Clinical Outcomes in Patients Treated With a Repositionable and Fully Retrievable Aortic Valve　- REPRISE Japan Study.

BACKGROUND: The REPRISE Japan study, a prospective multicenter single-arm trial, was undertaken to confirm the safety and effectiveness of transcatheter aortic valve replacement (TAVR) with the LOTUS valve in Japanese subjects with severe symptomatic calcific aortic stenosis at extreme or high surgical risk.Methods and Results:REPRISE Japan enrolled 40 subjects in the transfemoral (TF) cohort (mean age 84 years; mean [±SD] Society of Thoracic Surgeons [STS] score 6.4±2.9%); 10 additional subjects were treated with a transaortic (TAo) approach (mean age 84 years; mean STS score 6.3±3.3%). A subanalysis was also performed on subjects treated with the 21-mm LOTUS valve (n=15; mean age 84 years; mean STS score 5.3±2.1%). The primary safety endpoint (a composite of all-cause mortality, stroke, life-threatening or major bleeding events, acute kidney injury [Stage 2/3], and major vascular complications at 30 days) occurred in 15% of TF subjects. The primary effectiveness endpoint (a composite of all-cause mortality, disabling stroke, and moderate or greater paravalvular leak [PVL; core laboratory assessed] at 6 months) occurred in 5.3% of TF subjects. Across the TF, TAo, and 21-mm LOTUS valve cohorts, no subjects exhibited moderate or greater PVL at 6 months. The 30-day rate of pacemaker implantation was 22.5% in the TF cohort (TAo: 20%; 21 mm: 13.3%). CONCLUSIONS: Data from REPRISE Japan confirm the safety and efficacy of the LOTUS Valve when used in Japanese clinical practice.

Outcome of valve sparing root replacement for diverse indications.

OBJECTIVES: We report the mid-term outcomes of valve-sparing aortic root replacement (VSRR) in a cohort including patients with bicuspid aortic valve (BAV), connective tissue disorder (CTD), aortic dissection (AD), and congenital heart disease (CHD). Design. From 2005 to 2017, 174 patients underwent VSRR with the reimplantation technique. The mean age was 46 ± 14 years. The mean follow-up time was 4.8 ± 2.8 years. The indication for operation was aortic aneurysm for 127 (73%), aortic insufficiency (AI) for 38 (22%), and AD for 9 patients (5%). Preoperatively, 53 patients (31%) had ≥ moderate AI. BAV, CTD (Marfan or Loyes-Dietz), previous Ross procedure, or CHD was present in 57 (33%), 28 (16%), 7 (4%) and 12 patients (7%), respectively. Concomitant aortic valve repair was performed for 103 patients (59%). Results. Thirty-day mortality was zero. Four patients underwent aortic valve replacement (AVR) during follow-up. Kaplan-Meier estimates for survival, freedom from AVR, and freedom from ≥ moderate AI or reoperation were 96, 98, and 97% at 5 years. There was no difference in survival, freedom from AVR, or freedom from ≥ moderate AI or reoperation in patients with and without BAV, CTD, leaflet repair, or preoperative ≥ moderate AI. In Cox regression analysis, BAV, CTD, aortic valve repair, preoperative ≥ moderate AI, or aortic dimension were not risk factors for reoperation or valve dysfunction. Conclusions. Mid-term outcomes of VSRR for patients with diverse indications in terms of survival, reoperation rate, and valve dysfunction rate were excellent in a center with a limited annual volume of VSSR.

SOURCE 3 Registry: Design and 30-Day Results of the European Postapproval Registry of the Latest Generation of the SAPIEN 3 Transcatheter Heart Valve.

BACKGROUND: The SOURCE 3 Registry (SAPIEN Aortic Bioprosthesis European Outcome) is a European multicenter, observational registry of the latest generation of transcatheter heart valve, the SAPIEN 3 (Edwards Lifesciences, Irvine, CA). Its purpose is to document outcomes of clinical safety and performance after European approval was given. METHODS: Here, we present the 30-day outcome of the SOURCE 3 Registry. All data are self-reported, and all participating centers have committed to support their consecutive experience with the SAPIEN 3 transcatheter heart valve, dependent on patient consent, before the start of the study. Adverse events are defined with Valve Academic Research Consortium 2 criteria and adjudicated by an independent clinical events committee. RESULTS: A total of 1950 patients from 80 centers in 10 countries were enrolled between July 2014 and October 2015. Of those, 1947 patients underwent transcatheter aortic valve implantation (TAVI) with the SAPIEN 3 (mean age, 81.6±6.6 years; 48.1% female). Main comorbidities included coronary artery disease (51.5%), renal insufficiency (27.4%), diabetes mellitus (29.5%), chronic obstructive pulmonary disease (16.0%), and a mean logistic EuroSCORE of 18.3±13.2. Transfemoral access was used in 87.1% (n=1695); nontransfemoral, in 252 patients. Conscious sedation was used in 59.9% of transfemoral procedures, and in 50% of patients, TAVI was performed without aortic balloon valvuloplasty. Implantation success (1 valve in the intended location) was 98.3%. Conversion to conventional surgery (0.6%) and use of cardiopulmonary bypass (0.7%) were rare. Adverse events were low, with site-reported 30-day all-cause mortality of 2.2%, cardiovascular mortality of 1.1%, stroke of 1.4%, major vascular complications of 4.1%, life-threatening bleeding of 5%, and post-TAVI pacemaker implantation of 12%. Moderate or greater paravalvular regurgitation was observed in 3.1% of reporting patients. CONCLUSIONS: Results from the SOURCE 3 Registry demonstrate contemporary European trends and good outcomes of TAVI in daily practice when this third-generation TAVI device is used.

Early and midterm outcomes after endovascular treatment of degenerative aneurysms of the descending thoracic aorta: a Finnish multicenter study.

PURPOSE: To evaluate results of endovascular stent-graft placement for aneurysms of the descending aorta in 3 Finnish university hospitals during 1998-2010. METHODS: Among 158 consecutive patients treated with stent-graft placement for disease of the descending thoracic aorta, all 69 patients (58 men; mean age 71.7 years, range 54-90) with an aneurysm were included in the analysis. Medical records, radiological images, and national death records were collected and analyzed on an intention-to-treat basis. RESULTS: The 30-day mortality rate was 3.7% in 54 elective patients and 46.7% in 15 urgently treated acute patients. The paraparesis rate was 4.3%, and the major stroke rate was 4.3% after the operation. There were 4 aneurysm ruptures, all in the urgent group, two of whom had access failure. The other two died despite seemingly good initial results. The mean follow-up was 34.8±29 months. Two late ruptures occurred in patients who were lost to follow-up. In all, 12 type I (10 early, 2 late) and 1 late type III endoleaks were encountered in the observation period. CONCLUSION: Based on our findings, endovascular treatment of aneurysms of the descending aorta is relatively safe. To reduce the risk of postoperative complications, optimal preoperative imaging is mandatory. Postoperative regular imaging controls are indicated for early detection and prompt treatment of late type I or III endoleaks and to reduce the risk of late ruptures.

Thromboembolisms related to post-operative electrical cardioversions for atrial fibrillation in patients with surgical aortic valve replacement.

Aims: Post-operative atrial fibrillation (POAF) is a frequent complication after open-heart surgery, and cardioversions (CV) are commonly performed to restore sinus rhythm. However, little data exists on thrombo-embolic risk related to early post-operative CV and on the recurrence of POAF after CV. CAREAVR study sought to assess the rate of strokes, transient ischaemic attacks (TIA), and mortality shortly after POAF-triggered CV in patients who underwent isolated surgical aortic valve replacement (SAVR) with a bioprosthesis. Methods and results: Altogether 721 patients underwent isolated SAVR with a bioprosthesis at four Finnish university hospitals. During post-operative hospitalization, after patients with prior chronic AF were excluded, 309/634 (48.7%) of patients had at least one episode of POAF [median time (interquartile range) 3 (3) days], and an electrical CV was performed in 113/309 (36.6%) of them. The length of hospital stay was not affected by CV. At 30 days follow-up, the rate of stroke, TIA or mortality was higher in those AF patients who underwent CV vs. those who did not (9.7% vs. 3.6%, P = 0.04, respectively; adjusted hazard ratio 2.63, 95% confidence interval 1.00-6.92, P = 0.05). Similar proportion of patients in both groups were in AF rhythm at discharge (32.7% vs. 35.7%, P = 0.18); and at 3 months (25.0% vs. 23.6%, P = 0.40), respectively. Conclusion: In this real-world population of patients undergoing isolated SAVR, the rate of POAF was nearly 50%. One-third of these patients underwent an electrical CV, and they exhibited over two-fold risk for thromboembolisms and mortality. Cardioversion did not affect the short-term prevalence of AF.

Transcatheter aortic valve implantation in patients with small aortic annuli using a 20†mm balloon-expanding valve.

BACKGROUND: While transcatheter aortic valve implantation (TAVI) is established for treating high-operative risk surgical aortic valve replacement candidates, until recently the smallest transcatheter heart valve (THV) measured 23 mm, posing greater risk for annular rupture and THV failure in patients with aortic stenosis (AS) with small aortic annuli (≤20 mm). OBJECTIVES: In the setting of a multicentre registry, we report on the safety, efficacy and early clinical outcomes of the SAPIEN XT 20 mm balloon-expanding THV. RESULTS: Among TAVI 55 recipients (n=30 for native AS, n=25 for a valve-in-valve procedure (V-in-V)), median age and Society of Thoracic Surgeons score were 85 (81 to 87) years and 7.8 (4.7 to 12.4)%, respectively. Mean and minimum annular diameters were 19±1 and 17±2 mm, respectively, in native patients with AS, and 17±1 mm (internal diameter) in V-in-V recipients. Successful device implantation rate was 96%, with no procedural-related death. Overall in-hospital-30-day death, stroke and major bleeding rates were 5%, 2% and 9%, respectively. In native AS TAVI recipients, mean transaortic gradient decreased from 54±20 to 12±5 mm Hg (p<0.001), and from 45±17 to 24±8 mm Hg (p<0.001) in V-in-V recipients. Severe prosthesis-patient mismatch (PPM) rates were 10% and 48% in native AS and V-in-V TAVI recipients, respectively (p=0.03). Post-TAVI, the rate of moderate aortic regurgitation was 7% and 0% in native AS and V-in-V TAVI recipients, respectively. CONCLUSIONS: TAVI with the 20 mm SAPIEN XT THV appears safe and technically feasible, with acceptable short-term clinical outcomes and low rates of severe PPM in those with native AS.

Efficacy and safety of the Lotus Valve System for treatment of patients with severe aortic valve stenosis and intermediate surgical risk: Results from the Nordic Lotus-TAVR registry.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become an established therapeutic option for patients with symptomatic, severe aortic valve stenosis (AS) who are ineligible or at high risk for conventional valvular surgery. In Northwestern Europe, the TAVR technology is also increasingly used to treat patients with an intermediate risk profile. METHODS AND RESULTS: The study was designed as an independent Nordic multicenter registry of intermediate risk patients treated with the Lotus Valve System (Boston Scientific, MA, USA; N=154). Valve Academic Research Consortium (VARC)-defined device success was obtained in 97.4%. A Lotus Valve was successfully implanted in all patients. There was no valve migration, embolization, ectopic valve deployment, or TAV-in-TAV deployment. The VARC-defined combined safety rate at 30days was 92.2%, with a mortality rate of 1.9% and stroke rate of 3.2%. The clinical efficacy rate after 30days was 91.6% - only one patient had moderate aortic regurgitation. When considering only those patients in the late experience group (N=79), the combined safety and clinical efficacy rates were 93.7% and 92.4%, respectively. The pacemaker implantation rate was 27.9% - this rate was 12.8% in case of a combined implantation depth <4mm and a device/annulus ratio<1.05. CONCLUSIONS: The present study demonstrates the efficacy and safety of the repositionable, retrievable Lotus Valve System in intermediate risk patients with AS. The VARC-defined device success rate was 97.4% with a 30-day patient safety and clinical efficacy rate of more than 90%. Less than moderate aortic regurgitation was obtained in 99.4% of patients.

Expanding indications for valve-sparing aortic root reconstruction: early and midterm results.

BACKGROUND: Valve-sparing aortic root reconstruction (VSRR) is an accepted method to treat patients with aortic root dilation. The role of the VSRR is less well defined for patients with bicuspid aortic valve, severe aortic valve insufficiency, congenital heart defects, and type A aortic dissection. We studied the clinical outcome of patients who underwent VSRR for expanded indications. METHODS: Seventy-eight patients underwent VSRR between the 2005 and 2012. Seventy-two patients (92%) underwent reimplantation and 6 patients (8%) were operated on with the remodeling technique. The mean age was 51 ± 12 years (range 24 to 73). For 71 patients (91%), the operation was elective, and for 7 (9%; all with type A aortic dissection), on an emergency basis. Preoperatively, the degree of aortic insufficiency was graded as 2+ or greater for 27 patients (35%). Connective tissue disorder (Marfan or Loeys-Dietz), bicuspid aortic valve, or congenital heart disease was present in 15 (19%), 15 (19%), and 7 patients (9%), respectively. Concomitant aortic valve leaflet repair was performed for 39 patients (50%). The mean follow-up time was 2.4 ± 1.7 years (range, 0.1 to 7.0). RESULTS: Thirty-day mortality was zero. The rate of postoperative complications was low: stroke 3%, renal failure 3%, prosthesis infection 1%, and low cardiac output syndrome 1%. Survival was 100% at 1 year and 97% at 5 years. Freedom from recurrent aortic valve insufficiency (≥2+) during the follow-up was 94%. CONCLUSIONS: The midterm results of VSRR in terms of survival, freedom from recurrent aortic valve insufficiency, and the need for reoperation are excellent, even for high-risk patients.

Comparison of the novel Medtentia double helix mitral annuloplasty system with the Carpentier-Edwards Physio annuloplasty ring: morphological and functional long-term outcome in a mitral valve insufficiency sheep model.

BACKGROUND: The prevalence of mitral regurgitation in cardiac diseases requires annuloplasty systems that can be implanted without excessive patient burden. This study was designed to examine the morphological and functional outcome of a new double helix mitral annuloplasty ring in an ovine model in comparison to the classical Carpentier-Edwards (CE) annuloplasty ring as measured by reduction of mitral regurgitation and tissue integration. The Medtentia annuloplasty ring (MAR) is a helical device that is rotated into the annulus self-restoring the valve geometry, enabling a faster fixation without the need of elaborate repair of the valve geometry. The ventricular part of the helical ring encircles the valve chords. METHODS: Twenty adult sheep were overpaced until 2+ level mitral valve regurgitation was achieved. Seven animals per group received either the MAR or the CE ring. Implantation was performed on-pump in a beating heart through the left atrial appendix. The animals were sacrificed 3.6 ± 0.3 months after surgery following an echocardiography for assessing mitral regurgitation as primary endpoint. The annuloplasty rings with surrounding tissue were harvested for histological analyses as secondary endpoints. The remaining six sheep received the MAR system and were sampled seven, nine or 12 months after surgery. RESULTS: Implantation time (p < 0.01) and perfusion time (p < 0.001) as clinical secondary endpoints were significantly shorter in the MAR group. Echocardiography follow-ups showed sufficient valve function repair in nearly all animals with a normalization of the ventricle diameters in both groups (group difference: p = 0.147). The weights of the hearts did not differ significantly. Histology revealed adequately covered atrial annuloplasty rings with functional endothelium and lack of excessive granulation tissue or fibrosis in all specimens. The ventricular projections of the MAR systems encircling the chordae tendineae were not completely covered with neointimal tissue, although in no case were microthrombi detected and no thromboembolic events were recorded. CONCLUSIONS: The new MAR system is an easy to use annuloplasty system with a functional outcome comparable to that of the well-proven CE ring. Mitral valve regurgitation is effectively stopped both by restricting the pathological expansion of the annulus and by gathering the chords without thrombus formation.

Early clinical outcome of aortic transcatheter valve-in-valve implantation in the Nordic countries.

OBJECTIVE: Transcatheter valve-in-valve implantation has emerged as an option, in addition to reoperative surgical aortic valve replacement, to treat failed biologic heart valve substitutes. However, the clinical experience with this approach is still limited. We report the comprehensive experience of transcatheter valve-in-valve implantation in the Nordic countries from May 2008 to January 2012. METHODS: A total of 45 transcatheter aortic valve-in-valve implantations were performed during the study period in 11 centers. The mean age of the patients was 80.6 years (range, 61-91), 26 were male and 19 were female, and the mean EuroSCORE, EuroSCORE II, and Society of Thoracic Surgeons score was 35.4, 16.3, and 14.6, respectively. The type of failure was stenosis and combined in 58% (mean and peak aortic valve gradient, 77 and 45 mm Hg, respectively) and regurgitation in 42% of cases. The SAPIEN/XT (Edwards LifeSciences, Irvine, Calif) and CoreValve (Medtronic Inc, Minneapolis, Minn) system was used in 33 and 12 cases, respectively. The access route was transapical in 25, transfemoral in 17, transaortic in 2, and subclavian in 1 case. The mean follow-up was 14.4 months. The periprocedural and postoperative outcomes were assessed using the Valve Academic Research Consortium criteria. RESULTS: No intraprocedural mortality occurred. The technical success rate was 95.6% (1 second valve implantation, 1 conversion to open surgery). The all-cause 30-day mortality was 4.4% (1 cardiac-related and 1 aspiration pneumonia). The major complications within 30 days included stroke in 2.2%, periprocedural myocardial infarction in 4.4%, and major vascular complication in 2.2% of patients. At 1 month, all but 1 patient had either no or mild paravalvular leakage, with a mean and peak valve gradient of 17 mm Hg (range, 4-38) and 30 mm Hg (range, 7-68), respectively. The mean gradient was greater than 20 mm Hg in 17% of patients and remained unchanged at 12 months. The 1-year survival was 88.1%. CONCLUSIONS: Transcatheter valve-in-valve implantation is widely performed, albeit in small numbers, in most centers in the Nordic countries. The short-term results were excellent in this high-risk patient population, demonstrating a low incidence of device- or procedure-related complications. However, a considerable number of patients were left with suboptimal systolic valve performance with unknown long-term effects, warranting close surveillance after transcatheter valve-in-valve implantation.

Isolated gonococcal ascending aorta aneurysm.

We present a very rare case of an acute septic infection and vegetative mycotic aneurysm caused by Neisseria gonorrhoeae in a 52-year old male. The aortic valve was bicuspid and calcified. He was successfully treated by the resection of the ascending aorta and the aortic valve with a replacement by separate prostheses, followed by 2 weeks of intravenous antibiotic therapy. The patient was followed up 18 months postoperatively with no signs of reinfection.

Transaortic valve-in-valve implantation after previous aortic root homograft.

Catheter-based valve implantation techniques are becoming a viable option in various clinical situations to replace difficult redo open heart surgical procedures. This is a report of a first, to our knowledge, successful valve-in-valve (VinV) transcatheter aortic valve implantation (TAVI) into a homograft through the transaortic (TAo) access route using an Edwards SAPIEN valve prosthesis (Edwards Lifesciences, LLC, Irvine, CA) in a patient with poor left ventricular function and generalized severe atherosclerosis.

Clinical value of intra-operative transit-time flow measurement for coronary artery bypass grafting: a prospective angiography-controlled study.

OBJECTIVE: Transit-time flow measurement (TTFM) is the most widely used method for intra-operative graft quality control in coronary artery bypass surgery. Although it may provide the opportunity for the surgeon to promptly revise the graft before the patient is discharged from the operating room, controlled clinical data on the ultimate usefulness of the TTFM are scarce. Clear cut-off values for when to revise grafts have not been set. METHODS: A total of 204 consecutive grafts (left internal mammary artery (n=46), vein graft (n=155), and radial artery (n=3)) underwent TTFM in 75 elective coronary artery bypass grafting (CABG) patients. The following parameters were recorded: mean graft flow (MGF), pulsatility index (PI), and insufficiency ratio (IR). After a mean follow-up of 199 ± 42 days, coronary angiography was performed for assessment of graft patency. RESULTS: A total of 166 grafts were found to be patent (85%), and 29 (15%) were completely occluded. The median and interquartile range (IQR) of MGF for the occluded grafts at the time of surgery was 38 ml min(-1) (IQR, 2549 ml min(-1)) and for the patent grafts 45 ml min(-1) (IQR, 31-71 ml min(-1); p=ns]. The corresponding PI values were 3.3 (IQR, 2.8-5.0) and 2.2 (IQR, 1.7-3.2; p=0.003), and the IR values were 1.6 (IQR, 0.6-6.1) and 0.2 (IQR, 0-2.2; p=0.03). By receiver operating characteristic (ROC) analysis, the highest sensitivity (72%) and specificity (70%) were associated with a PI value>3.0. However, 49 out of 70 such grafts (70%) were found to be patent. Furthermore, 10 out of 16 (63%) grafts, that had a combination of low flow (MGF<15 ml min(-1)) and high PI (>3.0), were patent at control angiography. CONCLUSIONS: TTFM predicts graft failure within the 6 months after CABG. However, specific cut-off recommendations for when to revise a graft cannot be set on the basis of TTFM. The cut-off values suggested in the literature lead to unnecessary graft revisions in the majority of cases, and, on the other hand, many technical defects probably remain unnoticed. Better methods to assess the quality of coronary artery bypass grafts are needed.

A giant cavernous hemangioma of the heart.

Cardiac hemangiomas are exceptionally rare, vascular neoplasms of the heart, with an incidence of 1% to 2% among all detected benign heart tumors. With the availability of the advanced imaging modalities of the heart, asymptomatic cardiac tumors are detected more frequently. These tumors are composed either of capillaries or larger cavernous channels. Herein, we report a rare case of a huge cardiac hemangioma involving both ventricles, which is not amenable to a curative surgical resection.

Clinical outcomes of combined aortic root replacement with mitral valve surgery.

OBJECTIVE: This study was undertaken to examine the operative mortality and morbidity and late outcomes in patients who required combined aortic root replacement with mitral valve surgery. METHODS: These combined procedures were performed in 123 patients with a mean age of 51 +/- 16 years; 67% were men. The aortic root pathology was an aneurysm in 76 patients and other disorders in 47 patients. The mitral valve pathology was degenerative disease in 62 patients and other diseases in 61 patients. Sixty-four patients (52%) underwent previous cardiac surgery. The aortic valve was preserved in 21 patients, and the mitral valve was preserved in 67 patients; the remaining patients underwent valve replacement. In addition, 57 patients underwent other procedures. The mean follow-up was 4.9 +/- 4.3 years and complete. RESULTS: The operative mortality rate was 6.5% (8 patients), and late mortality was 9.7% (12 patients). Reexploration of the mediastinum for bleeding (15%) and implantation of permanent pacemaker (18%) were the most common postoperative complications. Urgent surgery and functional class IV were predictors of operative mortality by univariate analysis. Survival at 1, 5, and 10 years was 90.9% +/- 2.6%, 86.1% +/- 3.3%, and 79.3 +/- 4.9%, respectively. Six patients required reoperation. Freedom from reoperation at 1, 5, and 10 years was 100%, 96.4% +/- 2.5%, and 85.7% +/- 6.4%, respectively. At the latest follow-up, 98 patients were alive and free from reoperation; 92 patients were in functional classes 1 and 2, and 88 patients were free from any cardiac or valve-related complication. CONCLUSION: Aortic root replacement combined with mitral valve surgery is a complex operation associated with high morbidity, but the operative mortality is reasonably low and the long-term outcomes are gratifying.

Adjuvant arteriovenous fistula as means of rescue for infrapopliteal venous bypass with poor runoff.

OBJECTIVE: The aim of this study was to assess the outcome of infrapopliteal bypass when an adjuvant arteriovenous (AV) fistula was reconstructed as means of rescue as a result of poor runoff. The design was a retrospective multicenter case-control study. METHODS: Seventy-seven infrapopliteal vein bypasses required an adjuvant AV fistula among 1813 patients operated on for critical leg ischemia in 3 vascular centers between 1996 and 2003. The mean age was 74 years (range, 39-90 years). A total of 70% of the patients had diabetes, and 24% had undergone previous vascular surgery. In 25% of the bypasses, the distal anastomosis was in a crural artery, in 55% it was in the dorsal pedal artery, and in 20% it was in a plantar artery. An adjuvant AV fistula was reconstructed in all cases because of poor intraoperative arterial status, intraoperative angiography, or low intraoperative flow. A control group was retrieved that matched the study group according to the recipient artery and runoff score. RESULTS: The primary and secondary patency were 61% and 75%, respectively, at 1 year in the AV fistula group and 57% and 71% in the control group. The 3-year patency rates were 49% and 62% for the AV fistula group and 46% and 71% for the control group, respectively. There was a 76% leg-salvage rate at 3 years in the study group, compared with 87% in the control group. There were no major complications related to the AV fistula. Intraoperative flow was increased from a median of 20 mL/min to 115 mL/min by the AV fistula (P = .003). The graft flow was significantly higher in the AV fistula group than in the control group (P = .001). CONCLUSIONS: The adjuvant AV fistula increased graft flow significantly in a poor-outflow venous bypass. In this extreme patient group, acceptable patency and leg salvage was achieved without adverse effects. Despite this, the AV fistula did not improve the outcome.

Vascular endothelial growth factor C-induced collateral formation in a model of myocardial ischemia.

BACKGROUND: Besides being a known lymphangiogenic activator, vascular endothelial growth factor (VEGF)-C may express angiogenic potential by proteolytic cleavage and activation of endothelial cells. We assessed myocardial collateral formation and functional changes after adenovirus-mediated VEGF-C gene transfer in an ischemic porcine model. METHODS: Fifteen Landrace piglets underwent Ameroid-induced gradual occlusion of the left circumflex artery (LCx) and consequent progressive myocardial ischemia. Three weeks after Ameroid placement, the animals underwent gated 99mTc SPECT during rest and stress, in vivo angiography and 18FDG PET. Pigs were randomized to intramyocardial injections of adenoviruses encoding vascular endothelial growth factor (VEGF-C; n = 7) or control beta-galactosidase (LacZ; n = 5). Four weeks later, the examinations were repeated and histology was analyzed. RESULTS: Angiography showed significant progression of LCx stenosis in both groups during the treatment period. Left ventricular wall thickening (LVWT) at the LCx area in gated 99mTc SPECT remained unchanged in the VEGF-C group, indicating that VEGF-C prevented progression of myocardial ischemia, whereas LVWT deteriorated in the LacZ group (p = 0.042). Semi-quantitative assessment of 18FDG PET suggests more reduction in ischemia in the adVEGF-C group than in controls (p = 0.052). Angiography showed significant clustering of collaterals in the adVEGF-C gene transfer area compared that in LacZ (p = 0.004). von Willebrand factor staining revealed a significantly (p = 0.03) greater number of microvessels in the adVEGF-C-treated myocardium. CONCLUSIONS: This appears to be the first large-animal study in which, during progressive ischemia, functional and metabolic benefits of intramyocardial VEGF-C gene transfer were apparent. VEGF-C-induced collateral formation occurred at the site of gene transfer. The angiogenic potency of VEGF-C deserves further study as a therapeutic option.