Increased Lymphangiogenesis and Lymphangiogenic Growth Factor Expression in Perivascular Adipose Tissue of Patients with Coronary Artery Disease.

Experimental and human autopsy studies have associated adventitial lymphangiogenesis with atherosclerosis. An analysis of perivascular lymphangiogenesis in patients with coronary artery disease is lacking. Here, we examined lymphangiogenesis and its potential regulators in perivascular adipose tissue (PVAT) surrounding the heart (C-PVAT) and compared it with PVAT of the internal mammary artery (IMA-PVAT). Forty-six patients undergoing coronary artery bypass graft surgery were included. Perioperatively collected C-PVAT and IMA-PVAT were analyzed using histology, immunohistochemistry, real time PCR, and PVAT-conditioned medium using cytokine arrays. C-PVAT exhibited increased PECAM-1 (platelet endothelial cell adhesion molecule 1)-positive vessel density. The number of lymphatic vessels expressing lymphatic vessel endothelial hyaluronan receptor-1 or podoplanin was also elevated in C-PVAT and associated with higher inflammatory cell numbers, increased intercellular adhesion molecule 1 (ICAM1) expression, and fibrosis. Significantly higher expression of regulators of lymphangiogenesis such as vascular endothelial growth factor (VEGF)-C, VEGF-D, and VEGF receptor-3 was observed in C-PVAT compared to IMA-PVAT. Cytokine arrays identified angiopoietin-2 as more highly expressed in C-PVAT vs. IMA-PVAT. Findings were confirmed histologically and at the mRNA level. Stimulation of human lymphatic endothelial cells with recombinant angiopoietin-2 in combination with VEGF-C enhanced sprout formation. Our study shows that PVAT surrounding atherosclerotic arteries exhibits more extensive lymphangiogenesis, inflammation, and fibrosis compared to PVAT surrounding a non-diseased vessel, possibly due to local angiopoietin-2, VEGF-C, and VEGF-D overexpression.

A Multicenter Experience With a New Fenestrated-Branched Device for Endovascular Repair of Thoracoabdominal Aortic Aneurysms.

PURPOSE: To investigate the outcomes of patients who were treated for thoracoabdominal aortic aneurysms (TAAAs) using custom-made fenestrated-branched stent-grafts. METHODS: A consecutive series of 108 patients (mean age 73.5 years; 73 men) with TAAA were treated with E-xtra Design Engineering customized fenestrated-branched stent-grafts between November 2011 and January 2017. Data on baseline characteristics, procedures, and clinical follow-up were collected from 6 regional European surgical centers for retrospective analysis of endoleaks, reinterventions, and target vessel patency. The median aneurysm diameter was 6.75 cm (range 5.5-13). The distribution of the TAAA according to the modified Crawford classification of extent was 25 (24%) type I, 19 (17%) type II, 20 (18%) type III, 29 (27%) type IV, and 15 (14%) type V. RESULTS: Technical success was achieved in 95% (103/108) of cases. Major early perioperative complications occurred in 40 (37%) patients. The 30-day mortality was 9.2% (10/108), and perioperative spinal cord ischemia was observed in 6 (5.5%) patients [2 (1.8%) permanent]. During the mean follow-up of 17.6 months (range 3-52), 28 (26%) patients required late reintervention. Two patients died due to aneurysm- or procedure-related causes. The estimated survival rates at 1, 2, and 4 years were 87%, 84%, and 51%, respectively. The estimated target vessel patency rates at the same time points were 95%, 91%, and 90%, respectively. The freedom from reintervention estimates were 84% and 73% at 1 and 4 years, respectively. CONCLUSION: Endovascular repair of TAAA using Jotec customized fenestrated-branched stent-grafts appears to be safe and effective in the early to midterm. The considerable rate of secondary interventions indicates that further improvements, graft surveillance, and follow-up are required.

Adjunct Perfusion Branch for Reduction of Spinal Cord Ischemia in the Endovascular Repair of Thoracoabdominal Aortic Aneurysms.

BACKGROUND: To analyze utilization of a perfusion branch for temporary sac perfusion to reduce the spinal cord ischemia (SCI) in the endovascular repair of thoracoabdominal aortic aneurysms (TAAAs). METHODS: Between January 2012 and August 2016, 30 patients (18, men; median age 72 years) were treated for TAAAs with total endovascular repair using customized branched/fenestrated endografts in our institution. The median aneurysm size was 6.6 cm. Types of TAAA were: type I, 9 (30%), type II, 5 (16.6%), type III, 4 (13.3%), type IV, 6 (20%), and type V, 6 (20%). Ten patients received a perfusion branch to create an intentional endoleak, which was occluded with vascular plugs in mean interval time of 8.2 weeks (range: 6-10). Staged procedure and automated cerebrospinal fluid drainage were used in 23 (77%) and 24 (80%) patients, respectively. RESULTS: The technical success was 97%; 107 renovisceral target vessels were revascularized (32 fenestrations, 75 branches). At the time of the planned reinterventions, the mean arterial pressure (MAP) gradients were measured between the temporarily perfused aneurysm sac and the aortic endografts, and they were significantly higher (mean gradients 42.5 ± 10 mm Hg; range: 30-60) within the aortic grafts. The in-hospital and 30-day mortality was 3.3%. The incidence of postoperative SCI was 3/20 (15%) in the standard group and 0% in the group of the perfusion branch (p = 0.28). The mean follow-up was 12 months (range: 2-51). CONCLUSION: We experience that the use of a dedicated perfusion branch is feasible and may serve as protective adjunct to reduce the risk of SCI in endovascular treatment of TAAA. The risk of rupture in interval appears to be low. Larger series and multicenter studies are warranted to corroborate these results.

Three-Dimensional Analysis of Component Stability of the Nellix Endovascular Aneurysm Sealing System After Treatment of Infrarenal Abdominal Aortic Aneurysms.

PURPOSE: To assess short-term stability and conformational changes of the Nellix EndoVascular Aneurysm Sealing (EVAS) System using 3-dimensional (3D) analysis. METHODS: Postoperative computed tomography (CT) scans obtained at 0, 3, and 12 months in 24 patients (mean age 75±7 years; 22 men) who underwent EVAS between December 2013 and December 2014 for intact abdominal aortic aneurysm (within the instructions for use) were evaluated for stent-graft deviation in multiple planes using dedicated 3D analysis software. In addition, 2D analysis using an anatomically fixed reference landmark was performed to assess craniocaudal migration. Clinical and follow-up data of the patients were recorded and matched with results of the imaging analysis. RESULTS: Overall stability of the Nellix endografts was promising. Relevant conformational changes in the majority of cases were limited to the iliac graft segment and were clinically benign in all cases. Conversely, the only deviation of the proximal stent-graft segment was found in a patient with type Ia endoleak. Additional 2D analysis found relevant (≥5 mm) caudal migration of the Nellix stent-graft in 6 patients, including the one with the type Ia endoleak. In 3 patients, 3D analysis demonstrated the absence of relevant conformational changes of the endografts despite caudal migration. CONCLUSION: Overall stability of the separate EVAS stent-grafts is promising in the short term. Relevant conformational changes (stent-graft deviation) in the majority of cases were benign and confined to the iliac segment.

Endovascular Aneurysm Sealing (EVAS) and Chimney EVAS in the Treatment of Failed Endovascular Aneurysm Repairs.

PURPOSE: To assess the technical success and clinical outcome of reinterventions using the Nellix Endovascular Aneurysm Sealing (EVAS) System to treat complications after endovascular aneurysm repair (EVAR). METHODS: Fifteen consecutive patients (mean age 79 years; 14 men) with prior EVAR were treated with EVAS between March 2014 and December 2015 at 2 institutions. The failed prior EVARs included 13 bifurcated endografts, 1 bifurcated graft plus fenestrated cuff, and 1 tube endograft. Endoleaks were the predominant indications: type Ia in 10 and type III in 5 (3 type IIIa and 2 type IIIb). All patients presented with progressive aortic aneurysms (median 7.85-cm diameter; range 6.5-11). Eight patients were treated on an urgent or emergency basis (6 symptomatic aneurysms and 2 contained ruptures). All patients underwent Nellix relining of the failed stent-graft; 10 had chimney (Ch) procedures in combination with EVAS (chEVAS) because the proximal landing zones were inadequate. RESULTS: Technical success was 100%. All endoleaks were successfully sealed, and no additional intervention was required. No further endoleak after EVAS or chEVAS was recorded. Endobag protrusion occurred in 1 case without sequelae. One elderly patient with ruptured aneurysm died from multiple organ failure 2 months postoperatively. One renal artery guidewire injury led to nephrectomy because of active bleeding. No reinterventions, aneurysm-related mortalities, graft thrombosis, endoleaks, or chimney graft occlusions were observed during a median follow-up of 8 months (range 3-24). CONCLUSION: The present preliminary experience demonstrates that the use of EVAS/chEVAS is feasible for treatment of failed EVAR. This technique may be used as bailout or an alternative treatment when other established methods are infeasible or not available.

Treating iliac aneurysm using the Nellix Endovascular Sac Sealing System.

As endovascular treatment of abdominal aortic aneurysms has become established, there has been growing focus on treatment of the aneurysmal iliac artery. Isolated, large iliac aneurysms >30 mm pose a risk of rupture, but, in addition, 20% to 30% of abdominal aortic aneurysms are associated with iliac aneurysmal dilatation, which can compromise long-term outcomes. Endovascular solutions are evolving and until recently have utilized standard stent graft technology. The endovascular aortic sealing system was introduced as a new, effective method for the treatment of infrarenal aortic aneurysms. In this article, we present our recent extended use of the Nellix system, with or without a combination of adjuvant endovascular techniques, in the treatment of 84 common iliac artery aneurysms. The results support the use of endovascular aortic sealing system in endovascular therapy for aneurysmal iliac pathologies. Different endovascular sealing techniques for the treatment of common iliac artery aneurysms, re-interventions, and extended follow-up are also discussed.

Initial Experience in the Treatment of Extensive Iliac Artery Aneurysms With the Nellix Aneurysm Sealing System.

PURPOSE: To assess the feasibility and effectiveness of the Nellix prosthesis in the treatment of common iliac artery aneurysms. METHODS: Between May 2013 and June 2015, 230 patients underwent implantation of the Nellix device at 2 institutions. Fifty of these patients (mean age 76 years; 35 men) were identified as having 60 common iliac artery aneurysms (CIAAs) with a median diameter of 4 cm (range 3.5-7). The majority of patients had aortoiliac aneurysms (5, 70%), 10 (20%) had isolated CIAAs, and 5 (10%) had iliac anastomotic aneurysms after aortoiliac bypass. In 20 patients, the iliac aneurysm was the indication for the intervention; in the other 30 patients, the endovascular iliac repair was an adjunct procedure to endovascular aneurysm sealing (EVAS). An iliac branch device (IBD) was used when feasible to preserve flow to the internal iliac artery. RESULTS: Seventeen (34%) patients underwent elective implantation of the Nellix graft in combination with an IBD, 33 (66%) patients underwent Nellix sealing of the CIAA using 1 (n=5), 2 (n=22), or 3 Nellix grafts (2 bilateral grafts and 1 graft as an extension to the external iliac artery in 6 patients). The technical success rate was 100%, and no graft-related complications were reported postoperatively. No buttock claudication, reinterventions, graft thrombosis, or endoleaks were observed during a mean follow-up of 12 months. CONCLUSION: Our initial experience demonstrates that Nellix grafts are feasible and safe for the treatment of extensive iliac artery aneurysms. The long-term durability of these grafts should be validated in larger patient cohorts before this promising alternative endovascular technique can gain widespread acceptance.

Mortality in patients with acute aortic dissection type A: analysis of pre- and intraoperative risk factors from the German Registry for Acute Aortic Dissection Type A (GERAADA).

OBJECTIVES: Acute aortic dissection type A (AADA) is an emergency with excessive mortality if surgery is delayed. Knowledge about independent predictors of mortality on surgically treated AADA patients is scarce. Therefore, this study was conducted to identify pre- and intraoperative risk factors for death. METHODS: Between July 2006 and June 2010, 2137 surgically treated patients with AADA were enrolled in a multicentre, prospective German Registry for Acute Aortic Dissection type A (GERAADA), presenting perioperative status, operative strategies, postoperative outcomes and AADA-related risk factors for death. Multiple logistic regression analysis was performed to identify the influence of different parameters on 30-day mortality. RESULTS: Overall 30-day mortality (16.9%) increased with age [adjusted odds ratio (OR) = 1.121] and among patients who were comatose (adjusted OR = 3.501) or those who underwent cardiopulmonary resuscitation (adjusted OR = 3.751; all P < 0.0001). The higher the number of organs that were malperfused, the risk for death was (adjusted OR for one organ = 1.651, two organs = 2.440, three organs or more = 3.393, P < 0.0001). Mortality increased with longer operating times (total, cardiopulmonary bypass, cardiac ischaemia and circulatory arrest; all P < 0.02). Arterial cannulation site for extracorporeal circulation, operative techniques and arch interventions had no significant impact on 30-day mortality (all P > 0.1). No significant risk factors, but relevant increases in mortality, were determined in patients suffering from hemiparesis pre- and postoperatively (each P < 0.01), and in patients experiencing paraparesis after surgery (P < 0.02). CONCLUSIONS: GERAADA could detect significant disease- and surgery-related risk factors for death in AADA, influencing the outcome of surgically treated AADA patients. Comatose and resuscitated patients have the poorest outcome. Cannulation sites and operative techniques did not seem to affect mortality. Short operative times are associated with better outcomes.

Impact of previous cardiovascular surgery on postoperative morbidity and mortality after major pulmonary resection for non-small cell lung cancer.

PURPOSE: The aim of this study was to evaluate the impact of previous cardiovascular surgery on the postoperative morbidity and mortality following major pulmonary resection for non-small cell lung cancer (NSCLC). METHODS: Medical records of 227 patients, who underwent major pulmonary resection for NSCLC from 2003 to 2012 at our department, were reviewed retrospectively. Thirty-one patients with a mean age of 65.8 years had previous cardiovascular surgery (group A) including coronary artery revascularization in 11 patients, peripheral arterial revascularization in 6 patients, carotis endarterectomy in 9 patients, and combined coronary artery revascularization and carotis endarterectomy in 5 patients, whereas 167 patients (mean age = 62.0 years) had no cardiovascular comorbidity (group B). Twenty-nine patients with nonsurgically treated cardiovascular comorbidity were excluded from this study. RESULTS: There were no significant differences in overall postoperative morbidity (22.6 % in group A vs. 19.2 % in group B) and mortality (no mortality in group A vs. 2.4 % in group B) between both groups. CONCLUSIONS: Major pulmonary resections for NSCLC can be performed safely in patients with previous cardiovascular surgical history who are fulfilling the common cardiopulmonary criteria of operability. Operative risk in this subpopulation is comparable to that in patients without cardiovascular comorbidity.

How to do it: direct true lumen cannulation technique of the ascending aorta in acute aortic dissection type A.

In acute aortic dissection type A (AADA), direct true lumen cannulation (DTLC) of the ascending aorta is a fast and safe cannulation site providing antegrade perfusion of the supraaortic and visceral vessels. An Overholt clamp is passed around the ascending aorta to place a Mersilene tape for later securing of the arterial cannula. After draining venous blood into the cardiopulmonary bypass system (CPB), the ascending aorta is transected and the aortic lumen inspected. The true lumen is identified and an arterial cannula inserted directly. Finally, the cannula is secured with the previously placed tape and CPB is initiated. DTLC can be used as arterial cannulation standard technique in operations for AADA.

Postoperative non-invasive assessment of pulmonary vascular resistance using Doppler echocardiography.

Non-invasive monitoring of pulmonary vascular resistance (PVR) in postoperative cardiac surgery patients might be useful, particularly for management of pulmonary hypertension. For this purpose, we sought to assess Doppler echocardiography in the intensive care setting. In 73 patients, hemodynamics was measured using both, invasive gold standard (pulmonary artery catheter), and non-invasively by Doppler echocardiography. Four Doppler parameters: (1) tricuspid regurgitant velocity/time-velocity-integral of right ventricular outflow tract (TRV/VTI(RVOT)), (2) tricuspid annular systolic velocity (S'), (3) tricuspid annular strain, and (4) tricuspid annular strain rate, were compared with invasive PVR, using linear regression analysis and receiver-operating-characteristics. Patients without (n = 25, group 1) and patients with elevated left ventricular filling pressure (wedge pressure ≥ 15 mmHg, group 2, n = 48) were compared. Correlations were (1) R = 0.874, P < 0.0001, (2) R = -0.765, P < 0.0001, (3) R = 0.279, P = 0.009, (4) R = 0.378, P = 0.001. TRV/VTI(RVOT) showed prediction of PVR >300 dyn*s*/cm(5) (area-under-curve 0.975, cut-off 0.245, sensitivity 100%, specificity 91%). Strain correlated with PVR in group 2 patients only. TRV/VTI(RVOT) and tricuspid annular systolic velocity (S'), are useful for non-invasive monitoring of PVR in postoperative cardiac surgery patients with or without elevated left ventricular filling pressure. Strain may be used in patients with elevated filling pressure.

Wet-chemical approach for the cell-adhesive modification of polytetrafluoroethylene.

Polytetrafluoroethylene (PTFE), a frequently utilized polymer for the fabrication of synthetic vascular grafts, was surface-modified by means of a wet-chemical process. The inherently non-cell-adhesive polymer does not support cellular attachment, a prerequisite for the endothelialization of luminal surface grafts in small diameter applications. To impart the material with cell-adhesive properties a treatment with sodium-naphthalene provided a basis for the subsequent immobilization of the adhesion promoting RGD-peptide using a hydroxy- and amine-reactive crosslinker. Successful conjugation was shown with cell culture experiments which demonstrated excellent endothelial cell growth on the modified surfaces.

Successful management of fulminant pulmonary embolism using a novel portable extracorporeal life support system.

A 46-year-old man presented to the emergency room with pain in his left leg, dyspnea, and general cyanosis. During examination he collapsed and required resuscitation. Under suspicion of pulmonary embolism, a new portable "click 'n run" extracorporeal life support system (LIFEBRIDGE-B(2)T [Medizintechnik AG, Ampfing, Germany]) was implanted by the femoral vessels under resuscitation within 15 minutes of presentation. The patient was stabilized, despite severe decompensation (pH, 6.8), and could be transferred for a computed tomographic scan, which confirmed massive pulmonary embolism. Still connected to the life support system, the patient was transferred to the operating room. After a pulmonary thrombectomy was performed, the patient recovered without any organ dysfunction. A portable emergency extracorporeal life support may change clinical practice in the treatment of patients with severe hemodynamic deterioration at emergency care hospitals.

A minimally invasive approach for aortobifemoral bypass procedure.

Surgical aortobifemoral bypass procedure for aortoiliac occlusive disease remains the gold standard treatment despite rapidly expanding range of indications for endovascular repair. Besides several disadvantages such as dysparaesthesias, hernias, and unpleasant outcome, transperitoneal exposure of the aorta is also associated with operative autonomic nerve injury. In five male patients, infrarenal aorta was exposed through a small (8 cm) supraumbilical midline incision. Incision of the posterior peritoneum above the infrarenal aorta was limited to 3 cm. A 1 cm infraumbilical incision allowed transperitoneal placement of the distal aortic clamp outside of the operative field. Four centimeters transverse incisions were made over the femoral bifurcations and implantation of the aortobifemoral graft followed. Extubation was performed after an operating time of 200 to 150 minutes with 30 to 20 minutes aortic clamping time. Nonopioids or nonsteroidal anti-inflammatory drugs were intermittently administered during 12 hours of intermediate care unit monitoring. Oral alimentation started 6 hours and complete mobilization at 48 hours postoperatively. Hospital discharge followed on the fourth to tenth postoperative day. This minimally invasive technique allows a precise and controlled open performance of all vascular anastomoses minimizing intraoperative and postoperative complications and significantly decreasing patient discomfort related to standard abdominal surgery.

Liver transplantation and combined liver-heart transplantation in patients with familial amyloid polyneuropathy: a single-center experience.

Liver transplantation (LT) is the only curative option for patients with familial amyloid polyneuropathy (FAP) at present. Twenty patients with FAP underwent LT between May 1998 and June 2007. Transthyretin mutations included predominantly the Val30Met mutation but also 10 other mutations. Seven patients received a pacemaker prior to LT, and because of impairment of mechanical cardiac function, 4 combined heart-liver transplants were performed, 1 simultaneously and 3 sequentially. The first patient, who underwent simultaneous transplantation, died. Seven patients died after LT, with 5 dying within the first year after transplantation. The causes of death were cardiac complications (4 patients), infections (2 patients), and malnutrition (1 patient). One-year survival was 75.0%, and 5-year survival was 64.2%. Gly47Glu and Leu12Pro mutations showed an aggressive clinical manifestation: 2 patients with the Gly47Glu mutation, the youngest patients of all the non-Val30Met patients, suffered from severe cardiac symptoms leading to death despite LT. Two siblings with the Leu12Pro mutation, who presented only with grand mal seizures, died after LT because of sepsis. In conclusion, the clinical course in patients with FAP is very variable. Cardiac symptoms occurred predominantly in patients with non-Val30Met mutations and prompted combined heart-liver transplantation in 4 patients. Although early LT in Val30Met is indicated in order to halt the typical symptoms of polyneuropathy, additional complications occurring predominantly with other mutations may prevail and lead to life-threatening complications or a fatal outcome. Combined heart-liver transplantation should be considered in patients with restrictive cardiomyopathy.

Reevaluation of direct true lumen cannulation in surgery for acute type A aortic dissection.

BACKGROUND: The optimal mode of arterial cannulation in acute type A aortic dissection is controversial. We retrospectively investigated our experience with direct true lumen cannulation as an alternative to standard cannulation procedures. METHODS: From April 2004 to August 2007, 29 patients (20 men, 9 women; mean age of 63.2 +/- 12.6 years) underwent emergency operation for acute type A aortic dissection with direct true lumen cannulation. After venous drainage into the venous reservoir, the ascending aorta was completely transected in the region between the sinotubular junction and innominate artery. After visual and digital identification of the true lumen, the arterial cannula was directly inserted into the true lumen and secured with a ligature. RESULTS: Mean aortic cross-clamp time was 77.4 +/- 28.3 minutes, and hypothermic circulatory arrest for the distal anastomosis was 10.4 +/- 11.0 minutes. All patients survived the surgical procedure. No surgical problems were observed by applying this strategy. Mean intensive care unit stay was 4.0 +/- 3.5 days. Postoperative mean ventilation time was 43.3 +/- 41.3 hours. One patient had a prolonged postoperative course and required permanent ventilation. Two patients required temporary hemofiltration. Neurologic disorders occurred in 6 patients: 2 had severe cerebral hypoxia, and 4 had temporary hemiplegia under good regression. All patients were alive at discharge. CONCLUSIONS: Direct true lumen cannulation is a promising surgical strategy for emergency operations in type A aortic dissection. It is a simple, quick, and safe method to provide antegrade flow through the true aortic lumen.