Sarah A. Schubert

Natural history of coexistent mitral regurgitation after aortic valve replacement

OBJECTIVES The long-term evolution of coexistent mitral regurgitation (MR) after aortic valve replacement (AVR) for aortic stenosis remains poorly defined. Prior studies have demonstrated that acute improvement in MR after AVR is modest, and more aggressive approaches have been advocated. This study examines the evolution of MR after AVR and identifies prognostic indicators for MR improvement. METHODS We retrospectively evaluated demographic and echocardiographic data of 423 patients who underwent primary isolated AVR for aortic stenosis with coexistent mild (n = 314) or moderate (n = 109) MR at our institution, from 2004 to 2013. For each patient, preoperative and postoperative MR was extracted from 903 echocardiograms and graded on a 0 to 4+ scale. Hierarchic linear models were used to estimate postoperative residual MR over a 5-year follow-up period. Patients were then stratified by improvement in MR, and preoperative risk factors and survival were compared between groups. Cox proportional hazards regression was used to assess the association between survival and preoperative and postoperative MR. RESULTS The overall acute reduction in MR was -0.23 degrees per patient. Patients with moderate MR had a -0.53 degree reduction in MR, whereas patients with mild MR had only a -0.13 degree reduction in MR (P < .001). Residual MR, however, worsened over time and regressed back to baseline, particularly in patients with preoperative moderate MR. At last follow-up, 70 (17%) patients returned to 2+ or worse MR. Residual MR at last echocardiographic follow-up was not affected by left ventricular ejection fraction, severity of preoperative aortic valve gradient (AVG), magnitude of reduction of AVG, or other comorbidities. Degree of preoperative MR did not affect midterm survival. Patients whose MR improved after AVR demonstrated a trend toward improved survival (75% vs 65% 5-year survival; P = .06), compared with those without MR whose survival remained unchanged or worsened. CONCLUSIONS Coexistent MR modestly improves after AVR, but eventually regresses back to baseline or worsens over time in many patients. Preoperative AVG, reduction of AVG, heart failure, or atrial fibrillation was not predictive of residual MR. Moderate preoperative MR did not adversely affect 5-year survival. Patients with improvement in MR, however, demonstrated a trend toward improved survival at 5 years. More aggressive approaches for coexistent moderate MR should be considered in patients who need AVR for aortic stenosis.

Early Outcomes of Pulmonary Valve Replacement With the Mitroflow Bovine Pericardial Bioprosthesis

BACKGROUND Bovine pericardial valves are often used for pulmonary valve replacement (PVR) in patients with previously repaired congenital heart disease. Attention has recently focused on the safety of the Mitroflow (Sorin Group USA, Arvada, CO) bovine pericardial valve after a national alert describing several cases of sudden valve failure in young patients. In response, we reviewed our experience using the Mitroflow bioprosthesis for PVR. METHODS Medical records were reviewed for all patients who underwent PVR using a Mitroflow valve at our center (2008-2013). RESULTS The cohort included 84 patients with a median age of 18.3 years (range, 0.8-62.1 years) and weight of 48.4 kg (range, 5.7-167.8 kg). Indications for surgical intervention included native outflow tract insufficiency (59 patients), valved conduit failure (20 patients), and isolated prosthetic valve failure (5 patients). Median length of stay was 3 days (range, 2-13 days). There were no hospital deaths. Median follow-up was 2.4 years (range, 0.2-5.6 years). Pulmonary valve insufficiency and peak gradient increased with time. At latest follow-up, freedom from insufficiency greater than or equal to a moderate degree was 83%, and freedom from a peak gradient greater than or equal to 50 mm Hg was 92%. Reintervention was required in 4 patients. One patient experienced endocarditis and underwent surgical PVR (0.6 years after initial intervention). Three patients underwent transcatheter treatment for valve stenosis including PVR (at 4.2 and 4.4 years in 2 patients) and balloon valvuloplasty (at 5.2 years in the third patient). Kaplan-Meier freedom from reintervention at 5 years was 81%. CONCLUSIONS Early outcomes using the Mitroflow bovine pericardial valve for PVR in children and adults with repaired congenital heart disease appear acceptable and similar to reported outcomes for other tissue valve options. Valve failure from premature structural deterioration was not observed.

Increasing circulating sphingosine-1-phosphate attenuates lung injury during ex vivo lung perfusion

Background Sphingosine‐1‐phosphate regulates endothelial barrier integrity and promotes cell survival and proliferation. We hypothesized that upregulation of sphingosine‐1‐phosphate during ex vivo lung perfusion would attenuate acute lung injury and improve graft function. Methods C57BL/6 mice (n = 4‐8/group) were euthanized, followed by 1 hour of warm ischemia and 1 hour of cold preservation in a model of donation after cardiac death. Subsequently, mice underwent 1 hour of ex vivo lung perfusion with 1 of 4 different perfusion solutions: Steen solution (Steen, control arm), Steen with added sphingosine‐1‐phosphate (Steen + sphingosine‐1‐phosphate), Steen plus a selective sphingosine kinase 2 inhibitor (Steen + sphingosine kinase inhibitor), or Steen plus both additives (Steen + sphingosine‐1‐phosphate + sphingosine kinase inhibitor). During ex vivo lung perfusion, lung compliance and pulmonary artery pressure were continuously measured. Pulmonary vascular permeability was assessed with injection of Evans Blue dye. Results The combination of 1 hour of warm ischemia, followed by 1 hour of cold ischemia created significant lung injury compared with lungs that were immediately harvested after circulatory death and put on ex vivo lung perfusion. Addition of sphingosine‐1‐phosphate or sphingosine kinase inhibitor alone did not significantly improve lung function during ex vivo lung perfusion compared with Steen without additives. However, group Steen + sphingosine‐1‐phosphate + sphingosine kinase inhibitor resulted in significantly increased compliance (110% ± 13.9% vs 57.7% ± 6.6%, P < .0001) and decreased pulmonary vascular permeability (33.1 ± 11.9 &mgr;g/g vs 75.8 ± 11.4 &mgr;g/g tissue, P = .04) compared with Steen alone. Conclusions Targeted drug therapy with a combination of sphingosine‐1‐phosphate + sphingosine kinase inhibitor during ex vivo lung perfusion improves lung function in a murine donation after cardiac death model. Elevation of circulating sphingosine‐1‐phosphate via specific pharmacologic modalities during ex vivo lung perfusion may provide endothelial protection in marginal donor lungs leading to successful lung rehabilitation for transplantation.

Contemporary outcomes in reoperative mitral valve surgery

Objective Data suggest that redo mitral valve surgery is being performed in increasing numbers, possibly with superior results according to single-centre studies. The purpose of this study is to describe outcomes of redo mitral valve surgery and identify risk-adjusted predictors of poor outcomes. Methods All (11 973) open mitral valve cases were evaluated (2002–2016) from a regional Society of Thoracic Surgery (STS) database. Patients were stratified by primary versus redo mitral valve surgery. Mixed effects logistic regression models including hospital as a random effect were used to identify risk factors for patients undergoing redo mitral valve surgery. Results Of all mitral valve cases, 1096 (9.7%) had a previous mitral operation. Redo patients had higher rates of valve replacement and preoperative comorbidities resulting in more complications, operative mortalities (11.1%vs6.5%, p<0.0001) and higher resource utilisation. Several factors independently increased risk for composite STS major morbidity and 30-day mortality, including cardiogenic shock (OR 10.3, p=0.0001), severe tricuspid insufficiency (OR 2.3, p=0.001), urgent/emergent status (OR 1.8, p=0.001) and concurrent coronary artery bypass grafting (OR 2.4, p=0.002). The volume of redo mitral valve surgery increased 10% per year and the observed-to-expected ratios (O/E) for operative mortality in redo mitral surgery improved from 1.44 early in the study period to 0.72 in the most recent era. Conclusions Redo mitral valve surgery accounts for approximately 10% of mitral valve operations and is associated with increased risk and resource utilisation. However, as the volume of redo mitral surgery increases, outcomes have dramatically improved and are now better than predicted.

In vivo lung perfusion rehabilitates sepsis-induced lung injury

Background Sepsis is the leading cause of lung injury in adults and can lead to acute respiratory distress syndrome (ARDS). Using a novel technique of isolated in vivo lung perfusion (IVLP), we hypothesized that normothermic IVLP will improve oxygenation and compliance in a porcine model of sepsis‐induced lung injury. Methods Mature adult swine (n = 8) were administered lipopolysaccharide (LPS; 50 &mgr;g/kg over 2 hours) via the external jugular vein, followed by sternotomy and central extracorporeal membrane oxygenation (ECMO) cannulation (right atrium to ascending aorta). The left pulmonary artery (inflow) and left superior and inferior pulmonary veins (outflow) were dissected out and cannulated to deliver isolated perfusion to the left lung. After 4 hours of normothermic IVLP with Steen solution, the left lung then underwent 4 hours of reperfusion after IVLP decannulation. Airway pressures and lung‐specific pulmonary vein blood gases from the right lung (LPS control) and left lung (LPS + IVLP) of the same animal were compared. Results All animals demonstrated a significant reduction in the ratio of partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FiO2) (P/F ratio) and total lung compliance at 2 hours after the start of LPS infusion (mean, 469 ± 19.7 mm Hg vs 222.2 ± 21.4 mm Hg; P < .0001). After reperfusion, 6 animals (75%) exhibited improved lung function, allowing for ECMO decannulation. Lung‐specific oxygenation was superior in the left lung after 4 hours of reperfusion (mean, 310.5 ± 54.7 mm Hg vs 201.1 ± 21.7 mm Hg; P = .01). Similarly, total lung compliance improved after IVLP of the left lung. The lung wet weight to dry weight ratio demonstrated reduced edema in rehabilitated left lungs (mean, 6.5 ± 0.3 vs 7.5 ± 0.4; P = .04). Conclusions IVLP successfully rehabilitated LPS‐injured lungs compared to ECMO support alone in this preclinical porcine model.

Cardiothoracic Surgery Training Grants Provide Protected Research Time Vital to the Development of Academic Surgeons

Background: The Ruth L. Kirschstein Institutional National Research Service Award (T32) provides institutions with financial support to prepare trainees for careers in academic medicine. In 1990, the Cardiac Surgery Branch of the National Heart, Lung and Blood Institute (NHLBI) was replaced by T32 training grants, which became crucial sources of funding for cardiothoracic (CT) surgical research. We hypothesized that T32 grants would be valuable for CT surgery training and yield significant publications and subsequent funding. Methods: Data on all trainees (past and present) supported by CT T32 grants at two institutions were obtained (T32), along with information on trainees from two similarly sized programs without CT T32 funding (Non‐T32). Data collected were publicly available and included publications, funding, degrees, fellowships, and academic rank. Non‐surgery residents and residents who did not pursue CT surgery were excluded. Results: Out of 76 T32 trainees and 294 Non‐T32 trainees, data on 62 current trainees or current CT surgeons (T32: 42 vs Control: 20) were included. Trainees who were supported by a CT T32 grant were more likely to pursue CT surgery after residency (T32: 40% [30/76] vs Non‐T32: 7% [20/294], P < .0001), publish manuscripts during residency years (P < .0001), obtain subsequent NIH funding (T32: 33% [7/21] vs Non‐T32: 5% [1/20], P = .02), and pursue advanced fellowships (T32: 41% [9/22] vs Non‐T32: 10% [2/20], P = .02). Conclusions: T32 training grants supporting CT surgery research are vital to develop academic surgeons. These results support continued funding by the NHLBI to effectively develop and train the next generation of academic CT surgeons.

Aortic Valve Anatomy: Implications for Transcatheter Aortic Valve Replacement

Comprehensive knowledge of aortic valve and aortic root anatomy is essential for catheter-based interventions on the aortic valve. The aortic valve and aortic root complex extends from the left ventricular outflow tract to the sinuses of Valsalva and primarily functions to support forward cardiac output and provide coronary perfusion. Transcatheter valve prostheses sit within the aortic root. Understanding the normal, as well as abnormal, arrangement and structures of the aortic valve and adjoining structures allows proper sizing and positioning of the transcatheter aortic valve and helps to circumvent complications that may arise during and after implantation.