Progenitor Cell Function and Cardiovascular Remodelling Induced by SGLT2 Inhibitors.

Sodium-glucose cotransporters 2 (SGLT2) are high-capacity, low-affinity transporters, expressed mainly in the early portion of the proximal renal tube, mediating up to 90% of renal glucose uptake, while SGLT1 receptors are found mainly in the small intestine, facilitating glucose absorption. SGLT2 inhibitors (SGLT2i) originally emerged as agents for the treatment of type 2 diabetes mellitus; however, they soon demonstrated remarkable cardio- and renoprotective actions that led to their licensed use for the treatment of heart failure and chronic kidney disease, regardless of the diabetic status. Cardiovascular remodelling represents an umbrella term that encompasses changes that occur in the cardiovascular system, from the molecular and cellular level, to tissue and organs after local injury, chronic stress, or pressure. SGLT modulation has been shown to positively affect many of these molecular and cellular changes observed during pathological remodelling. Among the different pathophysiological mechanisms that contribute to adverse remodelling, various stem and progenitor cells have been shown to be involved, through alterations in their number or function. Recent studies have examined the effects of SGLT2i on stem and progenitor cell populations and more specifically on endothelial progenitor cells (EPCs). Although some found no significant effect, others showed that SGLT2i can modulate the morphology and function of EPCs. These preliminary observations of the effect of SGLT2i on EPCs may be responsible for some of the beneficial effects of gliflozins on pathological remodelling and, by extension, on cardiovascular disease. The purpose of this narrative review is to critically discuss recent evidence on the cardioprotective effects of SGLT2is, in the context of cardiac remodelling.

To Repair a Broken Heart: Stem Cells in Ischemic Heart Disease.

Despite improvements in contemporary medical and surgical therapies, cardiovascular disease (CVD) remains a significant cause of worldwide morbidity and mortality; more specifically, ischemic heart disease (IHD) may affect individuals as young as 20 years old. Typically managed with guideline-directed medical therapy, interventional or surgical methods, the incurred cardiomyocyte loss is not always completely reversible; however, recent research into various stem cell (SC) populations has highlighted their potential for the treatment and perhaps regeneration of injured cardiac tissue, either directly through cellular replacement or indirectly through local paracrine effects. Different stem cell (SC) types have been employed in studies of infarcted myocardium, both in animal models of myocardial infarction (MI) as well as in clinical studies of MI patients, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), Muse cells, multipotent stem cells such as bone marrow-derived cells, mesenchymal stem cells (MSCs) and cardiac stem and progenitor cells (CSC/CPCs). These have been delivered as is, in the form of cell therapies, or have been used to generate tissue-engineered (TE) constructs with variable results. In this text, we sought to perform a narrative review of experimental and clinical studies employing various stem cells (SC) for the treatment of infarcted myocardium within the last two decades, with an emphasis on therapies administered through thoracic incision or through percutaneous coronary interventions (PCI), to elucidate possible mechanisms of action and therapeutic effects of such cell therapies when employed in a surgical or interventional manner.

Cardiotrophin-1 in Asymptomatic Hypertensive Patients With Mild Diastolic Dysfunction: Potential Prognostic Value in Early Stages of Hypertensive Heart Disease.

BACKGROUND: Regardless of the advancements in modern technology and treatment options, heart failure (HF) exhibits impervious mortality and morbidity rates. Arterial hypertension poses one of the greatest risks for developing HF, yet the exact pathophysiological path and changes that lead from isolated hypertension to HF are still unclear. Cardiotrophin-1 (CT-1) serves as a promising prognostic biomarker for the onset of HF in hypertensive patients. The aim of this study was to investigate whether CT-1 levels are elevated in a selected group of asymptomatic hypertensive patients. METHODS: In a selected cohort of 40 asymptomatic patients with early diastolic dysfunction (grade I), without any signs of increased filling pressures in the left ventricle, as well as 20 healthy individuals, the levels of CT-1 brain natriuretic peptide (BNP) along with various echocardiographic parameters were evaluated. RESULTS: The mean age of the hypertensive patients was 56 ± 5 years and 52± 3.5 years for the normotensive controls. The hypertensive group exhibited higher levels of CT-1, which was not affected by left ventricular hypertrophy. Notably, in patients with normal E/E' < 8 (n = 30), CT-1 levels were 1165 ± 471 pg/ml compared to 2069 ± 576 pg/ml in patients with marginal E/E' > 8 and <14 (n = 10), p = 0.001. CONCLUSIONS: Our study demonstrated elevated CT-1 levels in a cohort of asymptomatic hypertensive patients, exhibiting mild diastolic dysfunction. These findings are suggestive of the potentially prognostic value of this particular biomarker in the early stages of hypertensive heart disease.

An asymptomatic double aortic arch with separate right vertebral artery and left subclavian artery originating from Kommerell Diverticulum combined with congenital asplenia and absence of celiac trunk.

This report describes the unique case of a completely patent Double Aortic Arch (DAA) combined with Kommerell Diverticulum (KD), absence of celiac trunk and congenital asplenia. The anatomical variants described were identified and assessed in a 51-year old female from a computed-tomography angiography (CTA) images with 3D-volume rendered reconstructions during her follow-up after hysterectomy. The reconstructed CTA images showed a DAA with the left common carotid artery stemming from the hypoplastic left aortic arch while the left subclavian artery originated from a KD in the descending thoracic aorta. A symmetric arrangement of the aortic arch branches was demonstrated, comprising a full vascular ring. Since the patient had been completely asymptomatic and with no symptoms of compression of the esophagus or trachea, no surgical management was advised. The abdomen CTA imaging revealed absence of the celiac trunk with direct origin of the common hepatic and the left gastric artery from the superior mesenteric artery as well as asplenia. We presented a case of asymptomatic DAA of completely patent arches with the right vertebral artery branching separately of and the left SCA originating from KD in the descending aorta. The term KD can be identified also in other arch anomalies than the one originally described. Since anatomical anomalies can be frequently combined, thorough imaging inspection with CTA of both thorax and abdomen is suggested.

Promising Novel Therapies in the Treatment of Aortic and Visceral Aneurysms.

Aortic and visceral aneurysms affect large arterial vessels, including the thoracic and abdominal aorta, as well as visceral arterial branches, such as the splenic, hepatic, and mesenteric arteries, respectively. Although these clinical entities have not been equally researched, it seems that they might share certain common pathophysiological changes and molecular mechanisms. The yet limited published data, with regard to newly designed, novel therapies, could serve as a nidus for the evaluation and potential implementation of such treatments in large artery aneurysms. In both animal models and clinical trials, various novel treatments have been employed in an attempt to not only reduce the complications of the already implemented modalities, through manufacturing of more durable materials, but also to regenerate or replace affected tissues themselves. Cellular populations like stem and differentiated vascular cell types, large diameter tissue-engineered vascular grafts (TEVGs), and various molecules and biological factors that might target aspects of the pathophysiological process, including cell-adhesion stabilizers, metalloproteinase inhibitors, and miRNAs, could potentially contribute significantly to the treatment of these types of aneurysms. In this narrative review, we sought to collect and present relevant evidence in the literature, in an effort to unveil promising biological therapies, possibly applicable to the treatment of aortic aneurysms, both thoracic and abdominal, as well as visceral aneurysms.

Methemoglobin as a marker of acute anemic stress in cardiac surgery.

Biological evidence supports plasma methemoglobin as a biomarker for anemia-induced tissue hypoxia. In this translational planned substudy of the multinational randomized controlled transfusion thresholds in cardiac surgery (TRICS-III) trial, which included adults undergoing cardiac surgery requiring cardiopulmonary bypass with a moderate-to-high risk of death, we investigated the relationship between perioperative hemoglobin concentration (Hb) and methemoglobin; and evaluated its association with postoperative outcomes. The primary endpoint was a composite of death, myocardial infarction, stroke, and severe acute kidney injury at 28 days. We observe weak non-linear associations between decreasing Hb and increasing methemoglobin, which were strongest in magnitude at the post-surgical time point. Increased levels of post-surgical methemoglobin were associated with a trend toward an elevated risk for stroke and exploratory neurological outcomes. Our generalizable study demonstrates post-surgical methemoglobin may be a marker of anemia-induced organ injury/dysfunction, and may have utility for guiding personalized approaches to anemia management. Clinicaltrials.gov registration NCT02042898.

Teaching vascular anatomy: the anatomy we know, the anatomy we see or the anatomy we need?

PURPOSE: This article presents the evolution of the subject of vascular anatomy and discusses the associated clinical applicability. METHODS: Clinically-driven surgical examples met in our everyday practice were used to depict characteristic anatomical paradoxes raised by the inconsistencies between classical anatomical perception, current imaging modalities and modern surgical techniques. RESULTS: Consequent anatomy-driven modifications of medical devices comprise a characteristic example of the vivid, modern and meaningful role that anatomy can have on clinical decision-making and improvement of technical and clinical success. Clinical experience provides a feedback that shifts the focus of anatomic research towards new fields of interest, such as the role of arterial collateral networks as therapeutic targets. The clinical feedback brings into light queries and issues where traditional anatomical answers may be vague and inadequate to apply, thereby necessitating further research, refinement and reevaluation. CONCLUSION: While the traditional teaching of vascular anatomy is based on information and illustrations derived from dissection and prosection courses, the development of modern imaging technologies applied in large numbers of living patients and application of minimally invasive techniques challenge our understanding of what should be perceived as fixed and permanent. Moreover, the recently introduced evidence-based philosophy in anatomy elaborate more robust data which not only update, validate and enrich the existing knowledge of anatomical variations but also enable subgroup analyses with respect to race, age and sex, identifying specific anatomic features associated with a significant impact on patient treatment.

Vieussens' Arterial Ring: Historical Background, Medical Review and Novel Anatomical Classification.

In coronary artery disease, the presence of Vieussens' arterial ring (VAR), a ring-shaped anastomosis between the conus branch of the right coronary artery with the left anterior descending artery (LAD), will allow blood flow to return to the obstructed coronary system. We have conducted a literature review, aiming to collect all the existing information about the documented VAR cases and any related pathological conditions. A total of 54 studies entered the review, including 56 patients. The mean age of the patients was 56.12 ± 16.2 years. Angina was present in 53.6% of the patients, with 7.2% of the cases being asymptomatic. Coronary artery disease outweighed (58.9%) as the patients' most frequent diagnosis. We propose a novel VAR anatomical classification, based on the sites of origin and termination of its course, with six distinct types, for a better understanding and surgical management of VAR. Type IA, originating from the conus branch and terminating in the proximal segment of the LAD was most frequently reported (51.8%). The recognition and the subsequent evaluation of the ring's anatomy and course are crucial for a customized clinical intervention. When right and left coronary angiographies fail to reveal any collateral circulation, selective conus artery catheterization should be in order. The proposed classification offers a manageable and comprehensive context for the assessment, evaluation and planning of therapeutic strategies of VAR and sets a new terminology frame for treatment guidelines.

Current knowledge and contemporary management of non-A non-B aortic dissections.

Non-A non-B aortic dissection (AAD) is an infrequently documented condition, comprising of only a small proportion of all AADs. The unique anatomy of the aortic arch and the failure of the existing classifications to adequately define individuals with non-A non-B AAD, have led to an ongoing controversy around the topic. It seems that the clinical progression of acute non-A non-B AAD diverges from the typical type A and B dissections, frequently leading to serious complications and thus mandating early intervention. Currently, the available treatment methods in the surgical armamentarium are conventional open, endovascular techniques and combined hybrid methods. The optimum approach is tailored in every individual case and may be determined by the dissection's location, extent, the aortic diameter, the associated complications and the patient's status. The management of non-A non-B dissections still remains challenging and a unanimous consensus defining the gold standard treatment has yet to be reached. In an attempt to provide further insight into this perplexing entity, we performed a minireview of the literature, aiming to elucidate the epidemiology, clinical course and the optimal treatment modality.

Giant aneurysm of the circumflex artery.

In this paper, we describe a rare case of a giant aneurysm of the circumflex artery that we managed. A 59-year-old female patient presented in cardiogenic shock after partial aneurysm rupture. Giant aneurysms of the circumflex artery are extremely rare entities. The optimal surgical management dictates meticulous preoperative planning and the operation should be carried out on an elective basis.

Stem cell genes in atheromatosis: The role of Klotho, HIF1α, OCT4, and BMP4.

During fetal development, shear stress regulates several aspects of vascular development. Alterations in signaling pathways due to disturbed flow in atheroprone regions closely mirror phenomena seen during embryogenesis. This flow-dependent dysregulation of developmental genes appears to promote atherogenesis by mediating inflammatory phenomena, cell cycle progression, apoptosis, cell migration, and oxidative stress. Indeed, several stem cell genes have been implicated in vascular health and atheromatosis. Klotho is key in maintaining endothelial integrity, reducing oxidative stress, and sustaining endothelial nitric oxide production. In atherosclerotic lesions, OCT4 mediates the conversion of vascular smooth muscle cells from contractile to a de-dedifferentiated proliferative phenotype with phagocytic ability. HIF1α drives atherosclerotic plaque progression by promoting intraplaque angiogenesis. BMP4 promotes osteochondrogenic development and arterial calcification. Strategic extracellular matrix changes are also seen during the various phases of atherosclerosis. The aforementioned conceptual framework explains how proatherogenic inflammation develops in response to low shear stress. In the present review, we explored the effect of cardinal atheroprotective (Klotho, OCT4) and proatherogenic (HIF1α, BMP4) genes in mediating proatherogenic inflammation.

Neuroprotective strategies with circulatory arrest in open aortic surgery - A meta-analysis.

OBJECTIVE: Deep hypothermic circulatory arrest (DHCA) in aortic surgery is associated with morbidity and mortality despite evolving strategies. With the advent of antegrade cerebral perfusion (ACP), moderate hypothermic circulatory arrest (MHCA) was reported to have better outcomes than DHCA. There is no standardised guideline or consensus regarding the hypothermic strategies to be employed in open aortic surgery. Meta-analysis was performed comparing DHCA with MHCA + ACP in patients having aortic surgery. METHODS: A systematic review of the literature was undertaken. Any studies with DHCA versus MHCA + ACP in aortic surgeries were selected according to specific inclusion criteria and analysed to generate summative data. Statistical analysis was performed using STATS Direct. The primary outcomes were hospital mortality and post-operative stroke. Secondary outcomes were cardiopulmonary bypass time (CPB), post-operative blood transfusion, length of ICU stay, respiratory complications, renal failure and length of hospital stay. Subgroup analysis of primary outcomes for Arch surgery alone was also performed. RESULTS: Fifteen studies were included with a total of 5869 patients. There was significantly reduced mortality (Pooled OR = +0.64, 95% CI = +0.49 to +0.83; p = 0.0006) and stroke rate (Pooled OR = +0.62, 95% CI = +0.49 to +0.79; p < 0.001) in the MHCA group. MHCA was associated significantly with shorter CPB times, shorter duration in ICU, less pulmonary complications, and reduced rates of sepsis. There was no statistical difference between the two groups in terms of circulatory arrest times, X-Clamp times, total operation duration, transfusion requirements, renal failure and post-op hospital stay. CONCLUSION: MHCA + ACP are associated with significantly better post-operative outcomes compared with DHCA for both mortality and stroke and majority of the secondary outcomes.

Aspergillus Endocarditis of Pulmonary Homograft in a Congenital Heart Disease Patient.

Aspergillus endocarditis (AE) is a life-threatening condition with mortality rates approximating 80%. Herein, we describe the case of a 19-year-old patient with congenitally corrected transposition of great arteries, ventricular septal defect, and pulmonary atresia, who underwent seven cardiac surgical procedures in the past. The patient was operated for AE of a previously implanted pulmonary valve homograft associated with septic pulmonary embolism and right heart failure but succumbed to multi-organ failure three months later. To our knowledge, this is one of two reported cases of Aspergillus infection of a pulmonary homograft, indicating the rarity of the disease.

Update on the TREO endograft device: overview of its safety and efficacy.

INTRODUCTION: The TREO abdominal aortic stent graft system (Terumo Aortic, Sunrise, Fla) is a low-profile, trimodular endovascular endoprosthesis for the endovascular repair of abdominal aortic aneurysm (AAA). The objective of the present study was to collect and discuss all the available modern data of this device highlighting especially its mid-and long-term clinical results. AREAS COVERED: This updated review article presents the most current results from great-scale clinical studies and the RATIONALE registry involving also angulated neck anatomies and challenging AAA geometries, reflecting the real-world experience. EXPERT OPINION: The global, multicenter RATIONALE registry prospectively enrolled 202 patients (mean age 73.0 ± 7.8 years) who underwent EVAR. Technical success, primary clinical success and assisted primary patency rate was 96%, 92.2% and 97%, respectively. The clinical success at 1 year was 96%. Another multicenter, non-randomized, clinical trial confirmed also high technical and clinical success. Additionally, a comparative study comparing favorable and hostile necks in AAA, demonstrated a comparable technical success (95.2%), achieving proper sealing and technical success in the hostile neck group. TREO endograft seems to be safe and effective for EVAR, especially in hostile neck anatomies. Long-term outcomes from ongoing registries are awaited to complete these results.

An alternative approach for complicated prosthetic aortic valve endocarditis.

BACKGROUND: Surgical treatment of prosthetic valve endocarditis (PVE) with destruction of the aortic root and aortomitral continuity is demanding even in experienced hands. CASE PRESENTATION: Herein, we describe a case of a 71-year-old female patient who presented with PVE that was further complicated by a fistulous abscess cavity. The patient underwent removal of the dehisced prosthetic valve, radical annular debridement, reconstruction of the aortomitral curtain with a pericardial patch as a patch exclusion technique and implantation of a sutureless valve. CONCLUSION: Patch exclusion technique, followed by sutureless valve implantation, might represent a feasible and safe alternative for the surgical treatment of complicated PVE.

Surgical repair of anomalous aortic origin of coronary artery in adults.

Anomalous aortic origin of a coronary artery is a congenital abnormality of the origin or course of a coronary artery that arises from the aorta. The surgical treatment of this anomaly is highly variable and controversial and is achieved by implementing elaborate techniques of anatomic repair or by simple coronary artery bypass grafting. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two independent reviewers determined whether studies met the inclusion criteria. Eligible papers were published in English, clinical studies describing surgical repair of anomalous aortic origin of a coronary artery including coronary artery bypass in adults, and enrolled >5 patients. In the absence of multicentre trials, 7 single-center retrospective series were included, which demonstrated comparable short- and midterm outcomes of anatomic repair and coronary artery bypass in adults with anomalous aortic origin of a coronary artery. Coronary unroofing was the preferred technique when the anomalous artery has an intramural component, but there is a risk of aortic insufficiency. Anatomic repair is technically demanding and should be carried out in experienced centers. Coronary artery bypass with internal thoracic artery or vein grafts is technically straightforward with low operative risk and comparable midterm outcomes, however, long-term outcomes are unknown. Coronary artery bypass grafting is the technique of choice for older patients, in those with concomitant coronary artery disease, as a bailout procedure for failed anatomic repair, or in centers without experience in anatomic repair for anomalous aortic origin of a coronary artery.

Cardio-Protective Effects of Sodium-Glucose Co-Transporter 2 Inhibitors: Focus on Heart Failure.

BACKGROUND: Type 2 diabetes mellitus (DM) is associated with a considerable risk of cardiovascular and renal diseases, including heart failure. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated unprecedented cardiorenal protective effects in large-scale clinical trials of patients with or without diabetes and either established cardiovascular disease (CV) or multiple CV risk factors. OBJECTIVE: Herein we aim to focus on the role of SGLT2 inhibitors regarding the improvement in heart failure outcomes and the proposed mechanisms of action by which these drugs confer their beneficial effect. METHODS: PubMed, Embase, and Google Scholar databases were searched to identify eligible articles that are comprehensively summarized and discussed in this study. RESULTS: The most commonly discussed mechanisms of action are diuresis and natriuresis, reduction in preload, afterload, and ventricular mass, as well as stimulation of erythropoietin production and improved myocardial energetics. SGLT2 inhibitors improve outcomes in patients with established heart failure (HF) and reduce the risk of death and HF admissions in patients with established chronic HF with reduced ejection fraction (HFrEF), either with or without diabetes. CONCLUSION: Potential key mechanisms that may explain the notable cardioprotective benefits of SGLT2 inhibitors have been outlined. These agents have recently received class Ia recommendation in specific groups of people with DM to lower the risk of hospitalization for HF and risk of death, while these benefits may also extend to people without diabetes. It remains to be seen whether they will also emerge as treatment approaches in the acute phase of CV episodes.