Mohamed Zeriouh

Long-term results after lung transplantation using organs from circulatory death donors: a propensity score-matched analysis †

OBJECTIVES Due to organ shortage in lung transplantation (LTx), donation after circulatory death (DCD) has been implemented in several countries, contributing to an increasing number of organs transplanted. We sought to assess long-term outcomes after LTx with organs procured following circulatory death in comparison with those obtained from donors after brain death (DBD). METHODS Between January 2007 and November 2013, 302 LTxs were performed in our institution, whereby 60 (19.9%) organs were retrieved from DCD donors. We performed propensity score matching (DCD:DBD = 1:2) based on preoperative donor and recipient factors that were significantly different in univariate analysis. RESULTS After propensity matching, there were no statistically significant differences between the groups in terms of demographics and preoperative donor and recipient characteristics. There were no significant differences regarding intraoperative variables and total ischaemic time. Patients from the DCD group had significantly higher incidence of primary graft dysfunction grade 3 at the end of the procedure (P = 0.014), and significantly lower pO2/FiO2 ratio during the first 24 h after the procedure (P = 0.018). There was a trend towards higher incidence of the need for postoperative extracorporeal life support in the DCD group. Other postoperative characteristics were comparable. While the overall cumulative survival was not significantly different, the DCD group had significantly poorer results in terms of bronchiolitis obliterans syndrome (BOS)-free survival in the long-term follow-up. CONCLUSIONS Long-term results after LTx with organs procured following DCD are in general comparable with those obtained after DBD LTx. However, patients transplanted using organs from DCD donors have a predisposition for development of BOS in the longer follow-up.

Ex vivo lung perfusion - state of the art in lung donor pool expansion.

Lung transplantation remains the gold standard for patients with end-stage lung disease. Nevertheless, the number of suitable donor lungs for the increasing number of patients on the waiting list necessitates alternative tools to expand the lung donor pool. Modern preservation and lung assessment techniques could contribute to improved function in previously rejected lungs. Ex vivo lung perfusion (EVLP) already demonstrated its value in identification of transplantable grafts from the higher risk donor pool. Moreover, lungs from EVLP did not show significantly different postoperative results compared to standard criteria lungs. This could be explained by the reduction of the ischemia-reperfusion injury through EVLP application. The aim of this article is to review technical characteristics and the growing clinical EVLP experience with special attention to EVLP application for donation after cardiac death (DCD) lungs.

Risk factors predictive of one-year mortality after lung transplantation

OBJECTIVES Lung transplantation (LTx) is a life-saving therapy for patients with end-stage lung disease. However, there remains a significant postoperative complication rate and mortality in this extreme patient group. The aim of the present study was to identify donor, recipient and perioperative risk factors for one-year mortality after LTx. METHODS A total of 252 LTxs were performed in our institution between 2007 and 2013. Donor and recipient demographics and clinical characteristics of 1-year survivors and non-survivors were collected and compared retrospectively. Multivariate logistic regression analysis was performed on univariate predictors for 1-year mortality with an entry criterion of P < 0.05. RESULTS Multivariate analysis revealed female-to-male transplantation (95% CI: 0.088-0.767; P = 0.015), lower pO2/FiO2-ratio at 72 h postoperatively (95% CI: 0.988-0.999; P = 0.024), need for postoperative extracorporeal membrane oxygenation (ECMO) support (95% CI: 0.035-0.658; P = 0.012) and on-pump technique (95% CI: 0.007-0.944; P = 0.045) as the only independent predictors for 1-year mortality. Mainly unplanned intraoperative conversion to cardiopulmonary bypass contributed to poorer survival in patients who underwent LTx using cardiopulmonary bypass (P < 0.001). CONCLUSIONS Our results show that the unplanned use of CPB (conversion from off- to on-pump) might adversely affect outcome after LTx. Also, the negative impact of female-to-male transplantation should not be underestimated during recipient selection. Furthermore, poor early postoperative oxygenation, particularly with the need for extracorporeal oxygenation, might be a very strong negative prognostic factor after LTx.

The influence of pre-operative risk on the number of circulating endothelial progenitor cells during cardiopulmonary bypass.

BACKGROUND AIMS The number of circulating endothelial progenitor cells (EPC) depends on cytokine release and is also associated with cardiovascular risk factors. During cardiopulmonary bypass (CPB) the endothelium is the first organ to be affected by mechanical and immunologic stimuli. We hypothesized that the magnitude of EPC mobilization by CPB correlates with the pre-operative cardiovascular morbidity profile. METHODS EPC were quantified in blood samples from 30 patients who underwent cardiac surgery by magnetic bead isolation and fluorescence-activated cell sorting (FACS) analysis, based on concomitant expression of CD34, CD133 and CD309. Patients were divided into two groups based on the European System for Cardiac Operative Risk Evaluation (EuroSCORE): low risk (LR) and high risk (HR). Ten healthy volunteers served as controls. Samples were obtained before the start of CPB and at 1 and 24 h post-operatively. Plasma samples were collected for determination of release levels of cytokines and growth factors. RESULTS All CPB patients showed a significantly reduced basal number of EPC compared with healthy individuals (LR 5.60 +/- 0.39/mL, HR 3.89 +/- 0.34/ mL, versus control 0.807 +/- 0.82/mL, P = 0.012 versus LR, P< 0.001 versus HR). CPB induced EPC release that peaked 1 h after surgery (pre-operative 4.79 +/- 0.32/mL, 1 h 57.49 +/- 5.31/mL, 24 h 6.67 +/- 1.05/mL, P< 0.001 pre-operative versus 1 h, P< 0.001 pre-operative versus 24 h) and was associated with the duration of CPB. However, EPC release was significantly attenuated in HR patients (33.09 +/- 3.58/mL versus 81.89 +/- 4.36/mL at 1 h after CPB, P < 0.0001) and inversely correlated with the pre-operative EuroSCORE. Serum granulocyte-colony-stimulating factor (G-CSF), stem cell factor (SCF) and vascular endothelial growth factor (VEGF) levels increased throughout the observation period and were also correlated with the EPC count. CONCLUSIONS Cardiovascular risk factors influence the mobilization of EPC from the bone marrow after stimulation by CPB. This could be secondary to impaired mobilization or the result of increased EPC turnover, and may have implications for future cell therapy strategies in cardiac surgical patients.

Utilization of the Organ Care System – A Game-Changer in Combating Donor Organ Shortage

For patients with end-stage heart failure, cardiac transplantation persists to be the gold standard. Nevertheless, the availability of organs remains a main constraint to the treatment. Through mounting usage of ex vivo heart perfusion an increase in organ availability was achieved by reconditioning of organs formerly not regarded as appropriate for transplantation. We propose the future standard application of this state-of-the-art technology to improve the pool of donor organs by evaluating hearts outside standard acceptability criteria.

Continuous-Flow Left Ventricular Assist Device Thrombosis: A Danger Foreseen is a Danger Avoided

Left ventricular assist devices (LVAD) are an increasingly implemented therapeutic intervention for patients with end-stage heart failure. A growing body of evidence, however, has shown an elevated risk of device thrombosis, a major complication jeopardizing the patient’s post-implantation survival. To date, multiple causative factors for LVAD thrombosis have been identified, such as internal shear stress, device material, infection, and inadequate anticoagulation. Understanding the mechanisms leading to LVAD thrombosis will not only enable device optimization, but also allow for better patient handling, hence improving post-implantation outcome. In this review we highlight the most commonly identified factors leading to LVAD thrombosis and discuss their mechanisms.

Strategies Preventing Contrast-Induced Nephropathy After Coronary Angiography A Comprehensive Meta-Analysis and Systematic Review of 125 Randomized Controlled Trials

This systematic review with meta-analysis sought to determine the strength of evidence for the effects of hydration (sodium bicarbonate [SB] and normal saline [NS]), supplementations (N-acetylcysteine [NAC] and vitamin C), and some common drugs (adenosine antagonists [AAs], statins, loop diuretics, and angiotensin-converting enzyme inhibitors [ACEIs]) on the incidence of contrast-induced nephropathy (CIN) and requirement for hemodialysis after coronary angiography. After screening, a total of 125 trials that reported outcomes were identified. Pooled analysis indicated beneficial effects of SB versus NS (odds ratio [OR] = 0.73; 95% confidence interval [CI]: 0.56-0.94; P = .01), NAC (OR = 0.79; 95% CI: 0.70-0.88; P = .001), vitamin C (OR = 0.64; 95% CI: 0.45-0.89; P = .01), statins (OR = 0.45; 95% CI: 0.35-0.57; P = .001), AA (OR = 0.28; 95% CI: 0.14-0.47; P = .001), loop diuretics (OR = 0.97; 95% CI: 0.33-2.85; P = .9), and ACEI (OR = 1.06; 95% CI: 0.69-1.61; P = .8). Overall, hydration with SB, use of supplements, such as NAC and vitamin C, and administration of statins and AA should always be considered for the prevention of CIN after coronary angiography.

Cardiac Hypertrophy: An Introduction to Molecular and Cellular Basis.

Ventricular hypertrophy is an ominous escalation of hemodynamically stressful conditions such as hypertension and valve disease. The pathophysiology of hypertrophy is complex and multifactorial, as it touches on several cellular and molecular systems. Understanding the molecular background of cardiac hypertrophy is essential in order to protect the myocardium from pathological remodeling, or slow down the destined progression to heart failure. In this review we highlight the most important molecular aspects of cardiac hypertrophic growth in light of the currently available published research data.

Utilization of the Organ Care System Lung for the assessment of lungs from a donor after cardiac death (DCD) before bilateral transplantation

In this manuscript, we present the first experience of evaluating donation after circulatory death (DCD) lungs, using the normothermic preservation Organ Care System (OCS) and subsequent successful transplantation. The OCS could be a useful tool for the evaluation of marginal lungs from DCD donors as it allows a proper recruitment and bronchoscopy in such donations in addition to continuous ex-vivo perfusion and assessment and treatment during transport. The OCS could potentially be a standard of care in the evaluation of marginal lungs from DCD.

Does postoperative blood pressure influence development of aortic regurgitation following continuous-flow left ventricular assist device implantation?

OBJECTIVES The true impact of postoperative blood pressure (BP) control on development of aortic regurgitation (AR) following continuous-flow left ventricular assist device (CF-LVAD) implantation remains uncertain. This study examines the influence of BP in patients with de novo AR following CF-LVAD implantation. METHODS All patients with no or <mild AR who underwent CF-LVAD implantation from July 2006 to July 2012 at our institute and with subsequent device-support of ≥3months (n = 90) were studied. Serial echocardiograms and BP readings were obtained preoperatively, postoperatively at 1, 3 and 6 months, and then at a minimum of 4-monthly intervals. BP readings were compared between patients who developed mild AR (AR group) versus those who did not (non-AR group). Logistic regression analysis was used to define independent predictors of ≥mild AR following CF-LVAD implantation. RESULTS Median duration of CF-LVAD support was 575 days (range: 98-2433 days). Forty-eight patients (53.3%) developed mild AR over a median duration of 126 days. BP readings (median values, mmHg) between AR and non-AR groups showed statistically significant differences: at 3 months-systolic 99.5 vs 92.5 (P = 0.038), diastolic 81.5 vs 66 (P < 0.001), mean 86.5 vs 74 (P < 0.001) and at 6 months-diastolic 73 vs 62 (P = 0.044), mean 83 vs 74.5 (P = 0.049), respectively. Systolic BP at 3 months (P = 0.047, 95% CI 0.453-0.994, OR 0.671), aortic valve (AoV) closure (P = 0.01, 95% CI 0.002-0.429, OR 0.029) and duration of support (P = 0.04, 95% CI 1.000-1.009, OR 1.004) were found to be independent predictors of AR following CF-LVAD implantation. CONCLUSIONS BP readings at 3 months and 6 months showed a statistically significant association with ≥mild AR following CF-LVAD implantation, with systolic blood pressure at 3 months, aortic valve closure and longer support duration being independent predictors. Clinical implications of these data may warrant consideration of aggressive early control of BP to protect against the development/progress of AR following CF-LVAD implantation.