Essential thrombocytosis: diagnosis, differential diagnosis, complications and treatment considerations of relevance for a cardiologist.

Essential thrombocytosis (ET) is a rare haematological malignancy, with an incidence rate of 1.5-2.5/100,000 per year. For many patients with ET the first manifestation of their underlying disease is a thrombotic or haemorrhagic complication. A recent retrospective study revealed an incidence rate of at least 2.1% in people under 40 years presenting with an acute coronary syndrome, although the diagnosis was initially missed in all cases. Thus, cardiologists face a much higher than average incidence rate of ET in their daily practice, but seem insufficiently aware of the disease. The current review summarises symptoms, (differential) diagnosis, complications and treatment considerations of ET of relevance for a cardiologist. Typical symptoms, besides thrombosis and haemorrhage, include erythromelalgia and aquagenic pruritus, while platelets > 450â€¯× 109/l are a diagnostic for ET once other myeloproliferative neoplasms, secondary and spurious thrombocytosis have been excluded. With regard to treatment, timing of revascularisation depends on the presence of ischaemia and concurrent platelet counts. In the presence of ischaemia, revascularisation should not be delayed and adequate platelet counts can be achieved by platelet apheresis. In the absence of ischaemia, revascularisation can be delayed until adequate platelet counts have been achieved by cytoreductive therapies. Cardiologists should be aware of/screen for possible ET.

Blockade of vascular endothelial growth factor receptor 2 inhibits intraplaque haemorrhage by normalization of plaque neovessels.

BACKGROUND: Plaque angiogenesis is associated with atherosclerotic lesion growth, plaque instability and negative clinical outcome. Plaque angiogenesis is a natural occurring process to fulfil the increasing demand of oxygen and nourishment of the vessel wall. However, inadequate formed, immature plaque neovessels are leaky and cause intraplaque haemorrhage. OBJECTIVE: Blockade of VEGFR2 normalizes the unbridled process of plaque neovessel formation and induces maturation of nascent vessels resulting in prevention of intraplaque haemorrhage and influx of inflammatory cells into the plaque and subsequently increases plaque stability. METHODS AND RESULTS: In human carotid and vein graft atherosclerotic lesions, leaky plaque neovessels and intraplaque haemorrhage co-localize with VEGF/VEGFR2 and angiopoietins. Using hypercholesterolaemic ApoE3*Leiden mice that received a donor caval vein interposition in the carotid artery, we demonstrate that atherosclerotic vein graft lesions at t28 are associated with hypoxia, Hif1α and Sdf1 up-regulation. Local VEGF administration results in increased plaque angiogenesis. VEGFR2 blockade in this model results in a significant 44% decrease in intraplaque haemorrhage and 80% less extravasated erythrocytes compared to controls. VEGFR2 blockade in vivo results in a 32% of reduction in vein graft size and more stable lesions with significantly reduced macrophage content (30%), and increased collagen (54%) and smooth muscle cell content (123%). Significant decreased VEGF, angiopoietin-2 and increased Connexin 40 expression levels demonstrate increased plaque neovessel maturation in the vein grafts. VEGFR2 blockade in an aortic ring assay showed increased pericyte coverage of the capillary sprouts. CONCLUSION: Inhibition of intraplaque haemorrhage by controlling neovessels maturation holds promise to improve plaque stability.

Myocardial bridges, neither rare nor isolated-Autopsy study.

PURPOSE: Myocardial bridge is a congenital anomaly with a markedly variable reported incidence on autopsy (4.7%-86%), likely related to geographical regions. Our previous retrospective study showed a prevalence of 0.8%, which we doubted to be the true one in the examined sample of the Serbian population. To assess the importance of the phenomenon we conducted a 2-year prospective study at the same institution. METHODS: Ninety-six cadaver hearts from adult individuals of both genders (51 men, 45 women) who died from natural causes underwent special dissection. Tunneled coronary arteries and myocardium were examined using light microscopy. RESULTS: A total of 14 myocardial bridges were found in 13 (13.54%) hearts. This anomaly was insignificantly more common in men (13.72% vs. 13.33%, p>0.05). In one heart we noted two myocardial bridges (the left anterior interventricular artery and left marginal artery were overbridged). None of the myocardial bridges had been diagnosed during life. The most common causes of death were cardiac related. Myocardial bridges were located in the following areas: left anterior interventricular (50%), left circumflex artery (28.6%), left marginal artery (14.3%), and right coronary artery (7.1%). In 92.3% of cases, the right coronary artery was dominant. The only heart with a balanced-type had two bridges. Most of the myocardial bridges were long and deep. All tunneled coronary arteries, and although surrounded by "coronary cushion," were not protected from atherosclerosis. In 30.8% of hearts with myocardial bridges, we found additional coronary artery anomalies. CONCLUSION: Myocardial bridges were not rare in the examined sample of the Serbian population and were often associated with other coronary artery anomalies, rendering the carriers at higher risk.

A change in inflammatory footprint precedes plaque instability: a systematic evaluation of cellular aspects of the adaptive immune response in human atherosclerosis.

BACKGROUND: Experimental studies characterize adaptive immune response as a critical factor in the progression and complications of atherosclerosis. Yet, it is unclear whether these observations translate to the human situation. This study systematically evaluates cellular components of the adaptive immune response in a biobank of human aortas covering the full spectrum of atherosclerotic disease. METHODS AND RESULTS: A systematic analysis was performed on 114 well-characterized perirenal aortic specimens with immunostaining for T-cell subsets (CD3/4/8/45RA/45RO/FoxP3) and the Th1/non-Th1/Th17 ratio (CD4(+)T-bet(+)/CD4(+)T-bet(-)/CD4(+)/interleukin-17(+) double staining). CD20 and CD138 were used to identify B cells and plasma cells, while B-cell maturation was evaluated by AID/CD21 staining and expression of lymphoid homeostatic CXCL13. Scattered CD4 and CD8 cells with a T memory subtype were found in normal aorta and early, nonprogressive lesions. The total number of T cells increases in progressive atherosclerotic lesions (≈1:5 CD4/CD8 T-cell ratio). A further increase in medial and adventitial T cells is found upon progression to vulnerable lesions.This critical stage is further hallmarked by de novo formation of adventitial lymphoidlike structures containing B cells and plasma cells, a process accompanied by transient expression of CXCL13. A dramatic reduction of T-cell subsets, disappearance of lymphoid structures, and loss of CXCL13 expression characterize postruptured lesions. FoxP3 and Th17 T cells were minimally present throughout the atherosclerotic process. CONCLUSIONS: Transient CXCL13 expression, restricted presence of B cells in human atherosclerosis, along with formation of nonfunctional extranodal lymphoid structures in the phase preceding plaque rupture, indicates a "critical" change in the inflammatory footprint before and during plaque destabilization.

Optical coherence tomography surveillance following drug-eluting stent implantation.

Drug-eluting stents are currently used in the majority of percutaneous coronary interventions. Preclinical investigations and human autopsy studies have shown that the high efficacy of drug-eluting stents (DES) in preventing restenosis is achieved at the expense of a delay in healing. Optical coherence tomography (OCT) represents a novel intracoronary imaging tool to evaluate vascular healing response after stent implantation. Owing to its outstanding resolution in the catheter near-field, quantitative morphometric measures were complemented by more qualitative description of neointimal tissue characterization. Clinical imaging studies employing these methodologies gained valuable insights into vascular healing responses after DES implantation and are reported in this review. However, an important limitation of OCT imaging analysis, despite its high resolution, remains the inability to assess the precise cellular composition and functional capability of the neointimal tissue, especially of the endothelium. Future long-term clinical studies are warranted to determine the clinical relevance of surrogate parameters derived from preliminary OCT surveillance studies.

A novel "pro-healing" approach: the COMBO™ dual therapy stent from a pathological view.

Current generations of monotherapy drug-eluting stents only inhibit neointimal hyperplasia. However, these stent designs have other drawbacks such as delayed arterial healing, hypersensitivity, late stent thrombosis, and neoatherosclerosis, creating a need for a new generation of safer devices. The novel 'pro-healing' COMBOTM dual therapy stent aims to address these issues by reducing neointimal hyperplasia via an abluminal bioabsorbable polymer eluting sirolimus, and by simultaneously capturing circulating endothelial progenitor cells via luminally immobilized anti-CD34+ antibodies. Short-term preclinical data shows promising results as compared to 1st generation and 2nd generation drug-eluting stents; however long-term literature remains unavailable until now. This review aims to evaluate, histopathologically, drawbacks of the current era of stents at autopsy, review short-term preclinical and clinical data from the REMEDEE trial, and present original long-term preclinical data. To date, preclinical data shows good performance of the COMBOTM stent comparable with the safety profile of bare metal stents with minimal inflammation, increased endothelialization, and acceptable neointimal hyperplasia with no statistical evidence of late catch-up. Clinical data from the REMEDEE trial at 12 months shows non-inferiority to paclitaxel drug-eluting stents, no evidence of late stent thrombosis, and a low rate of adverse clinical events.

Pathophysiology of superficial femoral artery in-stent restenosis.

Peripheral artery disease (PAD) is an emerging problem especially with aging population and increase in the incidence of diabetes and metabolic syndrome. The disease is histologically characterized by the presence of moderate to severe calcification and fibrous plaques as compared to coronary and carotid atherosclerotic disease, which are richer in necrotic core. Endovascular therapy for the superficial femoral artery (SFA), at least in the United States, has been largely limited to balloon angioplasty and stenting and these are considered safe and relatively effective therapies. However, the patency rates remain low even at one year and restenosis is a growing and challenging problem. Recently the development of newer devices, i.e., drug-eluting stent, and drug coated balloon are showing greater efficacy and are being adopted into daily practice. In this review, we will present the morphologic characteristics of the underlying SFA atherosclerotic disease and discuss in-stent restenosis and the mechanisms that may be involved in the induction of excessive smooth muscle cell proliferation and deposition of proteoglycans and collagen, that lead to restenosis.

Unique demands of the femoral anatomy and pathology and the need for unique interventions.

With the aging of the population the incidence of peripheral artery disease (PAD) is increasing, which is histologically characterized by fibrocalcific intimal plaques as well as underlying Mönckeberg's medial calcinosis as compared to coronary and carotid artery disease. Superficial femoral artery (SFA) is one of the longest and most dynamically active vessels in the body undergoing torsion, compression, flexion, and extension from leg motion, and is known to be more susceptible to atherosclerosis because of low shear stress or spiral flow, best appreciated in the long segment in its lesser curvature. Endovascular interventions are now considered the first-line strategy for the treatment of PAD patients presenting with claudication or critical limb ischemia, where physiologic stresses on the arterial wall, anatomic considerations, and lesion characteristics impact on their success. Stent fracture and malapposition, are a common phenomenon in PAD which are attributed to severe calcification and fibrosis along with greater motion of the lower extremity, that result in the dampening of the efficacy of stenting and balloon angioplasty. Better designs of self-expanding stents have resulted in either reduction in stent fracture rates or its elimination at least in the short-term follow-up studies, to date. Although drug-eluting stents (DES) have reduced restenosis rates in the coronary circulation, this benefit has not been consistently observed in PAD. However, recent clinical studies utilizing novel Zilver-PTX self-expanding stent (DES) have demonstrated favorable patency rate. Also, in patients with critical limb ischemia, better outcomes have been reported for below-the-knee utilization of DES. Nevertheless, drawbacks of stent technology remain and interests in the greater use of drug-coated balloons (DCB) for PAD have emerged. Randomized controlled trials have consistently shown superiority of DCB over uncoated balloons in reducing neointimal formation in patients with SFA disease. Moreover, there is a growing interest in atherectomy as an alternative treatment strategy for PAD, thus decreasing plaque burden with possibly avoidance of barotrauma. The results from registries support the effectiveness of the atherectomy devices; however, prospective randomized controlled trials are needed to confirm their benefit.

The influence of axial image resolution on atherosclerotic plaque stress computations.

Biomechanical models are used extensively to study risk factors, such as peak stresses, for vulnerable atherosclerotic plaque rupture. Typically, 3D patient-specific arterial models are reconstructed by interpolating between cross sectional contour data which have a certain axial sampling, or image, resolution. The influence of the axial sampling resolution on computed stresses, as well as the comparison of 3D with 2D simulations, is quantified in this study. A set of histological data of four atherosclerotic human coronary arteries was used which were reconstructed in 3D with a high sampling (HS) and low sampling (LS) axial resolution, and 4 slices were treated separately for 2D simulations. Stresses were calculated using finite element analysis (FEA). High stresses were found in thin cap regions and regions of thin vessel walls, low stresses were found inside the necrotic cores and media and adventitia layers. Axial sampling resolution was found to have a minor effect on general stress distributions, peak plaque/cap stress locations and the relationship between peak cap stress and minimum cap thickness. Axial sampling resolution did have a profound influence on the error in computed magnitude of peak plaque/cap stresses (±15.5% for HS vs. LS geometries and ±24.0% for HS vs. 2D geometries for cap stresses). The findings of this study show that axial under sampling does not influence the qualitative stress distribution significantly but that high axially sampled 3D models are needed when accurate computation of peak stress magnitudes is required.

From bench to bedside: initial experience with the Primus drug-coated balloon catheter.

AIM: Drug-coated balloon (DCB) technology has emerged as a promising therapy particularly in the treatment of coronary in-stent restenosis. Although a variety of devices are available for clinical use, clinical outcomes have been variable and scope for significant improvement exists. METHODS: In a preclinical study, a total of 10 juvenile healthy farm pigs underwent catheter-based DCB deployment in coronary arteries with angiographic and pathological follow-up at 7 or 28 days. Animals were randomly allocated to the PRIMUS or Dior® DCB (N.=10 per group) and evaluated by histopathology and morphometric analysis. In a first-in-man clinical study a total of 19 consecutive patients presenting with restenosis within drug-eluting stents were treated with the PRIMUS DCB. Clinical follow-up was performed out to 6 months. RESULTS: Neointimal thickness was similar between the PRIMUS and Dior® DCB groups, while fibrin deposition and inflammation were more sustained in the PRIMUS group at 28 days. In 19 consecutive patients presenting with in-stent restenosis of drug-eluting stents, treatment with the PRIMUS DCB catheter resulted in high procedural efficacy. There were no adverse clinical events observed out to 6 months. CONCLUSION: The PRIMUS DCB demonstrates high preclinical safety and excellent acute performance and safety. Further studies are needed to delineate the relative merits of this novel DCB compared to other devices.

Ex vivo and preclinical assessment of an endothelial progenitor cell capturing bioengineered stent.

Although drug-eluting stents (DES) have significantly reduced the rates of restenosis as compared to bare metal stents, late stent thrombosis remains a major drawback, especially for "off-label" use. Delayed arterial healing, characterized by persistent fibrin deposition and poor endothelialization, has been shown to correlate with late DES thrombosis. To overcome these limitations, a "pro-healing" approach has been developed to capture circulating endothelial progenitor cells (EPC) to enhance endothelialization of the stent surface. EPC have the ability to migrate to sites of vascular injury and aid the regeneration of damaged and dysfunctional endothelium. Clinically, the safety of EPC-capture stent has been proven in numerous clinical trials with low incidence of late stent thrombosis. The focus of this review is to demonstrate the efficacy of the Genous stent in preclinical studies, specifically to show the effectiveness of the anti-CD34+ coating in promoting endothelialization and reducing thrombogenicity.

Initial stress in biomechanical models of atherosclerotic plaques.

Rupture of atherosclerotic plaques is the underlying cause for the majority of acute strokes and myocardial infarctions. Rupture of the plaque occurs when the stress in the plaque exceeds the strength of the material locally. Biomechanical stress analyses are commonly based on pressurized geometries, in most cases measured by in-vivo MRI. The geometry is therefore not stress-free. The aim of this study is to identify the effect of neglecting the initial stress state on the plaque stress distribution. Fifty 2D histological sections (7 patients, 9 diseased coronary artery segments), perfusion fixed at 100 mmHg, were segmented and finite element models were created. The Backward Incremental method was applied to determine the initial stress state and the zero-pressure state. Peak plaque and cap stresses were compared with and without initial stress. The effect of initial stress on the peak stress was related to the minimum cap thickness, maximum necrotic core thickness, and necrotic core angle. When accounting for initial stress, the general relations between geometrical features and peak cap stress remain intact. However, on a patient-specific basis, accounting for initial stress has a different effect on the absolute cap stress for each plaque. Incorporating initial stress may therefore improve the accuracy of future stress based rupture risk analyses for atherosclerotic plaques.

The C-Port xV® vascular anastomosis system: results from an animal trial.

BACKGROUND: In this study, facilitated anastomosis using an anastomotic device was compared to conventional hand-sewn (HS) vascular anastomosis in an animal model. METHODS: A pig carotid bypass model was employed. C-Port xV® (xV) and HS anastomoses were compared by evaluating intraoperative performance, midterm graft patency, and histology. RESULTS: All animals survived; none developed early/late neurological deficits. Mean graft blood flow was comparable between groups (HS group: 161 ± 61 ml/min; xV group: 143 ± 44 ml/min). All anastomoses were patent at necropsy (at 111 ± 6 postoperative days). Histologically, no significant inflammation was found around the fasteners or in the vessel wall. Neointimal overgrowth on the lumen surface appeared organized and covered with endothelium. There was no adherence of fibrin, platelets, or inflammatory cells to the surface. The neointimal tissue appeared normal without any inflammation, hemorrhage, calcification, or necrosis. CONCLUSION: Facilitated vascular anastomosis using the xV anastomotic device is safe and effective in the pig carotid bypass model. Further studies should evaluate the efficacy of this device when used in confined spaces to define its potential role in minimally invasive procedures.

Identification of intraplaque hemorrhage on MR angiography images: a comparison of contrast-enhanced mask and time-of-flight techniques.

BACKGROUND AND PURPOSE: MRA is widely used to measure carotid narrowing. Standard CE- and TOF-MRA techniques use highly T1-weighted gradient-echo sequences that can detect T1 short blood products, so they have the potential to identify IPH, an indicator of plaque rupture. We sought to determine the accuracy and reliability of these MRA sequences to detect IPH. MATERIALS AND METHODS: 3D TOF and CE carotid MRA scans were obtained at 3T on 15 patients (age range, 58-86 years; 13 men) scheduled for CEA. The source images from the precontrast (mask) CE-MRA and the TOF sequences were reviewed by 2 independent readers for IPH presence (identified as hyperintense signal intensity compared with adjacent muscle). CEA specimens were stained with antibody against glycophorin A and Mallory stain to detect IPH and were correlated with MR images. RESULTS: Nine of 15 CEA specimens (61 of 144 MR images) contained IPH confirmed by histology. Compared with TOF, CE-MRA mask demonstrated greater sensitivity, specificity, PPV, and NPV for IPH detection. The accuracy for correctly identifying IPH by using CE-MRA mask images and TOF images was 94% and 84%, respectively. Inter- and intraobserver agreement for IPH detection was excellent by mask images (κ = 0.91 and κ = 0.94, respectively) and TOF images (κ = 0.77 and κ = 0.84, respectively). CONCLUSIONS: CE-MRA mask images are highly accurate and reliable for identifying IPH, more so than the TOF sequence, and can potentially provide valuable information about risk for rupture.

Long-term angiographic and histological results of a new hydrogel-containing filling coil in experimental rabbit aneurysms.

BACKGROUND: The aim of this study was to compare the performance of a new filling coil, the HydroFill device, to historical results of HydroSoft and bare platinum coil devices in experimental rabbit aneurysms. METHODS: Experimental aneurysms were constructed in rabbits and embolized with HydroFill (n=32), HydroSoft (n=48), or bare platinum coil (n=47) devices. Angiographic occlusion was evaluated post-treatment and at 1 month (n=55), 3 month (n=20), 6 month (n=35), and 12 month (n=12) follow-ups according to the Raymond scale. The aneurysms were analyzed histologically for neointima formation, thrombus organization, and inflammation. Continuous and discrete results were compared using ANOVA/t-test and chi (2) tests, respectively. RESULTS: Volumetric occlusion of the aneurysm sac was increased in the HydroFill group compared to the HydroSoft and platinum coil groups. Protrusions into the parent artery were common in all treatment groups due to the treatment of wide-necked aneurysms without the use of balloons or stents. Although angiographic occlusion post-treatment scores were reduced in the HydroFill group compared to the HydroSoft and platinum coil groups, stable/progressive occlusion was increased in the HydroFill group compared to the platinum coil group. Histologically, neointima formation and thrombus organization scores were increased in the HydroFill and HydroSoft groups compared to the platinum coil group at 3 months. Although there were some differences in the scoring, inflammation was generally minimal to mild in all three groups. CONCLUSION: The HydroFill device, with its high levels of volumetric filling, increased stable/progressive occlusion at follow-up, increased neointima formation, and increased thrombus organization, shows promise for clinical use.

Epithelioid hemangioendothelioma in the right auricle of an adult, male Rhesus macaque (Macaca mulatta).

BACKGROUND: A 9-year-old, male castrate, Rhesus macaque was euthanized following a prolonged history of chronic renal failure. RESULTS: Necropsy revealed a proliferative lesion within the right cardiac auricle composed of neoplastic epithelioid cells which infiltrated the myocardium and frequently exhibited intracytoplasmic luminae. Cells multifocally exhibited strong cytoplasmic immunoreactivity for Factor VIII-related protein (von Willebrand's factor). CONCLUSIONS: The histological characteristics of this tumor are consistent with a diagnosis of epithelioid hemangioendothelioma, an intermediate-grade vasoformative neoplasm which has to our knowledge not previously been reported in the heart of a non-human species.

The natural history of aortic atherosclerosis: a systematic histopathological evaluation of the peri-renal region.

BACKGROUND: Risk factor profiles for the different vascular beds (i.e. coronary, carotid, peripheral and aortic) are remarkably different, suggesting that atherosclerosis is a heterogeneous disorder. Little is known about the morphologic progression of atherosclerosis in the peri-renal aorta, one of the primary predilection sites of atherosclerosis. METHODS: A systematic analysis was performed in 260 consecutive peri-renal aortic patches (stained with Movat Pentachrome and H&E) collected during organ transplantation (mean donor age 46.5 (range 5-76) years; 54% male symbol; mean BMI 24.9; 40% smokers; 20% hypertensive). Plaque morphology was classified according to the modified AHA classification scheme proposed by Virmani et al. [4]. Immunostaining against CD68 was used to identify the distribution of intimal macrophages and monocytes in several predefined locations among various plaque types and fibrous cap thickness. RESULTS: There was significant intimal thickening (p<0.013) and medial thinning (p<0.032) with advancing age. The incidence of atherosclerotic plaques in the abdominal aorta correlated with age (r=0.640, p=0.01). During the first three decades of life adaptive intimal thickening and intimal xanthomas were the predominant lesions. In contrast, the fourth, fifth and sixth decades hallmarked more complicated plaques of pathological intimal thickening, early and late fibroatheromas (EFAs and LFAs), thin-cap FAs (TCFAs; cap thickness <155 microm), ruptured plaques (PRs), healed rupture and fibrotic calcified plaques. The mean percentage of lesional macrophages increased significantly from LFAs to TCFAs (5-17%; p<0.001). Macrophage infiltration of the fibrous cap was negatively correlated with fibrous cap thickness (p<0.0004); TCFAs and PRs (caps<100 microm) contained significantly more macrophages (19%) compared with caps 101-300 microm (6%) and >300 microm (2%). Macrophages in shoulder regions were highest in early and late FAs ( approximately 45%) followed by TCFAs (27%) and PR (20%). Further, intimal vasa vasorum were mostly seen adjacent to the necrotic core of advanced atherosclerotic plaques and remained confined to the intimo-medial border despite marked thickening of the intima. CONCLUSION: This study shows that peri-renal aortic atherosclerosis starts early in life. Gross plaque morphologies of the peri-renal abdominal aorta are similar to coronary atherosclerosis yet indications were found for site specific differences in macrophage content and neovascularization.

Vascular remodeling after coronary stent implantation.

Drug eluting stents (DES) have significantly reduced restenosis when compared to BMS and are considered the standard of care in the treatment of symptomatic coronary artery disease. However, late stent thrombosis has emerged as a major concern with the use of first generation DES. Pathologic studies of patients dying from late DES thrombosis (first generation sirolimus-eluting stents and paclitaxel-eluting stents) showed that DES are associated with delayed healing characterized by poor endothelialization of stent struts and persistence of fibrin as compared to BMS. Additional risk factors for LST include long lesions, left main coronary artery, bifurcation stenting, ruptured plaques, and hypersensitivity reactions. Currently, the next generation DES are being developed to optimize the three major components of DES: the stent platform, the polymer coating and the drug. New technologies include biodegradable polymers and stents, polymer free drug delivery and prohealing approaches. Further preclinical testing and evaluation through large clinical trials are needed to determine the safety and efficacy of future DES in clinical practice.

First-In-Man application of a miniature self-contained intracoronary magnetic resonance probe. A multi-centre safety and feasibility trial.

AIMS: To assess safety and feasibility of intracoronary Magnetic Resonance (MR) Spectroscopy in living patients, using a self-contained MR catheter. METHODS AND RESULTS: Prospective, multi-centre study in patients with stable or unstable angina that were scheduled for percutaneous coronary diagnostic or therapeutic catheterization. We assessed the feasibility of an intravascular MR catheter, capable of analysing the arterial wall without external magnets or coils, by differentiating lipid rich, intermediate and fibrotic areas of the atherosclerotic plaque on the basis of differential water diffusion.Twenty-nine patients were included at 4 centres. The intracoronary MR-spectroscopy procedure was well tolerated; no MACE and no device related serious adverse event was observed. The MR catheter was successfully advanced into the lesion in 28 patients. Introduction of the MR catheter was not possible in one patient with a tortuous proximal right coronary artery. MR data were obtained in 22 patients. According to the predominant MR pattern, lesions were classified as fibrous plaque in 4 patients, as intermediate plaque in 4 patients and as lipid-rich plaque in 8 patients. Six patients were excluded from analysis because artifacts impeded the quality of the MR signal. Plaque type did not show a correlation with angina status (p=0.552; all groups) or angiographic parameters, such as minimal lumen diameter and diameter stenosis. CONCLUSIONS: This prospective, multi-centre study demonstrates for the first time that coronary artery assessment of potentially vulnerable, non-flow limiting lesions using a dedicated intravascular MR catheter, free of external magnets or coils, is feasible in clinical practice. Assessment of the coronary wall may provide important data regarding the composition of the atherosclerotic lesion, which then could contribute to predicting the likelihood of eventual rupture and clinical instability.