Valved stents for transapical pulmonary valve replacement.

OBJECTIVES: Pulmonary valve insufficiency remains a leading cause for reoperations in congenital cardiac surgery. The current percutaneous approach is limited by the size of the access vessel and variable right ventricular outflow tract morphology. This study assesses the feasibility of transapical pulmonary valve replacement based on a new valved stent construction concept. METHODS: A new valved stent design was implanted off-pump under continuous intracardiac echocardiographic and fluoroscopic guidance into the native right ventricular outflow tract in 8 pigs (48.5 +/- 6.0 kg) through the right ventricular apex, and device function was studied by using invasive and noninvasive measures. RESULTS: Procedural success was 100% at the first attempt. Procedural time was 75 +/- 15 minutes. All devices were delivered at the target site with good acute valve function. No valved stents dislodged. No animal had significant regurgitation or paravalvular leaking on intracardiac echocardiographic analysis. All animals had a competent tricuspid valve and no signs of right ventricular dysfunction. The planimetric valve orifice was 2.85 +/- 0.32 cm(2). No damage to the pulmonary artery or structural defect of the valved stents was found at necropsy. CONCLUSIONS: This study confirms the feasibility of direct access valve replacement through the transapical procedure for replacement of the pulmonary valve, as well as validity of the new valved stent design concept. The transapical procedure is targeting a broader patient pool, including the very young and the adult patient. The device design might not be restricted to failing conduits only and could allow for implantation in a larger patient population, including those with native right ventricular outflow tract configurations.

Severe mitral valve insufficiency after transcatheter atrial septal defect closure with the amplatzer septal occluder: a device-related complication.

Atrial septal defect (ASD) is the one of the most common congenital cardiac diseases. Percutaneous device closure of the ASD has developed as an alternative to traditional surgical closure with a similar outcome, decreased surgical trauma, and shorter hospital stay. However, several complications have been reported. We now report a rare complication of late severe mitral insufficiency (MI) after a successful closure of a secundum ASD with an Amplatzer device. The potential mechanisms may be the continual traction of the oversized mismatched device on the root of the mitral annulus and the insufficient rim to the mitral annulus. The patient was sent for a surgical operation to remove the device, and the defect was closed. No MI was found at the one-year follow-up.

Ascending aorta measurements as assessed by ECG-gated multi-detector computed tomography: a pilot study to establish normative values for transcatheter therapies.

The aim of this study was to provide an insight into normative values of the ascending aorta in regards to novel endovascular procedures using ECG-gated multi-detector CT angiography. Seventy-seven adult patients without ascending aortic abnormalities were evaluated. Measurements at relevant levels of the aortic root and ascending aorta were obtained. Diameter variations of the ascending aorta during cardiac cycle were also considered. Mean diameters (mm) were as follows: LV outflow tract 20.3 +/- 3.4, coronary sinus 34.2 +/- 4.1, sino-tubular junction 29.7 +/- 3.4 and mid ascending aorta 32.7 +/- 3.8 with coefficients of variation (CV) ranging from 12 to 17%. Mean distances (mm) were: from the plane passing through the proximal insertions of the aortic valve cusps to the right brachio-cephalic artery (BCA) 92.6 +/- 11.8, from the plane passing through the proximal insertions of the aortic valve cusps to the proximal coronary ostium 12.1 +/- 3.7, and between both coronary ostia 7.2 +/- 3.1, minimal arc of the ascending aorta from left coronary ostium to right BCA 52.9 +/- 9.5, and the fibrous continuity between the aortic valve and the anterior leaflet of the mitral valve 14.6 +/- 3.3, CV 13-43%. Mean aortic valve area was 582.0 +/- 131.9 mm(2). The variation of the antero-posterior and transverse diameters of the ascending aorta during the cardiac cycle were 8.4% and 7.3%, respectively. Results showed large inter-individual variations in diameters and distances but with limited intra-individual variations during the cardiac cycle. A personalized approach for planning endovascular devices must be considered.

Acceptance and introduction of disruptive technologies - simple steps to build a fully functional pulmonary valved stent.

Valved stents are new land for cardiac surgeons even though they are being used more frequently by interventional disciplines. This paper presents simple steps to build a patient-specific pulmonary valved stent and its delivery device. The design concept was tested by random participants at a med-tech meeting. The valved stent is constructed by linking an endoprosthetic graft with a valved-jugular-vein. The delivery device is made from a modified 5-ml syringe. Of 72 participants, 66 (92%) built and 60 participants implanted the device successfully into the targeted pulmonary position via a trans-infundibular access.

Benefits of cardiac surgery in octogenarians--a postoperative quality of life assessment.

OBJECTIVE: Assessment of postoperative quality of life in patients over 80 years after cardiac surgery including coronary artery bypass grafting (CABG), aortic valve replacement (AVR) and combined procedures. METHODS: Quality of life of n=136 patients over 80 years at operation (82.3+/-2.1 years), undergoing isolated CABG in 61 patients (45%), isolated AVR in 34 patients (25%) and a combination of CABG and AVR in 41 patients (30%) between January 1999 and December 2003 was reviewed. Preoperatively 66.2% presented in NYHA-class III/IV or CCS-class III/IV. Mean ejection fraction (EF) was 59.5%+/-14.0 (range 25-90%). Quality of life assessment was performed via a Seattle Angina Questionnaire. Follow-up was 100% complete for a total of 890 days (69-1853 days). RESULTS: Five-year survival was 70% for the CABG group, 75% for the AVR group and 65% for the CABG/AVR group. Quality of life was remarkable in all of the three groups after surgery. Overall 97 patients (81%) were not or little disabled in their daily activity. One hundred and twelve patients (93%) were free or considerably less symptomatic. Seventy-eight patients or 65% reported to be very satisfied with their current quality of life and 112 patients (93%) felt very reassured to have continuous full access to medical treatment despite of their advanced age. CONCLUSIONS: A remarkable quality of life and important improvement in the functional status after cardiac surgery in patients over 80 paired with a satisfactory medium-term survival justify early intervention for heart disease in this age group. Therefore, referral practice for patients over 80 years for heart surgery should be handled liberally.

Direct access valve replacement (DAVR) - are we entering a new era in cardiac surgery?

OBJECTIVE: This study validates the off-pump antegrade trans-ventricular route for ultrasound-guided direct access aortic valve replacement. Direct access aortic valve replacement using a transthoracic and valved stent-based approach offers numerous advantages over the remote access percutaneous approach and may one day provide an alternative treatment modality for aortic valve disease. METHODS: Valved stents were implanted off-pump in 17 pigs (72.10+/-8.4 kg) via the direct access transapical approach using a left-sided mini-thoracotomy and continuous ultrasonic and fluoroscopic guidance. Acute valved stent function was studied with intravascular and two-dimensional intracardiac ultrasound. The invasive valve gradient was assessed with pull-back pressure catheter. All valved stents were tested in vitro before insertion. Macroscopic analysis was performed at necropsy. RESULTS: In 11 of the 17 pigs, valved stents were delivered to the target site over the native aortic valve leaflets without interference of coronary blood flow and with good acute valve function. Three valved stents were deployed supra-annularly, two of those occluded the right coronary orifice and one the left coronary orifice, leading to fatal outcomes. Three valved stents dislodged into the left ventricle, one because of size-mismatch and two because of failure to unfold correctly. In 11 properly sized and deployed valved stents, two showed a moderate and one a severe paravalvular leak. CONCLUSIONS: Seventeen pigs underwent direct access valve replacement of the aortic valve with deployment of a valved stent into the native aorta. Eleven valves observed for an average 5-h period showed satisfactory, postimplantation valve function.

Direct-access valve replacement a novel approach for off-pump valve implantation using valved stents.

OBJECTIVES: This study validates the off-pump antegrade transventricular route for ultrasound-guided direct-access aortic valved stent implantation. BACKGROUND: Direct-access aortic valved stent implantation offers numerous advantages over the remote-access percutaneous approach and may one day provide an alternative to surgical aortic valve replacement. METHODS: Valved stents were implanted off-pump in 12 pigs (68.5.0 +/- 7.3 kg) via direct-access transapical approach using a left-sided mini-thoracotomy and continuous ultrasonic and fluoroscopic guidance. Acute valved stent function was studied with intravascular and intracardiac ultrasound. All valved stents were tested in vitro before insertion. Macroscopic analysis was performed at necropsy. RESULTS: In 8 of 12 pigs, valved stents were delivered to the target site over the native aortic valve leaflets without interference of coronary blood flow and with good acute valve function. Two valved stents were deployed and supra-annularly occluded the coronary orifice, leading to fatal outcome. Two valved stents dislodged into the left ventricle, one because of size mismatch and one that failed to unfold correctly. CONCLUSIONS: Twelve pigs underwent deployment of a valved stent in the aortic position. Six valves observed for an average 4.5-h period showed satisfactory postimplantation valve function.

Double-crowned valved stents for off-pump mitral valve replacement.

OBJECTIVE: An animal model has been designed to assess the feasibility of off-pump mitral valve replacement using valved stents. METHODS: Glutaraldehyde-preserved homograft was sutured inside a prosthetic tube (Dacron). Then, two self-expandable nitinol Z-stents were sutured on the external surface of the prosthesis in such a way to create two self-expanding crowns for fixation. In adult pigs and under general anesthesia, the left atrium was exposed through a left thoracotomy and atrio-ventricular roadmapping was performed with intravascular ultrasound (IVUS) and fluoroscopy. The double-crowned valved stents were loaded into a delivery sheath. The sheath was then introduced into the left atrium and the valved stents was deployed in mitral position in such a way that the part in between the two stents was at the level of the mitral annulus. Intracardiac Unltrasound (ICUS) was used to assess the valve function. Hemodynamic parameters were gathered as well. Animal survived for no more than 3h after the valve deployment and gross anatomy examination of the left heart was carried out. RESULTS: The mean height of the valved stents was 29.4+/-0.2 mm, with an internal diameter of 20.4+/-1.0mm, and an external diameter of 25.5+/-0.8 mm. The procedure was successfully carried out in eight animals. In vivo evaluation showed a native mitral annulus diameter of 24.9+/-0.6 mm, and a mean mitral valve area of 421.4+/-17.5 mm2. ICUS showed a mild mitral regurgitation in three out of eight animals. Mean pressure gradient across the valved stents was 2.6+/-3.1 mmHg. Mean pressure gradient across the left ventricular outflow tract (LVOT) was 6.6+/-5.2 mmHg. The mean survival time was 97.5+/-56.3 min (survival time range was 40-180 min). One animal died due to the occlusion of the LVOT because of valved stents displacement. Postmortem evaluation confirmed correct positioning of the valved stent in the mitral position in seven out of eight animals. No atrial or ventricular lesions due to the valved stents were found. CONCLUSIONS: Off-pump implantation of a self-expandable valved stent in the mitral position is technically feasible. Further studies will assess if this procedure is also feasible in humans.

Ultrasound navigation through the heart for off-pump aortic valved stent implantation: new tools for new goals.

PURPOSE: To validate the use of simultaneous intracardiac and intravascular ultrasound (IVUS) guidance for periprocedural dimension assessment, Residual-Coronary/Sinus-Stent Index (RCSSI) estimation, target site identification, deployment monitoring, and quality control of off-pump aortic Valved Stent implantation. METHODS: Five pigs (56+/-5 kg) underwent off-pump orthotopic aortic valve implantation using a custom-made self-expanding Valved Stent. Intracardiac ultrasound (AcuNav) was introduced via the right femoral vein. After left-sided thoracotomy, pursestring sutures were placed on the left ventricular apex. Following heparinization, a guidewire was inserted through the apex and advanced over the aortic valve under fluoroscopy. A wire-guided IVUS catheter transducer (6-F, 12.5-MHz) was inserted and the aortic target site identified. IVUS probe location was tracked with AcuNav, and measures of the aortic root were taken by both. After removal of the IVUS, the Valved Stent delivery system was introduced over the guidewire under fluoroscopy and AcuNav monitoring; the Valved Stent was deployed over the native valves. In vivo assessment included leaflet motion, planimetric valve orifice and RCSSI (stent to aortic wall distance/coronary diameter) calculations, coronary blood flow characteristics, transvalvular gradient, regurgitation, and paravalvular leaking in combination with continuous cardiac output measures. Macroscopic analysis was performed at necropsy. RESULTS: IVUS dimensions of the aortic root were equal to AcuNav and necropsy dimensions. Both tools showed good valvular function, with full valvular opening and closing in 3 of 5 valves. At necropsy, the 3 aortic Valved Stents were safely anchored. One Valved Stent was placed supra-annularly; 2 dislodged into the left ventricle because of size mismatch. One Valved Stent showed a moderate to severe paravalvular leak. CONCLUSIONS: Simultaneous intracardiac and intravascular ultrasound-guided off-pump orthotopic aortic Valved Stent implantation via left sided thoracotomy is feasible in an animal model. IVUS and intracardiac ultrasound allow adequate aortic dimension assessment and Valved Stent delivery monitoring, as well as postimplantation coronary flow evaluation.

Immunotherapy of cancer: from vision to standard clinical practice.

Until the end of the 19th century the possibility that a tumor could be rejected merely by the body's immune defense was no more than a vision. After more than 100 years of preclinical and clinical research in the field, the vision of cancer immunotherapy became real and has, with multiple tools, successfully entered clinical standard practice. Non-specific mediators of immune defense, such as BCG for treatment of superficial bladder cancer or interferon-alpha for treatment of chronic myelogenous leukemia and hairy cell leukemia, can induce durable remissions. In particular, antigen-specific mediators of immune defense represent promising agents for targeted cancer therapies. Antibody-based treatment of B-cell lymphomas and breast cancer has dramatically improved disease response without major toxicity. A large number of new antibodies targeting different epitopes on a variety of malignant cells are now approaching clinical approval. Allogeneic stem cell transplantation for treatment of leukemia and certain cancers represents the first T cell-based adoptive immunotherapy with large-scale clinical application. Experimental T cell-based immunotherapies with promising clinical perspectives include tumor vaccines, adoptive transfer of autologous tumor-specific effector cells and the genetic transfer of tumor-specific T cell receptors into the patient's lymphocytes. These facts demonstrate that immunotherapy has now been established as the fourth column of cancer therapy besides surgery, radiotherapy, and chemotherapy. On the basis of its already proven efficacy, the usually favorable toxicity profiles and the development perspectives of the experimental approaches a further and more rapid expansion can be expected.

Do valved stents compromise coronary flow?

OBJECTIVE: The aim of the present study is to evaluate a new self-expanding valved stent design for minimal invasive aortic valve implantation and its interference with coronary flow. METHODS: An equine pericardial valve mounted onto a self-expanding nitinol stent (3F Therapeutics trade mark, CA, USA), outer diameter 23 mm, was evaluated (A) in vitro in a dynamic pulsatile mock loop and (B) in vivo in six calves (75+/-2.5 kg). In four animals valve stents were implanted on-pump and in two animals off-pump after induction of ventricular fibrillation. Target site for deployment was the orthotopic aorta, over the native valves. In vivo assessment was performed with intracardiac (AcuNav) and intravascular ultrasound including leaflet motion, planimetric valve orifice and residual-coronary\sinus-stent-index (RCSSI, distance stent to aortic wall/coronary diameter) calculations, coronary blood flow characteristics, transvalvular gradient, regurgitation and paravalvular leaking, in combination with continuous cardiac output measures. Macroscopic analysis was performed at necropsy. RESULTS: Two-dimensional intracardiac ultrasound showed good leaflet motion, with full valvular opening and closing in five of six valves. Planimetric valve orifice was 1.75+/-0.4 cm(2). There were no signs of coronary flow impairment with an RCSSI of 1.8+/-1.2. The implanted valved stents showed a low transvalvular gradient of 5.3+/-3.9 mmHg (mean, peak-to-peak) on invasive measurements and 4.7+/-2.5 mmHg in two-dimensional intracardiac sonography. One of six valves showed mild to moderate regurgitation and one of six valves a minor to moderate paravalvular leak due to size mismatch. CONCLUSIONS: This new self-expanding valved stent design allows for on- and off-pump aortic valve implantation in the orthotopic aorta, over the native valves without interference of the coronary blood flow and excellent acute valve function in properly sized devices.

No drive line, no seal, no bearing and no wear: magnetics for impeller suspension and flow assessment in a new VAD.

The new magnetically suspended axial pump is free of seals, bearings, mechanical friction and wear. In the absence of a drive shaft or flow meter, pump flow assessment is made with an algorithm based on currents required for impeller rotation and stabilization. The aim of this study is to validate pump performance, algorithm-based flow and effective flow. A series of bovine experiments was realized after equipment with pressure transducers, continuous-cardiac-output-catheter, intracardiac ultrasound (AcuNav) over 6 h. Pump implantation was through a median sternotomy (LV-->VAD-->calibrated transonic-flow-probe-->aorta). A transonic-HT311-flow-probe was fixed onto the outflow cannula for flow comparison. Animals were electively sacrificed and at necropsy systematic pump inspection and renal embolus score was realized. Observation period was 340+/-62.4 min. The axial pump generated a mean arterial pressure of 58.8+/-14.3 mmHg (max 117 mmHg) running at a speed of 6591.3+/-1395.4 rev./min (min 5000/max 8500 rev./min) and generating 2.5+/-1.0 l/min (min 1.4/max 6.0 l/min) of flow. Correlation between the results of the pump flow algorithm and measured pump flow was linear (y=1.0339x, R2=0.9357). VAD explants were free of macroscopic thrombi. Renal embolus score was 0+/-0. The magnetically suspended axial flow pump provides excellent left ventricular support. The pump flow algorithm used is accurate and reliable. Therefore, there is no need for direct flow measurement.