Coronary Artery Vein Graft Research Articles

Spatial Transcriptomic Profiling of Human Saphenous Vein Exposed to Ex Vivo Arterial Haemodynamics-Implications for Coronary Artery Bypass Graft Patency and Vein Graft Disease.

Vein graft disease is the process by which saphenous vein grafts, utilised for revascularisation during coronary artery bypass graft surgery, undergo an inflammation-driven intimal hyperplasia and accelerated atherosclerosis process in subsequent years after implantation. The role of the arterial circulation, particularly the haemodynamic properties' impact on graft patency, have been investigated but have not to date been explored in depth at the transcriptomic level. We have undertaken the first-in-man spatial transcriptomic analysis of the long saphenous vein in response to ex vivo acute arterial haemodynamic stimulation, utilising a combination of a custom 3D-printed perfusion bioreactor and the 10X Genomics Visium Spatial Gene Expression technology. We identify a total of 413 significant genes (372 upregulated and 41 downregulated) differentially expressed in response to arterial haemodynamic conditions. These genes were associated with pathways including NFkB, TNF, MAPK, and PI3K/Akt, among others. These are established pathways involved in the initiation of an early pro-inflammatory response, leukocyte activation and adhesion signalling, tissue remodelling, and cellular differentiation. Utilising unsupervised clustering analysis, we have been able to classify subsets of the expression based on cell type and with spatial resolution. These findings allow for further characterisation of the early saphenous vein graft transcriptional landscape during the earliest stage of implantation that contributes to vein graft disease, in particular validation of pathways and druggable targets that could contribute towards the therapeutic inhibition of processes underpinning vein graft disease.

Percutaneous coronary intervention of native coronary artery versus saphenous vein graft in patients with prior coronary artery bypass graft surgery: Rationale and design of the multicenter, randomized PROCTOR trial

Patients with prior coronary artery bypass grafting (CABG) frequently require repeat percutaneous revascularization due to advanced age, progressive coronary artery disease and bypass graft failure. Percutaneous coronary intervention (PCI) of either the bypass graft or the native coronary artery may be performed. Randomized trials comparing native vessel PCI with bypass graft PCI are lacking and long-term outcomes have not been reported. PROCTOR (NCT03805048) is a prospective, multicenter, randomized controlled trial, that will include 584 patients presenting with saphenous vein graft (SVG) failure and a clinical indication for revascularization, as determined by the local Heart Team. The trial is designed to compare the clinical and angiographic outcomes in patients randomly allocated in a 1:1 fashion to either a strategy of native vessel PCI or SVG PCI. The primary study endpoint is a 3-year composite of major adverse cardiac events (MACE: all-cause mortality, non-fatal target coronary territory myocardial infarction [MI], or clinically driven target coronary territory revascularization). At 3-years, after evaluation of the primary endpoint, follow-up invasive coronary angiography will be performed. Secondary endpoints comprise individual components of MACE at 1, 3 and 5 years follow-up, PCI-related MI, MI >48 hours after index PCI, target vessel failure, target lesion revascularization, renal failure requiring renal-replacement therapy, angiographic outcomes at 3-years and quality of life (delta Seattle Angina Questionnaire, Canadian Cardiovascular Society Grading Scale and Rose Dyspnea Scale). PROCTOR is the first randomized trial comparing an invasive strategy of native coronary artery PCI with SVG PCI in post-CABG patients presenting with SVG failure.

Novel percutaneous strategy to chronic total occlusion of the native right coronary artery and associated vein graft aneurysm and giant pseudoaneurysm.

Hnin, Theta; Mandal, Amit K.J.a; Smith, Elliotb; Iyengar, Srikantha; Missouris, Constantinos G.a,c; Baker, Christopherd Author Information

Guiding Catheters for Transradial Approach: New Designs and Summary of Experiences with VDL/VDR Catheters. A Novel Score for PCI Technical Complexity

In one multicenter and several single-center studies involving 202 cases, new shapes of transradial access PCI guide catheters were tested following a standardized original protocol. The evaluation included a newly designed score for PCI complexity. Three operators successfully performed the 40 cases of the multicenter study, scoring intermediate to difficult 66% of the cases. New shapes were tested for left and right coronary artery and saphenous vein graft PCIs, with right or left transradial access. The new shapes performed adequately, including in 5F sizing. PCI success and fluoroscopy time were related to the score of complexity.

Casein kinase-2 (CK2) inhibition by TBCA attenuates VSMC and fibroblast proliferation without adverse effects on endothelial cell behaviour or inflammation

Aim: Intimal thickening within human saphenous vein (HSV) grafts leads to unacceptably high failure rates of coronary artery vein grafts. Treatments to reduce intimal thickening need to attenuate vascular smooth muscle cell (VSMC) and fibroblast proliferation without detrimental effects on endothelial cells (ECs). In this study we compared the effect of four CK2 inhibitors on VSMC, fibroblast and EC behaviour to determine their potential use in retarding intimal thickening.

Vitamin D deficiency and periprocedural myocardial infarction in patients undergoing percutaneous coronary interventions.

Vitamin D deficiency has been implicated in the progression of atherosclerosis and acute thrombotic events. We aimed at evaluating the impact of vitamin D deficiency on periprocedural myocardial infarction (PMI) in patients undergoing percutaneous coronary interventions (PCI). We included 934 patients undergoing non-urgent PCI. Assessment of myocardial biomarkers was performed from 6 to 48 h after PCI. PMI was defined as Creatine Kinase-MB increase by 3 times the Upper Limit Normal or by 50% of an elevated baseline value, periprocedural myocardial damage as Troponin I increase by 3 × ULN or 50% of baseline. Patients were divided according to vitamin D tertiles values (<10.2 ng/ml; 10.2-18.7 ng/ml; ≥18.8 ng/ml). Lower tertiles values of vitamin D were associated with age (p = 0.04), female gender, (p = 0.001), and a higher cardiovascular risk profile. Lower vitamin D levels related with PCI of descending anterior coronary artery or bypass vein grafts (p = 0.03), treatment of bifurcations (p = 0.05) and side branch loss (p = 0.05) and inversely with direct stenting (p = 0.002). However, lower vitamin D levels did not influence the risk of PMI (adjusted OR [95% CI] = 0.81[0.65,1.18], p = 0.09) or periprocedural myocardial damage (adjusted OR [95% CI] = 0.93[0.77,1.13], p = 0.48). Similar results were achieved when considering the severity of vitamin D deficiency. Therefore, in patients undergoing PCI, no association was observed between vitamin D deficiency and the risk of periprocedural MI and myocardial damage.

Influence of stent implantation on erythrocyte aggregation in human native coronary arteries and saphenous vein grafts.

Stent implantation into atherosclerotic coronary vessels induces the release of particulate debris and soluble vasoactive substances, which impair downstream microvascular function. Microvascular perfusion, however, is also determined by hemorheological parameters. We therefore analyzed now changes in erythrocyte (RBC) aggregation in coronary arterial blood during stent implantation. Symptomatic male patients with stable angina pectoris and stenosis in their native right coronary artery (RCA) or saphenous vein graft on right coronary artery (SVG-RCA) were enrolled. Coronary arterial blood was taken before and coronary aspirate during stent implantation with a distal occlusion/aspiration device. RBC aggregation was determined using the erythrocyte adhesiveness/aggregation test. The ratio of clot-free area to whole area of a spread blood drop was quantified (rCFA). To evaluate the impact of soluble factors within aspirate plasma on RBC aggregation, separated RBCs of healthy volunteers were exposed to patients' coronary arterial blood and aspirate samples. rCFA was comparably increased in coronary aspirate of RCAs and SVG-RCAs after stent implantation (RCA: 25.7±2.1% vs 32.2±2.1%; SVG-RCA: 28.9±1.9% vs 33.3±2.0%, P<.01). The rCFA of healthy volunteers was increased after adding coronary aspirate plasma. Stent implantation into atherosclerotic coronary arteries induces an increase in RBC aggregation, potentially contributing to impaired microvascular perfusion.

Improved Outcomes of Total Arterial Myocardial Revascularization in Elderly Patients at Long-Term Follow-Up: A Propensity-Matched Analysis

Despite the proven advantages of total arterial grafting in patients undergoing coronary artery bypass operation, its benefits in the elderly population at long-term follow-up have been widely debated to date. Among 988 consecutive patients scheduled to undergo coronary artery bypass grafting operation, we performed a propensity-matched analysis in a population with double and triple vessel disease and older than 70 years and compared patients receiving total arterial grafting (G1; n= 315 patients) with conventional myocardial revascularization (left internal mammary artery on left anterior descending coronary artery plus saphenous vein grafts; G2; n= 201 patients). Two groups of 175 patients were obtained after matching. Primary end points were overall survival and survival free from cardiac-related mortality, whereas secondary end point was the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs; cardiac death, myocardial infarction, repeated revascularization on grafted vessels, stroke). Preoperative and intraoperative patients' characteristics were similar among the groups, as well the incidence of hospital mortality (none in both groups). At a median follow-up time of 89 months, total arterial grafting was associated with significantly improved actuarial overall survival (G1: 67.5% ± 4.6%, G2: 57.0% ± 4.4%, p=0.029), survival free from cardiac-related mortality (G1: 86.9% ± 3.4%, G2: 75.9 ± 4.0%, p= 0.02), and occurrence of MACCEs (G1: 78.8 ± 3.9%, G2: 65.5% ± 4.4%, p= 0.017). Multivariate Cox regression analysis depicted conventional myocardial revascularization as an independent predictor of cardiac-related mortality (hazard ratio [HR] 2.5, 95% confidence interval [CI]: 1.3 to 4.8, p= 0.005) and MACCEs (HR 2.1, 95% CI: 1.2 to 3.4, p=0.005). Total arterial myocardial revascularization in elderly patients is associated with a reduced late incidence of cardiac-related mortality and major cerebral and cardiovascular events compared with the use of saphenous grafts, thereby providing improved long-term benefits also in this specific subset of patients.

New Imaging Methods of Coronary Arteries in Acute Coronary Syndromes

Abstract Coronary angiography is still the most widely used method for the assessment of lumen of coronary arteries and for diagnosis and treatment of coronary artery disease. New imaging modalities of coronary arteries play an increasing role in interventional cardiology. Intravascular ultrasound (IVUS) is the oldest technology, however due to its high tissue penetration remains very important for imaging of left main coronary artery and saphenous vein grafts. IVUS was used in many clinical trials and clinical experience with it is huge. Optical coherence tomography (OCT) is a new, very fast developing method. It has ten times higher axial resolution than IVUS. It gives us the opportunity to assess the inner structures of coronary artery wall, to evaluate the characteristics of atherosclerotic plaques, quality of stent implantation and its healing. It helps us to find the culprit lesion of acute coronary syndrome in some cases, to diagnose the cause of stent thrombosis, and to evaluate stent apposition which has a direct relation to prognosis. We use it to perform complex percutaneous coronary interventions and after heart transplantation to diagnose the vascular graft disease. We strongly believe that OCT is important for the assessment of plaque instability and patient´s prognosis. Near infrared spectroscopy combined with IVUS can distinguish fibrous from lipid core plaques. Lipid core burden index is in relation to a risk of periprocedural myocardial infarction and to prognosis. It is the only method which can sufficiently detect the amount of lipids in coronary wall.

New imaging methods of coronary arteries

Coronary angiography is still the most widely used method for assessment of lumen of coronary arteries and for diagnostics and treatment of coronary artery disease. New imaging modalities of coronary arteries play increasing role in interventional cardiology. Intravascular ultrasound (IVUS) is the oldest technology. Due to high tissue penetration it is very important for imaging of left main coronary artery and saphenous vein grafts. IVUS was used in many clinical trials and clinical experience with it is huge. Optical coherence tomography (OCT) is a new, very fast developing method. It has ten times higher axial resolution than IVUS. It gives us the opportunity to assess the inner structures of coronary artery wall, to evaluate the characteristics of atherosclerotic plaques, quality of stent implantation and its healing. It helps us to find the culprit lesion of acute coronary syndrome in some cases, to diagnose the cause of stent thrombosis, to evaluate stent apposition which has a direct relation to prognosis. We use it for performing of complex percutaneous coronary interventions and after heart transplantation to diagnose the vascular graft disease. We strongly believe that OCT is important for assessment of plaque instability and patient´s prognosis. Near infrared spectroscopy combined with IVUS can distinguish fibrous from lipid core plaques. Lipid core burden index is in relation to a risk of periprocedural myocardial infarction and to prognosis. It is the only method which can sufficiently detect the amount of lipids in coronary wall.

Spatial correlation between patterns of wall permeability and patterns of multidirectional disturbed blood flow in rabbit aorta

Spatial correlation between patterns of wall permeability and patterns of multidirectional disturbed blood flow in rabbit aorta

Wnt inducible soluble protein 1 (WISP-1) promotes VSMC migration and intimal thickening

Vascular smooth muscle cell (VSMC) migration promotes coronary artery restenosis and vein graft failure. Therefore investigating factors involved in VSMC migration may enable us to improve treatments and therefore patient outcomes. We have previously shown that augmented Wnt2 expression occurred in and increased VSMC migration in vitro. This study aimed to further elucidate the mechanism of action of Wnt2. Addition of recombinant Wnt2 protein increased WISP-1 mRNA by 1.7±0.1 fold (p<0.05, n=4), while siRNA knockdown of Wnt-2 reduced WISP-1 mRNA (64.8±6.13%, p<0.05, n=3). Treatment with recombinant WISP-1, after a scratch-wound, significantly increased VSMC migration by 1.5±0.15 fold (p<0.05 n=4), while WISP-1 siRNA knockdown reduced migration by 36.0±11.8% (p<0.01 n=5). The effects of Wnt2 and WISP-1 were not additive, intimating that Wnt2 promotes VSMC migration via induction of WISP-1. We also saw that the location of Wnt2 and WISP-1 were significantly correlated in human diseased coronary arteries (r=0.647, r2=0.419, n=13 P<0.02). Using mouse carotid artery ligation we assessed the effect of reducing Wnt2 levels with Wnt2+/- mice; and elevation of plasma WISP-1 levels using tail-vein injection of WISP-1 adenovirus, on intimal thickening. Reduction in Wnt2 suppressed intimal thickening from 52.21±5.85% occlusion in controls to 37.16±8.2% in Wnt2+/- (p<0.05, n=14). Elevation of WISP-1 significantly increased intimal thickening compared to mice receiving control virus, (97±3% vs. 67±13% occlusion, p<0.05 n=11 and 9, respectively). This study demonstrates that Wnt2 promotes VSMC migration at least in part via WISP-1 and therefore inhibition of WISP-1 may provide a potential therapy for restenosis and vein graft failure.

Clinical outcomes with 6 months dual antiplatelet therapy after implantation of Biolimus-A9 drug eluting coronary stents

IntroductionDuration of dual antiplatelet therapy (DAPT) following drug eluting stent (DES) implantation remains poorly defined. Endothelialisation of biodegradable polymer biolimus-eluting stents occurs early, and 6 months DAPT may be adequate. AimsWe evaluated long term outcome in patients treated with biolimus-eluting stents who were treated with 6 months DAPT. Endpoints included cardiac death and non-fatal stent thrombosis occurring 6 to 12 months after stent implantation. Methods692 patients (77.2% male), aged 65.6±12.5years received biolimus-eluting DES (March 2008 –November 2011). Vital status was tracked through the Medical Research Information Service. Episodes of non-fatal stent thrombosis, (Academic Research Consortium definition) between months 6 and 12 were tracked via systematic database searches (5 PCI centres). ResultsPresentations included acute coronary syndrome (47.2%) and stable coronary disease (52.8%). Vessels treated included left main stem (6.8%), left anterior descending (37.4%), circumflex (19.1%), right coronary artery (34.5%) and saphenous vein graft (2.1%) respectively. High-risk subsets included diabetes (15.6%); AHA type C lesions (35.1%) and chronic total occlusions (12.8%). During median follow-up of 700 days (0 to 1392) there were 42 deaths (6.1%); 4.2% at 0–6months, 1.0% at 6–12months and 0.9% at >12months. Of the 7 deaths between 6 and 12months, one death was adjudicated as possible stent thrombosis. There were no cases of non-fatal known stent thrombosis. All cause mortality accrued with smooth decremental incidence. Statistical examination showed no evidence of event clustering between 6 and 12 months. ConclusionsAfter implantation of biodegradable polymer biolimus-eluting coronary stents, 6 months DAPT appears to be adequate, safe and effective.

Saphenous vein graft pseudoaneurysm mimicking cardiac myxoma

A 67-year-old woman had been operated on with the left internal thoracic artery anastomosed to the left anterior descending coronary artery and saphenous vein grafts anastomosed to the right and the first diagonal coronary arteries at the age of 46 years. Because …

Wnt signalling in smooth muscle cells and its role in cardiovascular disorders

Vascular smooth muscle cells (SMCs) are the major cell type within blood vessels. SMCs exhibit low rates of proliferation, migration, and apoptosis in normal blood vessels. However, increased SMC proliferation, migration, and apoptosis rates radically alter the composition and structure of the blood vessel wall and contribute to cardiovascular diseases, such as atherosclerosis, and restenosis that occur after coronary artery vein grafting and stent implantation. Consequently, therapies that modulate SMC proliferation, migration, and apoptosis may be useful for treating cardiovascular diseases. The family of Wnt proteins, which were first identified in the wingless drosophila, has a well-established role in embryogenesis and development. It is now emerging that Wnt proteins also regulate SMC proliferation, migration, and survival. In this review article, we discuss recently emerging research that has revealed that Wnt proteins are important regulators of SMC behaviour via activation of β-catenin-dependent and β-catenin-independent Wnt signalling pathways.

Fistula between right coronary artery vein graft and right atrium as an immediate complication of percutaneous coronary intervention

Fistula between saphenous vein graft (SVG) and a cardiac chamber or structure is a rare complication after coronary artery bypass grafting (CABG). We report the first case of a fistula between SVG and the right atrium (RA) as an immediate complication after a percutaneous coronary intervention (PCI) in an 86-year-old female. She presented with inferior ST-elevation myocardial infarction (STEMI) and was treated with thrombolytic therapy in a peripheral hospital, which was unsuccessful. PCI to SVG to the right coronary (RCA) was complicated by a fistula to RA. Cardiac magnetic resonance (CMR) confirmed the site of the fistula and also presence of a significant arteriovenous (AV) shunt. Reversal of anticoagulation had no effect on fistula closure. Therefore, a covered stent was deployed for closure of the fistula to avoid long-term complications of the significant AV shunt. In summary, the diagnosis and appropriate management of this rare complication is challenging, but excellent result can be achieved by the use of appropriate percutaneous techniques.

Sustained Reduction of Vein Graft Neointima Formation by Ex Vivo TIMP-3 Gene Therapy

Coronary artery vein graft failure, resulting from thrombosis, intimal thickening, and atherosclerosis, is a significant clinical problem, with approximately 50% of vein grafts failing within 10 years. Intimal thickening is caused by migration of vascular smooth muscle cells from the media to the intima, where they proliferate. Interventions using gene transfer to inhibit vascular smooth muscle cells proliferation and migration are attractive because ex vivo access to the graft is possible. The involvement of matrix-degrading metalloproteinases in intimal thickening is well established, and we previously showed that adenoviral-delivered overexpression of an endogenous inhibitor, the tissue inhibitor of metalloproteinases-3 (TIMP-3), significantly retarded intimal thickening in short-term autologous porcine arteriovenous interposition grafts (28 days). However, it is essential to determine whether this approach will provide longer-term benefits. We assessed whether a recombinant adenovirus that overexpresses TIMP-3 (RAdTIMP-3) affects vein graft intimal thickening in the longer term (at 3 months). Porcine saphenous veins were subjected to luminal infection with 2.5×10(10) pfu/mL RAdTIMP-3 or RAd60 (control virus) or vehicle control, for 30 minutes before implantation into the carotid artery. Analysis of grafts harvested 3 months after delivery revealed that RAdTIMP-3-infected grafts had significantly reduced intimal areas compared with both controls (3.2 ± 0.4 mm(2) versus 5.6 ± 0.7 mm(2) and 5.9 ± 0.5 mm(2), RAdTIMP-3, RAd60, and vehicle, respectively). Medial areas were also significantly decreased by TIMP-3 (3.8 ± 0.3 mm(2) versus 6.7 ± 1.0 mm(2) and 5.2 ± 0.4 mm(2), RAdTIMP-3, RAd60, and vehicle, respectively). Overexpression of TIMP-3 provides a sustained retardation of vein graft intimal thickening and highlights the translational potential for ex vivo TIMP-3 gene therapy.

Interview: David R Holmes Jr speaks to Laura Dormer, Commissioning Editor

Dr David Holmes is currently a Professor of Medicine at the Mayo Clinic College of Medicine and a consultant in the Division of Cardiovascular Diseases and the Department of Internal Medicine at Mayo Clinic in Rochester, Minnesota. Holmes has also been named the Edward W and Betty Knight Scripps Professor in Cardiovascular Medicine in Honor of George M Gura Jr. In 2009, he was elected Vice President of the American College of Cardiology. His special areas of interest include acute coronary syndromes, interventional cardiology, restenosis, vascular biology, risk outcomes analysis and telemedicine. In addition, he is involved in the development of new catheter design and new approaches for the treatment of a wide variety of patients with coronary artery disease and vein graft disease. Finally, he is involved in the development of continued application of percutaneous coronary intervention technology to noncoronary vascular beds. Holmes received his medical degree at Marquette University Medical School in Mi...

Giant Coronary Artery Aneurysm Associated with Medial Mucoid Degeneration

A 52-year-old man underwent surgical repair for coronary arteriovenous fistula including patch closure of two exitus of the fistula, double ligation of the dilated right coronary artery, and coronary bypass grafting to the right coronary artery with saphenous vein graft at the age of 25. Then, twenty-seven years later, a multi-detector computed tomographic scan revealed an aneurysmally dilated right coronary artery (4.8 cm), fistula, and saphenous vein graft. The aneurysm was resected and histologically mucoid degeneration in the media of the aneurysmal wall was detected.

The accuracy of length measurements using different intravascular ultrasound motorized transducer pullback systems

Accurate length measurements by intravascular ultrasound (IVUS) are necessary for stent length selection and for IVUS volumetric analysis. The comparative accuracy of commercially available transducer pullback systems--a necessity for accurate IVUS length and volume measurements--has never been studied. We evaluated the accuracy of four IVUS pullback systems by studying 180 patients (45 in each group) who had been treated with a single stent of known length. Stented lesions were located in the left anterior descending artery (n = 77), left circumflex artery (n = 41), right coronary artery (n = 41), left main (n = 2), and saphenous vein grafts (n = 19). The known lengths of implanted stents ranged from 8 to 33 mm. The correlations between known stent length and IVUS-measured stent length in each group were 0.92 for CVIS, 0.83 for BSC Galaxy, 0.63 for Endosonics TrackBack, and 0.69 for Volcano Model R-l00 research pullback device, respectively. Furthermore, the absolute value of the difference between the two measurements was 9.1 +/- 13.1%, 8.8 +/- 10.2%, 18.6 +/- 21.5%, and 17.5 +/- 31.4%, respectively. With the Volcano Model R-l00 research pullback device, there were 3 extreme outliers; if these three outliers were excluded, then the correlation improved from 0.69 to 0.91; and the absolute deviation from known stent length improved from 17.5 +/- 31.4% to 9.7 +/- 8.3%. Thus, there is a significant variation in length measurement accuracy among IVUS pullback devices. This should be taken into account both clinically and when planning scientific studies.