A randomized trial of everolimus-based quadruple therapy vs standard triple therapy early after lung transplantation.

Calcineurin inhibitor (CNI) therapy after lung transplantation increases risk of kidney failure. Early everolimus-based quadruple low CNI immunosuppression may improve renal function without compromising efficacy or safety. A prospective, randomized, open-label, 12-month multicenter trial was conducted at 8 German sites. Patients 3-18 months after lung transplantation were randomized (1:1), stratified by baseline estimated glomerular filtration rate (eGFR). In the quadruple low CNI regimen, patients received everolimus (target trough level 3-5 ng/mL) with reduced CNI (tacrolimus 3-5 ng/mL or cyclosporine 25-75 ng/mL) and a cell cycle inhibitor plus prednisone. In the standard triple CNI regimen, patients received tacrolimus (target trough level >5 ng/mL) or cyclosporine (>100 ng/mL) and a cell cycle inhibitor plus prednisone. Of the 180 patients screened, 130 were randomized: 67 in the quadruple low CNI group and 63 in the standard triple CNI group. The primary endpoint (eGFR after 12 months) demonstrated superiority of the quadruple low CNI regimen: 64.5 mL/min vs 54.6 mL/min for the standard triple group (least squares mean, analysis of covariance; P < .001). Key efficacy parameters (biopsy-proven acute rejection, chronic lung allograft dysfunction, and death) and safety endpoints were similar between both groups. Quadruple low CNI immunosuppression early after lung transplantation was demonstrated to be efficacious and safe. Clinical trials registry: ClinicalTrials.gov NCT01404325.

Comparison of Outcomes of Tricuspid Valve Surgery in Patients with Reduced and Normal Right Ventricular Function.

Background: To study the effect of tricuspid valve repair/replacement on outcomes of patients with reduced systolic right ventricular function. Methods: Between January 2012 and July 2016, 191 patients with isolated tricuspid valve regurgitation and/or in combination with other valve diseases were enrolled into this retrospective study. We compared early postoperative outcomes (i.e., 30 days after surgery) between patients' cohort with a preoperative reduced (i.e., at least moderately) versus normal (or mildly reduced) right ventricular function as defined by means of preoperative echocardiography. Results: A total of 82 (43%) patients had preoperatively reduced right ventricle function with tricuspid annular plane systolic excursion (TAPSE) of 13.3 ± 3.3 versus 20.2 ± 4.9 mm (p < 0.001). Ring annuloplasty was the most common surgical technique (i.e., 91% in both groups). Time of procedure (317 ± 123 vs. 262 ± 88 minutes, p < 0.01) and time on cardiopulmonary bypass (163 ± 77 vs. 143 ± 57 minutes, p = 0.036) were significantly longer in patients with impaired right ventricular function. Postoperative lactate (3.5 ± 3 vs. 2 ± 1 mmol/L, p = 0.001) and dose of catecholamines (epinephrine, 0.07 ± 0.15 vs. 0.013 ± 0.02 µg/kg/min, p = 0.001; norepinephrine, 0.18 ± 0.23 vs. 0.07 ± 0.09 µg/kg/min, p = 0.007) were also higher in this group. Postoperative rate of low cardiac output syndrome (10 vs. 27%, p = 0.005) and early mortality (n = 2 vs. n = 9, p = 0.018) were significantly increased in patients with reduced right ventricular function. Previous cardiac operation (p = 0.045), preoperative higher number of acute decompensations of heart failure (p < 0.001), reduced right ventricular function (p = 0.018), postoperative low cardiac output syndrome (p < 0.001), and renal replacement therapy (p < 0.001) were identified as risk factors for early mortality. Echocardiography at discharge revealed tricuspid valve regurgitation grade of 0.9 ± 0.7 versus 0.7 ± 0.6 (p = 0.052) and TAPSE of 12 ± 3 versus 15 ± 5 mm (p = 0.026) in patients with reduced right ventricular function. The New York Heart Association (NYHA) class improved to 1.7 ± 0.7 versus 1.3 ± 1 (p < 0.001) in this group of patients. Conclusion: Tricuspid valve repair/replacement effectively eliminated severe tricuspid regurgitation and improved clinical signs of heart failure. Although mortality and morbidity were increased in the group with reduced right ventricular function, even these patients benefitted from improved functional status and right ventricular systolic function early postoperatively.

Association of HbA1c and utilization of internal mammary arteries with wound infections in CABG.

Background: Deep sternal wound infection (DSWI) remains a serious complication after coronary artery bypass grafting (CABG). We herein aimed to stratify diabetic patients who underwent CABG using bilateral internal mammary artery (BIMA) for levels of glycated hemoglobin A1C (HbA1c) and compare postoperative outcomes. Methods: Between January 2010 and August 2020, 4,186 consecutive patients underwent isolated CABG at our center. In 3,229 patients, preoperative HbA1c levels were available. Primary endpoints were wound healing disorder (WHD), DSWI, and 30-day mortality. Patients were stratified according to preoperative HbA1c levels. Patients were further divided into subgroups according to utilization of BIMA. Results: After adjustment, no differences in mortality and stroke rates were seen between group 1 (HbA1c < 6.5%) vs. group 2 (HbA1c ≥ 6.5%). WHD was more frequent in group 2 [2.8 vs. 5.6%; adjusted p = 0.002; adjusted odds ratio (OR), 1.853 (1.243-2.711)] but not DSWI [1.0 vs. 1.5%; adjusted p = 0.543; adjusted OR, 1.247 (0.612-2.5409)]. BIMA use showed a higher rate of WHD [no BIMA: 3.0%; BIMA: 7.7%; adjusted p = 0.002; adjusted OR, 4.766 (1.747-13.002)] but not DSWI [no BIMA: 1.1%; BIMA: 1.8%; adjusted p = 0.615; adjusted OR, 1.591 (0.260-9.749)] in patients with HbA1c ≥ 6.5%. Conclusions: Intraoperative utilization of BIMA is not connected with an increase of DSWI but higher rates of WHD in patients with poor diabetic status and HbA1c ≥ 6.5%. Therefore, application of BIMA should be taken into consideration even in patients with poor diabetic status, while identification of special subsets of patients who are at particular high risk for DSWI is of paramount importance to prevent this serious complication.

Transcatheter valve-in-valve therapies: patient selection, prosthesis assessment and selection, results, and future directions.

The development of transcatheter valve implantations (TAVI) has induced profound changes in the treatment of valvular heart disease over the past decade. At the same time, due to excellent clinical results, bioprostheses continuously outperformed mechanical prostheses. The increasing number of elderly patients has led to numerous patients presenting with deteriorated bioprostheses needing reoperation. In selected high-risk patients or patients with unreasonable surgical risk, valve-in-valve TAVI has advanced to a viable alternative to conventional redo surgery. High procedural success, good hemodynamics and acceptable clinical results were reported up until now. Valve-in-valve TAVI seems to be safe and effective in treatment of deteriorated valve prostheses in high-risk patients. The valve-in-valve concept presents the next step toward an individual treatment strategy for patients at prohibitive risk for conventional surgery. Present studies were reviewed with special concern to patient selection, prosthesis assessment, device selection, clinical outcome and technical challenging aspects as well.

Prediction of volume responsiveness using pleth variability index in patients undergoing cardiac surgery after cardiopulmonary bypass.

BACKGROUND: The pleth variability index (PVI) is derived from analysis of the plethysmographic curve and is considered to be a noninvasive parameter for prediction of volume responsiveness. The aim of our prospective clinical study was to evaluate if volume responsiveness can be predicted by PVI in patients undergoing cardiac surgery after cardiopulmonary bypass. METHODS: Eighteen patients were prospectively studied. Directly after cardiac surgery, PVI, stroke volume variation (SVV), and cardiac index (CI) were recorded. Colloid infusion (4 ml/kg body weight) was used for volume loading, and volume responsiveness was defined as increase of CI more than 10 %. RESULTS: SVV and PVI measures were found to be highly correlated at r = 0.80 (p < 0.001). Receiver operating characteristics curve (ROC) analysis resulted in an area under the curve of 0.87 for SVV and 0.95 for PVI, which values did not differ statistically significant from each other (p > 0.05). The optimal threshold value given by ROC analysis was ≥11 % for SVV with a sensitivity and specificity of 100 % and 72.2 %. For PVI, optimal threshold value was ≥16 % with a sensitivity and specificity of 100 % and 88.9 %. Positive and negative predictive values estimating an increase of CI ≥10 % for SVV were 44.4 % and 100 % and 66.7 % and 100 % for PVI. CONCLUSIONS: For consideration of fluid responsiveness PVI is as accurate as SVV in patients after cardiopulmonary bypass. Methodological limitations such as instable cardiac rhythm after cardiopulmonary bypass and right- or left ventricular impairment seem to be responsible for low specificity and positive predictive values in both parameters PVI and SVV.

Prognostic impact of functional mitral regurgitation prior to left ventricular assist device implantation.

BACKGROUND: Functional mitral regurgitation (FMR) is a common finding of advanced heart failure with detrimental effects. The prognostic impact of uncorrected FMR prior to left ventricular assist device (LVAD) implantation remains controversial. METHODS: Between 2016 and 2019 77 patients underwent continuous-flow LVAD implantation at our institution. 34 patients showed FMR ≥ 2 (MR-group), whereas 43 patients showed FMR < 2 (Control-group). Data was retrospectively analyzed. Primary composite endpoint comprised freedom from death, stroke, pump-thrombosis, major bleeding and right heart failure (RHF) after 1 year. RESULTS: Baseline characteristics, including the severity of left and right ventricular dysfunction, and periprocedural results were comparable. The overall survival during a mean follow up of 24.9 months was 55.9% in the MR-group versus 58.1% in the Control-group (p = 0.963), whereas 1-year event-free survival was 35.3% in the MR-group compared to 44.2% in the Control-group (p = 0.404). RHF within the first postoperative year occurred more frequently in the MR-group (35.3% vs. 11.6%; p = 0.017). Furthermore, RV function was significantly reduced in comparison to baseline values in the MR-group. 12 months after surgery, 74% of patients in the MR-group were classified as NYHA III in comparison to 24% of patients in the Control-group (p < 0.001). CONCLUSIONS: Preoperative uncorrected FMR prior to LVAD implantation did not affect overall survival, nevertheless it was associated with an impaired RV function and increased incidence of right heart failure during follow-up. Furthermore, preoperative FMR ≥ 2 was associated with persistent symptoms of heart failure.

Development of an ovine model of pediatric complete heart block.

BACKGROUND: Complete heart block is a significant clinical problem that can limit the quality of life in affected children. To understand the pathophysiology of this condition and provide for development of novel therapies, we sought to establish a large animal model of permanent, pacemaker-dependent atrioventricular block (AVB) that mimics the size and growth characteristics of pediatric patients. MATERIALS AND METHODS: We utilized nine immature lambs weighing 10.5 ± 1.4 kg. After implantation of dual-chamber pacemaker devices with fixed leads, AVB was produced by interrupting His-bundle conduction using radio-frequency ablation at the base of the non-coronary cusp of the aortic valve. Ablations (30 to 60 s in duration) were performed under fluoroscopic guidance with electrophysiological monitoring. Interrogation of pacemakers and electrocardiography (ECG) determined the persistence of heart block. Ovine hearts were also examined immunohistochemically for localization of conduction tissue. RESULTS: AVB was produced in eight animals using an atypical approach from the left side of the heart. One animal died due to ventricular fibrillation during ablation proximal to the tricuspid annulus and one lamb was sacrificed postoperatively due to stroke. Four sheep were kept for long-term follow-up (109.8 ± 32.9 d) and required continuous ventricular pacing attributable to lasting AVB, despite significant increases in body weight and size. CONCLUSIONS: We have created a large animal model of pediatric complete heart block that is stable and technically practicable. We anticipate that this lamb model will allow for advancement of cell-based and other innovative treatments to repair complete heart block in children.

Creation of a tricuspid valve regurgitation model from tricuspid annular dilatation using the cardioport video-assisted imaging system.

BACKGROUND AND AIM OF THE STUDY: Experimental models of tricuspid valve regurgitation (TR) are used to study novel annuloplasty techniques (including prosthetic rings), and they can also serve as physiologic models to investigate TR pathophysiology. The study aim was to develop an appropriate simple and reproducible experimental model of TR from annular dilatation. METHODS: Acute TR was successfully created through multiple small 3- to 5-mm incisions in the annulus using a custom-made optical port with an instrument shaft (the Cardioport) that accepts a standard endoscopic imaging system. The Cardioport was inserted, via a thoracotomy, through the right atrium of seven Yorkshire pigs, and directed towards the tricuspid valve annulus to create the annular incisions. Tricuspid valve anatomy and function were evaluated using 2D and 3D echocardiography. The presence and severity of TR, annulus diameter, and changes in heart rate and atrial pressures after making the annular incisions were documented. To monitor tricuspid annular dilatation and the progression of TR, follow up echocardiography and color Doppler examinations were performed at two and eight weeks postoperatively. RESULTS: The acute onset of TR was well tolerated, and there were no deaths or significant morbidity associated with the procedure. The annular diameter was increased from a preoperative mean of 23.1 +/- 1.7 mm, to 32.2 +/- 2.5 mm at two weeks postoperatively, and to 37.3 +/- 3.6 mm at eight weeks postoperatively. Overall, the TR progressed from mild (grade I) to severe (grade III) in all of the animals. CONCLUSION: This novel porcine model represents a relatively simple and a reproducible surgical technique for the creation of annular dilatation and TR, and may also serve as a chronic model of the latter condition.

Fate of the aortic valve following the arterial switch operation.

OBJECTIVE: We evaluated the long-term outcome of aortic valve after arterial switch operation (ASO). METHODS: A retrospective review of 324 hospital survivors after ASO was performed. Echocardiographic findings and incidence and progression of aortic regurgitation (AR) were investigated. Endpoints of the study were the first documented occurrence of moderate or severe AR or need for aortic valve replacement (AVR). RESULTS: Upon discharge from hospital 5.2% of the patients showed mild AR, progressing to 11.4% after 1 year. At a mean follow-up time of 14.4 ± 0.54 years, AR was absent in 307 (94.7%), trivial in six (1.8%), mild in nine (2.7%), and moderate-to-severe in two (0.6%) patients. There is a progression of AR with time after ASO (p < 0.001). A total of two patients reached the combined endpoint, both of whom underwent AVR at a mean time of 10.82 years after ASO. Freedom from aortic valve reoperation was 98.7 ± 0.9% at 5 and 10 years and 94.7 ± 4% at 15 years. Univariate analysis identified the following risk factors: ventricular septal defect (VSD) (p = 0.005), prior pulmonary artery banding (p < 0.003), and postoperative incidence of mild AR (p < 0.0001). CONCLUSION: AR is not rare after ASO, but it is stable without progressive intensity; new AR developed in 5.2% after 10 years, and is present only in 2.7% after a median follow-up 14.4 ± 0.54 years. If trivial AR is excluded, it is present only in 0.9%. New AR can develop even up to 15 years. However, severe AR and need for AVR are rare.

Left Ventricular Assist Device Implantation and Concomitant Dor Procedure: a Single Center Experience.

OBJECTIVE: Left ventricular assist device (LVAD) implantation with concomitant Dor plasty is only reported anecdotally. We herein aimed to describe our experience with LVAD and concomitant Dor procedures and describe long-term outcomes of this special subset of heart failure patients. METHODS: Between January/2010 and December/2018, 144 patients received LVAD therapy at our institution. Of those, five patients (80% male, 60.4±7.2 years) presented with an apical aneurysm and received concomitant Dor plasty. Apical aneurysms presented diameter between 75 and 98 mm, with one impending rupture. RESULTS: Procedural success was achieved in all patients. No unplanned right ventricular assist device implantation occurred. Furthermore, no acute 30-day mortality was seen. In follow-up, one patient was lost due to intentional disconnection of the driveline. One patient underwent heart transplantation on postoperative day 630. The remaining three patients are still on device with sufficient flow; pump thromboses were successfully managed by lysis therapy in one patient. CONCLUSION: LVAD implantation with concomitant Dor procedure is feasible, safe, and occasionally performed in patients with ischemic cardiomyopathy. Major advantages are prevention of thromboembolism and facilitation of LVAD placement by improving pump stability and warranting midventricular, coaxial alignment of the inflow cannula. In long-term follow-up, no adverse event associated with Dor plasty was observed.

Gender differences and outcomes in left ventricular assist device support: The European Registry for Patients with Mechanical Circulatory Support.

BACKGROUND: Despite the increasing use of ventricular assist devices (VADs), gender differences in indications, hemodynamics, and outcome are not well understood. We examined gender differences and gender-specific predictors for perioperative outcome in patients on ventricular support. METHODS: Multicenter data of 966 patients (median age 55 years, 151 women) from the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) were analyzed. Median follow-up was 1.26 years. RESULTS: At the time of VAD implantation, women were more often in an unstable condition (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS] profile 1 and 2) (51.7% vs 41.6% in men), experiencing significantly more often major bleeding (p = 0.0012), arrhythmias (p = 0.022), and right ventricular (RV) failure (p < 0.001) with need for additional RV support. The survival of women on isolated LVAD support was significantly worse (1-year survival 75.5% vs 83.2% in men). Age-adjusted Cox regression analyses showed significant associations with mortality for preoperative inotropic therapy, percutaneous mechanical support, INTERMACS profile 1 and 2, RV dysfunction, major bleeding, cerebral bleeding, ischemic stroke, and RV failure. In women, pump thrombosis was more strongly related with mortality compared to men, while the direction of the association of renal dysfunction with mortality was different for women and men (p-value interaction 0.028 and 0.023, respectively). CONCLUSIONS: Women and men differ in perioperative hemodynamics, adverse events, and mortality after VAD implantation. A gender-dependent association of pump thrombosis with mortality was seen. The impact on treatment practice needs to be shown.

Endothelin-1 in humans is increased by oxygen-derived radicals ex vivo and in vivo.

Endothelin-1, angiotensin II, and oxygen-derived radicals are pivotal factors in the development and progression of atherosclerosis. In vitro studies suggest that generation of oxygen-derived radicals by angiotensin II is an important mechanism increasing endothelin-1 synthesis, which consecutively may trigger effects such as cell proliferation and hypertrophy. The aim of this study was to confirm our previous data in an ex vivo and an in vivo setting. Explanted segments of internal mammary arteries were analyzed for big endothelin-1 expression following incubation with xanthine oxidase, angiotensin II, superoxide dismutase, and catalase to stimulate or to specifically inactivate oxygen-derived radicals. Endothelin-1 concentrations were determined by immunostaining and enzyme-linked immunosorbent assay. Further, oxypurinol was given to patients undergoing coronary angioplasty, a procedure known to increase plasma endothelin-1 concentrations. Angiotensin II and xanthine oxidase dose-dependently increased big endothelin-1 concentrations (p < .01 and p < .0001); the effects could be inhibited by coincubation with superoxide dismutase and catalase as determined by both semiquantitative immunofluorescence and enzyme-linked immunosorbent assay (p < .01). Patients undergoing coronary angioplasty exhibited significantly elevated big endothelin-1 concentrations 60 minutes after angioplasty (p = .03); in patients also receiving oxypurinol immediately after angioplasty, big endothelin-1 concentrations decreased (p = .001). Our results may explain the association between elevated angiotensin II levels, increased oxidative stress, and increased endothelin-1 concentrations in atherosclerosis. The data therefore support the concept that oxygen-derived free radicals stimulate the release of endothelin-1, which subsequently induces effects such as proliferation and enhanced agonist-induced vasoconstriction, previously attributed directly to angiotensin II.

Preoperative Ticagrelor administration leads to a higher risk of bleeding during and after coronary bypass surgery in a case-matched analysis.

OBJECTIVES: To evaluate the effect of Ticagrelor on intra- and postoperative bleeding complications in patients undergoing coronary bypass surgery. METHODS: For this study, patients who underwent on-pump or off-pump coronary bypass surgery with preoperative acetylsalicylic acid (ASA) and Ticagrelor administration, between January 2014 and December 2014, were included. In the matched control group, continued dual antiplatelet therapy (DAPT) consisted of Clopidogrel and ASA. A total of 28 consecutive patients (24 males; 73 ± 6.6 years) with preoperative Ticagrelor intake underwent elective (n = 22), urgent (n = 2) or emergency (n = 4) cardiac bypass surgery. The postoperative blood loss, red blood cell units given and intra- and postoperative bleeding complications were documented. To evaluate the effect of Ticagrelor treatment on bleeding during and after coronary bypass surgery in a non-randomized study, we used a case-matched analysis. RESULTS: Baseline parameters showed no important differences between the study group and the control group regarding the matching variables, left ventricular function, preoperative clinical status and risk stratification. The preoperative laboratory analysis showed no important differences regarding coagulation and blood cell count parameters. Overall blood loss was significantly higher in the study group with a mean loss of 1028.8 ± 735.5 ml (P = 0.0002). Accordingly, units of red blood cells administered were also significantly higher in the study group (P = 0.0002). In the Ticagrelor group, there were six rethoracotomies due to postoperative bleeding with a blood loss of more than 1200 ml in the first 3 h. With no rethoracotomies in the Clopidogrel group, this also showed statistical significance for the postoperative course (P = 0.02). There were no differences found regarding ICU stay and ventilation time. Comparing the mean hospital stay, the study group presented a significantly longer stay than the control group (P = 0.001). CONCLUSIONS: Recent studies about bleeding complications in patients with Ticagrelor intake undergoing CABG in a real-life scenario presented inconsistent data. We were able to show in a case-matched analysis that Ticagrelor administration leads to significantly higher blood loss, more red blood cell units transfused and a higher rate of rethoracotomies. The data also present a longer hospital stay to the disadvantage of the study group. Consequently, Ticagrelor intake before CABG procedures should be avoided or at least discontinued 3 days before cardiac surgery.

Failing stentless Bioprostheses in patients with carcinoid heart valve disease.

BACKGROUND: Carcinoid tumor with consecutive endocardial fibroelastosis of the right heart, known as carcinoid heart valve disease (CHVD) or Hedinger's syndrome, is accompanied by combined right-sided valvular dysfunction with regurgitation and stenosis of the affected valves. Cardiac surgery with replacement of the tricuspid and/or pulmonary valve is an established therapeutic option for patients with Hedinger's syndrome. Little is known about the long term outcome and the choice of prosthesis for the pulmonal position is still a matter of debate. METHODS: The authors report three cases of pulmonary valve replacement with stentless bioprostheses (Medtronic Freestyle, Medtronic PLC, Minneapolis, MN, USA) due to severe pulmonary valve degeneration in consequence of Hedinger's syndrome. RESULTS: All patients presented with re-stenosis of the pulmonal valve conduit at the height of the anastomoses in a premature fashion. Due to the increased risk for repeat surgical valve replacement, two patients were treated by transcatheter heart valves. CONCLUSION: We do not recommend the replacement of the pulmonary valve with stentless bioprostheses in patients with CHVD. These valves presented with an extreme premature degeneration and consecutive re-stenosis and heart failure.

Left ventricular assist device implantation and concomitant dor procedure: a single center experience

Abstract Objective: Left ventricular assist device (LVAD) implantation with concomitant Dor plasty is only reported anecdotally. We herein aimed to describe our experience with LVAD and concomitant Dor procedures and describe long-term outcomes of this special subset of heart failure patients. Methods: Between January/2010 and December/2018, 144 patients received LVAD therapy at our institution. Of those, five patients (80% male, 60.4±7.2 years) presented with an apical aneurysm and received concomitant Dor plasty. Apical aneurysms presented diameter between 75 and 98 mm, with one impending rupture. Results: Procedural success was achieved in all patients. No unplanned right ventricular assist device implantation occurred. Furthermore, no acute 30-day mortality was seen. In follow-up, one patient was lost due to intentional disconnection of the driveline. One patient underwent heart transplantation on postoperative day 630. The remaining three patients are still on device with sufficient flow; pump thromboses were successfully managed by lysis therapy in one patient. Conclusion: LVAD implantation with concomitant Dor procedure is feasible, safe, and occasionally performed in patients with ischemic cardiomyopathy. Major advantages are prevention of thromboembolism and facilitation of LVAD placement by improving pump stability and warranting midventricular, coaxial alignment of the inflow cannula. In long-term follow-up, no adverse event associated with Dor plasty was observed.

Superparamagnetic iron oxide nanoparticles function as a long-term, multi-modal imaging label for non-invasive tracking of implanted progenitor cells.

The purpose of this study was to determine the ability of superparamagnetic iron oxide (SPIO) nanoparticles to function as a long-term tracking label for multi-modal imaging of implanted engineered tissues containing muscle-derived progenitor cells using magnetic resonance imaging (MRI) and X-ray micro-computed tomography (µCT). SPIO-labeled primary myoblasts were embedded in fibrin sealant and imaged to obtain intensity data by MRI or radio-opacity information by µCT. Each imaging modality displayed a detection gradient that matched increasing SPIO concentrations. Labeled cells were then incorporated in fibrin sealant, injected into the atrioventricular groove of rat hearts, and imaged in vivo and ex vivo for up to 1 year. Transplanted cells were identified in intact animals and isolated hearts using both imaging modalities. MRI was better able to detect minuscule amounts of SPIO nanoparticles, while µCT more precisely identified the location of heavily-labeled cells. Histological analyses confirmed that iron oxide particles were confined to viable, skeletal muscle-derived cells in the implant at the expected location based on MRI and µCT. These analyses showed no evidence of phagocytosis of labeled cells by macrophages or release of nanoparticles from transplanted cells. In conclusion, we established that SPIO nanoparticles function as a sensitive and specific long-term label for MRI and µCT, respectively. Our findings will enable investigators interested in regenerative therapies to non-invasively and serially acquire complementary, high-resolution images of transplanted cells for one year using a single label.

Transapical transcatheter valve-in-valve implantation for deteriorated mitral valve bioprostheses.

BACKGROUND: The transcatheter valve-in-valve concept has been described for patients requiring redo valve surgery. We report our experience with transapical mitral valve-in-valve implantation. METHODS: Since 2008, 301 patients were treated with transapical transcatheter valve implantation. Seven of these patients presented with a deteriorated mitral valve bioprosthesis and underwent transapical mitral valve-in-valve implantation. Median age was 79 years. Preoperatively, all patients presented in New York Heart Association functional class III. For risk estimation, The Society of Thoracic Surgeons and European System for Cardiac Operative Risk scores were used and predicted high mortality (mean ± standard error of mean: Society of Thoracic Surgeons mortality, 12.3% ± 2.1%; European System for Cardiac Operative Risk mortality, 58.0% ± 7.0%). Mean follow-up time was 93 ± 29 days, with a total of 21.6 patient-months. RESULTS: Preoperatively, all patients who had deteriorated bioprostheses presented with severe regurgitation and increased transvalvular pressure gradients (maximal pressure gradient, 23.9 ± 0.9 mm Hg; mean pressure gradient, 11.3 ± 1.0 mm Hg). One patient was identified with mitral valve stenosis (effective orifice area, 0.25 cm(2)). All patients underwent successful transapical mitral valve-in-valve implantation. Sizes of previously implanted bioprostheses were 27, 29, and 31 mm; Edwards SAPIEN valves at sizes 26 and 29 mm were implanted. Postoperatively, echocardiography revealed excellent hemodynamics with no remaining mitral regurgitation in 5 patients and minimal regurgitation in 2 patients. Transvalvular pressure gradients decreased significantly (maximal pressure gradient, 13.8 ± 2.1 mm Hg; mean pressure gradient 5.7 ± 0.8 mm Hg, p < 0.05). One patient had fatal pneumonia on postoperative day 34. No patient died during further follow-up, and all patients remained in New York Heart Association class I or II. CONCLUSIONS: Our results demonstrate the feasibility of transapical mitral valve-in-valve implantation for treatment of a degenerated bioprosthesis (size range, 27 to 31 mm) using the Edwards SAPIEN valve in sizes 26 and 29 mm.

Transcatheter valve-in-valve implantation for deteriorated aortic bioprosthesis: initial clinical results and follow-up in a series of high-risk patients.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has become a viable alternative in maximum risk patients. For those patients requiring aortic valve re-replacement, the "valve-in-valve" concept has been described. We report our experience with transapical valve-in-valve implantation in 7 patients with deteriorated aortic bioprosthesis at 1-year follow up. METHODS: Since November 2008, 210 patients received transapical TAVI due to severe aortic stenosis. Seven patients presented with deteriorated aortic valve bioprosthesis and received transapical valve-in-valve implantation. Mean age was 78.7±0.8 years. Preoperatively, all patients were at New York Heart Association (NYHA) functional class III. For risk estimation, the Society of Thoracic Surgeons (STS) and European System for Cardiac Operative Risk Evaluation (ES) risk scores were used and predicted high mortality (means±standard error of the mean: STSMortality 21.6±2.8%, ESadd 14.9±1.1, ESlog 52.6±9.0%). Mean follow-up time was 517±65 days (range, 280 to 799 days). RESULTS: Six patients showed a severely deteriorated bioprosthesis in terms of a stenotic valve (aortic valve area: 0.64±0.04 cm2, maximum/mean developed transvalvular pressure gradient: dPmax 63.3±10.9 mm Hg, dPmean 40.4±5.6 mm Hg). One patient's deteriorated prosthesis was highly insufficient. Procedural success rate was 100%, mean procedure time was 46.7±12.3 minutes. Echocardiography revealed excellent hemodynamics of implanted prosthesis (dPmax 31.1±5.5 mm Hg; dPmean 19.4±4.3 mm Hg). Overall, postoperative course was uneventful. No patient died during follow-up, which ranged up to 26 months. All patients, except 1, remained in NYHA class I or II. CONCLUSIONS: Our results demonstrate feasibility and safety of the transapical valve-in-valve approach with excellent hemodynamic and clinical results. Decision making in a multidisciplinary setting is mandatory. Further studies with more patients and longer follow-up are needed to identify candidates benefiting from transapical transcatheter valve-in-valve implantation.

Surgical technique of lower lobe lung transplantation.

Among patients with end-stage lung disease awaiting lung transplantation, pediatric and small adult patients have a significantly lower chance of getting size-matched pulmonary grafts in time because of the severe scarcity of small donors. It is our strategy to perform lobar lung transplantations in small recipients with restrictive pulmonary disease once their clinical status demands urgent transplantation. Here we describe our surgical technique and discuss the benefits and risks of this procedure.