Myocardial perfusion and resistive vessel function in coronary artery disease

Myocardial blood flow (MBF) is regulated by the coronary resistive vessels which continuously adapt the coronary blood flow he myocardial metabolic requirements, modulated by neural and humoral mechanisms, and this adaptation can compensate for increased resistance of an epicardial stenosis to a considerable extent. In patients with coronary artery disease, we postulate t dysfunction of the coronary resistive vessels may cause or contribute to myocardial ischaemia. Thus, impaired myocardial fusion maybe due to the abnormal behaviour of collateral and resistive vessels rather than to epicardial disease alone. We ipose that this alteration in resistive vessel function occurs, not only in regions subtended by epicardial disease, but is present in rote myocardium and may be altered by coronary intervention such as coronary angioplasty (PTCA) and after myocardial irction (MI). To investigate coronary resistive vessel function, positron emission tomography (PET) may be used to evaluate ional MBF using the flow tracer lsO-labelled water. Using vasodilator (or vasoconstrictor) stimuli, the coronary vasodilator ponse (CVR=maximal/basal coronary [myocardial] blood flow), an index of coronary resistive vessel function, may be measured 1 compared in regions of interest and in remote myocardium.Recovery of Resistive Vessel Dysfunction After Successful PTCA. To investigate the frequency and the time course of abnormal onary resistive vessel function after successful PTCA, patients with single vessel coronary disease and normal left ventricular ction underwent intracoronary (IC) Doppler measurement of coronary flow velocity, before and after successful PTCA, at basal I after intravenous (IV) dipyridamole. PET was performed on 3 occasions after PTCA. There was no change in CVR at Doppler ;r PTCA. In patients without restenosis, the CVR was reduced in the PTCA region for >7 days, but returned to normal at 3 nths, due to increased basal MBF for >7 days in the PTCA region, with a reduction in the dipyridamole-induced maximal MBF > 24 hours.Altered Nitric Oxide Synthesis/Release and Resistive Vessel Dysfunction After PTCA. Impaired production or release of nitric de (NO) in the from resistive vessel endothelium may cause this alteration in the CVR after PTCA. As the CVR to exogenous rates is enhanced by the endothelial dysfunction, large doses of IC sodium nitroprusside, an NO donor, were infused at the peak ?ct of IV dipyridamole to test this hypothesis using Doppler catheterisation in patients with single vessel disease, roprusside in doses sufficient to cause ultimately a fall in blood pressure did not augment the dipyridamole-induced increase in onary blood flow velocity.Altered Flow and Metabolism in Regions Subtended by Angiographically Normal Arteries in Coronary Artery Disease. The ional CVR was measured using PET in patients with stable single vessel disease. In a second group of patients and controls, [ultaneous arterial and great cardiac vein catheterisation was done at rest and during atrial pacing to measure myocardial tabolism in regions subtended by a diseased artery or by an angiographically normal artery with epicardial disease elsewhere. ; CVR was reduced in remote regions compared to controls. In the second group, at maximal pacing, there was net lactate duction in the diseased region compared to net extraction in both the remote and control.Resistive Vessel Dysfunction in Infarcted and Remote Myocardium After MI. To investigate acute resistive vessel dysfunction, ients were studied after thrombolysis for MI. Regional MBF and the CVR in infarct and remote regions was assessed, after a an of 8 days and 6 months after MI by PET. At early scanning^ the CVR was markedly reduced in the infarct region, and was tted to the amount of residual viable tissue. There was no correlation between the CVR and residual stenosis area. The remote R was less than that in remote regions, subtended by a normal artery, in controls with stable single vessel disease without MI. late scanning, the CVR improved in the infarct region, but the CVR in the remote region still remained lower than in controls.Impaired Flow Response to Cold Pressor in Collateral-Dependent Myocardium. To investigate the response of collateralpendent myocardium to reflex sympathetic stimulation (cold pressor stress), patients with stable angina and normal left itricular function were studied, in whom one coronary artery was occluded (without previous MI), and the other arteries were ;iographically normal supplying collaterals. Regional MBF and glucose uptake (using 18F-deoxyglucose) was measured using r at basal and at cold pressor. With cold pressor, no patients developed ECG changes. The cold pressor response (cold ssor/basal MBF) was low in the collateralised region, compared to remote regions, due to vasoconstriction in the majority, but in absence of demonstrable ischaemia.In summary, there is coronary resistive vessel dysfunction after PTCA which recovers over 3 months due to acute impairment of response to dipyridamole and a longer increase in basal flow, possibly due to the previous stenosis. This impairment is not due iltered production or release of NO in the microcirculation. In stable disease, there is both an impaired CVR and altered tabolism during pacing in regions subtended by a normal artery. This remote alteration is impaired acutely by myocardial irction elsewhere, with only incomplete recovery over at least 6 months. In addition to reduced vasodilator function, resistive sels in patients with atherosclerosis, have an increased tendency to vasoconstrict to a sympathetic stimulus. Thus, the erosclerotic process and the sympathetic nervous system may both play a role in determining the degree of resistive vessel function, which may cause or contribute to myocardial ischaemia in patients with coronary artery disease

Emergency Cardiology

This fully revised and updated second edition offers practical advice on the diagnosis and management of acute cardiac conditions. Throughout the book, the authors employ an evidence-based approach to clinical practice and provide detailed guidance for day-to-day practice in a wider variety of settings-from the emergency department to intensive care and the cardiac ward. Authored by four cardiologists with extensive experience in the emergency setting, it includes the results of the most groundbreaking clinical trials. Topics include arrhythmias, acute aortic syndromes, pericarditis, and cardiac trauma

Emergency Cardiology

This fully revised and updated second edition offers practical advice on the diagnosis and management of acute cardiac conditions. Throughout the book, the authors employ an evidence-based approach to clinical practice and provide detailed guidance for day-to-day practice in a wider variety of settings-from the emergency department to intensive care and the cardiac ward. Authored by four cardiologists with extensive experience in the emergency setting, it includes the results of the most groundbreaking clinical trials. Topics include arrhythmias, acute aortic syndromes, pericarditis, and cardiac trauma

A low-dose comprehensive cardiac CT protocol assessing anatomy, function, perfusion, and viability

AbstractRadiation exposure in cardiac imaging is a major healthcare concern and low-dose cardiac imaging has important implications for patients. We describe the application of a low-dose comprehensive cardiac computed tomography protocol that assesses anatomy, function, perfusion and viability with correlations to invasive coronary angiography and magnetic resonance imaging

Delayed recovery of coronary resistive vessel function after coronary angioplasty

AbstractObjectives. The aim of this study was to use Doppler catheterization and sequential dynamic positron emission tomography (PET) to investigate the role and time course of abnormal coronary resistive vessel function in the impairment of the coronary vasodilator response (maximal/basal coronary blood flow) after successful coronary angioplasty.Background. The coronary vasodilator response may be impaired immediately after coronary angioplasty, despite successful dilation of a flow-limiting stenosis.Methods. Twelve men (mean age 52 ± 10 years) with singlevessel coronary artery disease and normal left ventricular function were studied. The coronary vasodilator response to intravenous dipyridamole (0.5 mg·kg−1over 4 min) was determined from intracoronary Doppler measurement of coronary How velocity, before and after successful angioplasty. Basal and maximal myocardial blood flow in the angioplasty region and a normal region were determined in nine patients with positron emission tomography with H215O at 1 day (PET1), 7 days (PET2) and 3 months (PET3) after angioplasty.Results. The coronary vasodilator response, measured by Doppler catheterization, was similar before and immediately after angioplasty, 1.63 ± 0.41 and 1.62 ± 0.55, respectively (p = NS). After angioplasty, in seven of nine patients without restenosis, basal myocardial blood flow at PET1, PET2and PET3was 0.98 ± 0.16, 0.94 ± 0.09 and 0.99 ± 0.13 ml·min−1·g−1, respectively, in the remote region and 1.19 ± 0.23 (p < 0.01 vs. remote region), 1.17 ± 0.19 (p < 0.01 vs. remote region) and 1.10 ± 0.08 ml·min-1·g−1(p = NS vs. remote region), respectively, in the angioplasty region. Myocardial blood flow after dipyridamole at PET1, PET2and PET3was 3.04 ± 0.68, 3.00 ± 0.71 and 3.00 ± 0.60 ml·ml·min−1g−1, respectively, in the remote region and 2.11 ± 0.80 (p < 0.01 vs. remote region), 2.28 ± 0.73 (p = NS vs. remote region) and 3.06 ± 0.86 ml · min−1· g−1(p = NS vs. remote region), respectively, in the angioplasty region. The coronary vasodilator response at PET1, PET2and PET3was 3.15 ± 0.85, 3.18 ± 0.68 and 3.08 ± 0.75, respectively, in the remote region and 1.80 ± 0.68 (p < 0.01 vs. remote region), 1.94 ± 0.49 (p < 0.01 vs. remote region) and 2.77 ± 0.74 (p = NS vs. remote region), respectively, in the angioplasty region.Conclusions. After successful angioplasty, basal myocardial blood flow is increased for ≥7 days in the angioplasty region, with a reduction in the dipyridamole · induced increase in maximal myocardial blood flow for ≥24 h after the procedure. Thus, the coronary vasodilator response is impaired for ≥7 days after angioplasty, indicating that there is abnormal resistive vessel function in the coronary vascular bed distal to a coronary artery stenosis that persists for 7 days to 3 months

Optical coherence tomography versus intravascular ultrasound to evaluate stent implantation in patients with calcific coronary artery disease

AIMS: Stent underexpansion and malapposition are associated with adverse outcomes following percutaneous coronary intervention, but detection and treatment can be challenging in the presence of extensive coronary artery calcification. Frequency domain optical coherence tomography (FD-OCT) is a novel intravascular imaging technique with greater spatial resolution than intravascular ultrasound (IVUS) but its role in the presence of extensive coronary calcification remains unclear. We sought to determine the utility of FD-OCT compared to IVUS imaging to guide percutaneous coronary intervention in patients with severe calcific coronary artery disease. METHODS: 18 matched IVUS and FD-OCT examinations were evaluated following coronary stent implantation in 12 patients (10 male; mean age 70±7 years) undergoing rotational atherectomy for symptomatic calcific coronary artery disease. RESULTS: In-stent luminal areas were smaller (minimum in-stent area 6.77±2.18 vs 7.19±2.62 mm(2), p<0.05), while reference lumen dimensions were similar with FD-OCT compared with IVUS. Stent malapposition was detected in all patients by FD-OCT and in 10 patients by IVUS. The extent of stent malapposition detected was greater (20% vs 6%, p<0.001) with FD-OCT compared to IVUS. Postdilation increased the in-stent luminal area (minimum in-stent area: 8.15±1.90 vs 7.30±1.62 mm(2), p<0.05) and reduced the extent of stent malapposition (19% vs 34%, p<0.005) when assessed by FD-OCT, but not IVUS. CONCLUSIONS: Acute stent malapposition occurs frequently in patients with calcific coronary disease undergoing rotational atherectomy and stent implantation. In the presence of extensive coronary artery calcification, FD-OCT affords enhanced stent visualisation and detection of malapposition, facilitating improved postdilation stent apposition and minimal luminal areas. TRIAL REGISTRATION NUMBER: NCT02065102

Acetylcysteine has No Mechanistic Effect in Patients at Risk of Contrast-Induced Nephropathy - A Failure of Academic Clinical Science

Contrast‐induced nephropathy (CIN) is a major complication of imaging in patients with chronic kidney disease (CKD). The publication of an academic randomized controlled trial (RCT; n = 83) reporting oral (N)‐acetylcysteine (NAC) to reduce CIN led to > 70 clinical trials, 23 systematic reviews, and 2 large RCTs showing no benefit. However, no mechanistic studies were conducted to determine how NAC might work; proposed mechanisms included renal artery vasodilatation and antioxidant boosting. We evaluated the proposed mechanisms of NAC action in participants with healthy and diseased kidneys. Four substudies were performed. Two randomized, double‐blind, placebo‐controlled, three‐period crossover studies (n = 8) assessed the effect of oral and intravenous (i.v.) NAC in healthy kidneys in the presence/absence of iso‐osmolar contrast (iodixanol). A third crossover study in patients with CKD stage III (CKD3) (n = 8) assessed the effect of oral and i.v. NAC without contrast. A three‐arm randomized, double‐blind, placebo‐controlled parallel‐group study, recruiting patients with CKD3 (n = 66) undergoing coronary angiography, assessed the effect of oral and i.v. NAC in the presence of contrast. We recorded systemic (blood pressure and heart rate) and renal (renal blood flow (RBF) and glomerular filtration rate (GFR)) hemodynamics, and antioxidant status, plus biomarkers of renal injury in patients with CKD3 undergoing angiography. Primary outcome for all studies was RBF over 8 hours after the start of i.v. NAC/placebo. NAC at doses used in previous trials of renal prophylaxis was essentially undetectable in plasma after oral administration. In healthy volunteers, i.v. NAC, but not oral NAC, increased blood pressure (mean area under the curve (AUC) mean arterial pressure (MAP): mean difference 29 h⋅mmHg, P = 0.019 vs. placebo), heart rate (28 h⋅bpm, P < 0.001), and RBF (714 h⋅mL/min, 8.0% increase, P = 0.006). Renal vasodilatation also occurred in the presence of contrast (RBF 917 h⋅mL/min, 12% increase, P = 0.005). In patients with CKD3 without contrast, only a rise in heart rate (34 h⋅bpm, P = 0.010) and RBF (288 h⋅mL/min, 6.0% increase, P = 0.001) occurred with i.v. NAC, with no significant effect on blood pressure (MAP rise 26 h⋅mmHg, P = 0.156). Oral NAC showed no effect. In patients with CKD3 receiving contrast, i.v. NAC increased blood pressure (MAP rise 52 h⋅mmHg, P = 0.008) but had no effect on RBF (151 h⋅mL/min, 3.0% increase, P = 0.470), GFR (29 h⋅mL/min/1.73m², P = 0.122), or markers of renal injury. Neither i.v. nor oral NAC affected plasma antioxidant status. We found oral NAC to be poorly absorbed and have no reno‐protective effects. Intravenous, not oral, NAC caused renal artery vasodilatation in healthy volunteers but offered no protection to patients with CKD3 at risk of CIN. These findings emphasize the importance of mechanistic clinical studies before progressing to RCTs for novel interventions. Thousands were recruited to academic clinical trials without the necessary mechanistic studies being performed to confirm the approach had any chance of working

Non-invasive assessment of coronary artery bypass graft patency using 16-slice computed tomography angiography

<p>Abstract</p> <p>Background</p> <p>Invasive coronary angiography is the gold standard means of imaging bypass vessels and carries a small but potentially serious risk of local vascular complications, including myocardial infarction, stroke and death. We evaluated computed tomography as a non-invasive means of assessing graft patency.</p> <p>Methods</p> <p>Fifty patients with previous coronary artery bypass surgery who were listed for diagnostic coronary angiography underwent contrast enhanced computed tomography angiography using a 16-slice computed tomography scanner. Images were retrospectively gated to the electrocardiogram and two dimensional axial, multiplanar and three dimensional reconstructions acquired. Sensitivity, specificity, positive and negative predictive value, accuracy and level of agreement for detection of graft patency by multidetector computed tomography.</p> <p>Results</p> <p>A total of 116 grafts were suitable for analysis. The specificity of CT for the detection of graft patency was 100%, with a sensitivity of 92.8%, positive predictive value 100%, negative predictive value 85.8% and an accuracy of 94.8%. The kappa value of agreement between the two means of measuring graft patency was 0.9. Mean radiation dose was 9.0 ± 7.2 mSv for coronary angiography and 18.5 ± 4 mSv for computed tomography. Pooled analysis of eight studies, incorporating 932 grafts, confirmed a 97% accuracy for the detection of graft patency by multidetector computed tomography.</p> <p>Conclusion</p> <p>Computed tomography is an accurate, rapid and non-invasive method of assessing coronary artery bypass graft patency. However, this was achieved at the expense of an increase in radiation dose.</p

Observer variability in the assessment of CT coronary angiography and coronary artery calcium score:substudy of the Scottish COmputed Tomography of the HEART (SCOT-HEART) trial

Introduction Observer variability can influence the assessment of CT coronary angiography (CTCA) and the subsequent diagnosis of angina pectoris due to coronary heart disease. Methods We assessed 210 CTCAs from the Scottish COmputed Tomography of the HEART (SCOT-HEART) trial for intraobserver and interobserver variability. Calcium score, coronary angiography and image quality were evaluated. Coronary artery disease was defined as none (70%) luminal stenosis and classified as no (70%) coronary artery disease. Post-CTCA diagnosis of angina pectoris due to coronary heart disease was classified as yes, probable, unlikely or no. Results Patients had a mean body mass index of 29 (28, 30) kg/m2, heart rate of 58 (57, 60)/min and 62% were men. Intraobserver and interobserver agreements for the presence or absence of coronary artery disease were excellent (95% agreement, κ 0.884 (0.817 to 0.951) and good (91%, 0.791 (0.703 to 0.879)). Intraobserver and interobserver agreement for the presence or absence of angina pectoris due to coronary heart disease were excellent (93%, 0.842 (0.918 to 0.755) and good (86%, 0.701 (0.799 to 0.603)), respectively. Observer variability of calcium score was excellent for calcium scores below 1000. More segments were categorised as uninterpretable with 64-multidetector compared to 320-multidetector CTCA (10.1% vs 2.6%, p<0.001) but there was no difference in observer variability. Conclusions Multicentre multidetector CTCA has excellent agreement in patients under investigation for suspected angina due to coronary heart disease. Trial registration number NCT01149590