Ioannis Dimarakis

Characterization and Clinical Application of Human CD34+ Stem/Progenitor Cell Populations Mobilized into the Blood by Granulocyte Colony‐Stimulating Factor

A phase I study was performed to determine the safety and tolerability of injecting autologous CD34+ cells into five patients with liver insufficiency. The study was based on the hypothesis that the CD34+ cell population in granulocyte colony‐stimulating factor (G‐CSF)‐mobilized blood contains a subpopulation of cells with the potential for regenerating damaged tissue. We separated a candidate CD34+ stem cell population from the majority of the CD34+ cells (99%) by adherence to tissue culture plastic. The adherent and nonadherent CD34+ cells were distinct in morphology, immunophenotype, and gene expression profile. Reverse transcription‐polymerase chain reaction‐based gene expression analysis indicated that the adherent CD34+ cells had the potential to express determinants consistent with liver, pancreas, heart, muscle, and nerve cell differentiation as well as hematopoiesis. Overall, the characteristics of the adherent CD34+ cells identify them as a separate putative stem/progenitor cell population. In culture, they produced a population of cells exhibiting diverse morphologies and expressing genes corresponding to multiple tissue types. Encouraged by this evidence that the CD34+ cell population contains cells with the potential to form hepatocyte‐like cells, we gave G‐CSF to five patients with liver insufficiency to mobilize their stem cells for collection by leukapheresis. Between 1 × 106 and 2 × 108 CD34+ cells were injected into the portal vein (three patients) or hepatic artery (two patients). No complications or specific side effects related to the procedure were observed. Three of the five patients showed improvement in serum bilirubin and four of five in serum albumin. These observations warrant further clinical trials.

Early donor management increases the retrieval rate of hearts for transplantation in marginal donors

OBJECTIVES Organ donations continue to fall, failing to meet the clinical requirements for heart transplantation. Furthermore, the pathophysiology of brain stem death including hormonal and inflammatory changes may lead to significant donor heart injury. Early donor management may potentially alleviate these changes and therefore increase the number of available hearts for transplantation. We aimed to investigate whether early management of borderline donors can increase the heart retrieval rate. METHODS Between September 2011 and February 2013, we performed early donor management of 26 potential heart donors in the intensive care units of the respective donor hospitals. At the time of referral donors were considered as borderline based on high-dose inotrope requirements, history of hypertension and cardiopulmonary resuscitation. Our management protocol included insertion of a pulmonary artery catheter and performance of cardiac output studies, weaning noradrenaline and commencing arginine vasopressin, and administration of tri-iodothyronine, methylprednisolone and insulin. Our primary end-point was donor heart acceptance, depending collectively on the results of cardiac output studies, cardiac contractility and coronary artery patency at the time of retrieval operation. RESULTS We retrieved 14 (56%) borderline hearts after donor management (Group A) with a 30-day survival rate of 86%. Twelve (44%) organs were declined due to poor heart function (n=8; 66.7%; P<0.001) and/or palpable coronary artery disease (n=4; 33.3%; P=0.018) (Group B). The mean age of Groups A and B was 42.77 and 47.78 years, respectively (P=0.19). Most of the female donors, i.e. 10 (83%), were declined, and only 4 (27%) were accepted (P=0.005). Majority of patients in both groups (Group A: 71.4%; n=10; and Group B: 66.7%; n=8) were on high-dose noradrenaline (>0.08 μg kg(-1) min(-2)) at the time of donor offer. Group A had a mean cardiac output of 6.29 and 3.09 l/min for Group B (P=0.01). A positive smoking history was present in 28.6% (n=4) and 33.5% (n=4) in Groups A and B, respectively (P=0.793). Cardiopulmonary resuscitation was performed on 3 (21.4%) patients in Group A and 2 (16.7%) in Group B (P=0.759). A history of hypertension was present in 7.1% (n=1) of the Group A and 33.3% (n=4) of the Group B donors. CONCLUSIONS In our study, we were able to retrieve more than half of the potential heart donors as a result of early active donor management without impacting on the post-transplant recipient outcome. Early active donor management may assist in increasing the number of heart transplantations, thus warranting further investigation.

Conventional aortic valve replacement for high-risk aortic stenosis patients not suitable for trans-catheter aortic valve implantation: feasibility and outcome

OBJECTIVE High-risk patients with aortic stenosis are increasingly referred to specialist multidisciplinary teams (MDTs) for consideration of trans-catheter aortic valve implantation (TAVI). A subgroup of these cases is unsuitable for TAVI, and high-risk conventional aortic valve replacement (AVR) is undertaken. We have studied our outcomes in this cohort. METHODS Data prospectively collected between March 2008 and November 2009 for patients (n = 28, nine male) undergoing high-risk AVR were analysed. The mean age was 78.4 ± 9.2 years. The mean additive EuroSCORE (European System for Cardiac Operative Risk Evaluation) was 10.0 ± 3.6 and mean logistic EuroSCORE was 19.9 ± 18.8. Three patients had undergone previous coronary artery bypass grafting (CABG). RESULTS The mean ejection fraction was 51 ± 16%, mean valve area 0.56 ± 0.19 cm², and mean peak gradient 91 ± 27 mm Hg. Ascending aortic, right axillary artery and femoral artery cannulation was used in 64%, 29% and 7% of cases, respectively. Median cross-clamp and cardiopulmonary bypass times were 84 (68-143) min and 111 (94-223) min. The median (range) inserted valve size was 21 (19-25) mm. Median intensive care and overall hospital stay were 5 (2-37) and 11 (5-44) days, respectively. In-hospital mortality was 4% (one patient). Postoperative complications included re-operation for bleeding (7%), renal failure (21%), tracheostomy (14%), sternal wound infection (7%), atrial fibrillation (25%) and permanent pacemaker implantation (7%). Kaplan-Meier survival at median follow-up of 359 (148-744) days was 81% (one further death of non-cardiac aetiology). Quality-of-life assessment at follow-up also yielded satisfactory results. CONCLUSIONS MDT assessment of high-risk aortic stenosis in the era of TAVI has increased the number of referrals. Conventional open surgery remains a valid option for these patients, with acceptable in-hospital mortality and early/midterm outcomes but high in-hospital morbidity.

Impact of hepatic cirrhosis on outcome in adult cardiac surgery.

Increasing prevalence of hepatic disease is likely to translate in a growing number of patients with significant hepatic disease requiring cardiac surgery. Available cardiac risk stratification models do not address the risk associated with hepatic disease. However, weighted mean mortality rates based on previous studies of cardiac surgery in patients with hepatic disease demonstrate operative mortality rates that range from 9.88% (standard deviation [SD] 9.69) for patients in Child-Turcotte-Pugh (CTP) class A cirrhosis to 69.23% (SD 28.55) for patients with CTP class C cirrhosis. This review comprehensively appraises the pathophysiology of hepatic disease, reported clinical outcomes and considerations for risk stratification.

The interval between brainstem death and cardiac assessment influences the retrieval of hearts for transplantation

OBJECTIVES The optimum time after brainstem death (BSD) at which to assess the function of donor hearts is unknown. We hypothesized that a longer interval may be associated with a higher transplantation rate due to improved function. METHODS Data were obtained from the UK Transplant Registry for the period between April 2010 and March 2015. The time when fixed dilated pupils were first noted in the donor was considered as the time of BSD. Retrieval was defined as the time when the abdominal organs were surgically perfused. RESULTS BSD to retrieval duration was available for 1947 donors, of which 458 (24%) donated their heart. In the univariable analysis (not adjusting other donor risk factors), evidence was available to suggest that the BSD to cardiac assessment duration had a non-linear association with heart utilization (P < 0.0001). Adjusting for donor risk factors, the relationship remained with longer intervals being associated with increased transplantation (P = 0.0056). The modelled probability of heart utilization had a similar pattern to the observed rate of heart utilization. However, the probability of heart donation began to plateau after approximately 48 h. The analysis of the subset of donors attended by a cardiothoracic retrieval team showed a similar pattern. CONCLUSIONS These data suggest that time interval from BSD to organ retrieval influences the heart retrieval rate. When the sole reason for declining a donor heart is poor function, a period of further observation and optimization up to 2 days should be considered.

Hemi-Cabrol Aortic Root Replacement in Complex Aortic Reconstructions

The Cabrol aortic root replacement with subsequent modifications remains an extremely useful technique within the armamentarium of the aortic surgeon. The technical considerations detailed here allow for the uncompromised creation of a hemi-Cabrol anastomosis in complex aortic reconstructions.

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.

Durable left ventricular assist device as a bridge to recovery for addisonian crisis related cardiomyopathy

A 19‐year‐old female with addisonian crisis‐related cardiomyopathy underwent temporary mechanical circulatory support followed by insertion of a durable left ventricular assist device. Successful device explanation was possible 2.5 years following implantation.

Miniaturized cardiopulmonary bypass in adult cardiac surgery: a clinical update.

ABSTRACT Introduction: Cardiopulmonary bypass has undoubtedly been the cornerstone in the rapid development of cardiac surgery, allowing even the performance of procedures beyond the scope of cardiothoracic surgery. Its use however, is associated with significant complications that arise from the mechanical effects of the circuit on circulating blood components as well as the contact of blood with non-endothelial surfaces. Miniature cardiopulmonary bypass systems have been developed in an attempt to minimize these complications. Areas covered: Herein clinical outcomes from the most recent studies in adult cardiac surgery are discussed. The main benefits of miniaturisation as well as potential areas of further application are described. Expert commentary: Data is critically appraised in the context of current guidelines. Finally the need for further basic science in addition to large multi-centre randomized controlled trial data is highlighted.

Homograft Aortic Root Replacement with ­Saphenous Vein Graft Hemi-Cabrol for ­Prosthetic Aortic Valve Endocarditis

A 44-year-old female presented with prosthetic valve endocarditis with periannular abscess involving the left coronary ostium. We describe cryopreserved aortic homograft root replacement with hemi-Cabrol reimplantation of the left coronary ostium using the long saphenous vein.