Apical closure device for full-percutaneous transapical structural and valve procedures with large-sized introducer sheaths: The final preclinical study.

BACKGROUND: Closed-chest transapical valve implantations (aortic, mitral, and tricuspid) and cardiac structural procedures requiring large-sized introducer sheaths cannot be safely performed with the available technology. We tested a self-expanding apical closure device in a closed-chest animal model, using large-sized introducer sheaths and human-sized animals to establish the technique for future tests in humans. METHODS: Six human-sized pigs (mean weight: 89.7 ± 3.7 kg) received general anesthesia, intubation, and full heparinization (15,000 IU/animal; expected activated clotting time >200 s). Under fluoroscopy and multimodality imaging guidance with next-generation fusion imaging prototypes, a 15-cm long needle and a standard guidewire were percutaneously inserted under the xiphoidal aponeurosis and into the ventricular apex. After the exchange with a stiff guidewire, a 21-Fr introducer sheath for transapical procedures (outer diameter: 25-Fr) was placed in the left ventricle through the apex. The self-expanding closure device was inserted and deployed under fluoroscopic guidance while the 21-Fr sheath was gently removed. Hemodynamic conditions were monitored for 30 min and then the chest was opened to inspect the closure device and quantify the blood loss in the pericardium. Animals were killed and the hearts were removed and inspected. RESULTS: All six apical closure devices were successfully deployed without adverse events. No death, hemodynamic collapse, or cardiac tamponade occurred during the 30-min observational period (mean systolic and diastolic pressures: 88 ± 11 and 58 ± 13 mmHg, respectively; mean heart rate: 60 ± 11 beats per minutes). Pre- and postdeployment (after protamine administration) mean activated clotting time was 541 ± 263 and 217 ± 62 s, respectively. The plugs provided good sealing with a mean of 27.2 ± 13.86 ml of blood lost in the pericardium. Postmortem inspection showed good plug fixation without myocardial damage. CONCLUSION: This self-expanding apical closure device successfully sealed the percutaneous access sites made with large-sized introducer sheaths in human-sized animals. This preclinical study suggests that transapical valve and structural procedures requiring large-sized introducer sheaths can be performed percutaneously.

Outcome of right ventricular assist device implantation following left ventricular assist device implantation: Systematic review and meta-analysis.

OBJECTIVES: The main aim was a systematic evaluation of the current evidence on outcomes for patients undergoing right ventricular assist device (RVAD) implantation following left ventricular assist device (LVAD) implantation. METHODS: This systematic review was registered on PROSPERO (CRD42019130131). Reports evaluating in-hospital as well as follow-up outcome in LVAD and LVAD/RVAD implantation were identified through Ovid Medline, Web of Science and EMBASE. The primary endpoint was mortality at the hospital stay and at follow-up. Pooled incidence of defined endpoints was calculated by using random effects models. RESULTS: A total of 35 retrospective studies that included 3260 patients were analyzed. 30 days mortality was in favour of isolated LVAD implantation 6.74% (1.98-11.5%) versus 31.9% (19.78-44.02%) p = 0.001 in LVAD with temporary need for RVAD. During the hospital stay the incidence of major bleeding was 18.7% (18.2-19.4%) versus 40.0% (36.3-48.8%) and stroke rate was 5.6% (5.4-5.8%) versus 20.9% (16.8-28.3%) and was in favour of isolated LVAD implantation. Mortality reported at short-term as well at long-term was 19.66% (CI 15.73-23.59%) and 33.90% (CI 8.84-59.96%) in LVAD respectively versus 45.35% (CI 35.31-55.4%) p ⩽ 0.001 and 48.23% (CI 16.01-80.45%) p = 0.686 in LVAD/RVAD group respectively. CONCLUSION: Implantation of a temporary RVAD is allied with a worse outcome during the primary hospitalization and at follow-up. Compared to isolated LVAD support, biventricular mechanical circulatory support leads to an elevated mortality and higher incidence of adverse events such as bleeding and stroke.

Performance characteristics of the new Eurosets magnetically suspended centrifugal pump.

OBJECTIVE: The aim was to evaluate the performance of a newly developed magnetically suspended centrifugal pump head intended for use as a ventricular assistance device with a newly developed extracorporeal membrane oxygenator setup. METHODS: In an experimental setup, an extracorporeal membrane oxygenator circuit was established in three calves with a mean weight of 68.2 ± 2.0 kg. A magnetically levitated centrifugal pump was tested, along with a newly designed extracorporeal membrane oxygenator console, at three different flow ranges: (a) 0.0 to 5.2 L/min, (b) 0.0 to 7.1 L/min, and (c) 0.0 to 6.0 L/min. For each setup, the animals were supported by a circuit for 6 h. Blood samples were collected just before caridiopulmonary bypass (CPB) after 10 min on bypass and after 1, 2, 5, and 6 h of perfusion for hemolysis determination and biochemical tests. Values were recorded for blood pressure, mean flow, and pump rotational speed. Analysis of variance was used for repeated measurements. RESULTS: Mean pump flows achieved during the three 6 h pump runs for the three pump heads studied were as follows: (a) flow range 0.0 to 5.2 L/min, 3.6 ± 1.5 L/min, (b) flow range 0.0 to 7.1 L/min, 4.9 ± 1.3 L/min, and (c) flow range 0.0 to 6.0 L/min, 3.8 ± 1.5 L/min. Blood trauma, evaluated by plasma hemoglobin and lactate dehydrogenase levels, did not help in detecting any significant hemolysis. Thrombocytes and white blood cell count profiles showed no significant differences between the groups at the end of the 6 h perfusion. At the end of testing, no clot deposition was found in the oxygenator, and there was no evidence of peripheral emboli. CONCLUSION: The results suggest that the newly developed magnetically suspended centrifugal pump head provides satisfactory hydrodynamic performance in an acute perfusion scenario without increasing hemolysis.

Effects of PDE-5 Inhibition on the Cardiopulmonary System After 2 or 4 Weeks of Chronic Hypoxia.

PURPOSE: In pulmonary hypertension (PH), hypoxia represents both an outcome and a cause of exacerbation. We addressed the question whether hypoxia adaptation might affect the mechanisms underlying PH alleviation through phosphodiesterase-5 (PDE5) inhibition. METHODS: Eight-week-old male Sprague-Dawley rats were divided into two groups depending on treatment (placebo or sildenafil, a drug inhibiting PDE5) and were exposed to hypoxia (10% O2) for 0 (t0, n = 9/10), 2 (t2, n = 5/5) or 4 (t4, n = 5/5) weeks. The rats were treated (0.3 mL i.p.) with either saline or sildenafil (1.4 mg/Kg per day). RESULTS: Two-week hypoxia changed the body weight (- 31% vs. - 27%, respectively, P = NS), blood hemoglobin (+ 25% vs. + 27%, P = NS) and nitrates+nitrites (+ 175% vs. + 261%, P = 0.007), right ventricle fibrosis (+ 814% vs. + 317%, P < 0.0001), right ventricle hypertrophy (+ 84% vs. + 49%, P = 0.007) and systolic pressure (+ 108% vs. + 41%, P = 0.001), pulmonary vessel density (+ 61% vs. + 46%, P = NS), and the frequency of small (< 50 µm wall thickness) vessels (+ 35% vs. + 13%, P = 0.0001). Most of these changes were maintained for 4-week hypoxia, except blood hemoglobin and right ventricle hypertrophy that continued increasing (+ 52% vs. + 42%, P = NS; and + 104% vs. + 83%, P = 0.04). To further assess these observations, small vessel frequency was found to be linearly related with the right ventricle-developed pressure independent of hypoxia duration. CONCLUSIONS: Thus, although hypoxia adaptation is not yet accomplished after 4 weeks, PH alleviation by PDE5 inhibition might nevertheless provide an efficient strategy for the management of this disease.

Outcome of inter-hospital transfer of patients on extracorporeal membrane oxygenation in Switzerland.

AIMS OF THE STUDY: An extracorporeal membrane oxygenation system (ECMO), as a bridge to either recovery, a ventricular assist device (VAD), or heart or lung transplantation, may be the only lifesaving option for critically ill patients suffering from refractory cardiac, respiratory or combined cardiopulmonary failure. As peripheral hospitals may not offer ECMO treatment, tertiary care centres provide specialised ECMO teams for on-site implantation and subsequent patient transfer on ECMO to the tertiary hospital. This study reports the results of the largest ECMO transportation programme in Switzerland and describes its feasibility and safety. METHODS: Patients transported on ECMO by our mobile ECMO team to our tertiary centre between 1 September 2009 and 31 December, 2016 underwent retrospective analysis. Implantation was performed by our specialised ECMO team (primary transport) or by the medical staff of the referring hospital (secondary transport) with subsequent transfer to our institution. Type of ECMO, transport data, patient baseline characteristics, operative variables and postoperative outcomes including complications and mortality were collected from medical records. RESULTS: Fifty-eight patients were included (three patients excluded: one repatriation, two with incomplete medical records). Thirty-five patients (60%) received veno-venous, 22 (38%) veno-arterial and one patient (2%) veno-venoarterial ECMO. Forty-nine (84%) patients underwent primary and nine (16%) secondary transport. Thirty-five (60%) patients were transferred by helicopter and 23 (40%) by ambulance, with median distances of 38.1 (13–225) km and 21 (3-71) km respectively. No clinical or technical complications occurred during transportation. During hospitalisation, three patients had ECMO-associated complications (two compartment syndrome of lower limb, one haemothorax after central ECMO upgrade). Median days on ECMO was 8 (<1–49) and median days in hospital was 17 (<1–122). ECMO weaning was successful in 41 patients (71%), on-transport survival was 100%, 40 patients survived to discharge (69%), and overall survival was 67% (39 patients) at a median follow-up of 58 days (<1–1441). Cumulative survival was significantly affected by cardiogenic shock vs. ARDS (p = 0.001), veno-arterial and veno-venoarterial vs. veno-venous ECMO (p = 0.001) and after secondary vs. primary transport (p <0.001). The ECMO weaning rate was significantly lower after secondary transfer (22%, two patients, both vaECMO) vs. primary transfer (80%, p = 0.002, 39 patients of which 35 (71%) had vvECMO). CONCLUSIONS: The first results of our ECMO transportation programme show its feasibility, safety and efficacy without on-site implant or on-transport complications or mortality. The favourable early survival may justify the large effort with respect to logistics, costs and manpower. With rising awareness, referring centres may increasingly consider this lifesaving option at an early stage, which may further improve outcomes.

New, optimized, dual-lumen cannula for veno-venous ECMO.

OBJECTIVE: The present study was designed to assess in vivo a new, optimized, virtually wall-less, dual-lumen, bi-caval cannula for veno-venous ECMO in comparison to a commercially available cannula. METHODS: Veno-venous extracorporeal membrane oxygenation (ECMO) was carried out in a bovine study (n=5, bodyweight 75±5kg). Following systemic heparinization, ECMO was established in a trans-jugular fashion through a calibrated 23F orifice, using a new, optimized, virtually wall-less, dual-lumen, bi-caval 24F cannula (Smartcanula LLC, Lausanne, Switzerland) versus a commercially available 23F bi-caval, dual-lumen control cannula (Avalon Elite®, Maquet, Rastatt, Germany) in a veno-venous ECMO setup. Veno-venous ECMO was initiated at 500 revolutions per minute (RPM) and increased by incremental steps of 500 RPM up to 2500 RPM. Catheter outlet pressure, catheter inlet pressure, oxygen saturation and pump flow were recorded at each stage. RESULTS: Mean flow accounted for 0.37±0.04 L/min for wall-less versus 0.29± 0.07 L/min for control at 500 RPM, 0.97±0.12 versus 0.67±0.06 at 1000 RPM, 1.60±0.14 versus 1.16±0.08 at 1500 RPM, 2.31±0.13 versus 1.52±0.13 for 2000 RPM and 3.02±0.5 versus 2.11±0.18 (p<0.004). The mean venous suction required was 19±8 mmHg for wall-less versus 20±3 mmHg for control at 500 RPM, 7±3 versus 9±4 for 1000 RPM, -11±10 versus -12±8 at 1500 RPM, -39±15 versus -49±10 for 2000 RPM and -60±28 versus -94±7 for 2500 RPM. The mean venous injection pressure accounted for 29±7 mmHg for wall-less versus 27±5 mmHg for control at 500 RPM, 50±6 versus 61±7 at 1000 RPM, 89±10 versus 99±17 for 1500 RPM, 142±14 versus 161±9 at 2000 RPM and 211±41 versus 252 ±3 for 2500 RPM. CONCLUSION: Compared to the commercially available control cannula, the new, optimized, virtually wall-less, dual-lumen, bi-caval 24F cannula allows for significantly higher blood flows, requires less suction and results in lower injection pressures in vivo.

Clinical Experience in Minimally Invasive Cardiac Surgery With Virtually Wall-Less Venous Cannulas.

OBJECTIVE: Inadequate peripheral venous drainage during minimally invasive cardiac surgery (MICS) is a challenge and cannot always be solved with increased vacuum or increased centrifugal pump speed. The present study was designed to assess the benefit of virtually wall-less transfemoral venous cannulas during MICS. METHODS: Transfemoral venous cannulation with virtually wall-less cannulas (3/8″ 24F 530-630-mm ST) was performed in 10 consecutive patients (59 ± 10 years, 8 males, 2 females) undergoing MICS for mitral (6), aortic (3), and other (4) procedures (combinations possible). Before transfemoral insertion of wall-less cannulas, a guidewire was positioned in the superior vena cava under echocardiographic control. The wall-less cannula was then fed over the wire and connected to a minimal extracorporeal system. Vacuum assist was used to reach a target flow of 2.4 l/min per m with augmented venous drainage at less than -80 mm Hg. RESULTS: Wall-less venous cannulas measuring either 630 mm (n = 8) in length or 530 mm (n = 2) were successfully implanted in all patients. For a body size of 173 ± 11 cm and a body weight of 78 ± 26 kg, the calculated body surface area was 1.94 ± 0.32 m. As a result, the estimated target flow was 4.66 ± 0.78 l/min, whereas the achieved flow accounted for 4.98 ± 0.69 l/min (107% of target) at a vacuum level of 21.3 ± 16.4 mm Hg. Excellent exposure and "dry" intracardiac surgical field resulted. CONCLUSIONS: The performance of virtually wall-less venous cannulas designed for augmented peripheral venous drainage was tested in MICS and provided excellent flows at minimal vacuum levels, confirming an increased performance over traditional thin wall cannulas. Superior results can be expected for routine use.

Impact of aortic root annuloplasty on 3D aortic root geometry.

BACKGROUND: The aim was to evaluate the impact of aortic root (AoR) annuloplasty on 3D AoR deformation. METHODS: In experimental setup, Yacoub procedure and Yacoub with annuloplasty were performed. Results were compared to native AoR. In each AoR modality, six microsonometric (2 mm, 200 Hz) crystals were implanted at the sinotubular junction (STJ) and at the AoR base (AoB). 3D deformation of the AoR was determined by AoR tilt (α) and rotation (ß) angle changes. RESULTS: Tilt angle in Yacoub AoR with annuloplasty and in Yacoub AoR was maximal at ejection, 26.71 ± 0.18° and 24.91 ± 0.13°, respectively, and minimal at diastole, 25.34 ± 0.15° and 21.90 ± 0.15°, respectively. Rotation angle in Yacoub AoR with and without annuloplasty was maximal at ejection, 27.04 ± 0.25° and 23.53 ± 0.54°, respectively, and minimal at diastole, 24.84 ± 0.14° and 21.62 ± 0.16°, respectively. In native AoR, tilt angle and rotation were minimal at ejection, 14.34 ± 0.81° and 18.1 ± 3.20°, respectively, and maximal at diastole, 18.78 ± 0.84° and 21.23 ± 021°, respectively. AoB and STJ had maximal expansion at ejection; 2.59 ± 2.40% and 6.05 ± 0.66 for Yacoub and 3.75 ± 0.66% and 3.08 ± 0.24% for Yacoub with annuloplasty. In native AoR, the expansion at ejection for AoB was 7.13 ± 2.68% and for STJ was 16.42 ± 0.63%. CONCLUSIONS: AoB annuloplasty reduces AoB deformation and has an impact on STJ dynamics. In both the Yacoub AoR modalities, during ejection, the AoR takes on more of a cone-like geometry, whereas in native AoR, it is of a cylinder-like shape.

Impact of the bicuspid aortic valve on aortic root haemodynamics: three-dimensional computed fluid dynamics simulation.

OBJECTIVES: The aim was to evaluate the impact of a bicuspid aortic valve (BAV) on local shear stress and on the pressure profile on the elements of the aortic root (AoR). METHODS: The experiment setup included a BAV with aortic valve stenosis (n = 5 pigs, 67 ± 3.5 kg) and insufficiency (n = 5 pigs, 66.7 ± 4.4 kg). By implanting 6 high-fidelity microsonometric crystals in each AoR, we determined the 3-dimensional (3D) geometry of the AoR. Experimental and geometric data were used to create a 3D time- and pressure-dependent computed fluid dynamic model of the AoR with the BAV. RESULTS: 3D AoR geometry was determined by AoR tilt (α) and rotation angle (ß). Both values were maximal at the end of diastole: 24.41 ± 1.70° (α) and 20.90 ± 2.11° (ß) for BAV with stenosis and 31.92 ± 11.51° (α) and 20.84 ± 9.80° (ß) for BAV with insufficiency and minimal at peak ejection 23.42 ± 1.65° (α), 20.38 ± 1.61° (ß) for stenosis and 26.62 ± 7.86° (α), 19.79 ± 8.45° (ß) for insufficiency. In insufficiency, low shear stress of 0-0.08 Pa and moderate pressure (60-80 mmHg) were present. In BAV with stenosis, low shear stress of 0-0.5 Pa and moderate pressure (0-20 mmHg) were present at diastole; at peak ejection high shear stress >2 Pa and elevated pressure of >80 mmHg were present. CONCLUSIONS: In a BAV with aortic valve stenosis, the haemodynamics are less favourable. The elevated pressure with elevated shear stress may over the long term promote degenerative processes in the leaflets and consequently valve function failure.

Endovascular treatment of non-dissected ascending aorta disease: a systematic review.

Severe ascending aorta disease includes aneurysms, pseudoaneurysms (ascending aorta pseudoaneurysms), penetrating aortic ulcers and Type A aortic dissections. Surgical replacement of the aortic root, ascending aorta or aortic arch is the common treatment for severe ascending aortic disease involving the root, the ascending aorta and/or the arch. Despite good surgical results, there is still a risk for morbidity and mortality following surgery for ascending aorta replacement when elderly patients or patients at high risk for surgery are concerned. Less invasive endovascular treatments for ascending aorta repair are under evaluation, and some reports appeared in the available literature in the last decade. However, clinical series or randomized studies are not yet available, and the use of these techniques is still questionable. In this study, we analysed the outcomes of reported cases of endovascular treatment for ascending aorta disease, excluding Type A aortic dissection. We reviewed reports published until February 2017, and we evaluated the employed technology, the devices, the procedural steps and the outcomes. A total of 26 articles reported 67 patients (mean age 65 ± 17 years) who received endovascular treatment for ascending aorta disease: aneurysms, ascending aorta pseudoaneurysms, penetrating aortic ulcers, intramural haematoma, thrombosis, iatrogenic coarctation and aortic rupture. Complications included endoleak (9 cases), stroke (3 cases), non-ST-elevation myocardial infarction (1 case) and splenic infarction (1 case). Three patients required conversion to open surgery, and 1 patient underwent endovascular reintervention. Early mortality was 2.9%. As an alternative treatment for ascending aorta disease in selected high-risk patients, the endovascular repair will gain popularity, but further analysis is required.

Long-term Outcomes of a Telementoring Program for Distant Teaching of Endovascular Aneurysm Repair.

PURPOSE: To prospectively evaluate the long-term outcomes after a telementoring program for distant teaching of endovascular aneurysm repair (EVAR) and the degree of EVAR procedure assimilation into routine practice. METHODS: A telementoring protocol using stepwise introduction of EVAR was implemented between a university care center and a remote vascular health care site; from March 1999 to October 2003, 49 EVAR patients (mean age 72 years; 48 men) were treated during telementoring at the remote center. After the telementoring period, 86 patients (mean age 71 years; 77 men) underwent EVAR procedures carried out at the secondary care center from November 2003 to July 2011. The long-term outcomes were compared between the EVAR procedures performed during telementoring with the procedures performed independently thereafter. RESULTS: No significant difference was appreciated between telementored and not telementored procedures either in 30-day mortality (4.1% vs 2.3%, p=0.621) or in the initial technical success (93.9% vs 97.7%, p=0.353). The telementored group showed no significant difference in overall aneurysm-related mortality (6.1% vs 2.3%, p=0.353) or in the overall complication rates (p=0.985). The reintervention rate was significantly lower among the unmentored procedures (11.6% vs 32.7%, p=0.004). In particular, significantly fewer patients underwent late endovascular procedures (1.2% vs 12.2%, p=0.009) and late percutaneous interventions (7.0% vs 20.4%, p=0.027) after telementoring ceased. CONCLUSION: The telementoring program followed here allowed excellent EVAR skill assimilation into the routine practice of a remote health care site. Telementoring is a feasible strategy to support skill introduction in remote medical facilities.

Aortic Valve Pathology as a Predictive Factor for Acute Aortic Dissection.

BACKGROUND: In this study, the effect of aortic valve (AV) pathology on local hemodynamic conditions was evaluated as a potential trigger for the onset of acute type A and B aortic dissection. METHODS: A time- and pressure-related four-dimensional (4-D) computed fluid dynamic model of the aorta was established. In an experimental setup, AV stenosis and AV insufficiency were created. 4-D pressure-related geometry of the aortic root (AR) with valve insufficiency and valve stenosis were determined by high-fidelity (200 Hz) microsonometric crystals. Flow and pressure were obtained at the left ventricle, ascending aorta, and aortic arch. RESULTS: Expansion of the AR in AV insufficiency was higher with expansion in AV stenosis, at peak ejection, and at the end of systole. In AV insufficiency, there was low shear stress (0 to 0.6 Pa), turbulent flow, and high pressure (80 to 95 mm Hg) at the anterior wall of the ascending aorta, at the proximal aortic arch, and at the aortic isthmus. In stenosis, high shear stress (>2 Pa) and high pressure (>95 mm Hg) were found at the ascending aorta and at the bifurcation of the brachiocephalic trunk. CONCLUSIONS: In AV insufficiency, low shear stresses and turbulent flow regions were documented at the traditional levels of entry tears for acute type A and B dissection. In AV stenosis, high shear stress with elevated pressure at the ascending aorta may be a trigger element for vessel dilatation, aneurysm formation, and intimal tear, which is typical for type A aortic dissection.

Apical closure device for full-percutaneous transapical valve implantation: stress-test in an animal model†.

OBJECTIVES: Transapical valve implantation is traditionally performed through a left antero-lateral mini-thoracotomy. A self-expandable apical closure device has recently been developed for full-percutaneous transapical valve implantation. We performed haemodynamics stress-tests on an animal model to evaluate the sealing properties. METHODS: Under general anaesthesia 5 pigs (mean weight: 67 ± 6 Kg) received full heparinization (100 IU/Kg; activated clotting time >250 s and, through inferior mini-sternotomies, 21-Fr introducer sheaths for transapical aortic valve implantation (outer diameter: 25-Fr) were placed over-the-wire in the apexes. Delivery-catheters carrying folded occluders (SAFEX TM final design) were inserted in the introducer sheaths and plugs were then deployed under fluoroscopic guidance. Phase 1: after protamine injection, apical bleeding was monitored for 1 h with standard haemodynamics condition. Phase 2: we induced systemic hypertension with adrenaline infusion to test the sealing properties under stress. Animals were sacrificed after Phase 2 and hearts were removed and inspected. RESULTS: Five plugs were successfully introduced and deployed in 5 pig hearts. Plugs provided good apical sealing in each animal and a mean of 7 ± 4 ml of blood lost per animal was collected during Phase 1: haemodynamics remained stable and no plug dislodgement was detected (mean blood pressure: 52 ± 9 mmHg). During Phase 2, mean systolic and diastolic peak levels reached 268 ± 24 mmHg and 175 ± 17 mmHg, respectively, without plug dislodgment or bleeding. Post-mortem inspection showed good plug deployment and fixation without myocardial damage. CONCLUSIONS: The new apical occluder seals large-sized apical access sites in animal models also during induced systemic hypertension. This pilot study is a further step towards full-percutaneous transapical valve procedures in the clinical setting.

Sildenafil attenuates hypoxic pulmonary remodelling by inhibiting bone marrow progenitor cells.

The recruitment of bone marrow (BM)-derived progenitor cells to the lung is related to pulmonary remodelling and the pathogenesis of pulmonary hypertension (PH). Although sildenafil is a known target in PH treatment, the underlying molecular mechanism is still elusive. To test the hypothesis that the therapeutic effect of sildenafil is linked to the reduced recruitment of BM-derived progenitor cells, we induced pulmonary remodelling in rats by two-week exposure to chronic hypoxia (CH, 10% oxygen), a trigger of BM-derived progenitor cells. Rats were treated with either placebo (saline) or sildenafil (1.4 mg/kg/day ip) during CH. Control rats were kept in room air (21% oxygen) with no treatment. As expected, sildenafil attenuated the CH-induced increase in right ventricular systolic pressure and right ventricular hypertrophy. However, sildenafil suppressed the CH-induced increase in c-kit+ cells in the adventitia of pulmonary arteries. Moreover, sildenafil reduced the number of c-kit+ cells that colocalize with tyrosine kinase receptor 2 (VEGF-R2) and CD68 (a marker for macrophages), indicating a positive effect on moderating hypoxia-induced smooth muscle cell proliferation and inflammation without affecting the pulmonary levels of hypoxia-inducible factor (HIF)-1α. Furthermore, sildenafil depressed the number of CXCR4+ cells. Collectively, these findings indicate that the improvement in pulmonary haemodynamic by sildenafil is linked to decreased recruitment of BM-derived c-kit+ cells in the pulmonary tissue. The attenuation of the recruitment of BM-derived c-kit+ cells by sildenafil may provide novel therapeutic insights into the control of pulmonary remodelling.

Impact of synthetic elements on aortic root haemodynamics: computed fluid dynamics of aortic root reconstruction and valve reimplantation.

Objectives: The aim was to evaluate the impact of the aortic valve reimplantation (David) and of the aortic root (AoR) remodelling (Yacoub) on the AoR haemodynamics. Methods: In an experimental setup where the clinical scenario of Yacoub, ( n = 5, domestic pig) and of David ( n = 5, domestic pig) procedure was performed in each AoR, six high-fidelity (200 Hz) sonomicrometric crystals were implanted. Crystals were positioned at three commissures with their projection at the root base. In post-measurement processing 3D deformation of both AoR was determined and used for computed fluid dynamic modelling in order to evaluate pressure, velocity and shear stress profiles. Results: In David AoR: high pressure (> 150 mmHg) and low to moderate shear stress (0-30 Pa) were found from the period of isovolemic contraction to the closure of the aortic valve. At mid diastole pressure augmentation (> 120 mmHg) a low shear stress (0-10 Pa) was registered at the leaflets, three commissures, and intervalvular triangles. In Yacoub AoR: high pressure (110-130 mmHg) with moderate low shear stress (0-30 Pa) was only registered at isovolemic contraction. Conclusions: The results show that haemodynamic conditions following a David procedure have a less favourable pattern as compared to a Yacoub AoR. In David AoR, high pressure and low shear stress are present during 2/3 of the cardiac cycle, whereas in Yacoub root, these conditions are present only for a short period of isovolemic contraction.

How can cardiothoracic and vascular medical devices stay in the market?

Surgeons, as the consumers, must engage in commercial activity regarding medical devices since it directly has impacts on surgical practice and patient outcomes. Unique features defy traditional economic convention in this specific market partly because consumers do not usually pay directly. Greater involvement with commercial activity means better post-market surveillance of medical devices which leads to improved patient safety. The medical device industry has exhibited astonishing levels of growth and profitability reaching $398 billion on a global scale with new product development focusing on unmet clinical need. The industry has rapidly emerged within the context of an ageing population and a global surge in healthcare spending. But the market remains fragmented. The split of consumer, purchaser and payer leads to clinical need driving demand for new product development. This demand contributes to potentially large profit margins mainly contained by regulatory burden and liability issues. Demographic trends, prevalence of diseases and a huge capacity to absorb technology have sustained near unparalleled growth. To stay in the market, incremental development over the short term is essentially aided by responsiveness to demand. Disruptive product development is now more likely to come from multinational companies, in an increasingly expensive, regulated industry. Understanding healthcare organization can help explain the highly complex process of diffusion of innovations in healthcare that include medical devices. The time has come for surgeons to become actively involved with all aspects of the medical device life cycle including commercial activity and post-market surveillance. This is vital for improving patient care and ensuring patient safety.

Aortic root haemodynamics following David procedure: numerical analysis of 3-dimensional haemodynamics.

OBJECTIVES: The aim was to determine 3-dimensional (3D) geometrical deformation of the aortic root (AoR) following the David procedure in order to evaluate local haemodynamical conditions of individual AoR elements. METHODS: In the experimental set-up, the David procedure was performed on 10 domestic pigs. Data were compared with the measurements obtained in 10 native AoRs. In each AoR, six high-resolution ultrasonometric crystals (200 Hz) were implanted, being positioned at each commissure and at the AoR base. 3D geometrical deformation of the AoR, torsion and tilt angle was determined. Computed fluid dynamics (CFD) simulation analysis was used to evaluate local pressure, flow and shear stress. RESULTS: In David AoRs, the tilt angle was maximal at a peak ejection of 25.9 ± 1.49° and minimal at the end of isovolemic contraction at 23.5 ± 0.80°. David root rotation was maximal at a peak ejection of 27.93 ± 1.54° and minimal at the end of the isovolemic contraction at 25.7 ± 1.32°. In the native AoR, the opposite was observed. Here, the tilt and rotation angle were maximal at the end of isovolemic contraction (17.25 ± 0.68° and 19.71 ± 0.73°) and decreased to its minimal values at peak ejections (14.1 ± 0.62° and 16.33 ± 0.47°). In David AoR, high pressure (>140 mmHg) combined with low-to-moderate shear stress (0-40 Pa) was found at the leaflet body from the beginning of isovolemic contraction till the opening of the aortic valve. Similar high pressure (>140 mmHg) and shear stress (0-40 Pa) were found in the period from aortic valve closure till the beginning of the isovolemic contraction. In native AoRs, high pressure (>95 mmHg) was conjoined with low-to-moderate shear stress (0-30 Pa) at the leaflets and was registered at the end of isovolemic contraction. CONCLUSIONS: The David AoR is haemodynamically less favourable when compared with the native AoR. During almost two-thirds of the time period of the cardiac cycle, AoR elements are exposed to high pressure and low shear stress. In contrast, in native AoRs, similar conditions were present only during the short period of isovolemic contraction.

Numerical analysis of the 3-dimensional aortic root morphology during the cardiac cycle.

OBJECTIVES: The aim was to define the 3-dimensional (3D) geometrical changes of the aortic root and to determine the local shear stress profile of aortic root elements during the cardiac cycle. METHODS: Six sonomicrometric crystals (200 Hz) were implanted into the aortic root of five pigs at the commissures and at the aortic root base (AoB). 3D aortic root deformation including volume, torsion and tilt angle were determined. Geometrical data with measured local flow and pressure conditions was used for computed fluid dynamics modelling of the aortic root. RESULTS: Compared with end-diastole, the sinotubular junction and AoB have maximal expansion at peak ejection: 16.42 ± 6.36 and 7.60 ± 2.52%, and minimal at isovolaemic relaxation: 2.87 ± 1.62 and 1.85 ± 1.79%. Aortic root tilt and rotation angle were maximal at the end of diastole: 17.7 ± 8.8 and 21.2 ± 2.09°, and decreased to 15.24 ± 8.14 and 18.3 ± 0.1.94° at peak ejection. High shear stress >20 Pa was registered at peak ejection at coaptations, and during diastole at the superior two-thirds of the leaflets and intervalvular triangles (IVTs). The leaflet body, inferior one-third of the IVTs and valve nadir were exposed to moderate shear stress (8-16 Pa) during the cardiac cycle. CONCLUSIONS: Aortic root geometry demonstrates precise 3D changes of tilt and rotation angle. Reduction of angles during ejection results in a straight cylinder with low shear stress that facilitates the ejection; the increase during diastole results in a tilted frustum with elevated shear stress. Findings can be used for comparative analysis of native and synthetic structures with individual compliance.