What influences recruitment to randomised controlled trials? A review of trials funded by two UK funding agencies

Background

Traditional harvesting of the internal thoracic artery (ITA) for use as a conduit in coronary bypass surgery involves the dissection of a rim of tissue surrounding the artery on either side. Recent studies, primarily observational, have suggested that skeletonization of the ITA can improve conduit flow, increase length, and reduce the risk of deep sternal infection in high risk patients. Furthermore, skeletonization of the ITA can potentially preserve intercostal nerves and reduce post-operative pain and dysesthesias associated with ITA harvesting. In order to assess the effects of ITA skeletonization, we report a prospective, randomized, within-patient study design that shares many features of a cross-over study.

Methods

Patients undergoing bilateral internal thoracic artery harvest will be randomized to having one side skeletonized and the other harvested in a non-skeletonized manner. Outcome measures include ITA flow and length measured intra-operatively, post-operative pain and dysesthesia, evaluated at discharge, four weeks, and three months post-operatively, and sternal perfusion assessed using single photon emission computed tomography. Harvest times as well as safety endpoints of ITA injury will be recorded.

Discussion

This study design, using within-patient comparisons and paired analyses, minimizes the variability of the outcome measures, which is seldom possible in the evaluation of surgical techniques, with minimal chance of carryover effects that can hamper the interpretation of traditional cross-over studies. This study will provide a valid evaluation of clinically relevant effects of internal thoracic artery skeletonization in improving outcomes following coronary artery bypass surgery.     

选择性冠状静脉动脉化搭桥术中不同移植物的应用疗效比较

目的:对比选择性冠状静脉动脉化(SCVBG)搭桥治疗弥漫性右冠状动脉狭窄病变中选择乳内动脉和大隐静脉作为桥血管的治疗效果。方法:选择2008年10月到2014年10月在我院行SCVBG搭桥的84例患者资料,其中选择大隐静脉作为桥血管进行冠状静脉动脉化搭桥患者46例(大隐静脉桥组),选择乳内动脉作为桥血管进行冠状静脉动脉化搭桥患者38例(乳内动脉桥组)。随访记录两组患者的生存情况、近期复查超声心动图、冠状动脉CTA及心绞痛复发率。结果:乳内动脉桥组患者总生存率(100%)明显高于大隐静脉桥组(82.6%)(P0.05)。乳内动脉桥组患者桥血管和心中静脉通畅率(100%)明显大于大隐静脉桥组(54.35%)(P0.05)。两组患者左心室射血分数(LVEF)较治疗前明显增加,左心室舒张期末内径(LVEDD)较治疗前明显减小(P0.05)。治疗后,乳内动脉桥组患者心绞痛复发率明显小于大隐静脉桥组(P0.05)。结论:SCVBG搭桥治疗弥漫性右冠状动脉狭窄病变中,选择乳内动脉桥效果优于大隐静脉桥,能明显提高桥血管和心中静脉通畅率,降低心绞痛复发率。     

The Treatment of Multiple Coronary Occlusions by Internal Mammary Artery Implantation and Omental Graft: Report on Two Human Cases

The importance of triple coronary artery disease was evident in 125 patients undergoing internal mammary artery implantation, when some patients died from right coronary artery occlusion. This occurred even when the internal mammary artery was patent and revascularizing the left ventricle.In 1961 the free omental graft operation was developed to revascularize both right and left ventricles. In animals this operation has proved most effective in preventing death after application of Ameroid constrictors to all three coronary arteries. Arteriolar or larger-sized vessels rapidly formed between the aorta and omentum and the pericardium and omentum and the heart and omentum.Two patients with triple coronary artery disease underwent internal mammary artery implantation and free omental graft early in December 1962. Postoperative convalescence was uneventful. They have returned home and appear to be improved. Wrapping the entire heart with the free omental graft has produced little reaction, suggesting that, as in the animal, the grafts are surviving.     

Robotic totally endoscopic multivessel coronary artery bypass grafting: procedure development, challenges, results

Closed-chest totally endoscopic coronary artery bypass grafting (TECAB) is feasible using robotic technology. During the early phases, TECAB was restricted to single bypass grafts to the left anterior descending artery system. Because most patients referred for coronary artery bypass surgery have multivessel disease, development of endoscopic multiple bypass grafting is mandatory. Experimental work on multivessel TECAB was carried out in the early 2000s, and first clinical cases were already performed. With further technological development of operating robots, double, triple, and quadruple TECAB has become feasible both on the arrested heart and on the beating heart. To date, 161 cases of multivessel TECAB using the da Vinci telemanipulation systems are published in the literature. The main advances enabling multivessel TECAB were the availability of a robotic endostabilizer for beating heart procedures and increased surgeon skills using remote access heart-lung machine perfusion and endo-cardioplegia. Both internal mammary arteries can be harvested and both radial artery and vein graft can be used in multivessel TECAB. Y-grafting and sequential grafting are feasible. Multivessel endoscopic surgical revascularization can be combined with percutaneous coronary interventions in advanced hybrid coronary revascularization. Time requirements for multivessel TECAB are significant, and conversion rates to larger thoracic incisions are higher than those observed for single-vessel TECAB. Clinical short- and long-term outcomes, however, seem to meet the standards of open coronary bypass surgery through sternotomy. The main advantages of multivessel TECAB are a completely preserved sternum, use of double internal mammary artery even in risk groups, and a remarkably short recovery time.     

Measurement of the flow in coronary artery bypass grafts

The aim of our study was to measure the flow in coronary artery bypass grafts and to compare the flow between two groups of patients. In group A the arterial revascularization was performed with both internal thoracic arteries using as a Y graft and in group B conventional revascularization using left internal thoracic artery (ITA) attached to the left anterior descending artery (LAD) and venous grafts to the other branches of the left coronary artery was performed. The flow in all grafts was measured at six time points during the operation. The cumulative flow at the end of the operation in the group A (arterial Y graft) was 51.8 +/- 24.5 ml/min and in group B (conventional technique) it was 96.8 +/- 41.1 ml/min (p < 0.05). The flow in left ITA to LAD was similar in both groups (27.3 +/- 15.9 ml/min and 26.3 +/- 16.1 ml/min in group A and B). The flow in right ITA (25.2 +/- 18.4 ml/min) was significantly lower than in venous grafts (72.5 +/- 45.5 ml/min). The calculated flow reserve was 2.2 in group A and 2.1 in group B. We found that the cumulative flow in arterial Y graft was lower in comparison with conventional revascularization. This is due to the lower flow in the right ITA branch of the Y graft compared to venous grafts. However based on clinical results, we can postulate that the flow in the Y graft is sufficient to meet the demand of the myocardium originally supplied by the left coronary artery.     

Acute repair of a full-thickness right ventricular defect with a composite myofascial pedicle flap.

A full-thickness defect of the right ventricle presented acutely after mediastinitis and sternal dehiscence. This developed 29 days after bilateral internal mammary artery harvest for coronary artery bypass grafting. The defect was managed successfully with a pedicled left rectus abdominis muscle flap using an attached island of the anterior rectus sheath for endocardial lining. The vascular anatomic basis for viability of the rectus abdominis muscle flap after internal mammary artery harvest is derived primarily from musculophrenic, lumbar, lower sixth intercostal, and subcostal artery communications. In addition, the advantages of a myofascial pedicle flap for reconstruction of full-thickness cardiac defects are its ready availability and a strong anterior fascial sheath that can be used as a neoendocardial lining. The patient did well and remains asymptomatic after 3 years.     

The Continuity of Right and Left Ventricular Myocardial Sinusoidal Spaces and its Relation to Right Ventricular Implants

Evidence is presented which indicates that blood leaving side branches of an internal mammary artery implanted into the anterior wall of the right ventricle flows from the tunnel in which it lies through myocardial sinusoidal spaces of the anterior right ventricular wall across the midline to fill corresponding spaces in the anterior wall of the left ventricle and thence is carried to the left coronary sinus. The myocardial sinusoidal spaces of right and left ventricles have been well outlined, using injections of polyvinyl acetate and the technique of digestion casts. We have been able to show that there is no barrier between the myocardial sinusoids of the right circulation and those related to the anterior descending branch of the left coronary artery. In structure, these myocardial sinusoidal spaces are quite different from the intramyocardial coronary arteriolar zones which, in 93% of human hearts, are separated from one another without collateral communication.The continuity of the right and left ventricular myocardial sinusoids explains why implantation of a right internal mammary artery into the anterior wall of the right ventricle combined with a corresponding left implant, epicardiectomy and free omental graft, has been so effective in our hands in the treatment of far-advanced human coronary artery insufficiency.     

Endoscopic lesser saphenous vein harvesting for coronary artery bypass grafting: first reported case

Endoscopic vessel harvesting has become a widely used modality for harvesting venous and arterial conduits for coronary artery bypass grafting. Specifically, it has been used to harvest the greater saphenous vein, internal thoracic artery, and the radial artery. A case of endoscopic lesser saphenous vein harvesting for coronary artery bypass grafting is reported.     

Arterial end-to-side grafting in coronary artery bypass grafting: the Tector procedure

Background. The current treatment of choice in patients with three-vessel coronary disease is coronary artery bypass grafting. The use of the left internal mammary artery in bypass grafting has shown superior long-term outcomes compared with venous grafting. In our study we assess the safety and feasibility of all-arterial coronary artery bypass graft surgery using the procedure as described by Tector et al. in 2001.Methods. Between June 2001 and February 2007, we studied 133 patients eligible for non-emergency surgical revascularisation. Primary endpoints were death or re-infarction within a 30-day period. Secondary endpoints were the need for emergency coronary surgery, angioplasty and mediastinitis. Long-term follow-up had a mean duration of 33 months postoperatively.Results. All 133 patients were successfully revascularised, 98% with the off-pump technique. In 93% of the patients (n=124) full arterial grafting was achieved using both internal mammary arteries. Thirty-day mortality was 1.5% (n=2), ten re-thoracotomies were performed, one myocardial infarction and one case of mediastinitis were reported. In the next four years six additional patients died. Most of these deaths were due to non-cardiovascular causes. Two patients required angioplasty because of distal bypass graft failure and one for new native coronary artery disease. Conclusion. All-arterial bypass grafting using both internal mammary arteries with the technique as described by Tector is safe and feasible without excess deep sternal wound infections. Late major adverse cardiac events are rare and due to distal graft dysfunction, which can be treated by percutaneous coronary intervention. (Neth Heart J 2010;18:7-11.)     

The YUMIKO catheter: a useful tool for angiography of the right internal mammary artery via a right brachial approach

The YUMIKO catheter (Goodman, Nagoya, Japan) was recently developed for a left internal mammary artery (IMA) angiography with a right radial or brachial approach. The present authors experienced an interesting case where the YUMIKO catheter was useful for a right IMA angiography via a right brachial artery. A 53-year-old man with bilateral IMA grafts underwent follow-up coronary angiography via a right brachial artery. Native coronary artery and left IMA angiography were performed without difficulty using the Judkins Right and Left and YUMIKO catheters. Angiography of the right IMA was attempted with the Judkins Right catheter and IMA catheter, resulting in a nonselective angiogram with poor imaging. The YUMIKO catheter, however, enabled smooth cannulation to the right IMA and provided good images of the selective right IMA angiography.     

Variable ECG signs of ischemia during controlled occlusion of the left and right coronary artery in humans

Infarct size (IS) increases with vascular occlusion time, area at risk for infarction, lack of collateral supply, absence of preconditioning, and myocardial demand for O2 supply. ECG S-T segment elevation is used as a measure of severity of ischemia and a surrogate for IS. This study in 50 patients with coronary artery disease undergoing a first 120-s balloon occlusion of a stenosis sought to determine whether S-T segment elevation, corrected for the above-mentioned variables, in the left coronary artery (LCA group, n = 36) is different from that in the right coronary artery (RCA group, n = 14) territory. After consideration of all known determinants of IS, particularly mass at risk and collateral supply, the LCA territory is more sensitive than the RCA region to a 2-min period of myocardial ischemia.     

Robotically assisted coronary endarterectomy

Robotic assistance has enabled coronary artery bypass surgery to be performed safely in a completely endoscopic fashion, but diffusely diseased target vessels may pose a technical challenge. We present a case in which coronary endarterectomy was performed on the left anterior descending coronary artery during a two-vessel totally endoscopic coronary artery bypass procedure. A 52-year-old woman presented with intermittent substernal pain. Preoperative studies showed diffuse disease in the left coronary artery system. Bilateral internal mammary arteries were harvested robotically using a skeletonized technique in a completely endoscopic fashion. Cardiopulmonary bypass was achieved via peripheral cannulation, and the heart was arrested with intermittent cold antegrade hyperkalemic blood cardioplegia delivered via an ascending aortic occlusion balloon catheter. The first obtuse marginal anastomosis was performed. The left anterior descending coronary artery was diffusely diseased and heavily calcified. An end-to-side anastomosis was attempted to the right internal mammary artery with unsatisfactory results. A localized coronary endarterectomy was performed, and an extended anastomosis was completed using the right internal mammary artery. The patient recovered uneventfully and was discharged home on postoperative day 6. Diffuse coronary artery disease was once thought to be a prohibitive challenge for minimally invasive coronary bypass procedures. This case demonstrates that local coronary endarterectomy is feasible and safe in robotic totally endoscopic coronary artery bypass surgery.     

Right Internal Mammary Artery Implantation into Right Ventricular Myocardium for Revascularization of the Entire Heart: Experimental Data and Preliminary Report

The left internal mammary artery implant combined with epicardiectomy and free omental graft provides three extra-coronary sources of blood. This operation tested in dogs with 92% main-stem occlusion of three coronary arteries protected 75% of the animals. Applied clinically in over 100 patients, the operation resulted in 90% improvement. To obtain complete myocardial revascularization, the right internal mammary artery has been used as a fourth source of extra-coronary blood. In 57 animals, the right internal mammary arteries were implanted into the anterior walls of the right ventricle; in 80% this vessel formed anastomoses with the right coronary tree, and in 65% with the right and left coronary arteriolar systems. Six patients are described who underwent right internal mammary artery implantation; five of these in addition had the combined operation of left internal mammary artery implant, epicardiectomy and free omental graft. All patients had completely blocked right coronary arteries; in addition, five had advanced disease of the left coronary arterial tree.     

Capacities of multidetector spiral computed tomography in the planning and postoperative examination of patients undergoing coronary artery bypass surgery

Multiple investigations show that multidetector spiral computed tomography (MSCT) bypass grafting becomes an alternative to invasive coronary angiography in detecting coronary graft stenoses and occlusions. The investigation retrospectively estimated the patency of aortocoronary and mammary coronary artery anastomoses by MSCT bypass grafting. Examinations were made in 85 (326 anastomoses) patients who had undergone aortocoronary and mammary coronary artery bypass surgery and had MSCT bypass grafting within 3 years after the surgery. In the first year following the surgery, 18 patients with graft stenotic changes, as evidenced by MSCT, underwent intervention coronary angiography, the sensitivity and specificity of which was 100%. The results of clinical and instrumental examinations were also compared with graft incompetence, as shown on MSCT that revealed that MSCT bypass grafting was the only noninvasive technique to evaluate early coronary graft closure both in the absence of clear signs of myocardial ischemia according to the data of exercise tests and in the presence of recurrent angina pectoris.     

Contemporary use of arterial and venous conduits in coronary artery bypass grafting: anatomical,functional and clinical aspects

Although the benefits of using the left internal mammary artery to bypass the left anterior descending artery (LAD) have been extensively ascertained, freedom from major cardiovascular events and survival after coronary artery bypass grafting (CABG) also correlate with the completeness of revascularisation. Hence, careful selection of the second-best graft conduit is crucial for CABG success. The more widespread use of saphenous vein grafts contrasts with the well-known long-term efficacy of multiple arterial grafting, which struggles to emerge as the procedure of choice due to concerns over increased technical difficulties and higher risk of postoperative complications. Conduit choice is at the discretion of the operator instead of being discussed by the heart team, where cardiologists are not usually engaged in such decisions due to a hypothetical lack of technical knowledge. Furthermore, according to the ESC/EACTS guidelines, traditional CABG remains the gold standard for multi-vessel coronary artery disease with complex LAD stenosis, but hybrid procedures using percutaneous coronary intervention for non-LAD targets could combine the best of two worlds. With the aim of raising the cardiologist’s awareness of the surgical treatment options, we provide a comprehensive overview of the anatomical, functional and clinical aspects guiding the decision-making process in CABG strategy.     

A Comparison of Genome-Wide DNA Methylation Patterns between Different Vascular Tissues from Patients with Coronary Heart Disease

Epigenetic mechanisms of gene regulation in context of cardiovascular diseases are of considerable interest. So far, our current knowledge of the DNA methylation profiles for atherosclerosis affected and healthy human vascular tissues is still limited. Using the Illumina Infinium Human Methylation27 BeadChip, we performed a genome-wide analysis of DNA methylation in right coronary artery in the area of advanced atherosclerotic plaques, atherosclerotic-resistant internal mammary arteries, and great saphenous veins obtained from same patients with coronary heart disease. The resulting DNA methylation patterns were markedly different between all the vascular tissues. The genes hypomethylated in athero-prone arteries to compare with atherosclerotic-resistant arteries were predominately involved in regulation of inflammation and immune processes, as well as development. The great saphenous veins exhibited an increase of the DNA methylation age in comparison to the internal mammary arteries. Gene ontology analysis for genes harboring hypermethylated CpG-sites in veins revealed the enrichment for biological processes associated with the development. Four CpG-sites located within the MIR10B gene sequence and about 1 kb upstream of the HOXD4 gene were also confirmed as hypomethylated in the independent dataset of the right coronary arteries in the area of advanced atherosclerotic plaques in comparison with the other vascular tissues. The DNA methylation differences observed in vascular tissues of patients with coronary heart disease can provide new insights into the mechanisms underlying the development of pathology and explanation for the difference in graft patency after coronary artery bypass grafting surgery.     

SPY Imaging Assessment Correlates With Transesophageal Echocardiogram Assessment of Ventricular Function During Off-Pump Coronary Artery Bypass Grafting

Intraoperative assessment of graft anastomoses is commonly performed after off-pump coronary artery bypass grafting (OPCAB). The SPY imaging system allows intraoperative graft assessment. We document correlation between intraoperative SPY images and wall motion abnormality by transesophageal echocardiogram (TEE) during OPCAB. A 79-year-old female underwent OPCAB. Intraoperative graft patency assessment was performed with the SPY and left ventricular wall motion was assessed by TEE. SPY imaging demonstrated poor flow trough the distal vein graft anastomosis to the posterior descending artery, which correlated with a new posterior wall motion hypokinesis. After graft revision, SPY imaging demonstrated good distal flow and the TEE demonstrated normalization of the left ventricular posterior wall motion. SPY technology allows the surgeon to accurately assess graft patency intraoperatively and allows immediate correction of a technical problem.     

Bilateral coronary fistulae to pulmonic valve in presence of severe three-vessel coronary artery disease

A 62-year-old man was admitted to the coronary care unit due to anginal pain and palpitations--coronary angiography revealed three-vessel coronary artery disease. The unexpected finding was the presence of coronary to pulmonary artery fistulae bilaterally, from both the proximal RCA and the proximal LAD. Right heart catheterization revealed normal right ventricular and pulmonary artery pressure and absence of hemodynamically significant left to right shunt. The patient underwent a triple coronary bypass including the closure of bilateral fistulae, which were draining into the left sinus of the pulmonary valve. One month after the operation he was in good health and had no complaints. Bilateral coronary artery fistulae is a rare anomaly diagnosed in 0.002-0.0013% of adult coronary angiograms. (Int J Cardiovasc Intervent 1999; 2: 249-251).     

Transcatheter aortic valve implantation and hybrid coronary artery revascularization: time to combine them

We report on simultaneous off-pump coronary artery bypass grafting to the left anterior descending artery, modified transapical aortic valve implantation, and stenting of the circumflex and right coronary arteries in an 84-year-old patient. The poly-morbid patient with a logistic EuroSCORE of 85% experienced recent myocardial infarction; the left ventricular ejection fraction was reduced to 20%. Postoperative recovery was fast and short. The strategy described is the next logical step in broadening the indication for transcatheter aortic valve interventions.     

Hemodynamics of patient-specific aorta-pulmonary shunt configurations

Optimal hemodynamics in aorta-pulmonary shunt reconstruction is essential for improved post-operative recovery of the newborn congenital heart disease patient. However, prior to in vivo execution, the prediction of post-operative hemodynamics is extremely challenging due to the interplay of multiple confounding physiological factors. It is hypothesized that the post-operative performance of the surgical shunt can be predicted through computational blood flow simulations that consider patient size, shunt configuration, cardiac output and the complex three-dimensional disease anatomy. Utilizing only the routine patient-specific pre-surgery clinical data sets, we demonstrated an intelligent decision-making process for a real patient having pulmonary artery atresia and ventricular septal defect. For this patient, a total of 12 customized candidate shunt configurations are contemplated and reconstructed virtually using a sketch-based computer-aided anatomical editing tool. Candidate shunt configurations are evaluated based on the parameters that are computed from the flow simulations, which include 3D flow complexity, outlet flow splits, shunt patency, coronary perfusion and energy loss. Our results showed that the modified Blalock-Taussig (mBT) shunt has 12% higher right pulmonary artery (RPA) and 40% lower left pulmonary artery (LPA) flow compared to the central shunt configuration. Also, the RPA flow regime is distinct from the LPA, creating an uneven flow split at the pulmonary arteries. For all three shunt sizes, right mBT innominate and central configurations cause higher pulmonary artery (PA) flow and lower coronary artery pressure than right and left mBT subclavian configurations. While there is a trade-off between energy loss, flow split and coronary artery pressure, overall, the mBT shunts provide sufficient PA perfusion with higher coronary artery pressures and could be preferred for similar patients having PA overflow risk. Central shunts would be preferred otherwise particularly for cases with very low PA overflow risk.