Massimo Boffini

The Use of CO2 Removal Devices in Patients Awaiting Lung Transplantation: An Initial Experience

BACKGROUND Lung transplantation is the treatment of choice for patients with end-stage lung failure. Limitations are presented by the shortage of donors and the long waiting list periods. New techniques, such as extracorporeal membrane ventilator devices with or without pump support, have been developed as bridges to transplantation for patients with severe, unresponsive respiratory insufficiency. METHODS Between November 2005 and September 2009, 12 patients (7 males and 5 females), of overall mean age of 43.3 +/- 15.5 years underwent decapneization with extracorporeal devices. In 6 cases, a NovaLung system was used; in the remaining 6 patients, it was a Decap device. Causes of respiratory failure that led to implantation of such devices were cystic fibrosis (n = 6), pulmonary emphysema (n = 5), and chronic rejection of a previous double lung transplant (n = 1). RESULTS Mean time on extracorporeal decapneization was 13.5 +/- 14.2 days. Eight patients died on the device. Three patients were bridged to lung transplantation; 1 recovered and was weaned from the device after 11 days. Mean PaCO(2) on the extracorporeal gas exchanger was significantly lower for both the devices at 24, 48, and 72 hours after implantation (P < .05). No significant difference was observed for the 2 systems. CONCLUSION In our initial experience, decapneization devices have been simple, efficient methods to support patients with mild hypoxia and severe hypercapnia that is refractory to mechanical ventilation. This could represent a valid bridge to lung transplantation in these patients.

Incidence and severity of primary graft dysfunction after lung transplantation using rejected grafts reconditioned with ex vivo lung perfusion

OBJECTIVES Ex vivo lung perfusion (EVLP) is a novel technique used to evaluate and recondition marginal or rejected grafts. Primary graft dysfunction (PGD) is a major early complication after lung transplantation (LTx). The use of marginal or initially rejected grafts may increase its incidence and severity. The aim of this study is to evaluate the incidence of PGD after LTx using rejected grafts reconditioned with EVLP. METHODS PGD has been evaluated immediately after LTx (t0) and after 72 h (t72) in patients receiving standard (Group A) or reconditioned (Group B) grafts. EVLP was performed using a controlled acellular perfusion according to the Toronto technique. RESULTS From July 2011 to February 2013, 36 LTxs have been performed: 28 patients (21 M/7 F, mean age 51.7 ± 14.7 years) in Group A and 8 (6 M/2 F, mean age 46.6 ± 9.8 years) in Group B (successful recondition rate of 73%, 8 of 11 cases). Incidence rate of PGD 3 at t0 and at t72 (Group A versus Group B) was 50 vs 37% (P = NS) and 25 vs 0% (P = NS), respectively. Post-transplant extracorporeal membrane oxygenation was required in 5 and 2 patients in Groups A and B, respectively (P = NS). CONCLUSIONS The use of initially rejected grafts treated with EVLP does not increase the incidence and severity of PGD after LTx. Although comparison of PGD 3 incidence in the two groups did not reach a statistical difference, all EVLP patients suffering from severe PGD early after transplant recovered normal lung function at 72 h, suggesting a protective role of EVLP against PGD occurrence and severity.

Two cases of aneurysm of the anterior mitral valve leaflet associated with transcatheter aortic valve endocarditis: A mere coincidence?

From the Division of Cardiology, Erasmus MC, Thoraxcenter, Rotterdam, The Netherlands; the Division of Cardiology, University of Turin, San Giovanni Battista Hospital, Turin, Italy; the Division of Cardiology, St Paul’s Hospital, Vancouver, British Columbia, Canada; the Division of Cardiac Surgery, University of Turin, San Giovanni Battista Hospital, Turin, Italy; and the Division of Cardiac Surgery, Erasmus MC, Thoraxcenter, Rotterdam, The Netherlands. Disclosures: None. Received for publication Nov 1, 2009; accepted for publication Nov 6, 2009; available ahead of print Feb 18, 2010. Address for reprints: Patrick W. Serruys, MD, PhD, FACC, Ba 583, Thoraxcenter, Erasmus Medical Center, Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands (E-mail: p.w.j.c.serruys@erasmusmc.nl). J Thorac Cardiovasc Surg 2010;140:e36-8 0022-5223/

Role of Oral Sildenafil in the Treatment of Right Ventricular Dysfunction After Heart Transplantation

36.00 Copyright 2010 by The American Association for Thoracic Surgery doi:10.1016/j.jtcvs.2009.11.012

Aortic valve replacement and mitral valve repair as treatment of complications after percutaneous core valve implantation.

OBJECTIVE Right ventricular dysfunction (RVD) after heart transplantation is a major complication, especially in patients with pulmonary hypertension (PH). Herein we have presented our initial experience with oral sildenafil for RVD following heart transplantation. MATERIALS AND METHODS From February 2006 to February 2008, 10 patients (7 males and 3 females) of overall mean age of 56.7 +/- 9.5 years suffered from acute RVD immediately after heart transplantation. Preoperative hemodynamic data before and after a vasodilatation test (sodium nitroprusside; NTP) showed: systolic pulmonary arterial pressure (SPAP) 59.5 +/- 12.9 and 44.2 +/- 12.4 mm Hg; cardiac output (CO) 3.3 +/- 0.9 and 3.7 +/- 0.8 L/min; transpulmonary gradient (TPG) 11.7 +/- 3.9 and 8.7 +/- 3.6 mm Hg; and pulmonary vascular resistance (PVR) 3.9 +/- 2.1 and 2.4 +/- 1.3 wood units (WU), respectively. All patients required inotropes and inhaled nitric oxide (iNO) to be weaned from cardiopulmonary bypass (CPB). RESULTS Intravenous (IV) or inhaled vasodilators could be weaned using oral sildenafil in all patients. The hemodynamic data obtained during IV or inhaled drugs (between postoperative days 5 and 10) compared with those obtained on sildenafil therapy alone (about 1 month after transplantation) showed a significant decrease in SPAP (39.0 +/- 8.2 vs 32.0 +/- 6.5 mm Hg; P = .049). CONCLUSION These data suggested that oral sildenafil may have a role in the treatment of RVD after heart transplantation.

Single Versus Double Lung Transplantation in Pulmonary Fibrosis: A Debated Topic

CLINICAL SUMMARY We describe the case of a 66-year-old man who had surgical intervention for a core valve malfunction 3 months after transfemoral implantation. The patient was scheduled for percutaneous aortic valve implantation (PAVI) because of the presence of numerous risk factors, such as obesity (body mass index, 35%) and myelodysplasia. The main concern about elective standard aortic valve replacement was related to the patient’s pulmonary function. As a result of a history of smoking and obesity, he had severe chronic pulmonary disease (forced expiratory volume in 1 second, <35%) and obstructive sleep apnea syndrome requiring noninvasive mechanical ventilation. The patient presented with rapid worsening of dyspnea. An echocardiogram showed a severely calcified aortic stenosis with left ventricular hypertrophy and good ejection fraction (60%). For this reason, he was evaluated for aortic valve replacement. Preoperative coronary angiographic analysis revealed normal coronary arteries. Despite a relative low EuroSCORE, PAVI was indicated because of multiple comorbidities and requested by the patient. PAVI with a core valve bioprosthesis was performed without procedural complications. Only a second balloon dilatation was required for a moderate paraprosthetic aortic regurgitation detected immediately after the procedure, and a mild-to-moderate paraprosthetic aortic regurgitation re-

Lung transplantation: is it still an experimental procedure?

Idiopathic pulmonary fibrosis (IPF) represents the second most frequent indication for lung transplantation after chronic obstructive pulmonary disease. Survival rate after transplantation is poorer compared with other lung diseases for reasons that are not completely clear. Medical therapy with anti-inflammatory drugs may improve symptoms and quality of life, but it does not influence the survival rate. Lung transplantation is the best therapy for end-stage IPF. The debate regarding the superiority of double lung transplantation (DLT) compared with single lung transplantation (SLT) is still ongoing. Until some years ago, SLT was almost uniformly utilized for this indication. In the most recent years, a larger application of DLT has been observed worldwide, probably related to higher 1-year and 5-year survivals. The unanswered question is whether it is ethical to use two lungs for the same patient, considering the donor shortage, when a single lung would suffice. Many reports have demonstrated that SLT offers acceptable pulmonary function and satisfactory early and intermediate survival. Probably DLT should be reserved for younger recipients, for those with concomitant or possible chronic infection of the contralateral lung, or cases of marginal donors. Further studies will be needed to formulate recommendations regarding the preferred surgical approach in IPF.

Everolimus-based immunosuppressive regimens in lung transplant recipients: Impact on CMV infection

Purpose of review The number of lung transplants performed worldwide is low and early and late results are worse in comparison with other solid organ transplants. The present review will focus on these two aspects analyzing the causes and describing the possible strategies to overcome these limitations. Recent findings The use of grafts from marginal and from nonheart-beating donors may increase the number of lung transplantation (LTx) with good results. Implementation of donor protocol and optimization of donor management have been reported to be effective in increasing the pool of suitable grafts. Ex-vivo reconditioning technique may be also helpful to better evaluate and recondition usually rejected lungs. This may allow a significant increase in the number of lung transplants performed worldwide. Early and late results of LTx are mainly affected by primary graft dysfunction and the onset of obliterative bronchiolitis. Different strategies have been adopted to reduce the incidence of these two complications with controversial results. Summary LTx maintains some features of experimental procedure especially in terms of number of performed procedures and early and late results. The various strategies to overcome the limited number of available grafts appear effective but not universally applied and accepted. The different treatments of PDG and obliterative bronchiolitis are still disappointing. To date, the onset of PDG and obliterative bronchiolitis after LTx still significantly impacts on outcomes. A better understanding of the underlying mechanisms in the pathogenesis of primary graft dysfunction and obliterative bronchiolitis may provide improved therapeutic strategies.

Does Everolimus Associated With a Low Dose of Cyclosporine in Long-Term Cardiac Transplant Recipients Improve Renal Function? Initial Experience

UNLABELLED Cytomegalovirus (CMV) is one of the most important viral pathogen in solid organ transplant (SOT) recipients, with heart and lung transplant patients being at considerably high risk for CMV direct and indirect effects. Prevention strategies have resulted in significant reduction in disease and CMV related morbidity and mortality. Few studies reported a lower incidence of CMV infections in solid organ transplant recipients treated with immunosuppressive protocols including the mTOR inhibitor everolimus (EVR). PURPOSE The aim of the current study was to evaluate the impact of EVR-based immunosuppressive regimens on the occurrence and kinetics of CMV infection in a population of lung transplant recipients, at both systemic and pulmonary level. Thirty-two lung transplants (LT) were investigated; eighteen were on EVR-based immunosuppressive regimens. CMV events occurring in the first two years post-transplantation at both systemic and pulmonary levels were reported. PRINCIPAL RESULTS No differences were reported in CMV viraemia occurrence at both one- and two-year follow up between patients undergoing EVR-based and EVR-free immunosuppressive regimens. Considering CMV episodes at pulmonary levels, as determined by routinely performed broncho-alveolar lavages (BALs), during EVR-administration the patients experienced significantly fewer episodes of high-load CMV (as defined by viral loads⩾10(5) copies/mL) than during EVR-free immunosuppressive regimens. MAJOR CONCLUSION EVR-based immunosuppressive regimens in lung transplantation settings appear to be associated to lower incidence of clinically relevant CMV episodes at pulmonary levels, striking the possibility of extending the use of EVR to such a group of transplant recipients.

Ventilatory Management During Normothermic Ex Vivo Lung Perfusion: Effects on Clinical Outcomes.

BACKGROUND Cyclosporine (CsA) renal toxicity is a well-known side effect. Various immunosuppressive strategies have been developed to minimize renal insufficiency. The use of everolimus associated with low levels of CsA can be an alternative strategy. METHODS From October 2007 to April 2008, everolimus was started with a lower dose of cyclosporine (trough levels from 109.3 +/- 27.5 to 93.7 +/- 30.1 ng/mL after 45 days) in 21 cardiac transplant recipients (18 male and 3 female patients, mean age 56.4 +/- 10.7 years). Pre-everolimus therapy creatinine levels, creatinine clearances, and glomerular filtration rates were 1.9 +/- 0.9 mg/dL, 54.2 +/- 18.1 mL/mins and 44.3 +/- 16.5 mL/min/m(2), respectively. RESULTS We observed a significant reduction in creatinine levels (from 1.9 +/- 0.9 to 1.4 +/- 0.3 mg/dL, P = .022) as well as a significant improvement in creatinine clearances (from 54.2 +/- 18.1 to 69.0 +/- 19.0 mL/min, P = .020) and glomerular filtration rates (from 44.3 +/- 16.5 to 57.1 +/- 16.3 mL/min/m(2), P = .010) after 7 days of everolimus therapy. Upon univariate analysis patient age, pretransplantation creatinine clearance, creatinine clearance after everolimus introduction, glomerular filtration rate at 45 days, and time from transplantation were associated with renal improvement. Upon multivariate analysis, only creatinine clearance at 7 days was related to the renal improvement. CONCLUSIONS These preliminary data suggested that everolimus with a low dose of CsA may be safe and effective to reduce CsA-related renal insufficiency among selected, heart transplant patients.