ß-adrenergic stimulation augments transmural dispersion of repolarization via modulation of delayed rectifier currents IKs and IKr in the human ventricle.

Long QT syndrome (LQTS) is an inherited or drug induced condition associated with delayed repolarization and sudden cardiac death. The cardiac potassium channel, IKr, and the adrenergic-sensitive cardiac potassium current, IKs, are two primary contributors to cardiac repolarization. This study aimed to elucidate the role of ß-adrenergic (ß-AR) stimulation in mediating the contributions of IKr and IKs to repolarizing the human left ventricle (n = 18). Optical mapping was used to measure action potential durations (APDs) in the presence of the IKs blocker JNJ-303 and the IKr blocker E-4031. We found that JNJ-303 alone did not increase APD. However, under isoprenaline (ISO), both the application of JNJ-303 and additional E-4031 significantly increased APD. With JNJ-303, ISO decreased APD significantly more in the epicardium as compared to the endocardium, with subsequent application E-4031 increasing mid- and endocardial APD80 more significantly than in the epicardium. We found that ß-AR stimulation significantly augmented the effect of IKs blocker JNJ-303, in contrast to the reduced effect of IKr blocker E-4031. We also observed synergistic augmentation of transmural repolarization gradient by the combination of ISO and E-4031. Our results suggest ß-AR-mediated increase of transmural dispersion of repolarization, which could pose arrhythmogenic risk in LQTS patients.

Long-term follow-up of fenestrated endovascular repair for juxtarenal aortic aneurysm.

BACKGROUND: Fenestrated endovascular aneurysm repair (FEVAR) is increasingly being used for juxtarenal aortic aneurysms. The aim of this study was to review long-term results and assess the importance of changing stent-graft design on outcomes. METHODS: This was a retrospective review of all patients who underwent FEVAR within a single unit over 12 years (February 2003 to December 2015). Kaplan-Meier analysis of survival, and freedom from target vessel loss, aneurysm expansion, graft-related endoleak and secondary intervention was performed. Comparison between outcomes of less complex grafts (fewer than 3 fenestrations) and more complex grafts (3 or 4 fenestrations) was undertaken. RESULTS: Some 173 patients underwent FEVAR; median age was 76 (i.q.r. 70-79) years and 90·2 per cent were men. Median aneurysm diameter was 63 (59-71) mm and median follow-up was 34 (16-50) months. The adjusted primary technical operative success rate was 95·4 per cent. The in-hospital mortality rate was 5·2 per cent; there was no known aneurysm-related death during follow-up. Median survival was 7·1 (95 per cent c.i. 5·2 to 8·1) years and overall survival was 60·1 per cent (104 of 173). There was a trend towards an increasing number of fenestrations in the graft design over time. In-hospital mortality appeared higher when more complex stent-grafts were used (8 versus 2 per cent for stent-grafts with 3-4 versus fewer than 3 fenestrations; P = 0·059). Graft-related endoleaks were more common following deployment of stent-grafts with three or four fenestrations (12 of 90 versus 6 of 83; P < 0·001). CONCLUSION: Fenestrated endovascular aneurysm repair for juxtarenal aneurysm is associated with few aneurysm-related deaths in the long term. Significant numbers of secondary interventions are required, but the majority of these can be performed using an endovascular approach.

Technical advances in studying cardiac electrophysiology - Role of rabbit models.

Cardiovascular research has made a major contribution to an unprecedented 10 year increase in life expectancy during the last 50 years: most of this increase due to a decline in mortality from heart disease and stroke. The majority of the basic cardiovascular science discoveries, which have led to this impressive extension of human life, came from investigations conducted in various small and large animal models, ranging from mouse to pig. The small animal models are currently popular because they are amenable to genetic engineering and are relatively inexpensive. The large animal models are favored at the translational stage of the investigation, as they are anatomically and physiologically more proximal to humans, and can be implanted with various devices; however, they are expensive and less amenable to genetic manipulations. With the advent of CRISPR genetic engineering technology and the advances in implantable bioelectronics, the large animal models will continue to advance. The rabbit model is particularly poised to become one of the most popular among the animal models that recapitulate human heart diseases. Here we review an array of the rabbit models of atrial and ventricular arrhythmias, as well as a range of the imaging and device technologies enabling these investigations.

Arrhythmogenic and metabolic remodelling of failing human heart.

Heart failure (HF) is a major cause of morbidity and mortality worldwide. The global burden of HF continues to rise, with prevalence rates estimated at 1-2% and incidence approaching 5-10 per 1000 persons annually. The complex pathophysiology of HF impacts virtually all aspects of normal cardiac function - from structure and mechanics to metabolism and electrophysiology - leading to impaired mechanical contraction and sudden cardiac death. Pharmacotherapy and device therapy are the primary methods of treating HF, but neither is able to stop or reverse disease progression. Thus, there is an acute need to translate basic research into improved HF therapy. Animal model investigations are a critical component of HF research. However, the translation from cellular and animal models to the bedside is hampered by significant differences between species and among physiological scales. Our studies over the last 8 years show that hypotheses generated in animal models need to be validated in human in vitro models. Importantly, however, human heart investigations can establish translational platforms for safety and efficacy studies before embarking on costly and risky clinical trials. This review summarizes recent developments in human HF investigations of electrophysiology remodelling, metabolic remodelling, and ß-adrenergic remodelling and discusses promising new technologies for HF research.

Patch variability following carotid endarterectomy: a survey of Great Britain and Ireland.

INTRODUCTION: Evidence suggests a clinical benefit with patch angioplasty after carotid endarterectomy (CEA). The UK National Vascular Database has demonstrated variation in practice but does not record technical details. This study was intended to define indications and technique of patching after CEA. METHODS: An electronic questionnaire was emailed to all 402 members of the Vascular Society of Great Britain and Ireland. The email could not be received by 23 and 14 did not perform CEA. Some questions allowed multiple answers. Fisher's exact test was used for statistical analysis. RESULTS: There were 187 responses (51%). Fifteen members (8%) performed eversion CEA, which obviates patching. Of all the respondents, 121 surgeons (65%) always use a patch. Seventy of these (58%) use the full patch width (median: 8 mm, range: 4-10 mm). Fourteen (12%) variably trimmed the patch (median: 7.5 mm, range: 5-10 mm) and 34 (28%) routinely trimmed (median: 6 mm, range: 3-20 mm). Selective patching, dependent on internal carotid artery diameter, was performed by 48 respondents (26%), 23 of whom specified a median artery threshold diameter of 5 mm (range: 3-8 mm). General anaesthesia was always or usually used by 83 surgeons (45%), local anaesthesia by 77 (41%) and the remainder followed patient choice. Obligatory patching is performed by 68 of the 83 respondents (82%) who prefer general anaesthesia whereas only 40 of the 77 surgeons (52%) who use local anaesthesia always patch (p<0.0001). CONCLUSIONS: There is a variable rate of patching after CEA in the UK, which appears dependent on the vessel size and mode of anaesthesia. There are also differences in the patch width adopted.

Anchoring barbs and balloon expandable stents: what is the risk of perforation and failed stent deployment?

PURPOSE: Balloon expandable stents may on occasion be deployed in close proximity to the anchoring barbs of endovascular grafts. The aim of this study was to determine the risk and effect of balloon perforation by anchoring barbs and to assess whether these risks are different if the balloon is protected by a covered stent mounted upon it. METHODS: A bench-top model was developed to mimic the penetration of anchoring barbs into the lumen of medium sized blood vessels. The model allowed variation of angle and depth of vessel penetration. Both bare balloons and those with covered stents mounted upon them were tested in the model to determine whether there was a risk of perforation and which factors increased or decreased this risk. RESULTS: All combinations of barb angle and depth caused balloon perforation but this was most marked when the barb was placed perpendicular to the long axis of the balloon. When the deployment of covered stents was attempted balloon perforation occurred in some cases but full stent deployment was achieved in all cases where the perforation was in the portion of the balloon covered by the stent. The only situation in which stent deployment failed was where the barb was intentionally placed in the uncovered portion of the balloon. This resulted in only partial deployment of the stent. CONCLUSIONS: Balloon rupture is a distinct possibility when deploying balloon-expandable stents in close proximity to anchoring barbs. Care should be taken in this circumstance to ensure that the barb is well away from the uncovered portion of the balloon.

Surveillance after EVAR based on duplex ultrasound and abdominal radiography.

INTRODUCTION: Computed tomography angiography (CTA) is considered the gold standard imaging technique for surveillance following endovascular aneurysm repair (EVAR). Limitations of CTA include cost, risk of contrast nephropathy and radiation exposure. A modified surveillance protocol involving annual duplex ultrasound (DUS) and abdominal radiography (AXR) was introduced, with CTA performed only if abnormalities were identified or DUS was undiagnostic. METHODS: Prospective records were maintained on patients undergoing infra-renal EVAR at a UK, tertiary referral centre. All patients enrolled with at least one-year follow-up were reviewed. Primary outcomes identified were aneurysm rupture and aneurysm-related complications. Secondary outcomes included number of CTAs avoided and cost. RESULTS: Median follow-up was 36 months (range 12-57) for 194 patients. The total number of sets of surveillance imaging was 412 of which 70 (17%) required CTA. Abnormalities were found in 30 patients, 18 confirmed by CTA. Eleven patients required secondary intervention, three initially identified by AXR, three by DUS, three by both DUS and AXR, and two by CTA following undiagnostic DUS. No patient presented with rupture or aneurysm-related complications not identified by modified surveillance. Mean annual savings were €223. CONCLUSION: EVAR surveillance based on DUS and AXR is feasible and safe. The complimentary nature of AXR and DUS is demonstrated.

Fascial closure following percutaneous endovascular aneurysm repair.

INTRODUCTION: There are potential benefits of percutaneous over open femoral access for endovascular aneurysm repair (EVAR). Subsequent arterial closure using percutaneous devices is costly, whilst open repair risks potential wound complications and delayed discharge. The technique of fascial closure has perceived advantages but its efficacy is unclear. The aim of this study was to assess the safety and durability of fascial closure after EVAR. METHODS: Patients undergoing EVAR using devices up to 24 French were considered. Exclusion criteria included morbid obesity, high bifurcation, previous surgery, inadvertent high puncture, arteries < 5 mm and surgeon preference. The primary outcome measure was immediate technical success. All patients were followed-up clinically and with duplex at one and twelve months to determine secondary complications. RESULTS: Over a one-year period fascial closure of 69 common femoral arteries was attempted in 38 patients undergoing EVAR. Nine primary failures were due to haemorrhage in eight arteries and thrombosis in one artery; all had immediate, uncomplicated open revision. Of the 60 (87%) successful procedures, all had duplex surveillance at one month. Four pseudoaneurysms were identified, all treated conservatively. At one year, 61 fascial closures (88%) were imaged, four patients had died and two were lost to follow-up. Three of the pseudoaneurysms had resolved, the fourth patient had died (unrelated). No other complication attributable to fascial closure was found at either one or twelve months. CONCLUSION: Fascial closure is a safe, durable and cost-effective method of arterial closure following EVAR. Success and complication rates are comparable to other techniques.

Measurement of pulsatile haemodynamic forces in a model of a bifurcated stent graft for abdominal aortic aneurysm repair.

The longitudinal haemodynamic force (LF) acting on a bifurcated stent graft for abdominal aortic aneurysm repair has been estimated previously using a simple one-dimensional analytical model based on the momentum equation which assumes steady flow of an inviscid fluid. Using an instrumented stent-graft model an experimental technique was developed to measure the LF under pulsatile flow conditions. The physical stent-graft model, with main trunk diameter of 30mm and limb diameters of 12 mm, was fabricated from aluminium. Strain gauges were bonded on to the main trunk to determine the longitudinal strain which is related to the LF. After calibration, the model was placed in a pulsatile flow system with 40 per cent aqueous glycerol solution as the circulating fluid. The LF was determined using a Wheatstone bridge signal-conditioning circuit. The signals were averaged over 590 cardiac cycles and saved to a personal computer for subsequent processing. The LF was strongly dependent on the pressure but less so on the flowrate. The measured forces were higher than those predicted by the simplified mathematical model by about 6-18 per cent during the cardiac cycle. The excess measured forces are due to the viscous drag and the effect of pulsatile flow. The peak measured LF in this model of 30 mm diameter may exceed the fixation force of some current clinical endovascular stent grafts.

Wholly endovascular repair of thoracoabdominal aneurysm.

BACKGROUND: The aim was to evaluate a wholly endovascular approach to the repair of thoracoabdominal aortic aneurysm (TAAA). METHODS: Six patients (median age 71 years) underwent wholly endovascular repair of TAAA (maximum diameter 56-85 mm) employing individually customized endografts. Procedures were performed under general anaesthesia, with spinal drainage in five patients. Patients were followed by serial computed tomography, plain radiography and duplex imaging for a median of 17 (range 8-44) months. RESULTS: All grafts were deployed as intended, with preservation of all target vessels. There were no postoperative deaths, strokes or paraplegia. One patient suffered a silent myocardial infarction. In two patients a persistent paraostial endoleak was treated by further balloon dilatation of the stent within the endograft fenestration. Imaging before discharge confirmed aneurysm exclusion in all patients. Two patients required late secondary intervention to abolish endoleaks due to side-branch disconnection. One patient suffered late occlusion of the coeliac axis without clinical sequelae, and late occlusion of a solitary renal artery in another resulted in dependence on dialysis. There have been no late deaths and all aneurysms remain excluded. CONCLUSION: Wholly endovascular TAAA repair is relatively safe, but long-term follow-up is required to establish its durability.

Fenestrated endovascular repair for juxtarenal aortic aneurysm.

BACKGROUND: The outcome of fenestrated endovascular aneurysm repair (F-EVAR) was evaluated. METHODS: Between February 2003 and December 2006, 45 patients (median age 73 (range 53-85) years) underwent primary (41) or secondary (four) F-EVAR for an abdominal aortic aneurysm with infrarenal neck anatomy unsuitable for a standard stent-graft. Median aneurysm diameter was 68 (range 55-100) mm and median infrarenal aortic neck length was 6 (range 0-13) mm. Customized fenestrated Zenith stent-grafts were employed in all procedures, incorporating fenestrations to preserve flow into renal (80), superior mesenteric (35) and coeliac (two) arteries. Eighty-two target vessels were stented (61 bare metal, 21 covered). RESULTS: All aneurysms were isolated successfully, with preservation of the target vessels. One accessory renal artery was lost. One patient died after 5 days from myocardial infarction, and another at 3 months from multiorgan failure secondary to atheroembolism. At median follow-up of 24 (range 1-48) months, all aneurysms were stable or shrinking, with no late ruptures or graft-related endoleaks. Six patients required a secondary intervention. The primary vessel patency rate was 96.6 per cent. There were four late deaths, unrelated to the aneurysm. CONCLUSION: F-EVAR enabled successful treatment of juxtarenal aortic aneurysm with a low complication rate.

Twin-block re-activation.

This paper briefly reviews reasons for re-activating Twin-blocks, discussing different approaches and describing a new, simple, cost effective approach, which can be undertaken at the chairside.

Swirling flow pattern in a non-planar model of an interposition vein cuff anastomosis.

One of the main causes of long-term failure of ePTFE grafts is the development of anastomotic intimal hyperplasia which leads to graft thrombosis. Experimental studies with bypass grafts have shown an inverse relationship between mean wall shear stress and intimal hyperplasia. The geometry of the anastomosis has a strong influence on the flow pattern and wall shear stress distribution. The aim of this in vitro study was to investigate the influence of non-planarity in a model of a distal anastomosis with interposition vein cuff, an anastomosis configuration that is increasingly being used because of improved clinical results. Laser Doppler anemometer measurements were carried out in silicone rubber models of interposition vein cuff anastomoses with planar and non-planar inflow. The pulsatile flow waveforms were typical of those found in femoro-infrapopliteal bypass. Axial and radial velocities were measured in the proximal and distal outflow segments. As expected a symmetrical helical flow pattern (Dean flow) was evident in the planar model. The model with non-planar inflow, however, gave rise to swirling flow in both the distal and proximal artery outflow segments for during the systolic phase. In patients, the anastomosis is usually non-planar. Since the configuration depends in part upon the tunnelling of the graft, this may be altered to some extent. Non-planar anastomotic configurations induce a swirling flow pattern, which may normalise wall shear stress, thereby potentially reducing intimal hyperplasia.

Late complications after ligation and bypass for popliteal aneurysm.

BACKGROUND: Ligation and bypass is standard treatment for popliteal aneurysm. This technique does not abolish collateral circulation to the aneurysm, which may continue to expand and/or rupture. This study assessed whether complete thrombosis of the aneurysm sac occurs after operation and examined the long-term clinical outcome. METHODS: The records of all patients who underwent popliteal aneurysm repair in a university hospital over 10 years were reviewed. Patients who had undergone ligation and bypass were recalled for clinical and ultrasonographic examination to determine the fate of the aneurysm sac. RESULTS: Persistent blood flow in the aneurysm sac was present in 12 of 36 legs a median of 48 months after operation. This was associated with symptomatic enlargement of the aneurysm in six patients. The incidence of sac enlargement was lower in bypassed aneurysms with no intrasac flow on duplex examination. CONCLUSION: Ligation and bypass does not always abolish blood flow in the sac of a popliteal aneurysm. It may be associated with continued expansion and late complications.

Outflow distribution at the distal anastomosis of infrainguinal bypass grafts.

Outflow distribution at the distal anastomosis of infrainguinal bypass grafts remains unquantified in vivo, but is likely to influence flow patterns and haemodynamics, thereby impacting upon graft patency. This study measured the ratio of distal to proximal outflow in 30 patients undergoing infrainguinal bypass for lower limb ischaemia, using a flow probe and a transit-time ultrasonic flow meter. The mean outflow distribution was approximately 75% distal to 25% proximal, with above knee anastomoses having a greater proportion of distal flow (84%) compared to below knee grafts (73%). These in vivo flow characteristics differ significantly from those used in theoretical models studying flow phenomena (50:50 and/or 100:0), and should be incorporated into future research.

Autotransplantation of an impacted third molar: an orthodontic case report.

This case report describes the use of autotransplantation as part of an orthodontic treatment plan where there was early loss of an upper molar tooth secondary to irreversible pulpitis. An impacted lower third molar, which had symptoms of pericoronitis, was transplanted into the upper left second molar socket. Fixed orthodontic treatment, to correct the patient's initial complaint of crowding, was completed in 22 months. The transplanted tooth remained vital and functional throughout.

Aortic side branch perfusion alone does not account for high intra-sac pressure after endovascular repair (EVAR) in the absence of graft-related endoleak.

OBJECTIVE: to examine the effect of stent-graft deployment on pressure within an aneurysm sac and to investigate the potential sources of intra-sac pressure. MATERIAL AND METHODS: intra-sac pressure was monitored during and immediately after endovascular repair via an indwelling catheter. Intra-sac pressure was also monitored during conventional open repair and was compared with the pressure measured within patent lumbar and inferior mesenteric side-branches, both before and after restoration of iliac arterial blood flow. Intra-sac and side-branch pressures were recorded and expressed as ratios of simultaneously measured radial artery pressure. RESULTS: in the absence of a graft-related endoleak (23/25 patients), endovascular repair resulted in a significant reduction in intra-sac pulse pressure (median ratio 0.31 IQR 0.10-0.46). There was no corresponding reduction in mean intra-sac pressure (median ratio 0.91; IQR 0.83-1.00). Application of clamps at conventional open repair resulted in a fall in both intra-sac pressure (median ratio 0.39, IQR 0.32-0.64) and pressure within side-branches (median ratio 0.45, IQR 0.33-0.64). Restoration of iliac blood flow resulted in a modest recovery of the side-branch pressure (median ratio 0.63, IQR 0.57-0.81), which nonetheless remained significantly less than the intra-sac pressure recorded after EVAR (p=0.01). CONCLUSION: reperfusion of the aneurysm sac through patent side-branches seems insufficient to account for persistent pressurisation of the aneurysm after endovascular repair. This finding supports the hypothesis that pressure may be transmitted directly through stent-graft fabric.

The distaflo graft: a valid alternative to interposition vein?

INTRODUCTION: the rationale behind the Distaflo graft is inhibition of myointimal hyperplasia through optimisation of haemodynamic forces at the distal anastomosis. This prospective study reports our early clinical results. METHOD: patients with critical limb ischaemia, but no autologous vein, underwent infrainguinal bypass using Distaflo. Clinical and Duplex assessment provided prospective data from which one year cumulative patency, limb salvage and survival rates were calculated using Kaplan-Meier analysis. Log rank test enabled comparison with an historical control group of Miller cuff grafts. RESULTS: fifty Distaflo were inserted over 29 months into 46 patients, median age 68.5 years, 27 male (59%), of which 27 (54%) were re-do procedures. Proximal anastomoses were to common femoral arteries in 40 cases (80%); distal anastomoses were to popliteal vessels in 20 (40%), and tibial vessels in 30 (60%). The Distaflo graft had patency, limb salvage and survival rates of 39, 50 and 82% respectively compared to 49, 56 and 85% respectively in the control group, with no statistical difference (p = 0.39; 0.65; 0.67 respectively; log rank). CONCLUSION: in this non-randomised study, the Distaflo has similar one year patency, limb salvage and survival rates to the Miller cuff, potentially justifying its use an alternative in distal prosthetic arterial reconstruction for critical limb ischaemia.

Perianeurysmal fibrosis: a relative contra-indication to endovascular repair.

OBJECTIVE: Perianeurysmal fibrosis (PAF) with involvement of neighbouring viscera can render open repair of inflammatory aneurysms technically difficult and therefore hazardous. For this reason, endovascular repair (EVAR) has been advocated as the preferred approach for this condition. EVAR is known to induce a systemic inflammatory response in patients but the nature of the local response remains unknown. If significant, such a response could exacerbate rather than ameliorate PAF. The aim of the study was to examine the incidence, course and consequences of perianeurysmal fibrosis detected by computerised tomography (CT) before and after EVAR. MATERIAL AND METHODS: The clinical records of patients treated by EVAR and followed for at least 6 months were reviewed. Pre and post-operative CT images were independently graded for PAF by three radiologists according to a standard protocol. RESULTS: PAF was documented preoperatively in six out of a total of 61 patients. In two of these PAF worsened after EVAR resulting in ureteric obstruction and hydronephrosis requiring ureteric stents. In the remaining 4 patients PAF did not reduce postoperatively. PAF of low grade developed postoperatively in 10 out of 55 patients (18%) in whom there was no evidence of PAF on preoperative imaging. Median follow-up was 18 months (range 6-36 months). The development of periaortic fibrosis de novopostoperatively was statistically significant (McNemar's test p=0.002). CONCLUSION: EVAR does not seem to reverse PAF if this is present preoperatively and it induces this condition in approximately one sixth of patients without evidence of preoperative PAF. The potential for this adverse inflammatory local response should be taken into account when considering EVAR for treatment of aneurysms with perianeurysmal fibrosis and must be weighed against the perceived benefits of this approach.

Harnessing haemodynamic forces for the suppression of anastomotic intimal hyperplasia: the rationale for precuffed grafts.

OBJECTIVES: Standardisation of cuff geometry by manufacturing prosthetic precuffed grafts (PCG) theoretically optimises haemodynamic forces. This study was designed in order to determine whether these beneficial flow patterns are replicated in vivo in PCG. PATIENTS AND METHODS: Flow visualisation and Doppler studies performed on anatomically accurate PCG models characterised in vitro anastomotic flow patterns. Thirty-two patients (median age 68 years) in whom autologous vein was unavailable, underwent bypass using PCG. Post-operative analysis included qualitative assessment of flow within the distal anastomosis using Doppler colour flow mapping. Cardiac gating techniques and assessment of velocity distribution were performed to gain additional information. These in vivo results were validated against the bench studies. RESULTS: A cohesive vortex was identified within the distal anastomosis of in vitro models and had an integral relationship with the cardiac cycle. This flow structure was also characterised using Doppler colour flow mapping in both longitudinal and transverse planes, confirming the location of the vortex within the body and proximal part of the anastomosis. Twenty-two patients (69%) undergoing bypass with a PCG underwent successful Doppler assessment one week post-operatively, of whom 17 (77%) had a vortical flow structure identified at the distal anastomosis, similar to that characterised in vitro. Cardiac gating verified the same integral relationship of the vortex with the cardiac cycle as that described in vitro. CONCLUSION: The geometric configuration of precuffed grafts induced vortices within the distal anastomoses in 17 out of 22 patients undergoing arterial reconstruction, thereby harnessing the haemodynamic forces that may suppress anastomotic hyperplasia and improve patency rates.