Transcatheter aortic valve implantation for pure aortic insufficiency in a patient following David-type aortic valve-sparing root replacement after aortic dissection-A successful off-label procedure.

Transcatheter aortic valve implantation (TAVI) has traditionally been indicated for the treatment of aortic stenosis. However, in this case report, we describe a successful TAVI procedure in a 46-year-old male patient who had previously undergone David aortic valve-sparing aortic root replacement for type 1 aortic dissection. The patient presented with aortic valve insufficiency 4 years after the initial surgery and was subsequently treated with a 34 mm Medtronic CoreValve Evolut R prosthesis via TAVI. This case highlights the feasibility of TAVI as a viable treatment option for postoperative aortic valve insufficiency in patients with prior ascending aortic or aortic arch surgery.

Interventional versus Surgical Treatment of Degenerated Freestyle Prosthesis.

BACKGROUND: Bioprosthetic stentless aortic valves may degenerate over time and will require replacement. This study aimed to evaluate early- and mid-term outcomes after isolated surgical redo aortic valve replacement (redo-SAVR) and transcatheter valve-in-valve implantation (TAVI-VIV) for degenerated stentless Freestyle bioprostheses. METHODS: We reviewed records of 56 patients at a single center. Overall, 37 patients (66.1%) received TAVI-VIV and 19 (33.9%) received redo-SAVR. RESULTS: Thirty-day survival was similar in both groups (100%). One-year survival was comparable between groups (97.3% in TAVI-VIV and 100% in redo-SAVR, p = 1.0). The difference in mid-term survival after adjusting for age and EuroScore II was not significant (p = 0.41). The incidence of pacemaker implantation after TAVI-VIV was higher than after redo-SAVR (19.4% vs. 0%, p = 0.08). CONCLUSION: The 30-day and 1-year survival rates after both procedures were outstanding, irrespective of baseline characteristics. Isolated redo-SAVR should be favored in young patients, as the pacemaker implantation rate is lower. TAVI-VIV for degenerated Freestyle prosthesis can be a method of choice in elderly patients and those with high operative risk.

[Benefit of a Geriatric Evaluation before Operations, Interventions and Oncological Therapies]. / Nutzen altersmedizinischer Abklärungen vor Operationen, Interventionen und onkologischen Therapien.

Benefit of a Geriatric Evaluation before Operations, Interventions and Oncological Therapies Abstract: Older patients face an increased risk of complications and adverse outcomes during and after operations, interventions, and intense oncological therapies. At the same time, this patient group should not be excluded per se from potentially beneficial medical procedures based on chronological age alone. The timely identification of geriatric syndromes and increased vulnerability by means of comprehensive geriatric assessment is becoming increasingly important and is already recommended in the guidelines of professional societies of several medical disciplines. Nonetheless, the geriatric assessment should ideally be followed by proactive co-management in the sense of integrated care. The establishment of interdisciplinary and integrated care pathways for older hospital patients can contribute to significantly improved treatment outcomes. In addition to better patient-related outcomes and rising quality indicators, this approach may also offer positive health economic effects.

Valve-in-valve transcatheter aortic valve replacement in a young patient with a suspected COVID-19 infection: a surgical dilemma in the era of the COVID-19 pandemic.

We report on a case of a 57-year-old male patient, who underwent full root replacement in 2005 and now presented with high grade aortic insufficiency. On admission, the patient underwent a computed tomography scan which demonstrated interstitial infiltration in the left lung, highly suspicious for a COVID-19 infection that could not be confirmed by reverse transcription polymerase chain reaction (RT-PCR) testing. As there usually is a delay between infection and positive RT-PCR test results, the initial decision was to perform additional testing. However, the patient deteriorated quickly in spite of optimal medical therapy making urgent aortic valve replacement necessary. We decided to perform transcatheter aortic valve replacement to avoid cardiopulmonary bypass with shorter operative times, presumably shorter ventilation times and duration of intensive care unit stay, and thus a lesser risk for pulmonary complications.

Effects of pulsatile minimal invasive extracorporeal circulation on fibrinolysis and organ protection in adult cardiac surgery-a prospective randomized trial.

BACKGROUND: Minimal invasive extracorporeal circulation (MiECC) reduces the impact of cardiopulmonary bypass during cardiac surgery on inflammation and hemostasis. Pulsatile perfusion may enhance organ perfusion and help to prevent renal and neuronal damage. The present study investigated the impact of pulsatile MiECC in low-risk coronary artery bypass grafting (CABG) patients. METHODS: CABG patients were prospectively randomized for non-pulsatile (np: n=19) and pulsatile (p: n=21) MiECC. Blood and urine samples were collected at several time points until 72 h post-operative and analyzed for biochemical markers of fibrinolytic capacity, renal damage, and neuronal damage. RESULTS: Although intraoperative tissue plasminogen activator (tPA) levels tended to be higher in the p group, none of the fibrinolysis markers including plasminogen activator inhibitor (PAI-1) and the PAI-1/tPA ratio were significantly affected by pulsation. Hemolysis and markers of renal and neuronal damage were comparable between groups. Intraoperative urinary excretion [np: 400 mL (355 to 680) vs. p: 530 mL (360 to 900)] and cumulative 24 h volume intake [np: 7,090 mL (5,492 to 7,544) vs. p: 7,155 mL (6,682 to 8,710)] were increased by pulsation whereas blood losses up to 12 h post-operative [np: 365 mL (270 to 515) vs. p: 310 mL (225 to 470)] and up to 24 h post-operative [np: 760 mL (555 to 870) vs. p: 520 mL (460 to 670)] were attenuated. CONCLUSIONS: The present study did not find evidence for a beneficial effect of pulsation on markers of fibrinolysis, renal damage, and neuronal damage. However, pulsatile perfusion increased intraoperative urinary secretion and reduced post-operative blood losses.

First successful transcatheter double valve replacement from a transapical access and nine-month follow-up.

AIMS: While TAVI is the treatment of choice in patients with aortic stenosis considered inoperable or at high risk, interventional replacement of the mitral valve is still in the preclinical or early clinical phase. Our aim was to report on the first transcatheter double valve replacement into native valves from a transapical access. METHODS AND RESULTS: A 67-year-old, highly symptomatic female patient considered inoperable due to severe calcification of the mitral annulus and comorbidities was scheduled for transcatheter double valve replacement by the local Heart Team. Preoperative planning was carried out by multiplanar reconstruction from cardiac CT. Through a transapical access, the mitral valve was replaced first by an inverted 29 mm Edwards SAPIEN 3 prosthesis, then the aortic valve by a 23 mm SAPIEN 3, both during rapid pacing. Both prostheses revealed excellent function in angiography and echocardiography. The patient was extubated early after surgery and transferred to the normal ward the following day. After five months, she exhibited signs of cardiac failure again. Migration of the mitral prosthesis was detected, and the mitral valve was replaced surgically. CONCLUSIONS: Transcatheter double valve replacement can be performed through a transapical access. The key to success is thorough preoperative planning based on CT, not only for sizing, but also for estimating the anatomical relationship of the prostheses. However, late migration can be expected and may lead to LVOT obstruction.

The feasibility and safety of Algisyl-LVR™ as a method of left ventricular augmentation in patients with dilated cardiomyopathy: initial first in man clinical results.

BACKGROUND: A tissue engineering approach to augment the left ventricular wall has been suggested as a means to treat patients with advanced heart failure. This study evaluated the safety and feasibility of Algisyl-LVR™ as a method of left ventricular augmentation in patients with dilated cardiomyopathy undergoing open-heart surgery. METHODS AND RESULTS: Eleven male patients (aged 44 to 74years) with advanced heart failure (NYHA class 3 or 4), a left ventricular ejection fraction (LVEF) of <40% and requiring conventional heart surgery received Algisyl-LVR delivered into the LV myocardial free wall. Serial echocardiography, assessment of NYHA class, Kansas City Cardiomyopathy Questionnaire (KCCQ) and 24-hour Holter monitoring were obtained at baseline, days 3 and 8 (for echocardiography and Holter monitoring), and at 3, 6, 12, 18 and 24months. A total of 9 (81.8%) patients completed 24months of follow-up. Two patients withdrew consent after day 8 and at the 3month visit. Operative mortality was 0% (n=10 with 30day follow-up). There were no adverse events attributed to Algisyl-LVR. Mean LVEF improved from 27.1 (±7.3) % at screening to a mean LVEF of 34.8 (±18.6) % 24months post-discharge. Improvements of NYHA class were corroborated with improvements in KCCQ summary scores. Holter monitor data showed a significant decrease in the episodes of nonsustained ventricular tachycardia following administration of Algisyl-LVR. CONCLUSIONS: Administration of Algisyl-LVR to patients with advanced HF at the time of cardiac surgery is feasible and safe; warranting continued development of Algisyl-LVR as a potential therapy in patients with advanced HF.

Treatment of aortic stenosis with a self-expanding transcatheter valve: the International Multi-centre ADVANCE Study.

AIM: Transcatheter aortic valve implantation has become an alternative to surgery in higher risk patients with symptomatic aortic stenosis. The aim of the ADVANCE study was to evaluate outcomes following implantation of a self-expanding transcatheter aortic valve system in a fully monitored, multi-centre 'real-world' patient population in highly experienced centres. METHODS AND RESULTS: Patients with severe aortic stenosis at a higher surgical risk in whom implantation of the CoreValve System was decided by the Heart Team were included. Endpoints were a composite of major adverse cardiovascular and cerebrovascular events (MACCE; all-cause mortality, myocardial infarction, stroke, or reintervention) and mortality at 30 days and 1 year. Endpoint-related events were independently adjudicated based on Valve Academic Research Consortium definitions. A total of 1015 patients [mean logistic EuroSCORE 19.4 ± 12.3% [median (Q1,Q3), 16.0% (10.3, 25.3%)], age 81 ± 6 years] were enrolled. Implantation of the CoreValve System led to a significant improvement in haemodynamics and an increase in the effective aortic valve orifice area. At 30 days, the MACCE rate was 8.0% (95% CI: 6.3-9.7%), all-cause mortality was 4.5% (3.2-5.8%), cardiovascular mortality was 3.4% (2.3-4.6%), and the rate of stroke was 3.0% (2.0-4.1%). The life-threatening or disabling bleeding rate was 4.0% (2.8-6.3%). The 12-month rates of MACCE, all-cause mortality, cardiovascular mortality, and stroke were 21.2% (18.4-24.1%), 17.9% (15.2-20.5%), 11.7% (9.4-14.1%), and 4.5% (2.9-6.1%), respectively. The 12-month rates of all-cause mortality were 11.1, 16.5, and 23.6% among patients with a logistic EuroSCORE ≤10%, EuroSCORE 10-20%, and EuroSCORE >20% (P< 0.05), respectively. CONCLUSION: The ADVANCE study demonstrates the safety and effectiveness of the CoreValve System with low mortality and stroke rates in higher risk real-world patients with severe aortic stenosis.

Polymer-based restoration of left ventricular mechanics.

Heart failure continues to be a major health care concern with relatively few options for severely advanced heart failure patients. The hallmark of heart failure is the progressive dilatation of the left ventricle, thinning of the left ventricular wall leading to increased wall stress and increased myocardial oxygen consumption. Applying Laplace's law to the failing dilated ventricle, left ventricular augmentation utilizes a tissue engineering strategy to increase wall thickness and reduce chamber diameter, resulting in a decrease in wall stress and improved left ventricular function. A review of the rationale for an in situ tissue engineering approach for this treatment of heart failure and early clinical results of the Algisyl-LVR™ program are presented.

Selective automation and skill transfer in medical robotics: a demonstration on surgical knot-tying.

BACKGROUND: Transferring non-trivial human manipulation skills to robot systems is a challenging task. There have been a number of attempts to design research systems for skill transfer, but the level of the complexity of the actual skills transferable to the robot was rather limited, and delicate operations requiring a high dexterity and long action sequences with many sub-operations were impossible to transfer. METHODS: A novel approach to human-machine skill transfer for multi-arm robot systems is presented. The methodology capitalizes on the metaphor of 'scaffolded learning', which has gained widespread acceptance in psychology. The main idea is to formalize the superior knowledge of a teacher in a certain way to generate support for a trainee. In our case, the scaffolding is constituted by abstract patterns, which facilitate the structuring and segmentation of information during 'learning by demonstration'. The actual skill generalization is then based on simulating fluid dynamics. RESULTS: The approach has been successfully evaluated in the medical domain for the delicate task of automated knot-tying for suturing with standard surgical instruments and a realistic minimally invasive robotic surgery system.

Short- and mid-term safety and effectiveness of transcatheter aortic valve implantation in a failing surgical aortic bioprosthesis.

OBJECTIVES: The feasibility of transcatheter aortic valve implantation (TAVI) in patients with a failing surgical aortic bioprosthesis has been reported from single centres. We present results from a multi-centre feasibility study in such patients followed for 1 year after TAVI. METHODS: This study evaluated 18 patients undergoing implantation with the 18-Fr CoreValve TAVI prosthesis in a failing surgical aortic bioprosthesis at three centres in Germany. Subject inclusion requirements included ≥ 75 years old and either surgical risk with logistic European System for Cardiac Operative Risk Evaluation ≥ 15% or ≥ 1 high-risk co-morbidity. RESULTS: Implanted subjects were 79 ± 4 years old, 67% males, 78% NYHA Class III/IV, with logistic EuroSCORE 34 ± 14, and had failed surgical bioprostheses from six manufacturers. The procedure was considered technically successful in 94% (17/18) of cases. One subject was converted to surgery during the procedure. Mortality at 30 days and 1 year was 11% (2/18) and 28% (5/18), respectively. Two cardiac deaths occurred, including 1 within 30 days. Two subjects had strokes, both within 30 days. After 30 days and 1 year, respectively, 86 and 73% of subjects improved at least 1 NYHA class and the remainder had no change. No aortic regurgitation was reported beyond mild (Grade 1) at 6- and 12-month follow-up. CONCLUSIONS: Most patients with a failing aortic surgical bioprosthesis were successfully implanted with a TAVI prosthesis in this multi-centre feasibility study. Outcomes at 30 days were within expectations for this very high-risk subgroup and improvements were sustained through 12 months.

Preserved autonomic regulation in patients undergoing transcatheter aortic valve implantation (TAVI): a prospective, comparative study.

Heart rate and blood pressure variability as well as baroreflex sensitivity (BRS) lead to additional insights on the patients' prognosis after cardiovascular events. The following study was performed to assess the differences in the postoperative recovery of the autonomic regulation after transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR). Fifty-eight consecutive patients were enrolled in a prospective study; 24 underwent TAVI and 34 SAVR. BRS was calculated according to the Dual Sequence Method, heart rate variability (HRV) was evaluated using standard linear as well as nonlinear parameters. HRV and BRS parameters were reduced after surgery in patients with SAVR only (meanNN: p<0.001, sdNN: p<0.05, Shannon: p<0.01, BRS: p<0.01), while these indexes were preserved in patients after TAVI. Simultaneously, an increased complexity of blood pressure (BP) in SAVR patients (fwShannon: p<0.001, fwRenyi4: p<0.001), but not in TAVI patients was recorded. In this study we were able to demonstrate for the first time that, in contrast to patients undergoing conventional open surgery, there are fewer alterations of the cardiovascular autonomic system in patients with TAVI.

Long-term performance of the Hancock bioprosthetic valved conduit in the aortic root position.

BACKGROUND AND AIM OF THE STUDY: The study aim was to assess long-term morbidity and mortality with special regard to prosthesis durability after aortic root replacement with the Hancock bioprosthetic porcine conduit. METHODS: Between 1975 and 2004, a total of 81 patients (55 males, 26 females; mean age 58 +/- 18 years) underwent aortic root replacement with the Hancock conduit for aortic dissection (n = 22; 27%), ascending aortic aneurysm (n = 57; 70%), or porcelain aorta (n = 2; 3%). Twenty-five patients (31%) underwent an emergency operation, 12 (15%) presented with Marfan syndrome, and eight (10%) had undergone previous cardiac surgery. Concomitant procedures were performed in 26 cases (32%). The follow up was 98% complete; the mean follow up was 4.8 +/- 4.0 years (range: 1 day to 16.7 years), and the cumulative follow up was 403 patient-years. Actuarial event-free rates were calculated, and valve-related complications classified according to guidelines for reporting morbidity and mortality after cardiac valvular operations. RESULTS: There were seven (9%) operative deaths and four (5%) in-hospital deaths. Actuarial survival rates at five and 10 years (excluding operative deaths) were 77.0 +/- 5.3% and 54.0 +/- 7.5%, respectively. Actuarial freedom from aortic valve reoperation at five and 10 years was 98 +/- 1.6% and 64 +/- 10.2%, from structural valve deterioration 88.1 +/- 4.7% and 49.9 +/- 9.6%, from thromboembolic events 87.4 +/- 4.6% and 75.1 +/- 9.5%, and from major bleeding events 90.2 +/- 3.9% and 75.4 +/- 8.1%, respectively. Among redo procedures, the stentless Hancock valve could be excised without separating the synthetic graft from the left ventricular outflow tract, and a stented valve prosthesis thus implanted. Hence, it was possible to avoid a second Bentall operation. CONCLUSION: The long-term survival rates after aortic root replacement with the bioprosthetic Hancock conduit were reasonable for this demanding patient cohort. However, the durability of the prosthesis was inferior to that reported for the stented Hancock valve substitute. The key benefit of this bioprosthetic valved conduit was the simplified redo procedure.

Tumor necrosis factor-α -863 C/A promoter polymorphism affects the inflammatory response after cardiac surgery.

OBJECTIVE: Cardiac surgery using cardiopulmonary bypass (CPB) initiates an inflammatory response that shows a wide inter-individual range and determines postoperative morbidity. Previous research suggests that genetic diversity contributes to individual susceptibility to perioperative trauma and stress. Nevertheless, the genetic triggering of the tumor necrosis factor-alpha (TNF-α) release remains unclear. We tested two genetic single-nucleotide polymorphisms (SNPs) from the promoter region of the TNF-α gene for associations with perioperative TNF-α level after CPB. METHODS: We prospectively included 122 patients, who underwent elective coronary artery bypass grafting (CABG). Patients were genotyped for TNF-α -863 C/A (rs1800630) and TNF-α -308 G/A (rs1800629). Plasma level of TNF-α was obtained preoperatively, at the end of CPB, 6h postoperatively, and on the first postoperative day (POD). RESULTS: Demographic characteristics and operative data revealed no significant differences between the different genotypes. Multiple linear regression analyses revealed significant associations for the TNF-α 863 C/A polymorphism: the major -863 CC variant was associated with higher TNF-α level preoperatively (p = 0.003), after CPB (p = 0.005), and 6h postoperatively (p = 0.010), independently from CPB time, left ventricle (LV) function and age. Contrarily, the AA allele had lower TNF-α level preoperatively (p = 0.008), after surgery (p = 0.024) and 6h postoperatively (p = 0.001). For the TNF-α 308 G/A polymorphism, only few significant associations could be observed: -308 GG carriers were associated with lower TNF-α level immediately after CPB (p = 0.020), whereas 308 AA carriers were significantly associated with elevated TNF-α level preoperatively (p = 0.032) and immediately after CPB (p = 0.05). No heterozygote variant of both SNPs revealed any significant associations with perioperative TNF-α level. CONCLUSIONS: The current study suggests that the major -863 CC variant determines elevated TNF-α level preoperatively and throughout the postoperative course after CPB.

Incidence and treatment of procedural cardiovascular complications associated with trans-arterial and trans-apical interventional aortic valve implantation in 412 consecutive patients.

OBJECTIVE: Trans-catheter aortic valve implantation (TAVI) technology is rapidly evolving, with 412 procedures having been performed at our institution. Herein, we report a complete, prospective analysis of complications occurring during transvascular and trans-apical implantations with two different prostheses. METHODS: Between June 2007 and June 2010, 412 patients (258 female, mean age 80.3±7.2 years, logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) 20.2%±13.0%) underwent TAVI through either a retrograde (n=252 transfemoral, n=28 transaxillary, and n=5 transaortic) or antegrade (n=127 trans-apical) approach at our institution. The trans-apical access was chosen only in cases where transvascular implantation was not possible. As many as 283 CoreValve and 129 Edwards Sapien prostheses were implanted. RESULTS: Thirty-day survival was 90.9%. Vascular complications occurred in 42 patients (10.2%). In four patients, lethal aortic root (n=3) or abdominal (n=1) aortic rupture occurred. Pericardial effusion developed in 53 patients (12.8%), which resulted in cardiac tamponade in 12 patients (2.9%). Twenty-three patients (5.6%) with valve malplacement were treated interventionally. In five patients (1.2%), emergency institution of cardiopulmonary bypass was required during the procedure for temporary support; all patients survived. Seventeen patients underwent re-intervention on the catheter valve (4.1%). CONCLUSIONS: With growing experience, complications with TAVI may be avoided by proper patient selection and skillful management. Other complications, when they occur, require a specific treatment algorithm to avoid delay in decision making. A considerable number of complications after TAVI require surgical treatment. Therefore, the ideal environment for TAVI procedures is a hybrid operating room, where a multidisciplinary team of surgeons, cardiologists, and anesthesiologists is best fitted to meet the current needs associated with TAVI technology. A reduction in complications was seen after 300 cases. This finding attests to the complexity of the procedure in addition to the experience required to reduce the incidence of complications.

Twenty years of cardiac surgery in patients aged 80 years and older: risks and benefits.

BACKGROUND: Patients aged 80 years and older who require cardiac surgical procedures are an increasing population and usually present with considerable comorbidity. Detailed operative risk stratification versus long-term survival and quality of life after surgery is mandatory. METHODS: A retrospective analysis was performed on 1,003 patients aged 82.3 years (range, 80 to 94 years) who underwent aortic valve replacement (n = 303), coronary artery bypass grafting (n = 403), or aortic valve replacement with coronary artery bypass grafting (n = 297) between 1987 and 2006. Preoperative data, operative outcome, long-term survival, and predictors for early and late mortality were analyzed. Furthermore, the Short Form 36 Health Status questionnaire was used to evaluate the quality of life. RESULTS: Overall in-hospital mortality was 7.1%. Overall actuarial survival at 1, 5, and 10 years was 81.6% ± 1.2%, 60.4% ± 1.9%, and 23.3% ± 2.6% (mean survival time, 6.25 ± 0.2 years) and showed no significant difference compared with an age- and sex-matched general population. Multivariate analysis showed that preoperative creatinine concentration greater than 1.3 mg/dL (p < 0.001), preoperative atrial fibrillation (p < 0.005), and postoperative prolonged ventilation (p < 0.001) were independent predictors for poor long-term survival. The physical health summarized score of the Short Form 36 Health Status questionnaire was significantly increased in the study population compared with a German standard population aged 80 years and older (p < 0.05). CONCLUSIONS: Despite an increased operative mortality, octogenarians showed a considerable quality of life and an excellent long-term survival. To further improve surgical outcome in octogenarians, patient selection should be done with consideration of the identified independent preoperative risk factors.

Apical-access-related complications associated with trans-catheter aortic valve implantation.

OBJECTIVE: The left-ventricular trans-apical access has become well established for trans-catheter aortic valve implantation, especially for patients in whom a retrograde trans-arterial implantation is contraindicated. We report on the short- and long-term implications of the apical-access-site-specific complications. METHODS: Between June 2007 and August 2010, 143 patients were scheduled for trans-apical aortic valve implantation (mean age 80 ± 6 years, n=116 females, mean logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) 21 ± 13%). The patients are followed up at 30 days, 6 months, and then annually. RESULTS: Severe apical bleeding complications occurred in 10 patients (7%). In three of these patients, the procedure was terminated, and no valve was implanted. In the remaining, the bleeding was controlled with cardiopulmonary bypass support (n=3), via median sternotomy (n=1), or both (n=1) ± later re-exploration. Two additional patients required postprocedural re-exploration for apical bleeding. An apical pseudo-aneurysm developed in two patients (2%), one of whom was treated by surgical revision. Survival was significantly impaired when either apical bleeding, aneurysm, or re-exploration occurred (75% ± 0.082 survival at 30 days and 59% ± 0.122 at 1 year vs 94% ± 0.023 and 80% ± 0.043 in patients without apical complications, p=0.012). Twelve patients (8%) experienced secondary wound healing. An apical hypo- or akinesia was detected in 18/54 (33%) patients at 6 months' echocardiographic investigation, and in 11/30 (37%) 1 year after the procedure. CONCLUSIONS: The trans-apical access for trans-catheter aortic valve implantation might be challenging in elderly patients with fragile tissue. Severe bleeding complications or aneurysm formation significantly impairs survival. The clinical impact of subsequent apical hypo- or akinesia has to be further followed up.

Identification of an up-regulated anti-apoptotic network in the internal thoracic artery.

BACKGROUND: The radial artery (RA) is known as an atherosclerosis-prone vessel in contrast to the atherosclerosis-resistant internal thoracic artery (ITA). The purpose of the present study was to compare the gene expression profile of these arteries from the same patient in order to identify genes involved in atherogenesis or intimal hyperplasia. METHODS: Paired specimens of RA and ITA (n=6) were analyzed by histomorphometry and whole genome microarray. The microarray data underwent pathway analysis to identify biological networks. Laser microdissection (LMD) was used to identify the cellular expression of candidate genes in the intimal or medial layer of the ITA and RA. RESULTS: Histomorphometric analyses revealed a significantly higher degree of intimal hyperplasia in the RA compared to the ITA. 552 genes were differentially expressed in the ITA and RA. qRT-PCR confirmed a significant up-regulation of six anti-apoptotic genes. p21 (11.8-fold, p=0.011), CCL2 (5.4-fold, p=0.034), SOCS3 (7.2-fold, p=0.002), IER3 (4.1-fold, p=0.048), MCL-1 (2.6-fold, p=0.025) and IL-6 (17.8-fold, p=0.046) were up-regulated in the ITA. LMD confirmed that cells of the intimal layer of the ITA consistently expressed higher levels of all six candidate genes than those of the RA. CONCLUSIONS: Microarray analysis and qRT-PCR identified significantly up-regulated genes in the ITA involved in an anti-apoptotic network. LMD revealed a higher expression of all anti-apoptotic genes in the intimal area of the ITA. These genes may play an important role in protecting the intima of the ITA from developing hyperplasia and atherosclerosis.

Incidence and management of CoreValve dislocation during transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation is a highly specialized technique offering a new therapeutic option to patients at high risk for conventional surgery. Complications associated with this catheter procedure differ from complications after surgical aortic valve replacement. This is to report incidence, management, and impact on morbidity and mortality of CoreValve dislocation during catheter valve implantation. METHODS AND RESULTS: Between June 2007 and September 2009, the self-expandable CoreValve prosthesis (Medtronic Inc, Minneapolis, Minn) was implanted in 212 patients through a transarterial (femoral or subclavian) access. Patients with severe aortic stenosis who were at high risk for conventional surgery were included. We observed dislocation of the prosthesis during CoreValve implantation in 21 patients. In 16 cases, the CoreValve could be implanted in the correct annular position after retrieving it and reloading the catheter. In 4 patients, the completely deployed prosthesis had to be placed in the ascending or abdominal aorta before implanting a second one. One patient underwent open surgery. Overall 30-day mortality was 11.0%, 21.5% in the dislocation group and 9.9% in patients without dislocation (P=0.024). Coronary ischemia, stroke, and renal failure occurred more frequently in patients with dislocation, whereas pacemaker dependency did not differ significantly between the groups. CONCLUSIONS: CoreValve dislocation during transcatheter aortic valve implantation occurred in 10% of the cases and significantly increases perioperative risk for severe complications or death. It requires individual specific management and can be managed either interventionally or, rarely, results in open surgery.