Effect of angioplasty and grafting on porcine vascular nerves: a potential neurotropic role for endothelin-1

The most commonly performed procedure for treating coronary artery stenosis is percutaneous transluminal coronary angioplasty (PTCA) and, where the vessel lumen is severely narrowed, coronary artery bypass grafting (CABG). In PTCA, regions of atherosclerotic plaques are disrupted, and the vessel lumen increased by inflating a balloon catheter. In CABG an autologous saphenous vein into coronary artery interposition graft is performed in order to bypass occluded regions of epicardial coronary arteries. Both interventions cause varying degrees of vascular damage and the long-term efficacy of these procedures is limited by a high incidence of neointimal formation and subsequent vascular restenosis (Bach et al. 1994; Bryan & Angelini, 1994).
The endothelium-derived constrictor peptide, endothelin-1 (ET-1) (Yanagisawa et al. 1988), also possesses mitogenic activity on vascular smooth muscle cells (Hirata et al. 1989) and has been suggested as playing a role in atherosclerosis (Dashwood et al. 1993; Zeiher et al. 1994) and intimal hyperplasia (Dashwood et al. 1993; Douglas et al. 1994).     

The effect of previous coronary-artery bypass surgery on the prognosis of patients with diabetes who have acute myocardial infarction. Bypass Angioplasty Revascularization Investigation Investigators

BACKGROUND: Acute myocardial infarction in patients with diabetes is associated with high mortality. We studied whether previous revascularization by coronary-artery bypass grafting (CABG), as compared with percutaneous transluminal coronary angioplasty (PTCA), influences the prognosis in such patients. METHODS: We classified all patients eligible for the Bypass Angioplasty Revascularization Investigation who underwent coronary revascularization within three months after entry into the study according to whether they had diabetes and whether they had undergone CABG, either initially or after PTCA. The protective effect of CABG with regard to mortality in the presence and in the absence of subsequent spontaneous Q-wave myocardial infarction was estimated with the use of Cox regression models. RESULTS: Among the 641 patients with diabetes and the 2962 without diabetes, the cumulative five-year rates of death were 20 percent and 8 percent, respectively (P<0.001), and the five-year rates of spontaneous Q-wave myocardial infarction were 8 percent and 4 percent (P<0.001). CABG greatly reduced the risk of death after spontaneous Q-wave myocardial infarction in the patients with diabetes (relative risk, 0.09; 95 percent confidence interval, 0.03 to 0.29). Among patients with diabetes who had undergone CABG but did not have spontaneous Q-wave myocardial infarctions, the corresponding relative risk of death was 0.65 (95 percent confidence interval, 0.45 to 0.94). Among the patients without diabetes, no protective effect of CABG was evident. CONCLUSIONS: Among patients with diabetes, previous coronary bypass surgery, as compared with coronary angioplasty, has a highly favorable influence on prognosis after acute myocardial infarction and a smaller beneficial effect among patients who do not have infarction. These findings should influence the type of coronary revascularization procedure selected for patients with diabetes who have multivessel coronary artery disease.     

The role of balloon angioplasty in the management of coronary artery disease

PTCA is a new technique for the treatment of certain patients with coronary artery disease. It involves dilatation of stenotic segments of artery using a balloon catheter, and is carried out in cardiac catheterization laboratories. If successful, the need for coronary bypass surgery may be removed, although some patients with initially successful PTCA will come to surgery eventually. Successful PTCA is associated with relief of angina, improved angiographic appearances and coronary perfusion. The primary success rate is between 65% and 80%, and the restenosis rate approximately 25%. 80% of patients will be angina free one year after PTCA. In this paper the indications, contraindications, technology, results and complications are discussed.     

A comparison of angioplasty with medical therapy in the treatment of single-vessel coronary artery disease. Veterans Affairs ACME Investigators.

BACKGROUND. Despite the widespread use of percutaneous transluminal coronary angioplasty (PTCA), only a few prospective trials have assessed its efficacy. We compared the effects of PTCA with those of medical therapy on angina and exercise tolerance in patients with stable single-vessel coronary artery disease. METHODS. Patients with 70 to 99 percent stenosis of one epicardial coronary artery and with exercise-induced myocardial ischemia were randomly assigned either to undergo PTCA or to receive medical therapy and were evaluated monthly. The patients assigned to PTCA were urged to have repeat angioplasty if their symptoms suggested restenosis. After six months, all the patients had repeat exercise testing and coronary angiography. RESULTS. A total of 107 patients were randomly assigned to medical therapy and 105 to PTCA. PTCA was clinically successful in 80 of the 100 patients who actually had the procedure, with an initial reduction in mean percent stenosis from 76 to 36 percent. Two patients in the PTCA group required emergency coronary-artery bypass surgery. By six months after the procedure, 16 patients had had repeat PTCA. Myocardial infarction occurred in five patients assigned to PTCA and in three patients assigned to medical therapy. At six months 64 percent of the patients in the PTCA group (61 of 96) were free of angina, as compared with 46 percent of the medically treated patients (47 of 102; P less than 0.01). The patients in the PTCA group were able to increase their total duration of exercise more than the medical patients (2.1 vs. 0.5 minutes, P less than 0.0001) and were able to exercise longer without angina on treadmill testing (P less than 0.01). CONCLUSIONS. For patients with single-vessel coronary artery disease, PTCA offers earlier and more complete relief of angina than medical therapy and is associated with better performance on the exercise test. However, PTCA initially costs more than medical treatment and is associated with a higher frequency of complications.     

Underuse of coronary revascularization procedures in patients considered appropriate candidates for revascularization

BACKGROUND: Ratings by an expert panel of the appropriateness of treatments may offer better guidance for clinical practice than the variable decisions of individual clinicians, yet there have been no prospective studies of clinical outcomes. We compared the clinical outcomes of patients treated medically after angiography with those of patients who underwent revascularization, within groups defined by ratings of the degree of appropriateness of revascularization in varying clinical circumstances. METHODS: This was a prospective study of consecutive patients undergoing coronary angiography at three London hospitals. Before patients were recruited, a nine-member expert panel rated the appropriateness of percutaneous transluminal coronary angioplasty (PTCA) and coronary-artery bypass grafting (CABG) on a nine-point scale (with 1 denoting highly inappropriate and 9 denoting highly appropriate) for specific clinical indications. These ratings were then applied to a population of patients with coronary artery disease. However, the patients were treated without regard to the ratings. A total of 2552 patients were followed for a median of 30 months after angiography. RESULTS: Of 908 patients with indications for which PTCA was rated appropriate (score, 7 to 9), 34 percent were treated medically; these patients were more likely to have angina at follow-up than those who underwent PTCA (odds ratio, 1.97; 95 percent confidence interval, 1.29 to 3.00). Of 1353 patients with indications for which CABG was considered appropriate, 26 percent were treated medically; they were more likely than those who underwent CABG to die or have a nonfatal myocardial infarction--the composite primary outcome (hazard ratio, 4.08; 95 percent confidence interval, 2.82 to 5.93)--and to have angina (odds ratio, 3.03; 95 percent confidence interval, 2.08 to 4.42). Furthermore, there was a graded relation between rating and outcome over the entire scale of appropriateness (P for linear trend=0.002). CONCLUSIONS: On the basis of the ratings of the expert panel, we identified substantial underuse of coronary revascularization among patients who were considered appropriate candidates for these procedures. Underuse was associated with adverse clinical outcomes.     

Hemodynamic effects of the geometric dimensions of graft vessels in coronary artery bypass graft models.

The objectives of this investigation are to evaluate the rheologic properties in atherosclerotic disease treated with the various coronary artery bypass graft (CABG) models by numerical analysis, we used four different CABG models for the assessment of spatial fluctuation in wall shear stress, pressure variation and mass flow rate with Carreau model and Navier-Stokes equation. Wall shear stress was higher in a naturally tapered model (model 1) and a constant (non-tapered) diameter of the graft vessel the same as the distal LAD (model 4) than in others. Pressure variation along the native coronary artery and graft vessels was higher in a model 4, model 1 than in a reverse tapering model (model 2) and a constant diameter of the graft vessel the same as the proximal LAD (model 3). The mass flow rate of the distal part (kg/sec,.m(o)) was the highest in model 3. This study suggests that in vitro spatial simulation following CABG revealed that small caliber or tapered graft vessels have adverse hemodynamic effects on the native and graft vessels. By this technique it is possible to simulate the optimal distribution of local hemodynamic variables in patients treated with CABG, also to minimize the degeneration of graft vessel.     

Stenting versus Bypass Surgery for the Treatment of Left Main Coronary Artery Disease

Based on data comparing coronary-artery bypass grafting (CABG) with medical therapy, the current guidelines recommend CABG as the treatment of choice for patients with left main coronary artery (LMCA) disease. Percutaneous coronary intervention (PCI) can be selectively performed in patients who are candidates for revascularization but who are ineligible for CABG. Current evidence indicates that stenting results in mortality and morbidity rates compared favorably with those seen after CABG. Data from several extensive registries and a large clinical trial may have prompted many interventional cardiologists to choose PCI with stenting as an alternative treatment option for such patients. In addition, these data may inform future guidelines and support the need for well-designed, adequately powered, prospective, randomized trials comparing the two revascularization strategies.     

A procedure to simulate coronary artery bypass graft surgery

In coronary artery bypass graft (CABG) surgery the involved tissues are overstretched, which may lead to intimal hyperplasia and graft failure. We propose a computational methodology for the simulation of traditional CABG surgery, and analyze the effect of two clinically relevant parameters on the artery and graft responses, i.e., incision length and insertion angle for a given graft diameter. The computational structural analyses are based on actual three-dimensional vessel dimensions of a human coronary artery and a human saphenous vein. The analyses consider the structure of the end-to-side anastomosis, the residual stresses and the typical anisotropic and nonlinear vessel behaviors. The coronary artery is modeled as a three-layer thick-walled tube. The finite element method is employed to predict deformation and stress distribution at various stages of CABG surgery. Small variations of the arterial incision have relatively big effects on the size of the arterial opening, which depends solely on the residual stress state. The incision length has a critical influence on the graft shape and the stress in the graft wall. Stresses at the heel region are higher than those at the toe region. The changes in the mechanical environment are severe along all transitions between the venous tissue and the host artery. Particular stress concentrations occur at the incision ends. The proposed computational methodology may be useful in designing a coronary anastomotic device for reducing surgical trauma. It may improve the quantitative knowledge of vessel diseases and serve as a tool for virtual planning of vascular surgery.     

Intravenous thrombolytic treatment for acute myocardial infarction. Effects of early intervention and early examination

Intravenous thrombolytic treatment (streptokinase or anisoylated plasminogen streptokinase activator complex (APSAC) was given to 50 consecutive patients within 3 hours after onset of symptoms of acute myocardial infarction. Left heart catheterisation with coronary angiography and simultaneous double view left ventriculography were performed approximately 4 hours after start of thrombolytic treatment. This examination showed that the acute infarct-related coronary artery was open in 36 patients (72%) and closed in 14 patients (28%). A higher left ventricular ejection fraction was found among patients with open, than among patients with closed infarct-related artery (58.8% vs. 48.4%, p = 0.05). The group with open artery also had a lower score of regional left ventricular dysfunction (1.7 vs. 2.4, p less than 0.05, on a scale from 0-3). Single, double and triple vessel coronary heart disease was found in 22, 14 and 13 patients respectively. Mean age was lower in the group with single vessel disease as compared to double and triple vessel disease (48.4 years vs. 53.4 and 55.4 years, p less than 0.05 and p less than 0.005). Independently of whether the infarct-related artery was open or closed, there tended to be an inverse correlation between number of diseased vessels and preservation of left ventricular function (statistical significance only for single vessel versus triple vessel disease with respect to score of regional left ventricular dysfunction, 1.8 vs. 2.4, p less than 0.05). These findings suggest that early thrombolytic treatment within 3 hours of onset of symptoms may preserve myocardial tissue during the evolution of acute infarction. Furthermore, a presumably better collateralisation from adjacent coronary arteries without stenoses may be important for myocardial preservation. Finally, early angiographic examination can be performed safely and is a good support for determination of further treatment, which in the actual patients was coronary bypass surgery in 8 cases, transluminal angioplasty, PTCA, in 20 cases, and medical treatment alone in 22 cases.     

Percutaneous transluminal coronary angioplasty without thrombolytic therapy in acute myocardial infarction

Percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI) was performed in 42 patients (37 males, 5 females, average age 53 years). Recanalization of the stenosed or occluded infarction-related coronary artery was achieved within the first 14 to 50 min from the start of catheterization in 95% of cases. Three patients were transferred for emergency coronary bypass graft surgery (CABG) because of major multiple coronary lesions, immediately after angiographically successful PTCA. One of the patients died in cardiogenic shock. Four patients died between days 5 to 15 of hospitalization. Repeat coronary angiography was done in 27 of the 37 survivors at a mean interval of 2.5 months after AMI. Total reocclusion was found in 6 patients. The recanalized coronary artery had prevented its patency in 78% of the cases; restenosis was found in 5 patients, and was successfully dealt with renewed angioplasty in 3 patients. While the ejection fraction (EF) had remained largely unchanged, there was some improving tendency of left ventricular segmental kinetics, particularly in case of anterior wall infarction. PTCA without thrombolytic therapy seems to provide an effective and relatively prompt recanalizing procedure in the complex management of AMI.     

Factors influencing acute high-grade restenosis in emergency percutaneous transluminal coronary angioplasty for acute myocardial infarction

We studied the factors which may induce acute high grade restenosis in emergency percutaneous transluminal coronary angioplasty (PTCA). PTCA was attempted in 50 patients with acute myocardial infarction, and the balloon catheter passed successfully across the occlusion site in 47 (94%) of the patients. These 47 patients were analyzed. "Acute restenosis" was defined as a lesion which was revascularized to less than 50% luminal reduction narrowed again to more than 75% luminal reduction 5 min after the balloon inflation. Univariate and multivariate analyses were used for determining factors which significantly influenced acute restenosis. The incidence of at least one restenosis episode was 45%. Multiple regression analysis selected 5 factors associated significantly with an increased rate of acute restenosis: 1) angiographic evidence of dissection, 2) lesion in the right coronary artery (RCA), 3) lack of or insufficient administration of thrombolytic agent preceding PTCA, 4) curved lesion and 5) relatively small balloon/artery diameter ratio. Acute restenosis correlated significantly with late reocclusion. This study indicates that it is important to administer a thrombolytic agent prior to emergency PTCA, and to use an adequately sized balloon to the artery when the acute restenosis occurs by using relatively smaller sized balloon. The present data also demonstrated that patients with RCA and a curved lesion have a relatively high risk of acute restenosis. This study indicates how patients with relatively high risk of acute restenosis may be identified.     

Combined off-pump coronary revascularization and lung resection

Concomittant severe coronary artery disease and lung malignancies occur rarely. Combined conventional coronary artery bypass grafting (CABG) with the use of cardiopulmonary bypass (CPB) with lung resection posses several perioperative and postoperative problems related to extracorporeal circulation and heparinization. The avoidance of CPB may be advantageous by decreasing blood loss, pulmonary complications and hospital stay. Further, exposure to the immunosuppressive and inflammatory effects of CPB may have deleterious impact on tumor growth and dissemination. Off-pump CABG makes the combined procedure safer as it abolishes the complications of CPB. We report two patients with the diagnosis of severe coronary artery disease and lung malignancies, underwent off-pump CABG and lung resections in the same surgical setting.     

Uterine artery as an arterial conduit for coronary artery bypass graft (CABG) surgery in women: A role for estrogen-receptor alpha (ER-α) in the prevention of post-CABG accelerated atherosclerosis and graft disease

Coronary artery bypass graft (CABG) surgery is the standard of care in the treatment of advanced coronary artery disease (CAD). In order to bypass coronary occlusions, CABG surgery traditionally employs grafts from the left internal thoracic/mammary artery (LITA/IMA), radial artery (RA), and greater saphenous vein (SV). The risk of CABG failure is reported to be higher, or at best similar, for women than for men, and it relates primarily to post-operative accelerated atherosclerosis leading to graft stenosis and recurrent angina, a phenomenon known as “coronary artery bypass graft disease”. In this paper, the authors hypothesize that employing an alternative arterial conduit may help reduce the rate of post-CABG accelerated atherosclerosis in women, and propose that a uterine artery specimen be used instead. Given its greater density of estrogen-receptor alpha (ER-α) relative to other mammalian endothelial cells in the vasculature, uterine arteries may exhibit important anti-atherosclerotic properties. Theoretically, this effect may be amplified with the adjuvant administration of low-dose selective ER-α agonist modulator (SERM) therapy.     

Aggressive management of acute myocardial infarction

Acute transmural myocardial infarction is usually caused by a coronary thrombus along with fixed coronary artery stenosis. Myocardial necrosis can be interrupted by the prompt use of pharmacologic and mechanical thrombolysis. Intravenous streptokinase and urokinase have been associated with approximately a 45 percent recanalization rate while the newer agent, recombinant human tissue-type plasminogen activator (rt-PA), has an average lysis rate of 70 percent intravenously. Intracoronary streptokinase and urokinase have a similar 75 percent lysis rate, but with additional costs and morbidity. Percutaneous transluminal angioplasty (PTCA) is often indicated to correct an underlying stenosis, the time of which depends on the experience and expertise of the PTCA team.     

Coronary magnetic resonance angiography for the detection of coronary stenoses.

BACKGROUND: An accurate, noninvasive technique for the diagnosis of coronary disease would be an important advance. We investigated the accuracy of coronary magnetic resonance angiography among patients with suspected coronary disease in a prospective, multicenter study. METHODS: Coronary magnetic resonance angiography was performed during free breathing in 109 patients before elective x-ray coronary angiography, and the results of the two diagnostic procedures were compared. RESULTS: A total of 636 of 759 proximal and middle segments of coronary arteries (84 percent) were interpretable on magnetic resonance angiography. In these segments, 78 (83 percent) of 94 clinically significant lesions (those with a > or = 50 percent reduction in diameter on x-ray angiography) were also detected by magnetic resonance angiography. Overall, coronary magnetic resonance angiography had an accuracy of 72 percent (95 percent confidence interval, 63 to 81 percent) in diagnosing coronary artery disease. The sensitivity, specificity, and accuracy for patients with disease of the left main coronary artery or three-vessel disease were 100 percent (95 percent confidence interval, 97 to 100 percent), 85 percent (95 percent confidence interval, 78 to 92 percent), and 87 percent (95 percent confidence interval, 81 to 93 percent), respectively. The negative predictive values for any coronary artery disease and for left main artery or three-vessel disease were 81 percent (95 percent confidence interval, 73 to 89 percent) and 100 percent (95 percent confidence interval, 97 to 100 percent), respectively. CONCLUSIONS: Among patients referred for their first x-ray coronary angiogram, three-dimensional coronary magnetic resonance angiography allows for the accurate detection of coronary artery disease of the proximal and middle segments. This noninvasive approach reliably identifies (or rules out) left main coronary artery or three-vessel disease.     

冠状动脉旁路移植治疗冠状动脉肌桥9例分析

目的回顾冠状动脉旁路移植术治疗症状性肌桥的外科治疗经验及结果。方法选取2004年3月至2011年1月因冠状动脉肌桥导致冠状幼脉血流堵塞需行冠状动脉旁路移植术的患者资料9例,采用胸廊内动脉到前降支进行旁路移植,2例取大隐静脉与其他病变冠状动脉进行旁路移植。结果全组无患者死亡,无术中相关并发症发生。所有患者随访4个月至7年,临床症状均明显改善,无心绞痛发生,无心肌梗死及其他主要心血管不良事件（再血管化或死亡等）发生。结论冠状动脉旁路移植治疗有症状的肌桥安全、有效。     

Percutaneous transluminal coronary angioplasty in a child with Kawasaki disease.

A successful attempt at percutaneous transluminanl coronary angioplasty (PTCA) to relieve stenosis of the mid-portion of the left anterior descending artery was achieved in a 6-year 9-month old boy who had multiple coronary aneurysms and stenosis due to Kawasaki disease. Despite the progression of coronary stenosis he had been well except for the perfusion defect of the anterior wall of myocardium on 99mTc-MIBI SPECT with dipyridamole infusion until PTCA was carried out after 4-year 4-months of the onset of illness. The area of stenosis was 70% before PTCA and 20% after PTCA. No restenosis at the site of PTCA was observed on follow-up angiography at 26 months after PTCA. This successful attempt may indicate that this procedure should be considered early in subclinical stenosis to prevent ischemic cardiac damage.     

A randomized trial of immediate versus delayed elective angioplasty after intravenous tissue plasminogen activator in acute myocardial infarction

We compared the efficacy of immediate coronary angioplasty after acute myocardial infarction with that of elective angioplasty at 7 to 10 days in patients treated initially with intravenous tissue plasminogen activator. The plasminogen activator (150 mg) was administered 2.95 +/- 1.1 hours after the onset of symptoms, to 386 patients with acute myocardial infarction. Ninety minutes later, patency of the coronary artery serving the area of the infarct was demonstrated by coronary angiography in 288 patients (75 percent). Bleeding problems were frequently encountered, as evidenced by an average drop in hematocrit of 11.7 +/- 6.5 points from base line to nadir and by a need for transfusion not related to bypass surgery in 70 patients (18 percent). After successful thrombolysis, 197 patients with a patent but severely stenotic vessel suitable for angioplasty were randomly assigned to immediate angioplasty (n = 99) or, if indicated 7 to 10 days after infarction, to deferred (elective) angioplasty (n = 98). The incidence of reocclusion was similar in the two groups: 11 percent in the group assigned to immediate angioplasty and 13 percent in the group assigned to elective angioplasty. Neither group had a significant improvement in global left ventricular function, and regional wall motion in the infarct zone improved to a similar extent in the two groups. In the elective-angioplasty group, the rate of crossover to emergency angioplasty for recurrent ischemia was 16 percent (whereas 5 percent of the immediate-angioplasty group required emergency repeated angioplasty; P = 0.01). In 14 percent of the patients in the elective group, the stenosis was substantially reduced by the time of the seven-day follow-up angiography, obviating the need for angioplasty. We conclude that in patients with initially successful thrombolysis and suitable coronary-artery anatomy, immediate angioplasty offers no clear advantage over delayed elective angioplasty.     

Aspirin and dipyridamole in the prevention of restenosis after percutaneous transluminal coronary angioplasty

To examine the role of antiplatelet therapy in the prevention of arterial restenosis after percutaneous transluminal coronary angioplasty (PTCA), we conducted a randomized, double-blind, placebo-controlled study in 376 patients. The active treatment consisted of an oral aspirin-dipyridamole combination (330 mg-75 mg) given three times daily, beginning 24 hours before PTCA. Eight hours before PTCA, the oral dipyridamole was replaced with intravenous dipyridamole at a dosage of 10 mg per hour for 24 hours, and oral aspirin was continued. Sixteen hours after PTCA, the initial combination was reinstituted. Treatment was continued in patients with a successfully dilated vessel until follow-up angiography four to seven months after PTCA--or earlier, if symptoms dictated. Of 249 patients who underwent follow-up angiography, 37.7 percent of patients receiving the active drug had restenosis in at least one segment, as compared with 38.6 percent of patients taking placebo (P not significant). The number of stenotic segments was virtually the same in the two groups. Among the 376 randomized patients, there were 16 periprocedural Q-wave myocardial infarctions--13 in the placebo group and 3 in the active-drug group (6.9 percent vs. 1.6 percent, P = 0.0113). Although the use of this antiplatelet regimen before and after PTCA did not reduce the six-month rate of restenosis after successful coronary angioplasty, it markedly reduced the incidence of transmural myocardial infarction during or soon after PTCA. Thus, the short-term use of antiplatelet agents in relation to PTCA can be recommended.     

Immune and non-immune mechanisms that determine vasculitis and coronary artery aneurysm topography in Kawasaki disease and MIS-C

The overlap between multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) including coronary artery aneurysms (CAA) and broadly shared gastrointestinal and mucocutaneous disease is poorly defined. In this perspective, we highlight common age-related extravascular epicardial microanatomical and immunological factors that might culminate in CAA expression in both MIS-C and KD. Specifically, the coronary vasa vasorum originates outside the major coronary arteries. Widespread inflammation in the epicardial interstitial compartment in shared between KD and MIS-C. Age-related changes in the neonatal and immature coronary vasculature including the impact of coronary artery biomechanical factors including coronary vessel calibre, age-related vessel distensibility, flow, and vessel neurovascular innervation may explain the decreasing CAA frequency from neonates to older children and the virtual absence of CAA in young adults with the MIS-C phenotype. Other KD and MIS-C features including mucocutaneous disease with keratinocyte-related immunopathology corroborate that disease phenotypes are centrally influenced by inflammation originating outside vessel walls but a potential role for primary coronary artery vascular wall inflammation cannot be excluded. Hence, common extravascular originating tissue-specific responses to aetiologically diverse triggers including superantigens may lead to widespread interstitial tissue inflammation characteristically manifesting as CAA development, especially in younger subjects. Given that CAA is virtually absent in adults, further studies are needed to ascertain whether epicardial interstitial inflammation may impact on both coronary artery physiology and cardiac conduction tissue and contribute to cardiovascular disease- a hitherto unappreciated consideration.