Three-dimensional transesophageal echocardiography in degenerative mitral regurgitation.

The morphology of mitral valve (MV) prolapse and flail may be extremely variable, with dominant and secondary dynamic lesions. Any pathologic valve appears unique and different from any other. Three-dimensional (3D) transesophageal echocardiography is a powerful tool to evaluate the geometry, dynamics, and function of the MV apparatus and may be of enormous value in helping surgeons perform valve repair procedures. Indeed, in contrast to the surgical view, 3D transesophageal echocardiography can visualize MV prolapse and flail in motion and from different perspectives. The purpose of this special article is not to provide a comprehensive review of degenerative MV disease but rather to illustrate different types of mitral prolapse and flail as they appear from multiple 3D transesophageal echocardiographic perspectives using a series of clinical scenarios. Because in everyday practice, 3D transesophageal echocardiographic images of MV prolapse and flail are usually observed in motion, each scenario is accompanied by several videos. Finally, the authors provide for each scenario a brief description of the surgical techniques that are usually performed at their institution.

Bone marrow-derived cells for cardiovascular cell therapy: an optimized GMP method based on low-density gradient improves cell purity and function.

BACKGROUND: Cardiovascular cell therapy represents a promising field, with several approaches currently being tested. The advanced therapy medicinal product (ATMP) for the ongoing METHOD clinical study ("Bone marrow derived cell therapy in the stable phase of chronic ischemic heart disease") consists of fresh mononuclear cells (MNC) isolated from autologous bone marrow (BM) through density gradient centrifugation on standard Ficoll-Paque. Cells are tested for safety (sterility, endotoxin), identity/potency (cell count, CD45/CD34/CD133, viability) and purity (contaminant granulocytes and platelets). METHODS: BM-MNC were isolated by density gradient centrifugation on Ficoll-Paque. The following process parameters were optimized throughout the study: gradient medium density; gradient centrifugation speed and duration; washing conditions. RESULTS: A new manufacturing method was set up, based on gradient centrifugation on low density Ficoll-Paque, followed by 2 washing steps, of which the second one at low speed. It led to significantly higher removal of contaminant granulocytes and platelets, improving product purity; the frequencies of CD34+ cells, CD133+ cells and functional hematopoietic and mesenchymal precursors were significantly increased. CONCLUSIONS: The methodological optimization described here resulted in a significant improvement of ATMP quality, a crucial issue to clinical applications in cardiovascular cell therapy.

Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis and improve cardiac function after myocardial infarction.

AIMS: Recent evidence suggests that cardiac progenitor cells (CPCs) may improve cardiac function after injury. The underlying mechanisms are indirect, but their mediators remain unidentified. Exosomes and other secreted membrane vesicles, hereafter collectively referred to as extracellular vesicles (EVs), act as paracrine signalling mediators. Here, we report that EVs secreted by human CPCs are crucial cardioprotective agents. METHODS AND RESULTS: CPCs were derived from atrial appendage explants from patients who underwent heart valve surgery. CPC-conditioned medium (CM) inhibited apoptosis in mouse HL-1 cardiomyocytic cells, while enhancing tube formation in human umbilical vein endothelial cells. These effects were abrogated by depleting CM of EVs. They were reproduced by EVs secreted by CPCs, but not by those secreted by human dermal fibroblasts. Transmission electron microscopy and nanoparticle tracking analysis showed most EVs to be 30-90 nm in diameter, the size of exosomes, although smaller and larger vesicles were also present. MicroRNAs most highly enriched in EVs secreted by CPCs compared with fibroblasts included miR-210, miR-132, and miR-146a-3p. miR-210 down-regulated its known targets, ephrin A3 and PTP1b, inhibiting apoptosis in cardiomyocytic cells. miR-132 down-regulated its target, RasGAP-p120, enhancing tube formation in endothelial cells. Infarcted hearts injected with EVs from CPCs, but not from fibroblasts, exhibited less cardiomyocyte apoptosis, enhanced angiogenesis, and improved LV ejection fraction (0.8 ± 6.8 vs. -21.3 ± 4.5%; P < 0.05) compared with those injected with control medium. CONCLUSION: EVs are the active component of the paracrine secretion by human CPCs. As a cell-free approach, EVs could circumvent many of the limitations of cell transplantation.

Non-coronary atherosclerosis.

During the last decades, the clinical and research interest in atherosclerosis has been mostly focused on coronary arteries. After the publications of the European Society Guidelines and AHA/ACC Guidelines on Peripheral artery diseases, and of the Registry REduction in Atherothrombosis for Continued Health Registry, there has been an increased interest in atherosclerosis of the lower extremity arteries and its presence in multifocal disease. However, awareness in the general population and the medical community of non-coronary artery diseases, and of its major prognostic implications remain relatively low. The aim of this general review stemming out of an ESC Working Group on Peripheral Circulation meeting in 2011 is to enhance awareness of this complex disease highlighting the importance of the involvement of atherosclerosis at different levels with respect to clinical presentation, diagnosis, and co-existence of the disease in the distinct arterial territories. We also emphasize the need of an interdisciplinary approach to face the broad and complex spectrum of multifocal disease, and try to propose a series of tentative recommendations and measures to be implemented in non-coronary atherosclerosis.

Hybrid treatment of a case of obliterative hepatocavopathy (Budd-Chiari syndrome).

Progressive obliteration of the intrahepatic course of a inferior vena cava is an insidious disease that may lead to portal hypertension with progressive liver engorgement and ultimately to liver cirrhosis. Early diagnosis is extremely important so that therapeutic modalities can be offered that can favorably change the natural course of the disease. We present the case of a young woman whose obliterated vena cava could be successfully recanalized by a combined surgical and interventional technique.

Sutureless proximal anastomosis using the PAS-Port system: six-month patency and five-year follow-up in "all-comers".

BACKGROUND: The PAS-Port system (Cardica, Inc, Redwood City, CA) was used routinely for patients undergoing coronary surgery with at least one venous graft. Graft patency and clinical results were evaluated, respectively, at 6 months and 5 years after surgery. METHODS: A total of 100 patients (82 males, 18 females; mean age 68.9 ± 12 years) underwent coronary bypass surgery with at least one PAS-Port anastomosis (total number of PAS-Port implants: n = 117). At 6 months after surgery all patients were followed up clinically and 86 patients with 101 PAS-Port implants underwent either a multidetector computed tomographic scan or coronary angiography. Actuarial freedom from MACCE (major adverse cardiac and cerebrovascular events) was assessed at 5 years after surgery. RESULTS: Six-month PAS-Port patency was 88%. The inner diameter of the graft at the implant site (measured in 26 patients) did not reveal any pathologic narrowing (mean inner diameter 3.1 ± 0.6 mm). At 5 years, freedom from overall MACCE was 79% ± 5% and freedom from PAS-Port target vessel revascularization was 94% ± 6%. CONCLUSIONS: The routine use of PAS-Port was associated with good vein graft patency at 6 months and a low incidence of MACCE at 5 years after surgery. No evidence of implant-related graft stenosis was detected.

Bone marrow derived stem cells in regenerative medicine as advanced therapy medicinal products.

Bone marrow derived stem cells administered after minimal manipulation represent an important cell source for cell-based therapies. Clinical trial results, have revealed both safety and efficacy of the cell reinfusion procedure in many cardiovascular diseases. Many of these early clinical trials were performed in a period before the entry into force of the US and European regulation on cell-based therapies. As a result, conflicting data have been generated on the effectiveness of those therapies in certain conditions as acute myocardial infarction. As more academic medical centers and private companies move toward exploiting the full potential of cell-based medicinal products, needs arise for the development of the infrastructure necessary to support these investigations. This review describes the regulatory environment surrounding the production of cell based medicinal products and give practical aspects for cell isolation, characterization, production following Good Manufacturing Practice, focusing on the activities associated with the investigational new drug development.

Síndrome coronario agudo en pacientes con bypass arterial coronario previo / Acute coronary syndrome in patients with a coronary artery bypass graft

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Mitral valve replacement in pregnancy: a successful strategy for fetal survival.

The incidence of bacterial endocarditis (BE) during pregnancy is about 0.01%, while maternal and fetal mortality rates due to BE are 22% and 15%, respectively. Fetal survival is <15% until week 25 of gestation, and cesarean delivery is recommended before cardiopulmonary bypass in the third trimester. The case is described of a 24-year-old woman (a known drug addict), gravida 1, para 0, at week 22 of gestation, with an acute mitral valve endocarditis caused by Staphylococcus aureus. Following urgent mitral valve replacement, the strategy for fetal survival involved reducing the hemodilution and scavenging the cardioplegia solution from the right atrium, avoiding deep hypothermia to minimize rewarming, and maintaining a high pump flow rate (>2.5 l/min/m2) with a mean perfusion pressure of 70 mmHg, using pulsatile perfusion. The patient had an uneventful postoperative course, and at 34 weeks' gestation a normal newborn of 1780 g was delivered by cesarean section. No controlled clinical trials using extracorporeal circulation during pregnancy have been conducted, and reports are limited to single cases. A strategy was proposed to manage the present case of uncontrolled maternal BE at an early gestational age, by addressing several factors that would influence the outcome for both mother and baby.

Modalities and future prospects of gene therapy in heart transplantation.

Heart transplantation is the treatment of choice for many patients with end-stage heart failure. Its success, however, is limited by organ shortage, side effects of immunosuppressive drugs, and chronic rejection. Gene therapy is conceptually appealing for applications in transplantation, as the donor organ is genetically manipulated ex vivo before transplantation. Localised expression of immunomodulatory genes aims to create a state of immune privilege within the graft, which could eliminate the need for systemic immunosuppression. In this review, recent advances in the development of gene therapy in heart transplantation are discussed. Studies in animal models have demonstrated that genetic modification of the donor heart with immunomodulatory genes attenuates ischaemia-reperfusion injury and rejection. Alternatively, bone marrow-derived cells genetically engineered with donor-type major histocompatibility complex (MHC) class I or II promote donor-specific hyporesponsiveness. Genetic engineering of naïve T cells or dendritic cells may induce regulatory T cells and regulatory dendritic cells. Despite encouraging results in animal models, however, clinical gene therapy trials in heart transplantation have not yet been started. The best vector and gene to be delivered remain to be identified. Pre-clinical studies in non-human primates are needed. Nonetheless, the potential of gene therapy as an adjunct therapy in transplantation is essentially intact.

Comparison of brain natriuretic peptide plasma levels versus logistic EuroSCORE in predicting in-hospital and late postoperative mortality in patients undergoing aortic valve replacement for symptomatic aortic stenosis.

The accuracy of the logistic EuroSCORE (logES), a widely used risk prediction algorithm for cardiac surgery including aortic valve surgery, usually overestimates observed perioperative mortality. Elevated brain natriuretic peptide (BNP) in symptomatic patients with aortic stenosis (AS) is associated with a poor short-term outcome after aortic valve replacement. We aimed to compare BNP with the logES for predicting short- and long-term outcome in symptomatic patients with severe AS undergoing aortic valve replacement. We prospectively studied 144 consecutive patients referred for aortic valve replacement (42% women, 73 +/- 9 years, mean aortic gradient 51 +/- 18 mm Hg, and left ventricular ejection fraction 61 +/- 11%) undergoing either isolated aortic valve replacement (58%) or combined to bypass grafting. Both plasma BNP and logES was estimated before surgery. The median BNP plasma level and logES were 157 pg/ml (interquartile range [IQR] 61 to 440) and 6.6% (IQR 4.2 to 12.2), respectively. The perioperative mortality was 6% and the overall mortality by the end of the study was 13%. Patients with logES >10.1% (upper tertile) had a higher risk of dying over time (hazard ratio [HR] 2.86, p = 0.037), as had patients with BNP >312 pg/ml (HR 9.01, p <0.001). Discrimination (based on C statistic) and model performance (based on Akaike information criterion) were better for BNP than for logES. At the bivariable analysis, only BNP was an independent predictor of death (HR 8.2, p = 0.002). Preoperative BNP was even more accurate than logES in predicting outcome. In conclusion, in symptomatic patients with severe AS, high preoperative BNP plasma level and high logES confirm their predicting value for short- and long-term outcome.

Non-robotic thoracoscopic internal mammary artery preparation in the pig. A training model.

Notwithstanding non-robotic, thoracoscopic preparation of the internal mammary artery (IMA) is a difficult surgical task, an appropriate experimental training model is lacking. We evaluated the young domestic pig for this purpose. Four domestic female pigs (30-40 kg body weight) were used for this study. Bilateral thoracoscopic preparation of the IMA was carried out under continuous, pressure controlled CO(2) insufflation. A 30 degrees rigid thoracoscope was inserted through a 10-mm port in the 5th/6th intercostal space (ICS) dorsally to the posterior axillary line. The dissection instrument (Ultracision Harmonic Scalpel) was inserted (5-mm port) in the 7th ICS at the posterior axillary line and the endo-forceps (5-mm port) in the 5th ICS at the posterior axillary line. Thoracoscopic IMA preparation in pig resulted more difficult than in man. A total of seven IMAs were prepared in their full intrathoracic length. A change in the preparation technique (lateral detachment of the endothoracic muscle) improved the safety of the procedure, allowing all four respective IMAs to be prepared safely, while the initial technique ensued an injury for 2 out of 3 vessels. The described young domestic pig model is suitable for experimental training of bilateral thoracoscopic IMA preparation.

Direct epiaortic ultrasound scanning for the rapid confirmation of intraoperative aortic dissection.

We present a case of an intraoperative acute aortic type A dissection (AADA) extending from the distal ascending aorta to the distal aortic arch, initially not visible on the transesophageal echocardiography (TEE). The rapid confirmation of the diagnosis by means of direct epiaortic ultrasound scanning facilitated decision-making and the subsequent successful surgical treatment.

Unusual complication after aortic valve replacement.

We present a report of a postoperative left ventricular-right atrial (LV-RA) communication after aortic valve replacement. Such intracardiac defects are rare but encountered occasionally after valve surgery. The diagnosis was made by use of transesophageal echocardiography with echo-Doppler and color-flow imaging. Complications of LV-RA shunts and differential diagnosis are discussed.

Role of multislice computed tomography for preprocedural evaluation before revision of a chronically implanted transvenous left ventricular lead.

The purpose of this study was to determine the feasibility of multislice computed tomography (MSCT) to assess the coronary sinus (CS) and its tributaries in patients who are undergoing cardiac resynchronization therapy and need a left ventricular (LV) lead revision. Preprocedural imaging modality, which may enable delineation of the cardiac venous anatomy in patients who need LV lead replacement, has not yet been evaluated. Ten patients with heart failure with previously implanted cardiac resynchronization therapy devices, who presented with worsening heart failure, were studied with MSCT and tissue Doppler imaging echocardiography before LV lead replacement. MSCT was performed to evaluate patency of the CS and coronary veins, and tissue Doppler imaging echocardiography assessed the region and the magnitude of mechanical dyssynchrony. An excellent concordance in the vein diameter, location, and status between MSCT and angiography was found. Apart from the need to perform a venoplasty in 1 patient and an unsuccessful lead explantation in another patient, all other anatomic issues were correctly predicted by MSCT. CS or vein occlusion were present in 4 patients, and in 3 of them surgical LV lead replacement was performed. Identification of a patent venous system enabling successful transvenous lead implantation was possible in 2 patients. Direct visualization of the proximity of the target vein to the phrenic nerve and the diaphragm guided lead selection and position in 4 patients. In conclusion, MSCT may be used to delineate the coronary venous anatomy in patients in whom LV lead replacement is needed to help strategize whether a transvenous or transthoracic approach may be preferred for LV lead revision.

Multiple valve replacement in limited access: a case report.

Nowadays minimally invasive surgery represents an accepted technique to treat heart valve disease. We report a case of surgical correction of multiple valve disease in a 61-year-old woman through a minimally invasive right anterolateral minithoracotomy. The intervention was performed under transesophageal echocardiography and videoscopic guidance. High thoracic epidural anesthesia allowed a rapid weaning from mechanical ventilation and a faster recovery.

Rapid-growing left intraventricular cardiac hemangioma.

A 62 years old man with Child B liver cirrhosis, prostate cancer and a recent colon carcinoma resection was referred to our cardiology department for trans-thoracic-echocardiography (TTE) in order to establish left ventricular function before starting chemotherapy. TTE revealed a mobile mass (16 x 8 mm) attached to the anterior-medial left ventricular wall, protruding and swinging within the left ventricle cavity. At follow-up TTE showed growing of the intra-cardiac tumor up to 27 x 10 mm, corresponding to a size increase of 1 mm/month. Among different pathologies a rapid growing benign tumor with a high risk of systemic embolisation or an endocardial blood cyst were retained as possible diagnoses. Given the progression of the cardiac finding and the patient's improved general condition, surgical resection of the cardiac mass was performed. Histological examination revealed a mixed capillary/cavernous hemangioma. This case shows the unusual concomitant appearance of a rapid growing cavernous hemangioma which rarely located at ventricular level and the feasibility of cardiac resection without further sequelae in a poly-morbid patient.