Negative Carotid Artery Remodeling in Early Type 2 Diabetes Mellitus and Increased Carotid Plaque Vulnerability in Obesity as Assessed by Magnetic Resonance Imaging.

Background Ischemic stroke from carotid plaque embolism remains a major cause of morbidity in patients with type 2 diabetes mellitus (T2 DM ). However, the effect of early T2 DM and obesity on carotid remodeling and plaque burden remains elusive. We assessed carotid remodeling and plaque composition by carotid magnetic resonance imaging in patients with short-duration T2 DM compared with a sex- and age-matched control group. Methods and Results One hundred patients with T2 DM (duration <5 years) and 100 sex- and age-matched controls underwent bilateral carotid artery magnetic resonance imaging in a 1.5-T magnetic resonance imaging scanner. Plaque burden was quantified by normalized wall index, maximum wall thickness, maximum wall area, and minimum lumen size. Plaque morphology was quantified by calcified plaque volume, necrotic core volume, and loose matrix volume. Magnetic resonance imaging data were available for 149 and 177 carotid arteries from T2 DM patients and controls, respectively. Adjusted for age and sex, T2 DM was associated with increased plaque burden indicated by a higher normalized wall index (ratio 1.03 [95% confidence interval, 1.002; 1.06], P=0.03), and negative remodeling indicated by a lower minimum lumen area (ratio 0.81 [0.74; 0.89], P<0.001), and lower maximum wall area (ratio 0.94 [0.88; 1.00], P=0.048) compared with controls. In both T2 DM and controls, body mass index ≥30.0 kg/m2 was associated with an 80% increase in total calcified plaque volume, and a 44% increase in necrotic core volume compared with body mass index <25.0 kg/m2. Conclusions Short-duration T2 DM was associated with increased carotid plaque burden and negative remodeling. Obesity was associated with increased carotid artery necrotic core volume and calcification independently of diabetes mellitus status. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 00674271.

Is the knowledge of contact force beneficial in pulmonary vein antrum isolation?

OBJECTIVE: To investigate the effect of the operator knowing the real-time contact force (CF) on the efficacy of pulmonary vein antrum isolation (PVAI). METHODS: Fifty patients with paroxysmal atrial fibrillation (AF) or short lasting persistent AF were randomized to CF guided PVAI (n = 25) or conventional PVAI (n = 25). In the CF guided group, CF between 10 and 40 g was aimed at. Efficacy of PVAI was measured as reduction in AF burden (AFB) and time to AF recurrence detected by implantable cardiac monitor (ICM), inserted three months before PVAI. Blanking period was three months and follow-up 12 months. RESULTS: All pulmonary veins were isolated in the CF guided group and all but one in the conventional group. Mean CF was 25 g in the CF guided group and 24 g in the conventional group (p = 0.75). Compared to pre-ablation, median [IQR] relative reduction in AFB 3-12 months after ablation was 100 [99-100]% in the CF guided group (p < 0.001) and 99.4 [25-100]% in the conventional group (p < 0.001), not different between groups (p = 0.09). Nine patients (36%) had AF recurrence in the CF guided group and 13 (52%) in the conventional group (p = 0.21, log-rank test). CF differed between operators. When adjusted for operator by regression analysis, patients without recurrent AF had lower proportion of ablation time with CF <10 g than recurrent patients (p = 0.034). No complications occurred. CONCLUSIONS: Operator knowledge of real-time CF had no significant effect on AFB reduction or time to AF recurrence. Larger trials should be done to study benefit of real-time CF.

Carotid-femoral pulse wave velocity is associated with cerebral white matter lesions in type 2 diabetes.

OBJECTIVE: Patients with type 2 diabetes have a high incidence of cardiovascular events including stroke. Increased arterial stiffness (AS) predicts cardiovascular events in the general population. Cerebral white matter lesions (WMLs) are associated with an increased risk of stroke. It is unknown whether AS in patients with type 2 diabetes is associated with WMLs. RESEARCH DESIGN AND METHODS: We examined 89 patients recently diagnosed with type 2 diabetes (<5 years) and 89 sex- and age-matched controls. AS was assessed with carotid-femoral pulse wave velocity (PWV). WMLs were identified using magnetic resonance imaging and graded qualitatively with the Breteler scale (no/slight changes = 0, moderate changes = 1, severe changes = 2) and semiquantitatively. RESULTS: The diabetic population had excellent glycemic control (HbA(1c), 6.5% [6.2-6.8]; median [interquartile range {IQR}]) and had, compared with the controls, lower office blood pressure (BP) (127 ± 12/79 ± 8 vs. 132 ± 14/84 ± 10 mmHg) and total cholesterol (4.3[3.9-4.7] vs. 5.6 [5.1-6.4]; mmol/L; median [IQR]), (P < 0.01 for all). Despite this, PWV was higher in the patients with diabetes compared with controls (9.3 ± 2.0 vs. 8.0 ± 1.6 m/s; P < 0.0001). PWV was associated with Breteler score (OR 1.36 [95% CI 1.17-1.58]; P < 0.001) and WML volume (OR 1.32 [95% CI 1.16-1.51]; P < 0.001) per 1 m/s increase in PWV. These associations remained significant when adjusted for age, sex, diabetes, 24-h mean arterial BP, BMI, heart rate, and use of antihypertensives and statins (Breteler score: OR 1.28 [95% CI 1.03-1.60]; P < 0.05 and WML volume: OR 1.30 [95% CI 1.06-1.58]; P < 0.05). CONCLUSIONS: PWV was higher among patients with well-controlled type 2 diabetes compared with controls and was independently associated with WMLs. PWV may represent a clinically relevant parameter in the evaluation of cerebrovascular disease risk in type 2 diabetes.

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.

Computational fluid dynamics simulation of a-v fistulas: from MRI and ultrasound scans to numeric evaluation of hemodynamics.

PURPOSE: A-v anastomosis entails dramatic changes in hemodynamic conditions, which may lead to major alterations to the vessels involved; primarily dilatations and devastating stenoses. Wall shear stress is thought to play a key role in the remodeling of the vessels exposed to abnormal levels and oscillating wall shear stress. In this study we sought to develop a framework suitable for thorough in vivo analyses of wall shear stress and vessel morphology of a-v fistulas in patients. METHODS: Using ultrasound and magnetic resonance imaging (MRI) transverse image stacks from six patient a-v fistulas were obtained. From the image stacks three-dimensional geometries of the patient fistulas were created using dedicated segmentation software. Geometries of three a-v fistulas were imported into finite element software in order to perform fluid flow simulations of blood flows and frictional forces on the vessel walls in the a-v fistulas. Boundary conditions for the simulations were obtained using both a MRI phase contrast and an ultrasound Doppler technique. RESULTS: The segmentation of the six fistulas of very different age and morphology (two end-to-side and four side-to-side) showed the ability of the approach to create geometries of various fistula morphologies. Simulations of the three fistulas showed an instant picture of the present status of the exposure to different levels of wall shear stress and the morphological status in the vessel remodeling process. CONCLUSION: The study demonstrated the capability of the CFD framework to analyze patient a-v fistulas on a regular basis using both MRI and ultrasound-based approaches.

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.

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.

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.