Gérald Gahide

Effect of Cyclosporine on Reperfusion Injury in Acute Myocardial Infarction

BACKGROUND Experimental 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. METHODS We 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. RESULTS The 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. CONCLUSIONS In 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

OBJECTIVES This 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. BACKGROUND In a human study, administration of cyclosporine at the time of acute reperfusion was associated with a smaller infarct size. METHODS Twenty-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. RESULTS There 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. CONCLUSIONS Cyclosporine 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).

Preoperative Evaluation in Aortic Endocarditis: Findings on Cardiac CT

OBJECTIVE The purpose of this study was to study the feasibility and diagnostic capability of preoperative cardiac CT for depicting aortic valvular pseudoaneurysms and vegetations in patients referred for aortic endocarditis requiring surgical intervention. MATERIALS AND METHODS Consecutive patients presenting with active aortic endocarditis requiring surgical intervention were included. CT scan examinations were performed for assessing coronary artery status. Aortic valves were retrospectively analyzed. Contrast-enhanced CT scans were retrospectively gated to the ECG and obtained without the administration of a beta-blocker. The CT and intraoperative findings were systematically compared. RESULTS During a 4-year period, 19 consecutive patients (18 men and one woman) were included (mean age +/- SD, 55 +/- 13 years). Results are expressed on a per-patient basis. The sensitivity, specificity, positive predictive value, and negative predictive value of MDCT in depicting aortic valve pseudoaneurysms were 100%, 87.5%, 91.7%, and 100%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of the MDCT in depicting the extension of the aortic valve pseudoaneurysms into the intervalvular fibrous body were each 100%. The sensitivity, specificity, positive predictive value, and negative predictive value of MDCT in depicting aortic valve vegetations were 71.4%, 100%, 100%, and 55.5%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of MDCT for depicting aortic valve vegetations larger than 1 cm were all 100%. CONCLUSION Our study shows the feasibility of preoperative CT in aortic infective endocarditis for providing relevant data about the presence and relationships of aortic valvular pseudoaneurysms. A larger prospective study including a systematic comparison with transesophageal echocardiography should be performed to determine the respective value of each technique.

A cut-off value of plasma osteoprotegerin level may predict the presence of coronary artery calcifications in chronic kidney disease patients

BACKGROUND Expression of bone proteins resulting from transdifferentiation of vascular smooth muscle cells into osteoblasts suggests that vascular calcifications are a bioactive process. Osteoprotegerin (OPG) could play a key role in bone-vascular calcification imbalance and could be a marker of vascular calcification extent and progression. The purpose of this study was to evaluate relationships between vascular risk biomarkers (including classic risk factors and OPG) and coronary artery calcification (CAC) extent in chronic kidney disease (CKD) patients and to establish within the markers the appropriate cut-off value to predict CAC. METHODS A total of 133 non-dialyzed CKD patients at various stages of kidney disease [75 males/58 females, median age: 69.9 (27.4-94.6)] were enrolled, excluding extrarenal replacement therapy patients. All underwent chest multidetector computed tomography for CAC scoring. Blood samples were collected for measurement of vascular risk markers (kidney disease, inflammation, nutrition, calcium phosphate and OPG). A potential relationship between CAC and these biological markers was investigated, and a receiver-operating characteristic (ROC) curve was designed thereafter to identify a cut-off value of involved markers that best predicted the presence of CAC. RESULTS After adjustment for age, diabetes, smoking and gender, among biological markers, only low-estimated glomerular filtration rate using Modification of Diet in Renal Disease [OR = 3.63 (1.10-12.02)], high FEPO(4) [OR = 3.99 (1.17-13.6)] and high OPG levels [OR = 8.54 (2.14-34.11)] were associated with the presence of CAC. A protective effect of 1.25(OH)(2) vitamin D [OR = 0.20 (0.05-0.79)] and LDL cholesterol [OR = 0.27 (0.08-0.94)] on CAC was also observed. ROC curve analysis showed that the OPG best cut-off value predicting CAC was 757.7 pg/mL. CONCLUSION These results suggest that a CAC increase is strongly associated with a plasma OPG increase in CKD patients. The values of OPG >757.7 pg/mL allow us to predict the presence of CAC in these patients.

Evolution of Coronary Artery Calcifications Following Kidney Transplantation: Relationship with Osteoprotegerin Levels

We prospectively assessed the evolution of coronary artery calcification (CAC) and osteoprotegerin (OPG) levels after renal transplantation (RT). Eighty‐three recipients were followed‐up prospectively during 1 year. Blood was collected before (baseline) and after RT for determination of mineral metabolism parameters including OPG. CAC was measured by multidetector computed tomography at transplantation (baseline) and 1 year later. Progression of CAC was defined as a difference between the follow‐up square‐root transformed volume (SRV) and the baseline SRV ≥ 2.5. By multivariate analysis, baseline OPG level, age and low LDL levels were significantly associated with baseline CAC. RT was accompanied by mineral metabolism improvement with a decrease of OPG from 955 [395–5652] to 527 [217–1818] pg/mL and parathyroid hormone from 94 [1–550] to 62 [16–410] pg/mL. Thirty‐one percent of patients did not exhibit CAC at baseline. CAC diminished in 14.5%, stabilized in 59.2% and progressed in 26.3% of patients. Baseline CAC was associated with progression (OR 2.92 [1.02–8.36]). No significant association was found between OPG and CAC progression despite a higher baseline OPG level in progressors (1046 [456–3285]) vs. non‐progressors (899 [396–5952] pg/mL). CAC at baseline, but not 1 year after RT, is independently associated with baseline OPG; posttransplant CAC progression is predicted by baseline CAC score.

Myocardial Expression of a Dominant-Negative Form of Daxx Decreases Infarct Size and Attenuates Apoptosis in an In Vivo Mouse Model of Ischemia/Reperfusion Injury

Background— Apoptosis has been described extensively in acute myocardial infarction and chronic heart failure. Because Daxx (death-associated protein) appears to be essential for stress-induced cell death and acts as an antisurvival molecule, we tested the hypothesis that Daxx is involved in myocardial ischemia/reperfusion–induced cell death in vivo. Methods and Results— Transgenic mice overexpressing a dominant-negative form of Daxx (Daxx-DN) under the control of the &bgr;-actin promoter and control wild-type mice underwent an ischemia/reperfusion protocol: 40 minutes of left coronary artery occlusion and 60 minutes of reperfusion. Area at risk and infarct size were measured after dual staining by triphenyltetrazolium chloride and phthalocyanine blue dye. Apoptosis was measured in the ischemic versus the nonischemic part of the left ventricle by terminal deoxynucleotidyl transferase–mediated dUTP biotin nick end labeling staining, enzyme-linked immunosorbent assay, and Western blotting of caspase-3, caspase-8, and poly(ADP-ribose) polymerase. The mitogen-activated protein kinase status was investigated by Western blot analysis. Comparison between groups was assessed by ANOVA or Student t test (statistical significance: P<0.05). Left ventricle tissues from transgenic mice expressed Daxx-DN at the protein level. Area at risk/left ventricle values were comparable among groups. Infarct size/area at risk was 45% reduced in Daxx-DN versus wild-type mice (P<0.001). This cardioprotection was maintained for a 4-hour reperfusion. Ischemia/reperfusion-induced apoptosis was significantly decreased and ERK1/2 prosurvival pathway was activated in ischemic Daxx-DN hearts. Conclusions— Our study clearly indicates that Daxx participates in myocardial ischemia/reperfusion proapoptotic signaling in vivo.

Cor triatriatum sinister: a comprehensive anatomical study on computed tomography scan.

![Figure][1] [![Graphic][3] ][3] A 17-year-old patient was referred to our institution for recurrent syncopal episodes on exertion. He had no relevant past medical history. Peripheral blood pressure was 100/60 mm Hg. Electrocardiogram showed a right bundle branch block. Transthoracic

Effusive constrictive pericarditis: functional and anatomical magnetic resonance findings

A 32-year-old man presented with progressive dyspnoea several months after a second episode of acute pericarditis. Heart rate was 70 b.p.m., and blood pressure was 120/80 mmHg. He had marked jugular venous distension, hepatomegaly, ascites, and bilateral moderate pleural effusion on chest X-ray. …

058 Effect of Cyclosporine on Left Ventricle Remodeling after Reperfused Myocardial Infarction

Objective This study examined the effect of cyclosporine A used at the time of reperfusion, on LV remodeling and function by cardiac magnetic resonance (CMR) in the early days and several months after AMI. Background In a human study, administration of cyclosporine A at the time of acute myocardial infarction (AMI) reperfusion was associated with a smaller infarct size. However, experimental data suggest that cyclosporine A has a detrimental effect on left ventricular remodeling. Methods 28 patients of the original cyclosporine A study had an acute (day 5) and a follow-up (6 months) CMR study. Cine imaging was used to determine LV volumes, mass, ejection fraction and myocardial wall thickness in infarcted and remote non-infarcted myocardium, and late gadolinium imaging was used to determine infarct size. Results There was a persistent reduction of the absolute infarct size at 6 months in the cyclosporine A group compared with the control group of patients (29±15 grams VS 38±14 grams; 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 A group, compared with the control group, both at day 5 and at 6 months after infarction. There was no significant difference between the two groups in either global LV mass or regional wall thickness of the remote non-infarcted myocardium at day 5 or at 6 months. Attenuation of LV dilatation and improvement of LV ejection fraction by cyclosporine A at 6 months were correlated with infarct size reduction. Conclusion Cyclosporine A used at the moment of AMI reperfusion persistently reduces infarct size and does not have a detrimental effect on LV remodeling