Early Hemodynamic Performance of the Crown PRT Aortic Prosthesis: A Prospective Study.

BACKGROUND: Currently, only limited data are available on the rate of hemodynamic progression with clinical outcome in patients receiving the latest Crown PRT aortic prosthesis. The study aim was to report clinical and hemodynamic outcomes in 55 consecutive patients for a follow up of up to one year after Crown PRT implantation. METHODS: Between February and September 2015, a total of 55 patients (34 males, 21 females; mean age 77.3 ± 1.2 years) underwent aortic valve replacement (AVR) with the latest LivaNova Crown PRT bioprosthesis at the authors' institution. Left ventricular function was preserved in 79% of patients. Data relating to the patients' clinical, echocardiographic and functional capacities were obtained prospectively. RESULTS: There were no in-hospital deaths. Significant perioperative complications included stroke (3.6%), atrial fibrillation (27%), and permanent pacemaker insertion (1.8%). Pre-discharge echocardiography demonstrated peak (PG) and mean (MG) transprosthetic gradients of 24.4 ± 10.4 mmHg and 12.9 ± 6.2 mmHg, respectively. The Doppler velocity index (DVI) was 0.49 ± 0.13, and the effective orifice area index (EOAi) 0.89 ± 0.12 cm2/m2. At a mean follow up of 1.3 ± 0.3 years, the transprosthetic gradients, DVI and EOAi were not significantly different from postoperative or pre-discharge values. The patients' NYHA status was I or II in 95% of cases, and the mean left ventricular mass had decreased by 36% at the end of follow up. CONCLUSIONS: The Crown PRT is an effective bioprosthesis, with a low incidence of valve-related complications comparable to those of other current bioprostheses. The bioprosthesis demonstrated satisfactory results in terms of hemodynamics and freedom from reoperation.

Systematic coronary physiology improves level of agreement in diagnostic coronary angiography.

OBJECTIVE: The training of interventional cardiologists (ICs), non-interventional cardiologists (NICs) and cardiac surgeons (CSs) differs, and this may be reflected in their interpretation of invasive coronary angiography (ICA) and management plan. Availability of systematic coronary physiology might result in more homogeneous interpretation and management strategy compared with ICA alone. METHODS: 150 coronary angiograms from patients with stable chest pain were presented independently to three NICs, three ICs and three CSs. By consensus, each group graded (1) coronary disease severity and (2) management plan, using options: (a) optimal medical therapy alone, (b) percutaneous coronary intervention, (c) coronary artery bypass graft or (d) more investigation required. Each group was then provided with fractional flow reserve (FFR) from all major vessels and asked to repeat the analysis. RESULTS: There was only 'fair' level of agreement of management plan among ICs, NICs and CSs (kappa 0.351, 95% CI 0.295-0.408, p<0.001) based on ICA alone (complete agreement in 35% of cases), which almost doubled to 'good' level (kappa 0.635, 95% CI 0.572-0.697, p<0.001) when comprehensive FFR was available (complete agreement in 66% of cases). Overall, the consensus management plan changed in 36.7%, 52% and 37.3% of cases for ICs, NICs and CSs, respectively, when FFR data were available. CONCLUSIONS: Compared with ICA alone, the availability of systematic FFR of all major coronary arteries produced a significantly more concordant interpretation and more homogeneous management plan among IC, NIC and CS specialists. Comprehensive physiological assessment may be of value in routine care for Heart Team decision-making. TRIAL REGISTRATION NUMBER: NCT01070771.

Profiling inflammation and tissue injury markers in perfusate and bronchoalveolar lavage fluid during human ex vivo lung perfusion.

Objectives: Availability of donor lungs suitable for transplant falls short of current demand and contributes to waiting list mortality. Ex vivo lung perfusion (EVLP) offers the opportunity to objectively assess and recondition organs unsuitable for immediate transplant. Identifying robust biomarkers that can stratify donor lungs during EVLP to use or non-use or for specific interventions could further improve its clinical impact. Methods: In this pilot study, 16 consecutive donor lungs unsuitable for immediate transplant were assessed by EVLP. Key inflammatory mediators and tissue injury markers were measured in serial perfusate samples collected hourly and in bronchoalveolar lavage fluid (BALF) collected before and after EVLP. Levels were compared between donor lungs that met criteria for transplant and those that did not. Results: Seven of the 16 donor lungs (44%) improved during EVLP and were transplanted with uniformly good outcomes. Tissue and vascular injury markers lactate dehydrogenase, HMGB-1 and Syndecan-1 were significantly lower in perfusate from transplanted lungs. A model combining IL-1ß and IL-8 concentrations in perfusate could predict final EVLP outcome after 2 h assessment. In addition, perfusate IL-1ß concentrations showed an inverse correlation to recipient oxygenation 24 h post-transplant. Conclusions: This study confirms the feasibility of using inflammation and tissue injury markers in perfusate and BALF to identify donor lungs most likely to improve for successful transplant during clinical EVLP. These results support examining this issue in a larger study.

A role for dendritic cells in the dissemination of mycobacterial infection.

The ability of mycobacteria to disseminate from the initial site of infection has an important role in immune priming and in the seeding of disease in multiple organs. To study this phenomenon, we used flow cytometry to analyse the distribution of green fluorescent protein-labelled BCG amongst different populations of antigen-presenting cells in the lungs of mice following intranasal infection, and monitored appearance of live bacteria in the draining mediastinal lymph nodes. BCG predominantly infected alveolar macrophages (CD11c(+)/CD11b(-)) and dendritic cells (CD11c(+)/CD11b(+)) in the lungs. The bacteria that disseminated to the lymph node were found in dendritic cells. The results are consistent with a model in which mycobacterial dissemination from the lung is initiated by the migration of infected dendritic cells to the draining lymph nodes.

The effect of ex vivo lung perfusion on microbial load in human donor lungs.

BACKGROUND: Ex vivo lung perfusion (EVLP) has emerged as a technique to potentially recondition unusable donor lungs for transplantation. Beneficial effects of EVLP on physiologic function have been reported, but little is known about the effect of normothermic perfusion on the infectious burden of the donor lung. In this study, we investigated the effect of EVLP on the microbial load of human donor lungs. METHODS: Lungs from 18 human donors considered unusable for transplantation underwent EVLP with a perfusate containing high-dose, empirical, broad-spectrum anti-microbial agents. Quantitative cultures of bacteria and fungi were performed on bronchoalveolar lavage fluid from the donor lung before and after 3 to 6 hours of perfusion. The identification of any organisms and changes in number of colony forming units before and after EVLP were assessed and anti-microbial susceptibilities identified. RESULTS: Thirteen out of 18 lungs had positive cultures, with bacterial loads significantly decreasing after EVLP. Yeast loads increased when no anti-fungal treatment was given, but were reduced when prophylactic anti-fungal treatment was added to the circuit. Six lungs were ultimately transplanted into patients, all of whom survived to hospital discharge. There was 1 death at 11 months. CONCLUSIONS: Our study shows that EVLP with high-dose, empirical anti-microbial agents in the perfusate is associated with an effective reduction in the microbial burden of the donor lung, a benefit that has not previously been demonstrated.