Assessment of intramyocardial hemorrhage by T1-weighted cardiovascular magnetic resonance in reperfused acute myocardial infarction.

BACKGROUND: Intramyocardialhemorrhage (IMH) reflects severe reperfusion injury in acute myocardial infarction. Non-invasive detection of IMH by cardiovascular magnetic resonance (CMR) may serve as a surrogate marker to evaluate the effect of preventive measures to reduce reperfusion injury and hence provide additional prognostic information. We sought to investigate whether IMH could be detected by CMR exploiting the T1 shortening effect of methemoglobin in an experimental model of acute myocardial infarction. The results were compared to T2-weighthed short tau inversion recovery (T2-STIR), and T2*-weighted(T2*W) sequences. METHODS AND RESULTS: IMH was induced in ten 40 kg pigs by 50-min balloon occlusion of the mid LAD followed by reperfusion. Between 4-9 days (average 4.8) post-injury, the left ventricular myocardium was assessed by T1-weigthed Inversion Recovery(T1W-IR), T2-STIR, and T2*W sequences. All CMR images were matched to histopathology and compared with the area of IMH. The difference between the size of the IMH area detected on T1W-IR images and pathology was -1.6 ± 11.3% (limits of agreement, -24%-21%), for the T2*W images the difference was -0.1 ± 18.3% (limits of agreement, -36.8%-36.6%), and for T2-STIR the difference was 8.0 ± 15.5% (limits of agreement, -23%-39%). By T1W IR the diagnostic sensitivity of IMH was 90% and specificity 70%, for T2*W imaging the sensitivity was 70% and specificity 50%, and for T2-STIR sensitivity for imaging IMH was 50% and specificity 60%. CONCLUSION: T1-weigthed non-contrast enhanced CMR detects IMH with high sensitivity and specificity and may become a diagnostic tool for detection of IMH in patients with myocardial infarction.

Wall shear stress and local plaque development in stenosed carotid arteries of hypercholesterolemic minipigs.

BACKGROUND: Wall shear stress is thought to play a critical role in the local development of atherosclerotic plaque and to affect plaque vulnerability. However, current models and hypotheses do not fully explain the link between wall shear stress and local plaque development. We aimed to investigate the relation between wall shear stress and local plaque development in surgically induced common carotid artery stenoses of hypercholesterolemic minipigs. MATERIALS, METHODS AND RESULTS: We created a surgically induced stenosis of the common carotid artery in 10 minipigs using a perivascular collar. We documented the flow and shear stress changes by ultrasound, magnetic resonance imaging, and computational fluid dynamics. Carotid plaques were documented by microscopy. Atherosclerotic lesions, in both pre-stenotic and post-stenotic segments, were associated with thrombus in the stenosed segment. In patent carotid arteries, atherosclerotic lesions were found in the post-stenotic segments only. Atherosclerotic lesions developed where low and oscillatory shear stress were present simultaneously, whereas low or oscillatory shear stress alone did not lead to lesion formation. CONCLUSIONS: Low and oscillatory shear stress in combination promoted plaque development, including plaques with necrotic cores that are the key and dangerous characteristic of vulnerable plaques.

Oversized vein grafts develop advanced atherosclerosis in hypercholesterolemic minipigs.

BACKGROUND: Accelerated atherosclerosis is the main cause of late aortocoronary vein graft failure. We aimed to develop a large animal model for the study of pathogenesis and treatment of vein graft atherosclerosis. METHODS: An autologous reversed jugular vein graft was inserted end-to-end into the transected common carotid artery of ten hypercholesteroemic minipigs. The vein grafts were investigated 12-14 weeks later with ultrasound and angiograpy in vivo and microscopy post mortem. RESULTS: One minipig died during follow up (patent vein graft at autopsy), and one vein graft thrombosed early. In the remaining eight patent vein grafts, the mean (standard deviation) intima-media thickness was 712 µm (276 µm) versus 204 µm (74 µm) in the contralateral control internal jugular veins (P < .01). Advanced atherosclerotic plaques were found in three of four oversized vein grafts (diameter of graft > diameter of artery). No plaques were found in four non-oversized vein grafts (P < .05). CONCLUSIONS: Our model of jugular vein graft in the common carotid artery of hypercholesterolemic minipigs displayed the components of human vein graft disease, i.e. thrombosis, intimal hyperplasia, and atherosclerosis. Advanced atherosclerosis, the main cause of late failure of human aortocoronary vein grafts was only seen in oversized grafts. This finding suggests that oversized vein grafts may have detrimental effects on patient outcome.

Determination of acute vascular injury and edema in porcine carotid arteries by T2 weighted cardiovascular magnetic resonance.

Inflammation plays an essential role for destabilization and rupture of carotid atherosclerotic plaques causing embolic ischemic stroke. Inflammation of the vessel wall may result in the formation of edema. This study investigated whether edema in the carotid artery wall induced by acute balloon injury could be detected by cardiovascular magnetic resonance (CMR) using a T2-weighted short-tau inversion recovery sequence (T2-STIR). Edema was induced unilaterally by balloon injury in the carotid artery of six pigs. Four to nine days (average six) post injury, the carotid arteries were assessed by T2-STIR and multi-contrast weighted sequences. CMR images were matched to histopathology, validated against Evans blue, and correlated with the amount of fibrinogen in the arterial wall used as an edema marker. T2-STIR images showed that the carotid signal intensity (SI) divided by the sternocleid muscle SI of the injured carotid artery was on average 223% (P = 0.03) higher than that of the uninjured carotid artery. Using a threshold value of 4SD, T2-STIR detected edema in the vessel wall (i.e., hyperintense signal intensity) with a sensitivity of 100% and a specificity of 75%. Agreement was observed between carotid artery wall hyperintense signal intensity and Evans blue uptake (X(2) = 17.1, P < 0.001). The relative signal intensity correlated in a linear fashion with the amount of fibrinogen detected by histopathology (ρ = 0.9, P < 0.001). None of the multi-contrast weighted sequences detected edema in the carotid artery with reasonable sensitivity or specificity. T2-STIR CMR allowed carotid artery wall edema detection and may therefore be a useful non-invasive diagnostic tool for determination of inflammatory activity in the carotid artery wall.

Long-term incidence of myocardial infarct, stroke, and mortality in patients operated on for abdominal aortic aneurysms.

OBJECTIVE: The risks of myocardial infarction (MI) and stroke after abdominal aortic aneurysm (AAA) resection are not known. Prophylaxis with aspirin and statins is not generally recommended, although patients with AAAs have an increased prevalence of cardiovascular atherosclerosis. We report the incidences of MI, stroke, and death in an unselected national cohort of patients operated on for AAAs, with the general population as the control group. METHODS: In a matched cohort study, 11,094 Danish patients who underwent acute or elective open AAA repair from January 1986 through June 2009 were compared with four randomly chosen age- and sex-matched individuals (controls) from the general population (n = 44,364). Data were collected retrospectively from the Danish Vascular Registry (Karbase), the National Population Registry, and the National Inpatient Registry. The groups were analyzed for the incidences of MI, stroke, and death, with up to 20 years of follow-up. RESULTS: AAA patients had an annual MI incidence of 2.5% (hazard ratio, 2.1; 95% confidence interval [CI], 1.9-2.2) compared with the general population. The annual incidence of stroke was 2.9% (hazard ratio, 1.8; 95% CI, 1.6-1.9), and there was a 2.4-fold (95% CI, 2.3-2.4) increase in the hazard of all-cause mortality compared with the general population. CONCLUSION: AAA patients of both sexes have a high risk of atherosclerotic events (MI, stroke) and death, so lifelong prophylaxis must be considered from our epidemiologic data. Randomized trials investigating the potential benefit of aspirin and statin therapy in AAA patients are needed.

Determination of edema in porcine coronary arteries by T2 weighted cardiovascular magnetic resonance.

BACKGROUND: Inflammation plays a pivotal role in all stages of atherosclerosis. Since edema is known to be an integral part of inflammation, a noninvasive technique that can identify edema in the coronary artery wall may provide unique information regarding plaque activity. In this study, we aimed to determine whether edema induced in porcine coronary arteries by balloon injury could be reliably detected by cardiovascular magnetic resonance (CMR) using a water sensitive T2-weighted short tau inversion recovery sequence (T2-STIR). We also aimed to compare these results to those of conventional T2-weighted (T2W) imaging. METHODS: Edema was induced in the proximal left anterior descending (LAD) coronary artery wall in seven pigs by balloon injury. At baseline, and 1-10 days (average four) post injury, the proximal LAD was assessed by water sensitive T2-STIR and conventional T2W sequences in cross-sectional planes. CMR images were matched to histopathology, validated against Evans blue as a marker of increased vessel wall permeability, and correlated with the arterial amount of fibrinogen used as an edema surrogate marker. RESULTS: Post injury, the T2-STIR images of the injured LAD vessel wall showed a significant 72%, relative signal intensity (SI) increase compared with baseline (p = 0.028). Using a threshold value of SI 7 SD above the average SI of the myocardium, T2-STIR detected edema in the vessel wall (i.e. enhancement) with a sensitivity of 100 and a specificity of 71. Twelve out of the 14 (86%) T2-STIR images displaying coronary artery wall enhancement also showed Evans blue uptake in the corresponding histology. The relative signal intensity showed a linear correlation with the amount of fibrinogen detected on the corresponding histopathology (ρ = 0.750, p = 0.05). The conventional T2W images did not show significant changes in SI post injury. CONCLUSION: T2-STIR CMR enabled detection of coronary artery wall edema and could therefore be a non-invasive diagnostic tool for evaluation of inflammatory coronary artery wall activity.

CMR assessment of endothelial damage and angiogenesis in porcine coronary arteries using gadofosveset.

BACKGROUND: Endothelial damage and angiogenesis are essential for atherosclerotic plaque development and destabilization. We sought to examine whether contrast enhanced cardiovascular magnetic resonance (CMR) using gadofosveset could show endothelial damage and neovessel formation in balloon injured porcine coronary arteries. METHODS AND RESULTS: Data were obtained from seven pigs that all underwent balloon injury of the left anterior descending coronary artery (LAD) to induce endothelial damage and angiogenesis. Between one - 12 days (average four) after balloon injury, in vivo and ex vivo T1-weighted coronary CMR was performed after intravenous injection of gadofosveset. Post contrast, CMR showed contrast enhancement of the coronary arteries with a selective and time-dependent average expansion of the injured LAD segment area of 45% (p = 0.04; CI95 = [15%-75%]), indicating local extravasation of gadofosveset. Vascular and perivascular extravasation of albumin (marker of endothelial leakiness) and gadofosveset was demonstrated with agreement between Evans blue staining and ex vivo CMR contrast enhancement (p = 0.026). Coronary MRI contrast enhancement and local microvessel density determined by microscopic examination correlated (ρ = 0.82, p < 0.001). CONCLUSION: Contrast enhanced coronary CMR with gadofosveset can detect experimentally induced endothelial damage and angiogenesis in the porcine coronary artery wall.

Hemodynamic effects of closure of residual arteriovenous fistulae during in situ graft procedures.

The objective was to study the intraoperative hemodynamic effects of closure of residual arteriovenous fistulae during in situ saphenous vein graft procedures. Data on 60 residual arteriovenous fistulae in nine patients (five men) with a median age of 74 years (range 64-83 years) with critical lower limb ischemia were obtained. Direct measurements of proximal and distal blood pressures in the graft were taken and simultaneous determinations of volume blood flow proximally and distally in the graft with ultrasound transit time technique before and after closure of residual fistulae were made. Closure of a fistula with blood flow around or below 100 mL/min did not increase distal outflow, whereas closure of fistulae with higher blood flow resulted in unpredictable changes in distal outflow. Only fistulae with a blood flow above approximately 100 mL/min may be of hemodynamic significance.

Duplication of the superficial femoral artery.

A computed tomographic angiogram for pseudoaneurysm after previous puncture in the groin showed duplication of the superficial femoral artery in a 52-year-old man without symptoms or signs of arterial insufficiency. It is doubtful whether this very rare anatomic variant has clinical relevance, but it should be known by vascular specialists.

Familial hypercholesterolaemic downsized pig with human-like coronary atherosclerosis: a model for preclinical studies.

AIMS: A manageable and reproducible large animal model of human-like coronary atherosclerosis is lacking but highly needed for translational research in percutaneous coronary interventions and imaging. Farm pigs with familial hypercholesterolaemia develop advanced atherosclerosis in two to three years but then weigh >200 kg making them impractical and costly. We aimed at down-sizing this pig and accelerating coronary plaque development to make the model more useful and affordable. METHODS AND RESULTS: Familial hypercholesterolaemic farm pigs were downsized by crossing them with smaller pigs while preserving their hypercholesterolaemic trait ascribed to a mutation in the low density lipoprotein receptor. We accelerated coronary plaque development by atherogenic diet feeding whereby plasma total cholesterol rose to >20 mmol/l (>800 mg/dl). We further accelerated coronary plaque development site-specifically by inflicting coronary artery balloon injury. Both spontaneously developed and balloon accelerated coronary plaques mirrored pertinent human plaque features, including a large necrotic core covered by a thin and inflamed fibrous cap as seen in the most common type of thrombosis-prone (vulnerable) plaque in humans. Associated vulnerable plaque features included neovascularisation, intraplaque haemorrhage, and expansive remodelling. CONCLUSIONS: This human-like porcine model of coronary atherosclerosis is practical and highly relevant for translational research in percutaneous coronary interventions and imaging.

Unreliable assessment of necrotic core by virtual histology intravascular ultrasound in porcine coronary artery disease.

BACKGROUND: Intravascular ultrasound-derived virtual histology (VH IVUS) is used increasingly in clinical research to assess composition and vulnerability of coronary atherosclerotic lesions. However, the ability of VH IVUS to quantify individual plaque components, in particular the size of the destabilizing necrotic core, has never been validated. We tested for correlation between VH IVUS necrotic core size and necrotic core size by histology in porcine coronary arteries with human-like coronary disease. METHODS AND RESULTS: In adult atherosclerosis-prone minipigs, 18 advanced coronary lesions were assessed by VH IVUS in vivo followed by postmortem microscopic examination (histology). We found no correlation between the size of the necrotic core determined by VH IVUS and histology. VH IVUS displayed necrotic cores in lesions lacking cores by histology. CONCLUSIONS: We found no correlation between necrotic core size determined by VH IVUS and real histology, questioning the ability of VH IVUS to detect rupture-prone plaques, so-called thin-cap fibroatheromas.

Longitudinal distribution of mechanical stresses in carotid plaques of symptomatic patients.

BACKGROUND AND PURPOSE: Mechanical stress may contribute to plaque rupture in patients with carotid atherosclerosis. We determined longitudinal mechanical stresses in carotid atherosclerotic plaques and compared them with known markers of plaque vulnerability. METHODS: Nineteen symptomatic patients scheduled for carotid endarterectomy underwent carotid MRI with a multicontrast protocol to characterize plaque morphology and geometry. Longitudinal 2-dimensional computational models were generated from the MRI data, and the mechanical stresses were calculated. RESULTS: Peak longitudinal mechanical stresses occurred predominantly in the shoulder regions of the carotid plaque and correlated inversely with fibrous cap thickness (r(s)=-0.61; P=0.01), and increasing degrees of stenosis (r(s)=0.71; P=0.003). Peak stress levels were asymmetrically distributed longitudinally, with 50% occurring proximal to the maximal stenosis, 25% at the point of maximal stenosis, and 25% distal to the maximal stenosis. CONCLUSIONS: The peak longitudinal mechanical stresses in the fibrous caps of symptomatic patients with carotid atherosclerotic stenosis were located at known predilection sites for plaque rupture, suggesting that mechanical stresses may play a role in plaque destabilization.

Left ventricular longitudinal strain for perioperative cardiac monitoring in aortic aneurysm surgery using transthoracic 2-dimensional echocardiography: a feasibility and repeatability study.

OBJECTIVE: This study investigated perioperative echocardiographic image quality, the feasibility, and intra- and interobserver repeatability of left ventricular longitudinal two-dimensional strain echocardiography (2DSE) in aortic aneurysm surgery. DESIGN: A prospective, descriptive method evaluation. SETTING: A single-center study. PARTICIPANTS: Eighteen patients undergoing elective open infrarenal aortic aneurysm repair. INTERVENTION: No intervention was made. MEASUREMENTS AND MAIN RESULTS: Four echocardiographic examinations were made: E1, preoperatively; E2, within 4 hours after surgery; E3, the first postoperative day; and E4, the second postoperative day. Four-chamber, 2-chamber, and longitudinal axis apical views were achieved. Image quality was scored visually on a scale from 1 to 5 with 5 as the best, and the 2-dimensional strain echocardiography (2DSE) software was applied to measure peak systolic strain. Blinded analyses were performed twice by 1 observer and once by a second observer. Image quality decreased significantly after surgery as compared with the preoperative examination, but 72% of patients had at least 1 image scoring >/=3 through all examinations. The software was able to measure the segmental and global left ventricular peak systolic strain in 80% and 61%, respectively, for the first observer and 71% and 26%, respectively, for the second observer. The coefficients of repeatability for intra- and interobserver measurements were 5.5% and 7.3% for segmental strain and 1.6% and 3.5% for global strain. 2DSE was more feasible and repeatable when echocardiographic images were good. CONCLUSION: Feasibility and repeatability of 2DSE is good but affected by image quality. This study shows that 2DSE can be used in a clinical setting.

Mechanical stresses in carotid plaques using MRI-based fluid-structure interaction models.

Risk assessment in patients with carotid atherosclerosis relies on the degree of luminal stenosis. Incorporating morphological information on plaque composition obtained noninvasively through the use of magnetic resonance imaging (MRI) could include other variables besides the degree of stenosis into carotid plaque risk assessment. Knowledge of the morphologic composition of the plaque allows determination of mechanic stresses exerted on the protective fibrous cap, which may be of importance in the assessment of plaque vulnerability. Based on image processing of transverse MRI scans, longitudinal 2D fluid-structure interaction (FSI) simulations of carotid atherosclerotic plaques were performed facilitating in-vivo estimation of longitudinal internal fibrous cap stresses. The FSI simulation combined finite element analysis (FEA) with computational fluid dynamics (CFD) simulations of blood-flow variables. Preliminary results from two symptomatic patients revealed longitudinal stress levels (max. 254.1 and 143.2 kPa) approaching established criteria for plaque rupture at known predilection sites of plaque rupture. Determination of longitudinal fibrous cap stresses may prove useful in assessing plaque vulnerability and improve risk stratification in patients with carotid atherosclerosis.

Plaque in superficial femoral arteries indicates generalized atherosclerosis and vulnerability to coronary death: an autopsy study.

OBJECTIVES: Risk factors for atherosclerosis have limited ability to identify persons at high risk of coronary heart disease. Assessment of subclinical atherosclerosis in peripheral arteries might improve this limitation. We studied the relationship between atherosclerotic plaques in peripheral arteries, coronary plaques, and coronary death. METHODS: Predefined segments from the left anterior descending coronary artery, the right coronary artery, bilateral carotid, and superficial femoral arteries (SFA) were obtained from 100 autopsies (20-82 years, 30 females, 27 coronary deaths). Based on microscopic examination of 4756 sections, the extension of atherosclerosis (plaque burden) and the largest plaque area in each segment were quantified. RESULTS: Plaque burden in all arteries increased with age and was larger in coronary death (P < .05). SFA plaques occurred later than coronary and carotid plaques. When SFA plaque had developed, coronary plaque was also present. SFA plaque (odds ratio, 95% confidence interval: 7.07 [2.40-20.81]), but not carotid plaque, was significantly associated with coronary death, also after age and gender adjustment (21.25 [5.02-89.97]). The area under the receiver operating characteristic curves for the identification of coronary death individuals was 0.72 (95% confidence interval: 0.62-0.83) for coronary plaque, and 0.80 (0.72-0.89) for SFA plaque (age and gender adjusted). CONCLUSIONS: Atherosclerosis develops slower in SFA compared with coronary and carotid arteries. In persons with plaque in the SFA, plaque is always present in the coronary arteries. In younger persons, the presence of SFA plaque indicates a generalized susceptibility to atherosclerosis and vulnerability to coronary death.

Artery-related differences in atherosclerosis expression: implications for atherogenesis and dynamics in intima-media thickness.

BACKGROUND AND PURPOSE: Information about the expression of atherosclerosis in different arteries is important. The impact of cardiovascular risk factors is artery-related, and the assessment of arterial structure and function in peripheral arteries are increasingly used as surrogate markers for coronary atherosclerosis and the risk of developing heart attack. METHODS: In an autopsy study, we analyzed the coronary, carotid and superficial femoral arteries from 100 individuals (70 men; 20 to 82 years of age) of which 27 died from coronary atherosclerosis. Microscopic sections (n=4756) were analyzed blindly using a modification of the histological classification endorsed by the American Heart Association (AHA). RESULTS: We found distinct artery-dependent patterns of atherosclerosis with a high prevalence of foam cell lesions and lipid core plaques in the carotid arteries. The femoral arteries were least affected by atherosclerosis, foam cell lesions were rare, and the development of advanced atherosclerosis was strongly age-dependent and dominated by fibrous plaques. Plaques were most common in the left anterior descending coronary artery and the carotid bifurcation. In coronary (versus noncoronary) death, lipid core plaques were more prevalent in all arteries. CONCLUSIONS: The initiation, speed of development, and phenotypic expression of atherosclerotic plaques are artery-related. Foam cell lesions are frequent in the carotid arteries, probably explaining the dynamics in carotid intima-media thickness. Atherosclerosis develops slowly in femoral arteries, and severe atherosclerosis is dominated by fibrous plaques. The higher prevalence of lipid core plaques in all arteries in coronary death indicates a systemically more vulnerable expression of atherosclerosis in these individuals.

The status of vascular surgery as an independent specialty in Europe: are the relationships with general and cardiothoracic surgery a problem?

Vascular surgery has established a clear clinical and scientific profile in Europe over the last decade, but it presents a highly complex, disorganized, and unplanned pattern. It is a specialty in the majority of the present member states of the European Union (EU), but in the United Kingdom, Germany, the Netherlands, and Sweden this is not the case. With the current expansion of the EU with 13 countries, mainly from the former Eastern Bloc, it will be even more necessary to ensure at least some level of convergence in the standards of training, certification, quality assured practice, continuing medical education, recertification, access to and quality of care, etc, because free migration of doctors, and patients, is a derivative of the cornerstones of the EU treaties, namely free movement of the citizens (and capital). The profession has been successful in creating a simple and coherent system for organization within the European Union of Medical Specialists with a board of vascular surgery, for a (voluntary) European proficiency test for specialists (the EBSQ-Vasc), and for European continuing medical education, all in close collaboration with the premier scientific society, the European Society for Vascular Surgery. The fantastic reductions in working hours for young doctors in the EU represent a serious threat to standards of training and, ultimately, to the patients. This, in connection with increased litigation and compensation demands for incompetence and negligence, makes it even more necessary to establish European minimum standards for training, professional competence, and an obligatory European specialist examination. A key element in this difficult process is the establishment of vascular surgery as a specialty in all member states. Day-to-day collaboration with radiologic interventionalists has developed pragmatically at the local level in most places, but only when the administrative structures mature and vascular surgery becomes a specialty in all countries will the necessary tools be available for the avoidance of professional conflicts with colleagues from other specialties.