Clifford A. Bucknall

Circulating Humoral Factors and Endothelial Progenitor Cells in Patients With Differing Coronary Collateral Support

Background—The mechanisms underlying the variation in collateral formation between patients, even with similar patterns of coronary artery disease, remain unclear. This study investigates whether circulating humoral or cellular factors can provide an insight into this variation. Methods and Results—Thirty patients with isolated left anterior descending coronary artery disease underwent percutaneous coronary intervention with collateral flow index (CFI) determined using a pressure wire. Patients with inadequate (CFI <0.25) compared with those with adequate (CFI ≥0.25) collateral support had, or tended to have, lower concentrations of coronary sinus growth factors and plasma exerting a weaker effect on endothelial cell migration and angiogenesis in vitro. However, there was an inverse correlation between serum mitogenicity and CFI (r =−0.61, P <0.01). No significant differences were detected between the 2 groups in plasma levels of total vascular endothelial growth factor, vascular endothelial growth factor165, or placental growth factor. There was a strong positive correlation between numbers of CD34/CD133-positive circulating hemopoietic precursor cells and CFI (r =0.75, P <0.001). In patients with inadequate, compared with those with adequate, CFI, the numbers of differentiated endothelial progenitor cells (EPCs) appearing in the circulation and in culture were significantly reduced by 75% (P <0.05) and 70% (P <0.05), respectively. Conclusions—In this study, inadequate coronary collateral development is associated with reduced numbers of circulating EPCs and impaired chemotactic and proangiogenic but not mitogenic activity. These findings are consistent with current efforts to enhance collateral formation by augmentation of circulating EPCs.

Systemic inflammation in unstable angina is the result of myocardial necrosis

OBJECTIVES We investigated whether the source of the acute phase response in unstable angina (UA) lay within the culprit coronary plaque or distal myocardium. BACKGROUND An inflammatory response is an important component of the acute coronary syndromes. However, its origin and mechanism remain unclear. METHODS In 94 stable patients undergoing coronary angiography, the relationship between systemic levels of tumor necrosis factor (TNF)-alpha, interleukin-6 (IL-6) and C-reactive protein (CRP) and extent of atherosclerosis was studied. The temporal relationship between these markers and troponin T (TnT) was determined in 91 patients with UA. Cytokine levels were measured in the aortic root and coronary sinus of 36 unstable patients. RESULTS There was no relationship found between stable coronary atherosclerosis and inflammatory marker levels. Compared with this group, admission levels of IL-6 (3.6 +/- 0.3 ng/ml vs. 10.7 +/- 1.7 ng/ml, p < 0.05) and CRP (2.3 +/- 0.1 mg/l vs. 4.6 +/- 0.6 mg/l, p < 0.05) were elevated in patients with UA. In this group, IL-6 and CRP remained elevated in those who subsequently experienced major adverse cardiac events. This inflammatory response occurred in parallel to the appearance of TnT. Both TNF-alpha (19.2 +/- 3.4 ng/ml vs. 17.1 +/- 3.3 ng/ml, p < 0.001) and IL-6 (10.3 +/- 1.4 ng/ml vs. 7.7 +/- 1.1 ng/ml, p < 0.01) were elevated in the coronary sinus compared with aortic root in patients with UA. This was principally observed in those who were TnT positive. There was no cytokine gradient across the culprit plaque. CONCLUSIONS There is an intracardiac inflammatory response in UA that appears to be the result of low-grade myocardial necrosis. The ruptured plaque does not appear to contribute to the acute phase response.

Late intervention after anterior myocardial infarction: Effects on left ventricular size, function, quality of life, and exercise tolerance: Results of the open artery trial (TOAT study)

OBJECTIVE We sought to conduct a randomized trial comparing late revascularization with conservative therapy in symptom-free patients after acute myocardial infarction (AMI). BACKGROUND In the absence of ischemia, the benefits of reperfusion late after AMI remain controversial. However, the possibility exists that an open infarct related artery benefits healing post AMI. METHODS Of 223 patients enrolled with Q-wave anterior AMI, 66 with isolated persistent occlusion of the left anterior descending coronary artery (LAD) were randomized to the following treatments: 1) medical therapy (closed artery group; n = 34) or 2) late intervention and stent to the LAD + medical therapy (open artery group; n = 32). The study was powered to compare left ventricular (LV) end-systolic volume between the two groups 12 months post AMI. RESULTS Late intervention 26 +/- 18 days post AMI resulted in significantly greater LV end-systolic and end-diastolic volumes at 12 months than medical therapy alone (106.6 +/- 37.5 ml vs. 79.7 +/- 34.4 ml, p < 0.01 and 162.0 +/- 51.4 ml vs. 130.1 +/- 46.1 ml, p < 0.01, respectively). Exercise duration and peak workload significantly increased in both groups from 6 weeks to 12 months post AMI, although absolute values were greater in the open artery group. Quality of life scores tended to deteriorate during this time interval in the closed artery patients but remained unchanged in the open artery patients. Coronary angiography at 1 year documented a low incidence of intergroup cross-over (spontaneous recanalization in 19% and closure in 11%). CONCLUSIONS In the present study, recanalization of occluded infarct-related arteries in symptom-free patients approximately 1 month post AMI had an adverse effect on remodeling but tended to increase exercise tolerance and improve quality of life.

Simulation of cardiac pathologies using an electromechanical biventricular model and XMR interventional imaging

Simulating cardiac electromechanical activity is of great interest for a better understanding of pathologies and for therapy planning. Design and validation of such models is difficult due to the lack of clinical data. XMR systems are a new type of interventional facility in which patients can be rapidly transferred between X-ray and MR systems. Our goal is to design and validate an electromechanical model of the myocardium using XMR imaging. The proposed model is computationally fast and uses clinically observable parameters. We present the integration of anatomy, electrophysiology, and motion from patient data. Pathologies are introduced in the model and simulations are compared to measured data. Initial qualitative comparison on the two clinical cases presented is encouraging. Once fully validated, these models will make it possible to simulate different interventional strategies.

Exercise-induced ischemia initiates the second window of protection in humans independent of collateral recruitment

OBJECTIVES This study was designed to examine if exercise-induced ischemia initiated late preconditioning in humans that becomes manifest during subsequent exercise and serial balloon occlusion of the left anterior descending coronary artery (LAD). BACKGROUND The existence of late preconditioning in humans is controversial. We therefore compared myocardial responses to exercise-induced and intracoronary balloon inflation-induced ischemia in two groups of patients subjected to different temporal patterns of ischemia. METHODS Thirty patients with stable angina secondary to single-vessel LAD disease underwent percutaneous coronary intervention (PCI) after two separate exercise tolerance test (ETT) protocols designed to investigate isolated early preconditioning (IEP) alone or the second window of protection (SWOP). The IEP subjects underwent three sequential ETTs at least two weeks before PCI. The SWOP subjects underwent five sequential ETTs commencing 24 h before PCI. RESULTS During PCI there was no significant difference in intracoronary pressure-derived collateral flow index (CFI) between groups (IEP = 0.15 +/- 0.13, SWOP = 0.19 +/- 0.15). In SWOP patients, compared with the initial ETT, the ETT performed 24 h later had a 40% (p < 0.001) increase in time to 0.1-mV ST depression and a 60% (p < 0.05) decrease in ventricular ectopic frequency. During the first balloon inflation, peak ST elevation was reduced by 49% (p < 0.05) in the SWOP versus the IEP group, and the dependence on CFI observed in the IEP group was abolished (analysis of covariance, p < 0.05). The significant attenuation of ST elevation (47%, p < 0.005) seen at the time of the second inflation in the IEP patients was not seen in the SWOP patients. CONCLUSIONS Exercise-induced ischemia triggers late preconditioning in humans, which becomes manifest during exercise and PCI. This is the first evidence that ischemia induced by coronary occlusion is attenuated in humans by a late preconditioning effect induced by exercise.

Simulation of the electromechanical activity of the heart using XMR interventional imaging

Simulating cardiac electromechanical activity is of great interest for a better understanding of pathologies and therapy planning. Design and validation of such models is difficult due to the lack of clinical data. XMR systems are a new type of interventional facility in which patients can be rapidly transferred between x-ray and MR systems. Our goal is to design and validate an electromechanical model of the myocardium, using this XMR system. The proposed model is computationally fast and uses clinically observable parameters. We present the integration of anatomy, electrophysiology, and motion from patients. Pathologies are introduced in the model and the simulations are compared to measured data. Initial qualitative comparison is encouraging. Quantitative local validation is in progress. Once validated, these models will make it possible to simulate different interventional strategies.

Trends, indications and outcomes of cardiac implantable device system extraction: a single UK centre experience over the last decade: Lead extraction

Background:  The rising number of device implantation has seen a parallel in the rising numbers of lead extraction. Herein we have analysed our experience in cardiac device and lead extraction in a single tertiary centre over the last decade.

Trends, indications and outcomes of cardiac implantable device system extraction

Background:  The rising number of device implantation has seen a parallel in the rising numbers of lead extraction. Herein we have analysed our experience in cardiac device and lead extraction in a single tertiary centre over the last decade.