). Vein segments preserved with DuraGraft© showed a significant improvement of endothelium-dependent vasorelaxation in response to cumulative concentrations of bradykinin compared to saline treated segments (p < 0.05). Rat aortic segments stored in saline showed significantly impaired vasoconstriction (3.59 ± 4.20, p < 0.0001) and vasorelaxation when compared to KHS and DuraGraft© (p < 0.0001). Conclusions: DuraGraft© demonstrated a favorable effect on graft relaxation and contraction indicating preservation of vascular endothelial function. Clinical Trial Registration Number: NCT04614077.

The Role of Telocytes and Telocyte-Derived Exosomes in the Development of Thoracic Aortic Aneurysm.

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.

Subcutaneous implanted cardioverter-defibrillator in ventricular noncompaction, coronary artery disease and stroke.

Left ventricular hypertrabeculation/noncompaction (LVHT) is associated with arrhythmias. Guidelines for prevention of sudden cardiac death by implanted cardioverter-defibrillator (ICD) also apply to LVHT-patients. Right ventricular perforation by the ICD-lead is a matter of concern. Subcutaneous ICD (S-ICD) may overcome disadvantages of transvenous ICD in patients without a need for pacing therapy. We report a LVHT-patient with arterial hypertension, hyperlipidemia, coronary artery disease with an anterior-wall myocardial infarction 2004 and stroke without neurological deficits in 2018. Since ejection fraction of 33% remained unchanged despite bisoprolol, sacubitril/valsartan and spironolactone, he was treated with S-ICD for primary prevention of sudden cardiac death.

Left Ventricular Reverse Remodeling after Surgical Aortic Valve Replacement for Aortic Regurgitation-An Explorative Study.

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.

First-in-men experience with a novel frozen elephant trunk prosthesis featuring an endovascular side branch for left subclavian artery connection.

OBJECTIVES: The objective of this study was to enhance the efficiency of aortic arch replacement through the development of a novel frozen elephant trunk (FET) prosthesis with an endovascular side branch for left subclavian artery (LSA) connection. After successful pre-clinical testing, the feasibility and safety of implementing this innovative prosthesis in human subjects were investigated. METHODS: Between September 2020 and September 2021, 4 patients (mean age 67) with conditions such as penetrating ulcer, non A-non B aortic dissection and chronic arch aneurysm underwent surgery utilizing the customized device. Surgeries were performed under high moderate hypothermia (27°C), employing bilateral selective antegrade cerebral perfusion (SACP) and distal aortic perfusion. Anastomosis of the FET prosthesis with the aortic arch occurred in zone 1, followed by separate reimplantation of the left common carotid artery and the brachiocephalic artery. RESULTS: All patients were discharged in good clinical condition. The mean aortic cross-clamp, antegrade selective cerebral perfusion and distal aortic perfusion times were 111, 71 and 31 min, respectively. Endovascular extension of the side branch for the LSA was required in all cases to prevent endoleak formation. One patient received a stent graft extension at the end of the operation, while 2 others underwent the procedure during their hospital stay. One patient was diagnosed with an endoleak at the first follow-up after 3 months, and endoleak sealing was achieved via the brachial artery with an extension stent graft. CONCLUSIONS: Preliminary clinical outcomes suggest that the newly designed FET prosthesis shows promise in simplifying total arch replacement. These initial findings provide a foundation for planned clinical studies to further assess the effectiveness of this modified surgical hybrid graft, with particular attention to the length and diameter of the LSA sidearm.

Impact of CytoSorb® on interleukin-6 in cardiac surgery.

Objective: Cardiac surgery is known to activate a cascade of inflammatory mediators leading to a systemic inflammatory response. Hemadsorption (HA) devices such as CytoSorb® have been postulated to mitigate an overshooting immune response, which is associated with increased morbidity and mortality, and thus improve outcome. We aimed to investigate the effect of CytoSorb® on interleukin (IL)-6 levels in patients undergoing complex cardiac surgery in comparison to a control group. Methods: A total of 56 patients (28 CytoSorb®, 28 control) undergoing acute and elective cardiac surgery between January 2020 and February 2021 at the Department of Cardiac and Vascular Surgery, Clinic Floridsdorf, Vienna, were retrospectively analyzed. The primary endpoint was the difference in IL-6 levels between the CytoSorb® and control group. Secondary endpoint was periprocedural mortality. Results: CytoSorb®, installed in the bypass circuit, had no significant effect on IL-6 levels. IL-6 peaked on the first postoperative day (HA: 775.3 ± 838.4 vs. control: 855.5 ± 1,052.9 pg/ml, p = 0.856). In total, three patients died in the HA group, none in the control (logistic regression model, p = 0.996). Patients with an increased Euroscore II of 7 or more showed a reduced IL-6 response compared to patients with an Euroscore II below 7 (178.3 ± 63.1 pg/ml vs. 908.6 ± 972.6 pg/ml, p-value = 0.00306). Conclusions: No significant reduction of IL-6 levels or periprocedural mortality through intraoperative HA with CytoSorb® in patients undergoing cardiac surgery was observed. However, this study was able to show a reduced immunologic response in patients with a high Euroscore II. The routine application of CytoSorb® in cardiac surgery to reduce inflammatory mediators has to be scrutinized in future prospective randomized studies.

Long-Term Results with 187 Frozen Elephant Trunk Procedures.

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.

Graft preservation confers myocardial protection during coronary artery bypass grafting.

Background: During on-pump coronary artery bypass grafting (ONCAB), graft flushing for distal anastomoses testing also perfuses the downstream myocardium. This single-center retrospective study evaluated the impact of specific preservation solutions on myocardial protection during ONCAB. Materials and methods: Between July 2019 and March 2020 either DuraGraft (DG) or 0.9% Saline/Biseko (SB) was applied to 272 ONCAB. Overall, 166 patients were propensity-matched into two groups. Cardiac enzymes [high-sensitive Troponin I (hs-TnI) and creatine kinase (CK)] were evaluated 7 days post-surgery. Results: Post-surgery, hs-TnI values were significantly lower from 3 to 6 h (h) up to 4 days in the DG group: 3-6 h: 4,034 ng/L [IQR 1,853-8,654] vs. 5,532 ng/L [IQR 3,633-8,862], p = 0.05; 12-24 h: 2,420 ng/L [IQR 1,408-5,782] vs. 4,166 [IQR 2,052-8,624], p < 0.01; 2 days: 1,095 ng/L [IQR 479-2,311] vs. 1,564 ng/L [IQR 659-5,057], p = 0.02 and at 4 days: 488 ng/L [IQR 232-1,061] vs. 745 ng/L [IQR 319-1,820], p = 0.03. The maximum value: 4,151 ng/L [IQR 2,056-8,621] vs. 6,349 ng/L [IQR 4,061-12,664], p < 0.01 and the median area under the curve (AUC): 6,146 ng/L/24 h [IQR 3,121-13,248] vs. 10,735 ng/L/24 h [IQR 4,859-21,484], p = 0.02 were lower in the DG group. CK values were not significantly different between groups: maximum value 690 [IQR 417-947] vs. 631 [464-979], p = 0.61 and AUC 1,986 [1,226-2,899] vs. 2,081 [1,311-3,063], p = 0.37. Conclusion: Repeated graft flushing with DG resulted in lower Troponin values post-surgery suggesting enhanced myocardial protection compared to SB. Additional studies are warranted to further assess the myocardial protection properties of DG.

Taking the frozen elephant trunk technique to the next level by a stented side branch for a left subclavian artery connection: a feasibility study.

OBJECTIVES: Our goal was to develop a modified frozen elephant trunk (FET) prosthesis with a stented left subclavian artery (LSA) side branch for LSA connection and to perform preclinical testing in a human cadaver model. METHODS: We measured aortic diameters, distance between and diameters of supra-aortic vessels and the distance from the LSA offspring to the level of the left vertebral artery offspring in 70 patients. Based on these measurements, a novel FET prosthesis was developed (Cryolife/Jotec, Hechingen, Germany) featuring a stented side branch for an intrathoracic LSA connection. The feasibility and ease of implantation were tested in 2 human cadaver models at the Anatomical Institute of the Medical University Graz. A covered stent graft (Advanta V12™ by Atrium Medical Corp., Hudson, NH, USA) was used for an LSA extension. RESULTS: Accurate deployment of the novel FET prosthesis with anatomical orientation of the stented side branch towards the LSA ostium followed by consecutive stent graft deployment was feasible in both cases. Proximalizing the distal anastomosis level from zone 3 to zone 1 not only diminished the complexity of the procedure but substantially facilitated the completion of the distal anastomosis. A 2.5-cm long extension stent graft was sufficient to seal to the LSA and to maintain left vertebral artery patency in both cases. CONCLUSIONS: This initial study in human anatomical bodies could demonstrate the feasibility of implanting a newly designed FET prosthesis. This evolution of the FET technique has the potential to substantially ease total aortic arch replacement by proximalization of the distal anastomosis into zone 1 and by shortening spinal and lower body hypothermic circulatory arrest times via a stented side branch to the LSA. This direct connection enables early restoration of systemic perfusion.

Multicentre experience with two frozen elephant trunk prostheses in the treatment of acute aortic dissection†.

OBJECTIVES: The aim of this study was to evaluate early- and mid-term outcome and aortic remodelling in patients undergoing implantation of 2 different frozen elephant trunk prostheses, either the Thoraflex™ hybrid (Vascutek, Inchinnan, UK) and the E-vita Open (Jotec Inc., Hechingen, Germany) for acute aortic dissection. METHODS: All consecutive patients [n = 88; median age 59 (49-67) years; 69% male] undergoing surgery with a frozen elephant trunk prosthesis for acute aortic dissection from August 2005 until March 2018 were included in this study. The Thoraflex™ device was implanted in 55 patients and the E-vita Open graft in 33 patients. RESULTS: Preoperative characteristics did not differ significantly between groups. There was also no statistically significant difference in postoperative outcome: in-hospital mortality (11% vs 12%; P > 0.99), stroke (18% vs 6%; P = 0.12) and spinal cord injury (6% vs 6%; P > 0.99). While there was no statistically significant difference in the occurrence of distal stent graft-induced new entries (16% vs 18%; P = 0.77), there was a significantly higher rate of secondary endovascular aortic interventions in the Thoraflex™ hybrid group (22% vs 0%; P = 0.003). There was a trend towards a higher rate of false lumen thrombosis at the level of the stent graft (74% vs 95%; P = 0.085) and was comparable at the thoraco-abdominal transition (53% vs 80%; P = 0.36) 1 year after implantation of the prostheses. CONCLUSIONS: In this comparison of 2 frozen elephant trunk prostheses, there is no evidence that different surgical techniques influence in-hospital outcome. At 1-year follow-up, patients who underwent implantation of the E-vita Open prosthesis showed a significantly reduced rate of secondary aortic interventions and a trend towards a higher rate of false lumen thrombosis which might be attributed to a longer coverage of the descending aorta due to a longer stent graft design and significantly more frequent implantation in zone 3.