Background: Aortic valve stenosis is an increasingly prevalent degenerative and inflammatory disease. Transcatheter aortic valve implantation (TAVI) has revolutionized its treatment, thereby avoiding its life-threatening/disabling consequences. Whether aortic valve stenosis is accelerated by inflammation and whether it is itself a cause of inflammation are unclear. We hypothesized that the large shear forces exerted on circulating cells, particularly on the largest circulating cells, monocytes, while passing through stenotic aortic valves results in pro-inflammatory effects that are resolved with TAVI. Methods: TAVI provides a unique opportunity to compare the activation status of monocytes under high shear stress (before TAVI) and under low shear stress (after TAVI). The activation status of monocytes was determined using a single-chain antibody MAN-1 which is specific for the activated β2-integrin Mac-1. Monocyte function was further characterized by their adhesion to stimulated endothelial cells, phagocytic activity, uptake of oxidized LDL, and cytokine expression. In addition, we designed a microfluidic system to recapitulate the shear rate conditions before and after TAVI. We used this tool in combination with functional assays, Ca 2+ imaging, siRNA gene silencing, and pharmacological agonists and antagonists to identify the key mechanoreceptor mediating the shear stress sensitivity of monocytes. Finally, we stained for monocytes in explanted stenotic aortic human valves. Results: The resolution of high shear stress via TAVI reduces Mac-1 activation, cellular adhesion, phagocytosis, oxidized LDL uptake, and expression of inflammatory markers in monocytes and plasma. Using microfluidics, pharmacological and genetic studies, we could recapitulate high shear stress effects on isolated human monocytes under highly controlled conditions, showing that shear stress-dependent calcium influx and monocyte adhesion are mediated by the mechanosensitive ion channel Piezo-1. We also demonstrate that expression of this receptor is shear stress-dependent and downregulated in patients receiving TAVI. Finally, we show monocyte accumulation at the aortic side of leaflets of explanted aortic valves. Conclusions: We demonstrate that high shear stress, as present in patients with aortic valve stenosis, activates multiple monocyte functions and we identify Piezo-1 as the mainly responsible mechanoreceptor, representing a potentially druggable target. Importantly, we demonstrate an anti-inflammatory effect and therefore a novel therapeutic benefit of TAVI.

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Coronary artery disease (CAD) screening and diagnosis are core cardiac specialty services. From symptoms, autopsy correlations supported reductions in coronary blood flow and dynamic epicardial and microcirculatory coronaries artery disease as etiologies. While angina remains a clinical diagnosis, most cases require correlation with a diagnostic modality. At the onset of the evidence building process much research, now factored into guidelines were conducted among population and demographics that were homogenous and often prior to newer technologies being available. Today we see a more diverse multi-ethnic population whose characteristics and risks may not consistently match the populations from which guideline evidence is derived. While it would seem very unlikely that for the majority, scientific arguments against guidelines would differ, however from a translational perspective, there will be populations who differ and importantly there are cost-efficacy questions, e.g ., the most suitable first-line tests or what parameters equate to an adequate test. This article reviews non-invasive diagnosis of CAD within the context of multi-ethnic patient populations.

The combination of posttraumatic coronary artery-right ventricular fistula and multiple ventricular septal defects is a rare and interesting phenomenon. We describe a case of a 19-year-old male with these findings following a blunt chest trauma after a motorcycle accident.

Pseudoaneurysm of aorta is a rare condition usually seen after aortic surgeries or serious accidents. Here we report a 60 years old man without any previous medical condition who presented with non-specific symptoms and underwent different investigations for more than 1 year, until the presence of a continuous murmur raised suspicion toward his cardiovascular system. In echocardiographic and computed tomography (CT) angiographic studies a large pseudoaneurysm of aortic arch with compression effect on pulmonary artery was detected. At this stage he remembered having suffered a minor trauma 10 years ago. He finally underwent operation and his aortic wall was repaired successfully with a patch. This case highlights the importance of thorough history taking and physical examination in patients irrespective of symptoms and high index of suspicion to detect this life-threatening condition.