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.

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.

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.

The aberrant subclavian artery: approach to management.

PURPOSE OF REVIEW: Aberrant subclavian artery (ASCA) represents one of the most common congenital vascular anomalies of the aortic arch. The majority of ASCAs are associated with an aneurysm which occurs at their origin from the descending thoracic aorta, namely, the Kommerell's diverticulum. In this review, we discuss recent data with regards to indications of treatment and surgical management of these anatomical variants. RECENT FINDINGS: Various surgical methods have been described for the repair of ASCA and Kommerell's diverticulum. Traditionally, treatment included open surgery; however, recent studies describe a shift of conventional treatment to more hybrid or endovascular approaches. The heterogeneity in the anatomy and presentation of these clinical entities as well as patient-related factors have prevented conduction of randomized trials for the best available modality of treatment. This dearth of literature is well depicted in the current guidelines. SUMMARY: The optimal surgical procedure has to be tailored to every patient according to the presentation, individual anatomy, and patient's risk profile. Conventional surgery for ASCA and Kommerell's diverticulum has acceptable mortality and complication rates, whereas hybrid repairs report encouraging results. Further studies are required to provide sufficient evidence which will formulate a clear frame of treatment indications and optimal surgical methods, as well as evaluate long-term results following hybrid repair.

Morbidity After Cardiac Surgery in Patients With Adult Congenital Heart Disease in Comparison With Acquired Disease.

BACKGROUND: Due to the advancements in congenital cardiac surgery and interventional cardiology in the last 5 decades, more than 85% of congenital heart patients now survive to adulthood. METHODS: This retrospective study included 135 Adult Congenital Heart Disease (ACHD) patients, who had cardiac surgery at Southampton General Hospital over 3 consecutive years. We also included 42 patients with a structurally normal heart who had cardiac surgery for acquired cardiac conditions as a control group. Preoperative, intraoperative and postoperative data were analysed in both groups to identify risk factors for morbidity and mortality. RESULTS: In the ACHD group, in hospital mortality was 0.7%. In the control group no deaths were observed. Fifty-eight per cent of the ACHD patients had significantly higher perioperative morbidity with arrhythmias (26%), bleeding (3%), prolonged ventilation (11.3%) and renal replacement therapy 1.5%. In the non ACHD control group 32% (p=0.003) developed perioperative complications with arrhythmias (9.8%), bleeding (2.5%), prolonged ventilation (4.3%) and renal replacement therapy (2.5%). In ACHD patients total in-hospital stay was longer in patients with longer cardiopulmonary bypass (CPB) time (p=0.005), aortic cross clamp time (p=0.013) and higher preoperative alkaline phosphatase level (p=0.005). Early postoperative complications were higher in ACHD patients with longer cardiopulmonary bypass time (p=0.04) and presence of pulmonary artery hypertension (p=0.012). CONCLUSIONS: Even though the preoperative and operative characteristics are similar to both groups, the morbidity is more in ACHD group. Longer CBP time, aortic cross clamp time and presence of pulmonary hypertension are risk factors for higher morbidity in this group.

Sutureless aortic valves: who is the right patient?

PURPOSE OF REVIEW: Sutureless aortic valve replacement (AVR) has emerged as an alternative to traditional AVR for patients with aortic stenosis who present a higher surgical risk, such as the elderly, or those with small or highly calcified aortic roots. With transcatheter aortic valve implantation - the other major AVR alternative - being used in increasingly lower-risk patients, the place of sutureless valves in the AVR landscape needs to be defined. In this review, we discuss recent data and expert opinion as it pertains to the subject of sutureless AVR. RECENT FINDINGS: Several recent studies have evaluated the performance of sutureless valves in a variety of clinical contexts, including minimally invasive operations and high-risk surgical procedures. The optimal surgical technique for sutureless AVR has been refined through the publication of several reports addressing technical considerations. Reduction in operative times represents the main advantage of sutureless valves over conventional surgical prostheses, and the possibility of complete annular decalcification - and hence a reduced incidence of paravalvular leak - is the primary advantage over TAVI. SUMMARY: Sutureless valves have emerged as an attractive option for high-risk patients or for complex surgeries where a minimization of bypass time is critical. However, there is limited data regarding long-term outcomes, durability or reoperation.

Treatment of a pseudoaneurysm of the ascending aorta in association with aortopulmonary fistula following acute Type A dissection.

This report describes a rare case of aortic pseudoaneurysm with an aortopulmonary fistula in a 69-year-old woman two years following repair of a Type A aortic dissection. The patient presented with NYHA Class IV symptoms having deteriorated rapidly over a course of six weeks. We describe our successful surgical repair following a failed attempt of percutaneous closure with an atrial septal occlusion device.

Initial experience with xenograft bioconduit for the treatment of complex prosthetic valve endocarditis.

INTRODUCTION: The treatment of complex prosthetic valve endocarditis (PVE) with aortic root abscess remains a surgical challenge. Several studies support the use of biological tissues to minimize the risk of recurrent infection. We present our initial surgical experience with the use of an aortic xenograft conduit for aortic valve and root replacement. METHODS: Between October 2013 and August 2015, 15 xenograft bioconduits were implanted for complex PVE with abscess (13.3% female). In 6 patients, concomitant procedures were performed: coronary bypass (n=1), mitral valve replacement (n=5) and tricuspid annuloplasty (n=1). The mean age at operation was 60.3±15.5 years. The mean Logistic European system for cardiac operating risk evaluation (EuroSCORE) was 46.6±23.6. The median follow-up time was 607±328 days (range: 172-1074 days). RESULTS: There were two in-hospital deaths (14.3% mortality), two strokes (14.3%) and seven patients required permanent pacemaker insertion for conduction abnormalities (46.7%). The mean length of hospital stay was 26 days. At pre-discharge echocardiography, the conduit mean gradient was 9.3±3.3mmHg and there was either none (n=6), trace (n=6) or mild aortic insufficiency (n=1). There was no incidence of mid-term death, prosthesis-related complications or recurrent endocarditis. CONCLUSIONS: Xenograft bioconduits may be safe and effective for aortic valve and root replacement for complex PVE with aortic root abscess. Although excess early mortality reflects the complexity of the patient population, there was good valve hemodynamics, with no incidence of recurrent endocarditis or prosthesis failure in the mid-term. Our data support the continued use and evaluation of this biological prosthesis in this high-risk patient cohort.

Pseudoaneurysm of the Right Internal Mammary Artery Post Vacuum-Assisted Closure Therapy: A Rare Complication and Literature Review.

Vacuum-assisted closure (VAC) therapy in the management of sternal wound infection post cardiac surgery has gained popularity since last decade. It is very cost effective and has survival benefit compared with conventional management. Although there are few complications associated with VAC therapy including right ventricular free wall rupture and infectious erosion to aorta, there are now isolated reports of vein graft pseudoaneurysm associated with it. We describe an extremely rare complication of right internal mammary artery pseudoaneurysm post VAC therapy in a 56-year-old man which was successfully managed surgically. We also did a literature review on the possible complications of VAC therapy post cardiac surgery and its management.

The outcomes of triple-valve surgery: eleven years' experience from a single center.

BACKGROUND AND AIM OF THE STUDY: Triple-valve surgery is a challenging and complex procedure with significant risk, even at centers experienced at performing such operations. The study aim was to investigate the early and late outcomes of this surgery, performed at a single center for the past 11 years. METHODS: A total of 45 consecutive patients (19 males, 26 females; mean age 69.42 +/- 12.72 years) underwent triple-valve surgery at the authors' institution between 2000 and 2011. The mean logistic EuroSCORE was 22.46 +/- 12.8%. The most common aortic valve pathology was calcific degeneration (40%), while the mitral valves were mostly rheumatic (31%) or degenerative (26%). The tricuspid valve pathology was functional regurgitation in 64% of patients. The aortic valve procedures were all replacements, while the mitral valves were either repaired (n = 20) or replaced (n = 25). The tricuspid valves were almost exclusively repaired (n = 43). Univariate and multivariate analyses were performed to highlight predictors of mortality. A Kaplan-Meier analysis was also performed. RESULTS: The operative mortality was 8.9% (n = 4). Survival at one, three, and five years was 91%, 85.5% and 66.4%, respectively. Morbidity was not particularly high: the incidence of all postoperative neurological complications was 13%, that of transient renal impairment was 18%, and pacemaker implantation 8.9%. CONCLUSION: The results of triple-valve surgery were considerably improved compared to historical reports. Early mortality was close to that occurring after less complex procedures, while late survival was comparable to that after single-valve surgery. It is believed that the best results are achieved by centers experienced in valve procedures. Compared to older studies, rheumatic disease was not the most frequent requirement for of triple-valve surgery among the present patients.

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.

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.

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.

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.

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.

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.

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.

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.

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.