Didier Revel

Effect of Cyclosporine on Reperfusion Injury in Acute Myocardial Infarction

BACKGROUNDnExperimental evidence suggests that cyclosporine, which inhibits the opening of mitochondrial permeability-transition pores, attenuates lethal myocardial injury that occurs at the time of reperfusion. In this pilot trial, we sought to determine whether the administration of cyclosporine at the time of percutaneous coronary intervention (PCI) would limit the size of the infarct during acute myocardial infarction.nnnMETHODSnWe randomly assigned 58 patients who presented with acute ST-elevation myocardial infarction to receive either an intravenous bolus of 2.5 mg of cyclosporine per kilogram of body weight (cyclosporine group) or normal saline (control group) immediately before undergoing PCI. Infarct size was assessed in all patients by measuring the release of creatine kinase and troponin I and in a subgroup of 27 patients by performing magnetic resonance imaging (MRI) on day 5 after infarction.nnnRESULTSnThe cyclosporine and control groups were similar with respect to ischemia time, the size of the area at risk, and the ejection fraction before PCI. The release of creatine kinase was significantly reduced in the cyclosporine group as compared with the control group (P=0.04). The release of troponin I was not significantly reduced (P=0.15). On day 5, the absolute mass of the area of hyperenhancement (i.e., infarcted tissue) on MRI was significantly reduced in the cyclosporine group as compared with the control group, with a median of 37 g (interquartile range, 21 to 51) versus 46 g (interquartile range, 20 to 65; P=0.04). No adverse effects of cyclosporine administration were detected.nnnCONCLUSIONSnIn our small, pilot trial, administration of cyclosporine at the time of reperfusion was associated with a smaller infarct by some measures than that seen with placebo. These data are preliminary and require confirmation in a larger clinical trial.

Effect of Cyclosporine on Left Ventricular Remodeling After Reperfused Myocardial Infarction

OBJECTIVESnThis study examined the effect of a single dose of cyclosporine administered at the time of reperfusion on left ventricular (LV) remodeling and function by cardiac magnetic resonance 5 days and 6 months after myocardial infarction.nnnBACKGROUNDnIn a human study, administration of cyclosporine at the time of acute reperfusion was associated with a smaller infarct size.nnnMETHODSnTwenty-eight patients of the original cyclosporine study had an acute (at 5 days) and a follow-up (at 6 months) cardiac magnetic resonance study to determine LV volumes, mass, ejection fraction, myocardial wall thickness in infarcted and remote noninfarcted myocardium, and infarct size.nnnRESULTSnThere was a persistent reduction in infarct size at 6 months in the cyclosporine group compared with the control group of patients (29 +/- 15 g vs. 38 +/- 14 g; p = 0.04). There was a significant reduction of LV end-systolic volume (and a trend for LV end-diastolic volume; p = 0.07) in the cyclosporine group compared with the control group, both at 5 days and 6 months after infarction. There was no significant difference between the 2 groups in either global LV mass or regional wall thickness of the remote noninfarcted myocardium at 5 days or 6 months. Attenuation of LV dilation and improvement of LV ejection fraction by cyclosporine at 6 months were correlated with infarct size reduction.nnnCONCLUSIONSnCyclosporine used at the moment of acute myocardial infarction reperfusion persistently reduces infarct size and does not have a detrimental effect on LV remodeling. These results are preliminary and must be supported by further studies. (Ciclosporin A and Acute Myocardial Infarction; NCT00403728).

Combined Pulmonary Fibrosis and Emphysema Syndrome in Connective Tissue Disease

OBJECTIVEnConnective tissue diseases (CTDs) are associated with several interstitial lung diseases. The aim of this study was to describe the recently individualized syndrome of combined pulmonary fibrosis and emphysema (CPFE) in a population of patients with CTD.nnnMETHODSnIn this multicenter study, we retrospectively investigated data from patients with CTD who also have CPFE. The demographic characteristics of the patients, the results of pulmonary function testing, high-resolution computed tomography, lung biopsy, and treatment, and the outcomes of the patients were analyzed.nnnRESULTSnData from 34 patients with CTD who were followed up for a mean±SD duration of 8.3±7.0 years were analyzed. Eighteen of the patients had rheumatoid arthritis (RA), 10 had systemic sclerosis (SSc), 4 had mixed or overlap CTD, and 2 had other CTDs. The mean±SD age of the patients was 57±11 years, 23 were men, and 30 were current or former smokers. High-resolution computed tomography revealed emphysema of the upper lung zones and pulmonary fibrosis of the lower zones in all patients, and all patients exhibited dyspnea during exercise. Moderately impaired pulmonary function test results and markedly reduced carbon monoxide transfer capacity were observed. Five patients with SSc exhibited pulmonary hypertension. Four patients died during followup. Patients with CTD and CPFE were significantly younger than an historical control group of patients with idiopathic CPFE and more frequently were female. In addition, patients with CTD and CPFE had higher lung volumes, lower diffusion capacity, higher pulmonary pressures, and more frequently were male than those with CTD and lung fibrosis without emphysema.nnnCONCLUSIONnCPFE warrants inclusion as a novel, distinct pulmonary manifestation within the spectrum of CTD-associated lung diseases in smokers or former smokers, especially in patients with RA or SSc.

Determination of the myocardial area at risk with pre- versus post-reperfusion imaging techniques in the pig model

The purpose of this study was to compare the accuracy of post-reperfusion cardiac magnetic resonance (CMR) and pre-reperfusion multidetector computed tomography (MDCT) imaging to measure the size of the area at risk (AAR), using pathology as a reference technique in a porcine acute myocardial infarction model. Fifteen pigs underwent balloon-induced coronary artery occlusion for 40xa0min followed by reperfusion. The AAR was assessed with arterial enhanced MDCT performed during occlusion, while two different T2 weighted (T2W) CMR imaging sequences and the contrast-enhanced (ce-) CMR endocardial surface length (ESL) were performed after 90xa0min of reperfusion. Animals were euthanized and the AAR was assessed by pathology. Additional measurements of the myocardial water content in the AAR, remote and the AAR border zones were performed. AAR by pathology best correlated with measurements made by MDCT (R2xa0=xa00.88; pxa0<xa00.001) with little bias on Bland–Altman plots (bias 2.5%, SD 6.1% LV area). AAR measurements obtained by T2W STIR, T2W ACUTE sequences or the ESL on ce-CMR showed a fair correlation with pathology (R2xa0=xa00.72, R2xa0=xa00.65 and R2xa0=xa00.69, respectively; all pxa0≤xa00.001), but significantly overestimated the size of the AAR with important bias (17.4xa0±xa010.8% LV area; 11.7xa0±xa011.0% LV area; 13.0xa0±xa010.3% LV area, respectively). The myocardial water content in the AAR border zones was significantly higher than the remote (82.8 vs. 78.8%; pxa0<xa00.001). Our data suggest that post-reperfusion imaging methods overestimated the AAR likely due to the presence of edema outside of the boundaries of the AAR. Pre-reperfusion arterial enhanced MDCT showed the greatest accuracy for the assessment of the AAR.

Postconditioning attenuates no-reflow in STEMI patients

After acute myocardial infarction, the presence of no-reflow (or microvascular obstruction: MVO) has been associated with adverse left ventricular (LV) remodeling and worse clinical outcome. This study examined the effects of mechanical ischemic postconditioning on early and late MVO size in acute ST-elevation myocardial infarction (STEMI) patients. Fifty patients undergoing primary coronary angioplasty for a first STEMI with TIMI grade flow 0–1 and no collaterals were randomized to ischemic postconditioning (PC) (nxa0=xa025) or control (nxa0=xa025) groups. Ischemic PC consisted in the application of four consecutive cycles of a 1-min balloon occlusion, each followed by a 1-min deflation at the onset of reperfusion. Early (3xa0min post-contrast) and late (10xa0min post-contrast) MVO size were assessed by contrast-enhanced cardiac-MRI within 96xa0h after reperfusion. PC was associated with smaller early and late MVO size (3.9xa0±xa04.8 in PC versus 7.8xa0±xa06.6xa0% of LV in controls for early MVO, Pxa0=xa00.02; and 1.8xa0±xa03.1 in PC versus 4.1xa0±xa03.9xa0% of LV in controls for late MVO; Pxa0=xa00.01). This significant reduction was persistent after adjustment for thrombus aspiration, which neither had any significant effect on infarct size, nor on early or late MVO (Pxa0=xa0NS for all). Attenuation of MVO was associated to infarct size reduction. Mechanical postconditioning significantly reduces MVO in patients with acute STEMI treated with primary angioplasty.

Lung perfusion demonstrated by contrast-enhanced dynamic magnetic resonance imaging. Application to unilateral lung transplantation.

RATIONALE AND OBJECTIVESnThe authors evaluate the use of magnetic resonance (MR) to image pulmonary perfusion in healthy controls and to detect pulmonary defects in patients with unilateral lung transplantation, using dynamic images after contrast administration.nnnMETHODSnFive patients with right lung transplantation and nine healthy volunteers underwent MR imaging. Twenty-five subsecond contrast-enhanced MR images (turbo-fast low-angle shot [FLASH]) were obtained at the level of the pulmonary arteries after a single injection of gadopentetate dimeglumine (0.1 mmol/kg) in an antecubital vein. Perfusion lung scintigraphy was done within 24 hours after the MR imaging examination in the transplanted patients.nnnRESULTSnBefore administration of contrast material, MR images showed both lungs to be homogeneous and of low signal intensity in healthy controls and in patients with lung transplantation. After contrast administration in controls, the mean signal intensity of the dependent lung increased markedly to 171 +/- 24% above baseline, whereas the nondependent signal intensity lung increased by only 105 +/- 17%; these changes were significantly different. In all patients with lung transplantation, a clear perfusion defect was demonstrated in the native lung. This defect was confirmed in all cases by perfusion nuclear scintigraphy, which showed that the majority of lung perfusion is directed to the transplanted allograft, compared with the native contralateral lung.nnnCONCLUSIONSnOur results suggest that dynamic contrast-enhanced MR imaging is a potential method for detecting pulmonary perfusion defects in patients with lung transplantation.

CARBOXYMETHYL-DEXTRAN-GADOLINIUM-DTPA AS A BLOOD-POOL CONTRAST AGENT FOR MAGNETIC RESONANCE ANGIOGRAPHY : EXPERIMENTAL STUDY IN RABBITS

RATIONALE AND OBJECTIVESnThe authors evaluate the efficiency of various doses of a paramagnetic macromolecular contrast agent, a gadolinium (Gd)-DTPA-dextran conjugate, as a blood-pool contrast media, in a transverse three-dimensional time-of-flight (TOF) magnetic resonance (MR) angiography sequence of the abdominal aorta in rabbits.nnnMETHODSnImaging experiments were performed on a 1.5-T magnet, using a transverse three-dimensional TOF tilted optimized nonsaturating excitation (TONE) sequence. The macromolecular contrast media used was a carboxymethyl-dextran-Gd-DTPA (CMD-Gd-DTPA). Different concentrations of CMD-Gd-DTPA (0.005, 0.01, 0.03, 0.05 mmol Gd/kg) were evaluated. A comparative study using Gd-DOTA (0.01 and 0.1 mmol/kg) was performed. A visual analysis based on the gain in the visualized length of small arteries (renal arteries), and a quantitative analysis based on the percent contrast enhancement of the aorta plotted against distance in the slab from the top edge of the acquisition volume were obtained.nnnRESULTSnA signal-to-noise ratio enhancement of the distal part of the aorta and an improvement in the visualized length of the renal arteries were noted for concentrations of CMD-Gd-DTPA ranging form 0.01 to 0.05 mmol Gd/kg. Venous enhancement was noted for concentrations greater than 0.01 mmol Gd/kg when using CMD-Gd-DTPA or Gd-DOTA.nnnCONCLUSIONnCarboxymethyl-dextran-Gd-DTPA reduced, in part, the saturation effect in a three-dimensional transverse TOF TONE MR angiography in rabbits. To prevent venous enhancement, observed with the higher concentrations used in this study, a decrease in the polydispersity of the polymer should be a goal in the future. Rapid extravasation of the low-molecular weight fraction of the polymer could explain the venous enhancement.

Multidetector Computed Tomography in Reperfused Acute Myocardial Infarction: Assessment of Infarct Size and No-reflow in Comparison With Cardiac Magnetic Resonance Imaging

Objectives:(1) To determine the accuracy of delayed enhancement multidetector computed tomography (MDCT) in measuring the extent of acute myocardial infarct and no-reflow areas using cardiac magnetic resonance imaging (MRI) as standard of reference and (2) to define the optimum timing between injection and MDCT image acquisition to characterize infarcted myocardium and no-reflow areas after reperfusion therapy. Materials and Methods:Nineteen patients were prospectively included after acute myocardial infarction and revascularization. Each patient had an MDCT acquisition before and 5 and 10 minutes after injection of 1.5 mL/kg iodinated contrast medium, and a contrast-enhanced MRI at 5 and 10 minutes after injection of 0.2 mmol/kg gadolinium chelate. We assessed image quality and infarct extent using MDCT and MRI, and we measured parameters related to iodinated contrast media kinetics (&Dgr;HU and &Dgr;HU ratio). Results:The areas of hyperenhanced myocardium located on the MDCT corresponded to the occluded vessel located on the coronary angiogram (&kgr; = 0.9). There were strong correlations between the extent of hyperenhanced infarcted myocardium on MDCT and MRI at 5 minutes (20.4% ± 2.7% of left ventricle (LV) and 20.9% ± 2.4%, respectively, R = 0.85; P < 0.0001) and 10 minutes after injection (21.0% ± 2.9% of LV and 19.4% ± 2.5%, respectively, R = 0.80; P < 0.0001). However, the correlation between the area of hypoenhanced myocardium measured using MDCT and CMR 5 minutes after injection (R = 0.86; P < 0.0001) was better than the measurement obtained 10 minutes after injection (R = 0.64; P = 0.002). On contrast-enhanced MDCT, 5 minutes after injection, the signal-to-noise ratio was significantly higher than at 10 minutes after injection in LV blood (28 ± 1 to 21 ± 1, respectively; P = 0.0007), normal myocardium (18 ± 1 to 15 ± 1; P = 0.0009), and hyperenhanced infarcted myocardium (24 ± 1 to 20 ± 1; P = 0.004). MDCT image quality was significantly better at 5 minutes (3.2 ± 0.1) than at 10 minutes (2.8 ± 0.2, P = 0.01, &kgr; = 0.4). The &Dgr;HU ratio increased slightly but significantly between 5 minutes (0.83 ± 0.01) and 10 minutes (0.93 ± 0.01; P = 0.01), suggesting a slow wash-in and wash-out of contrast medium in infarcted myocardium. Conclusion:In ST segment elevation myocardial infarction patients contrast-enhanced MDCT is an accurate method for characterizing and sizing myocardial infarct and no-reflow. Contrast-enhanced MDCT performed 5 minutes after injection yields a higher signal-to-noise ratio and image quality than the 10 minutes time point with no difference in the extent of infarct measurement.

Contrast-enhanced magnetic resonance tomoangiography: A new imaging technique for studying thoracic great vessels

The authors propose a new imaging approach for studying thoracic great vessels, using high-speed MR imaging combined with intravenous rapid bolus injection of a paramagnetic contrast media. The decrease of the T1 relaxation time of flowing blood induced by the contrast agent (Gd-DOTA) caused an increased signal intensity within the vessel lumen for a time period allowing multiplanar imaging of various vascular structures. The intraluminal signal enhancement is mainly related to the blood concentration of the contrast agent as in conventional X-ray angiography. Information on the aorta and pulmonary arteries obtained by the so-called contrast-enhanced magnetic resonance tomoangiography appears complementary to that obtained with other vascular MR imaging procedures such as cine-MRI and magnetic resonance angiography (MRA).

Comparison of the angiographic myocardial blush grade with delayed-enhanced cardiac magnetic resonance for the assessment of microvascular obstruction in acute myocardial infarctions†

Background: Both myocardial blush grade (MBG) and cardiac magnetic resonance (CMR) are imaging tools that can assess myocardial reperfusion after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Objectives: We studied the relation between MBG and gadolinium‐enhanced CMR for the assessment of microvascular obstruction (MVO) in patients with acute ST‐elevated myocardial infarction (STEMI) treated by primary PCI. Material and Methods: MBG was assessed in 39 patients with initial TIMI 0 STEMI successfully treated by PCI, resulting in TIMI 3 flow grade and complete ST‐segment resolution. These MBG values were related to MVO determined by CMR, performed between 2 and 7 days after PCI. Left ventricular (LV) volumes were determined at baseline and at 6‐month follow‐up. Results: No statistical relation was found between MBG and MVO extent at CMR (P = 0.63). Regarding MBG 0 and 1 as a sign of MVO, the sensitivity and specificity of these scores were 53.8 and 75%, respectively. In this study, CMR determined MVO was the only significant LV remodeling predicting factor (β = 31.8; P = 0.002), whatever the MBG status was. Conclusion: MBG underestimates MVO after an optimal revascularization in AMI compared with CMR. This study suggests the superior accuracy of delayed‐enhanced magnetic resonance over MBG for the assessment of myocardial reperfusion injury that is needed in clinical trials, where the principal endpoint is the reduction of infarct size and MVO.