Francesco Ancona

Role of the Renin-Angiotensin-Aldosterone system in the pathogenesis of atherosclerosis

Renin-angiotensin-aldosterone (RAAS) is a hormone system which acts on multiple physiologic pathways primarily by regulating blood pressure and fluid balance, but also by local autocrine and paracrine actions. In pathophysiologic conditions RAAS also contributes to the development of atherosclerosis and its various manifestations, both directly and indirectly through the actions on other systems. RAAS mainly acts as a promoter of atherosclerosis by its action on vessels, and by promoting the development of hypertension, insulin resistance and diabetes, obesity, vascular and systemic inflammation. As RAAS plays a key role in the pathogenesis of cardiovascular diseases, RAAS genes have been extensively studied as candidate genes for atherosclerosis and coronary artery disease. Several polymorphisms of its genes have been found to be in relationship with atherosclerosis and cardiovascular diseases. In this review we will discuss these issues and present the most recent advances about this topic.

Plasma levels of active Von Willebrand factor are increased in patients with first ST-segment elevation myocardial infarction: A multicenter and multiethnic study

Aims: Von Willebrand factor (VWF), a key player in hemostasis and thrombosis, is released from endothelial cells during inflammation. Upon release, VWF is processed by ADAMTS13 into an inactive conformation. The aim of our study was to investigate whether plasma levels of active VWF, total VWF, ADAMTS13, osteoprotegerin (OPG) and the ratios between VWF and ADAMTS13 are risk factors for first ST-segment elevation myocardial infarction (STEMI). Methods and results: We assessed 1026 patients with confirmed first STEMI and 652 control subjects from China, Italy and Scotland, within six hours after their cardiovascular event. Median plasma levels of total VWF, active VWF, OPG and ratios VWF/ADAMTS13 were increased, while plasma levels of ADAMTS13 were decreased in patients compared to controls. The odds ratio (OR) of STEMI in patients with high plasma levels of active VWF was 2.3 (interquartile range (IQR): 1.8–2.9), total VWF was 1.8 (1.4–2.3), ADAMTS13 was 0.6 (05–0.8), OPG was 1.6 (1.2–2.0) and high VWF/ADAMTS13 ratios was 1.5 (1.2–2.0). The OR for total VWF, active VWF and ratios VWF/ADAMTS13 remained significant after adjustment for established risk factors, medical treatment, C-reactive protein, total VWF, ADAMTS13 and OPG. When we adjusted for levels of active VWF, the significance of the OR for VWF and ratios VWF/ADAMTS13 disappeared while the OR for active VWF remained significant. Conclusions: We found evidence that plasma levels of active VWF are an independent risk factor for first STEMI in patients from three different ethnic groups. Our findings confirm the presence of VWF abnormalities in patients with STEMI and may be used to develop new therapeutic approaches.

Raoultella planticola-associated cholangitis and sepsis: a case report and literature review

### Learning Point for Clinicians Raoultella planticola is a rare and possibly underestimated cause of severe human infection and its presence should be suspected in older patients with a history of cancer, immune-suppression and recent exposure to traumatic injuries or invasive medical procedures. The frequent involvement of the bilio-pancreatic tract suggests the importance of the gut flora as a bacterial reservoir in clinically relevant infections. Raoultella planticola 1 is a Gram-negative anaerobic bacterium and a rare cause of human infection. Twelve cases of clinically relevant human infections (two fatal) have been described so far in the English literature. A 70-year-old male with a history of chronic obstructive pulmonary disease and bronchiectasis was diagnosed with pancreatic adenocarcinoma. Due to significant mass-effect on the biliary …

Left Atrial Appendage: Physiology, Pathology, and Role as a Therapeutic Target

Atrial fibrillation (AF) is the most common clinically relevant cardiac arrhythmia. AF poses patients at increased risk of thromboembolism, in particular ischemic stroke. The CHADS2 and CHA2DS2-VASc scores are useful in the assessment of thromboembolic risk in nonvalvular AF and are utilized in decision-making about treatment with oral anticoagulation (OAC). However, OAC is underutilized due to poor patient compliance and contraindications, especially major bleedings. The Virchow triad synthesizes the pathogenesis of thrombogenesis in AF: endocardial dysfunction, abnormal blood stasis, and altered hemostasis. This is especially prominent in the left atrial appendage (LAA), where the low flow reaches its minimum. The LAA is the remnant of the embryonic left atrium, with a complex and variable morphology predisposing to stasis, especially during AF. In patients with nonvalvular AF, 90% of thrombi are located in the LAA. So, left atrial appendage occlusion could be an interesting and effective procedure in thromboembolism prevention in AF. After exclusion of LAA as an embolic source, the remaining risk of thromboembolism does not longer justify the use of oral anticoagulants. Various surgical and catheter-based methods have been developed to exclude the LAA. This paper reviews the physiological and pathophysiological role of the LAA and catheter-based methods of LAA exclusion.

Multimodality imaging of the tricuspid valve with implication for percutaneous repair approaches

Nowadays some percutaneous options for tricuspid valve (TV) repair are available: Tricinch (4Tech Cardio, Galway, Ireland) mimicking the Kay procedure, Trialign (Mitralign, Boston, MA, USA) aiming to bicuspidise TV, MitraClip (Abbott Vascular, Abbott Park, Illinois, USA) mimicking Alfieri’s stitch, direct transcatheter annuloplasty with Cardioband (Valtech Cardio, Or Yehuda, Israel) and transcatheter Forma Repair (Edwards Lifesciences, Irvine, California, USA) providing a surface for leaflet coaptation. A multimodality imaging approach is fundamental for defining the pathophysiology of tricuspid regurgitation (TR), preprocedural planning and intraprocedural monitoring. Both 2-dimensional and 3-dimensional (3D) transthoracic echocardiography and transoesophageal echocardiography (TOE) are essential for grading and anatomical characterisation of TR, and evaluation of dimensions and function of right ventricle (RV) and estimation of pulmonary pressure. In particular, 3D echocardiography provides a better anatomical definition of TV apparatus and tricuspid annulus (TA) and additional information about the anatomical relationships of TV and surrounding structures. CT offers complementary information during the preprocedural planning especially for procedures targeting TA such as annular structure and dimensions, quality and amount of annular tissue and its relationship with the right coronary artery, and the sizing of the inferior vena cava. Moreover, appropriate patient selection is crucial. The best candidate seems to be a patient with functional TR due to predominant annular dilatation with modest apical tethering, at least partial preservation of leaflets coaptation, not severe pulmonary hypertension and not advanced RV dilation and dysfunction. An example of intraprocedural multimodality imaging approach with TOE, fluoroscopy, angiography and intracardiac echocardiography is also reported.

Left atrial appendage closure: A single center experience and comparison of two contemporary devices

To compare indications and clinical outcomes of two contemporary left atrial appendage (LAA) percutaneous closure systems in a “real‐world” population.

Use of Echocardiography for Guiding Percutaneous Tricuspid Valve Procedures

Percutaneous tricuspid valve (TV) repair procedures are emerging therapies for patients with symptomatic severe tricuspid regurgitation (TR) who are deemed inoperable. Some of these procedures target the tricuspid annulus (TA), mimicking the Kay procedure, or the leaflets, mimicking Alfieri stitch

Echocardiographic features of post-transcatheter aortic valve implantation thrombosis and endocarditis.

Transcatheter heart valve thrombosis (THV‐t) and endocarditis (THV‐e) are relevant complications after transcatheter aortic valve implantation (TAVI). Transcatheter heart valve (THV) dysfunction definition is mostly based on Doppler (stenosis/regurgitation) without considering leaflets characteristics.

Sustained Reduction of Tricuspid Regurgitation After Percutaneous Repair With the MitraClip System in a Patient With a Dual Chamber Pacemaker

A 73-year-old woman presented with heart failure, systemic congestion, and fatigue despite optimal medical therapy. Her medical history included stage IV kidney disease and previous hepatitis B virus infection. In 2014, she experienced a non–ST-segment elevation myocardial infarction: coronary

Mechanical dyssynchrony and deformation imaging in patients with functional mitral regurgitation

Chronic functional mitral regurgitation (FMR) is a frequent finding of ischemic heart disease and dilated cardiomyopathy (DCM), associated with unfavourable prognosis. Several pathophysiologic mechanisms are involved in FMR, such as annular dilatation and dysfunction, left ventricle (LV) remodeling, dysfunction and dyssynchrony, papillary muscles displacement and dyssynchrony. The best therapeutic choice for FMR is still debated. When optimal medical treatment has already been set, a further option for cardiac resynchronization therapy (CRT) and/or surgical correction should be considered. CRT is able to contrast most of the pathophysiologic determinants of FMR by minimizing LV dyssynchrony through different mechanisms: Increasing closing forces, reducing tethering forces, reshaping annular geometry and function, correcting diastolic MR. Deformation imaging in terms of two-dimensional speckle tracking has been validated for LV dyssynchrony assessment. Radial speckle tracking and three-dimensional strain analysis appear to be the best methods to quantify intraventricular delay and to predict CRT-responders. Speckle-tracking echocardiography in patients with mitral valve regurgitation has been usually proposed for the assessment of LV and left atrial function. However it has also revealed a fundamental role of intraventricular dyssynchrony in determining FMR especially in DCM, rather than in ischemic cardiomyopathy in which MR severity seems to be more related to mitral valve deformation indexes. Furthermore speckle tracking allows the assessment of papillary muscle dyssynchrony. Therefore this technique can help to identify optimal candidates to CRT that will probably demonstrate a reduction in FMR degree and thus will experience a better outcome.