Unveiling cellular and molecular aspects of ascending thoracic aortic aneurysms and dissections.

Ascending thoracic aortic aneurysm (ATAA) remains a significant medical concern, with its asymptomatic nature posing diagnostic and monitoring challenges, thereby increasing the risk of aortic wall dissection and rupture. Current management of aortic repair relies on an aortic diameter threshold. However, this approach underestimates the complexity of aortic wall disease due to important knowledge gaps in understanding its underlying pathologic mechanisms.Since traditional risk factors cannot explain the initiation and progression of ATAA leading to dissection, local vascular factors such as extracellular matrix (ECM) and vascular smooth muscle cells (VSMCs) might harbor targets for early diagnosis and intervention. Derived from diverse embryonic lineages, VSMCs exhibit varied responses to genetic abnormalities that regulate their contractility. The transition of VSMCs into different phenotypes is an adaptive response to stress stimuli such as hemodynamic changes resulting from cardiovascular disease, aging, lifestyle, and genetic predisposition. Upon longer exposure to stress stimuli, VSMC phenotypic switching can instigate pathologic remodeling that contributes to the pathogenesis of ATAA.This review aims to illuminate the current understanding of cellular and molecular characteristics associated with ATAA and dissection, emphasizing the need for a more nuanced comprehension of the impaired ECM-VSMC network.

The Maastricht Acquisition Platform for Studying Mechanisms of Cell-Matrix Crosstalk (MAPEX): An Interdisciplinary and Systems Approach towards Understanding Thoracic Aortic Disease.

Current management guidelines for ascending thoracic aortic aneurysms (aTAA) recommend intervention once ascending or sinus diameter reaches 5-5.5 cm or shows a growth rate of >0.5 cm/year estimated from echo/CT/MRI. However, many aTAA dissections (aTAAD) occur in vessels with diameters below the surgical intervention threshold of <55 mm. Moreover, during aTAA repair surgeons observe and experience considerable variations in tissue strength, thickness, and stiffness that appear not fully explained by patient risk factors. To improve the understanding of aTAA pathophysiology, we established a multi-disciplinary research infrastructure: The Maastricht acquisition platform for studying mechanisms of tissue-cell crosstalk (MAPEX). The explicit scientific focus of the platform is on the dynamic interactions between vascular smooth muscle cells and extracellular matrix (i.e., cell-matrix crosstalk), which play an essential role in aortic wall mechanical homeostasis. Accordingly, we consider pathophysiological influences of wall shear stress, wall stress, and smooth muscle cell phenotypic diversity and modulation. Co-registrations of hemodynamics and deep phenotyping at the histological and cell biology level are key innovations of our platform and are critical for understanding aneurysm formation and dissection at a fundamental level. The MAPEX platform enables the interpretation of the data in a well-defined clinical context and therefore has real potential for narrowing existing knowledge gaps. A better understanding of aortic mechanical homeostasis and its derangement may ultimately improve diagnostic and prognostic possibilities to identify and treat symptomatic and asymptomatic patients with existing and developing aneurysms.

Aortic root replacement in severe left ventricular dysfunction: The added value of beating-heart surgery.

There are limits to the use of cardioplegic arrest during complex cardiac surgical procedures, especially in patients with severe left ventricular dysfunction. In the current report, we graphically present the detailed surgical strategy and technique for beating-heart aortic root replacement with concomitant coronary bypass grafting, for patients otherwise deemed inoperable. With support of cardiopulmonary bypass (CPB), beating-heart bypass surgery is realized, after which the bypass grafts can selectively be connected to the CPB, preserving coronary flow. Then, on the beating and perfused heart, a complex procedure such as aortic root replacement can be performed, without jeopardizing postoperative cardiac function. However, several important caveats and remarks regarding the use of beating-heart surgery should be considered, including: coronary perfusion verification and maintenance, temperature management, and prevention of air embolisms. By use of this strategy, risks associated with cardioplegic arrest are minimized, while it circumvents the potential need for long-term postoperative extracorporeal membrane oxygenation.

Intra-Operative Video-Based Measurement of Biaxial Strains of the Ascending Thoracic Aorta.

Local biaxial deformation measurements are essential for the in-depth investigation of tissue properties and remodeling of the ascending thoracic aorta, particularly in aneurysm formation. Current clinical imaging modalities pose limitations around the resolution and tracking of anatomical markers. We evaluated a new intra-operative video-based method to assess local biaxial strains of the ascending thoracic aorta. In 30 patients undergoing open-chest surgery, we obtained repeated biaxial strain measurements, at low- and high-pressure conditions. Precision was very acceptable, with coefficients of variation for biaxial strains remaining below 20%. With our four-marker arrangement, we were able to detect significant local differences in the longitudinal strain as well as in circumferential strain. Overall, the magnitude of strains we obtained (range: 0.02-0.05) was in line with previous reports using other modalities. The proposed method enables the assessment of local aortic biaxial strains and may enable new, clinically informed mechanistic studies using biomechanical modeling as well as mechanobiological profiling.