Pietro Bajona

Beating-heart, off-pump mitral valve repair by implantation of artificial chordae tendineae: An acute in vivo animal study

OBJECTIVE To evaluate the effectiveness of a new off-pump mitral valve repair technology in restoring valve competency in a porcine model of acute mitral regurgitation. METHODS Acute mitral regurgitation was induced in 6 anesthetized pigs by cutting anterior leaflet chordae. Artificial chordae were then transapically implanted on the prolapsing segment under epicardial echocardiographic guidance and secured outside the left ventricular apex. All intracardiac manipulations were performed off-pump, through a stab wound incision on the left ventricular apex. RESULTS Cutting the anterior leaflet chordae caused an eccentric, posteriorly directed jet of mitral regurgitation that could be visualized by color Doppler sonography. Implantation of chordae through the left ventricular apex completely eliminated valve regurgitation in 4 animals and reduced regurgitation in 2. Intraoperative measurement of artificial chordal tensions gave similar values to those reported for native chordae. CONCLUSIONS Off-pump, transapical implantation of artificial chordae between a prolapsing anterior mitral valve leaflet and the left ventricular apex was effective in reducing acutely induced mitral regurgitation. Long-term studies are planned to assess the stability in this animal model.

Pig‐to‐baboon heterotopic heart transplantation – exploratory preliminary experience with pigs transgenic for human thrombomodulin and comparison of three costimulation blockade‐based regimens

Three costimulation blockade‐based regimens have been explored after transplantation of hearts from pigs of varying genetic backgrounds to determine whether CTLA4‐Ig (abatacept) or anti‐CD40mAb+CTLA4‐Ig (belatacept) can successfully replace anti‐CD154mAb.

Costimulation blockade in pig artery patch xenotransplantation – a simple model to monitor the adaptive immune response in nonhuman primates

Ezzelarab MB, Ekser B, Echeverri G, Hara H, Ezzelarab C, Long C, Bajona P, Garcia B, Murase N, Ayares D, Cooper DKC. Costimulation blockade in pig artery patch xenotransplantation – a simple model to monitor the adaptive immune response in nonhuman primates. Xenotransplantation 2012; 19: 221–232.

Initial in vivo experience of pig artery patch transplantation in baboons using mutant MHC (CIITA-DN) pigs.

BACKGROUND In the pig-to-nonimmunosuppressed baboon artery patch model, a graft from an α1,3-galactosyltransferase gene-knockout pig transgenic for human CD46 (GTKO/CD46) induces a significant adaptive immune response (elicited anti-pig antibody response, increase in T cell proliferation on MLR, cellular infiltration of the graft), which is effectively prevented by anti-CD154mAb-based therapy. METHODS As anti-CD154mAb is currently not clinically applicable, we evaluated whether it could be replaced by CD28/B7 pathway blockade or by blockade of both pathways (using belatacept + anti-CD40mAb [2C10R4]). We further investigated whether a patch from a GTKO/CD46 pig with a mutant human MHC class II transactivator (CIITA-DN) gene would allow reduction in the immunosuppressive therapy administered. RESULTS When grafts from GTKO/CD46 pigs were transplanted with blockade of both pathways, a minimal or insignificant adaptive response was documented. When a GTKO/CD46/CIITA-DN graft was transplanted, but no immunosuppressive therapy was administered, a marked adaptive response was documented. In the presence of CD28/B7 pathway blockade (abatacept or belatacept), there was a weak adaptive response that was diminished when compared with that to a GTKO/CD46 graft. Blockade of both pathways prevented an adaptive response. CONCLUSION Although expression of the mutant MHC CIITA-DN gene was associated with a reduced adaptive immune response when immunosuppressive therapy was inadequate, when blockade of both the CD40/CD154 and CD28/B7 pathways was present, the response even to a GTKO/CD46 graft was suppressed. This was confirmed after GTKO/CD46 heart transplantation in baboons.

Prolonged use of right ventricular assist device for refractory graft failure following orthotopic heart transplantation

The use of mechanical circulatory support for posttransplant right ventricular (RV) failure is well described. Nakatani and colleagues first reported on the feasibility of the right heart assist for acute RV failure after heart transplantation. However, longest possible duration of the RV support is unknown for recovery following heart transplantation. We report a case of successful use of a Thoratec (Thoratec Corporation, Pleasanton, Calif) ventricular assist device (IVAD) as a bridge to recovery for prolonged RV failure following heart transplantation.

Further evidence for sustained systemic inflammation in xenograft recipients (SIXR)

In pig‐to‐baboon heart/artery patch transplantation models, adequate costimulation blockade prevents a T‐cell response. After heart transplantation, coagulation dysfunction (thrombocytopenia, reduced fibrinogen, increased D‐dimer) and inflammation (increased C‐reactive protein [CRP]) develop. We evaluated whether coagulation dysfunction and/or inflammation can be detected following pig artery patch transplantation.

Thoracic endovascular stent grafting inhibits aortic growth: an experimental study.

OBJECTIVE Dilatation of the aorta at the landing zone site may be exaggerated by the radial force of stent grafts potentially limiting long-term results of endovascular therapy. We evaluated growth patterns and morphology of the thoracic aorta in young piglets after thoracic stent-graft placement. METHODS Eight domestic piglets (37+/-2 kg) had an endovascular stent graft placed in the proximal descending thoracic aorta using retroperitoneal access. At implantation, the stent was oversized by 10%. Aortic size was documented after thoracotomy by intraoperative measurement and angiography. Subsequently the piglets were grown to adult size (181+/-42 kg). At explantation 6-15 months later, CT scan and surgical evaluation for endoleaks, defined as perigraft flow, was performed. Histopathological assessment of the explanted aorta was performed in stented and non-stented segments and compared to five normal porcine aortas. RESULTS No endoleak (perigraft flow) or stent migration occurred even in 230kg pigs. The stent grafts expanded to full size, but there was no further growth in the stented area. The aortic diameter increased significantly by 32+/-9% 1cm proximal to the stents (p=0.0012) and by 45+/-13% 1cm distal to the stents (p=0.0033). The stented area grew less than the proximal (p=0.0011) and distal aorta (p<0.0001). In all pigs, the distal aorta was larger than the proximal overstented segment. Histology of the stented aorta showed significant thickening of the intima (p=0.018) and media (p=0.006) with neointimal formation and segmental fibrosis of the inner 1/3 of the media with loss of smooth muscle cells and compression of the elastic fibers but normal architecture in the outer 2/3 of the media. CONCLUSIONS Endovascular stent grafting may inhibit growth of the nonatherosclerotic normal aorta and lead to intimal hyperplasia and focal fibrosis in the inner media part adjacent to the stent. Stent-graft interaction with aortic tissue over time is important and should receive more detailed evaluation. Testing this interaction in an animal model of nonatherosclerotic dilative aortic disease could be of great interest.

Hospital length of stay after lung transplantation: Independent predictors and association with early and late survival

BACKGROUND Duration of index hospitalization after lung transplantation (LTx) is an important variable that has not received much attention. We sought to determine independent predictors of prolonged hospital length of stay (LOS) and its association with early and late outcomes. METHODS The United Network of Organ Sharing database was queried for adult patients undergoing LTx between 2006 and 2014 (N = 14,320). Patients with dual organ or previous transplantation and patients who died during the first 25 days after LTx were excluded (n = 12,647, mean age 55.2 years ± 13.1). Primary outcome was prolonged LOS (>25 days) (3,251/12,647; 25.7%). Donor, recipient, and procedure-related variables were analyzed as potential predictors of prolonged LOS. Association of prolonged LOS with 1-year and 5-year survival was evaluated using Cox proportional hazards analysis. RESULTS Independent predictors of prolonged LOS included serum albumin, lung allocation score, functional status, and need of extracorporeal membrane oxygenation or ventilator support at the time of transplant; donor age >40 years; gender mismatch (female donor to male recipient); donor body mass index; African American ethnicity; ischemic time >6 hours; and double LTx. Prolonged LOS was independently associated with increased mortality at 1 year (hazard ratio, 3.96; 95% confidence interval, 3.48-4.50; p < 0.001) and 5 years (hazard ratio, 2.00; 95% confidence interval, 1.79-2.25; p < 0.001). CONCLUSIONS A significant proportion of patients have a prolonged LOS after LTx, and several recipient, donor, and procedure-related variables are independent predictors of this outcome. Patients with prolonged LOS after LTx have significantly increased risk of death at 1 year and 5 years.

Transapical off-pump removal of the native aortic valve: A proof-of-concept animal study

OBJECTIVE This study evaluates the feasibility of off-pump native aortic valve removal in preparation for transapical aortic valve replacement. Off-pump aortic valve replacement is performed by balloon predilatation of the native valve followed by insertion of a stented prosthesis. In patients with calcified annuli and cusps, particulate embolization, suboptimal prosthesis sizing, and perivalvular leaks may occur. Therefore, native valve removal may improve outcomes after transapical aortic valve replacement. METHODS The aortic cusps were sequentially removed from 10 pigs in an off-pump procedure. A temporary valve was inserted percutaneously into the ascending aorta to prevent aortic regurgitation. The electrocardiogram, coronary blood flow, and arterial, left atrial, and ventricular pressures were continuously monitored. RESULTS Removal of the aortic cusps caused a drop in diastolic arterial pressure and its equalization with left ventricular diastolic pressure. Systolic pressure decreased by 13.5%. Left atrial pressure increased by 86.0%. Coronary blood flow decreased by 39.9% and its pattern changed from mostly diastolic to mostly systolic. Electrocardiographic signs of ischemia appeared almost immediately. Percutaneous insertion of a temporary valve in the ascending aorta increased diastolic pressure and caused a tendency toward echocardiographic normalization. CONCLUSIONS Aortic valve removal in a healthy beating heart causes acute massive aortic regurgitation, hemodynamic instability, and the rapid onset of myocardial ischemia. Reduction of left ventricular volume overload, by placement of a temporary valve in the ascending aorta, mitigates myocardial distress, helps stabilize hemodynamic parameters, and may be a useful tool to allow surgical manipulations of the aortic valve and annulus during transapical aortic valve replacement procedures.

Aortic arch surgery after previous type A dissection repair: results up to 5 years

OBJECTIVES Open aortic arch surgery after type A dissection repair is challenging. We sought to review our surgical experience to analyse the causes and timing, establish the risk profile for this patient population, and better define outcomes. METHODS From 2000 to 2014, we identified 55 patients who required aortic arch surgery after a previous type A dissection repair. Medical records were available for review including computerized tomographic angiograms, cerebral protection strategies and follow-up. RESULTS The mean interval from previous type A dissection repair to aortic arch surgery was 5.7 ± 5.4 years. At reoperation 36 patients (65%) had total arch replacement and 19 (35%) had hemiarch replacement. Indications for reoperations were: enlarging aneurysm in 27 (49%), impending rupture in 12 (22%), chronic dissection in 10 (18%) and aneurysms in 6 (11%). Arterial peripheral cannulation was used in 80% of patients. Selective antegrade cerebral perfusion was used in 35 patients (64%) and retrograde perfusion in 2 (4%). There were 3 perioperative deaths (5%) and 4 cases of permanent stroke (7%). Survival rates were 90, 85 and 77% at the 1-, 3- and 5-year follow-up, respectively. The 5-year survival rate was 10% lower than that of an age- and sex-matched population (P < 0.001). The only predictor of the follow-up mortality was older age (odds ratio: 1.07, 95% confidence interval: 1.02-1.13, P = 0.007). CONCLUSIONS Aortic arch surgery after previous type A dissection repair can be performed with satisfactory early and mid-term results and acceptable risk of stroke. Cerebral perfusion strategies likely contribute to positive outcomes. Favourable mid-term survival justifies performing such difficult reoperations.