Hélène Vernhet

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).

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.

Reversible amiodarone-induced lung disease: HRCT findings.

Abstract. The aim of this study was to describe thoracic high-resolution computed tomography (HRCT) findings of reversible amiodarone-induced lung disease (AILD). The thoracic HRCT of 20 symptomatic patients who were considered as having reversible AILD by the medical staff of our institution were retrospectively reviewed. The patient-selection criteria used were the development of new respiratory symptoms while receiving amiodarone, the exclusion of other respiratory and cardiac diseases, and the decrease of both respiratory symptoms and radiological abnormalities after cessation of amiodarone and corticotherapy. The CT data recorded were those usually sought infiltrative lung diseases. The radiological findings using chest film (n=20) and HRCT (n=4) follow-up was noted. All patients had ground-glass opacities, associated with consolidations (n=4), thin intralobular reticulations (n=5), or both (n=11), with a subpleural (n=18) or central (n=2) location. Eight patients had high-density areas and 13 had pleural thickening (n=13). Bronchial abnormalities included dilation (n=16) and wall thickening (n=19). After therapeutic management, the radiological follow-up showed complete (n=17) or incomplete (n=3) improvement. Ground-glass opacities associated with thin intralobular reticulations and/or subpleural consolidations and bronchial abnormalities are common HRCT findings in reversible AILD.

Osteoprotegerin and sclerostin in chronic kidney disease prior to dialysis: potential partners in vascular calcifications

BACKGROUND Osteoprotegerin (OPG), sclerostin and DKK1 constitute opposite bone turnover inhibitors, OPG inhibiting osteoclastogenesis while sclerostin and DKK1 exerting their inhibitory effects on osteoblastogenesis. Both proteins have been recognized as strong risk factors of vascular calcifications in non-dialysis chronic kidney disease (ND-CKD) patients. The aim of this study was to investigate the relationships between these inhibitors and coronary artery calcifications (CAC) in this population. METHODS A total of 241 ND-CKD patients [143 males; 69.0 (25.0-95.0) years; median estimated glomerular filtration rate using CKD-EPI 35.1 (6.7-120.1) mL/min/1.73 m(2)] were enrolled in this cross-sectional study. All underwent chest multidetector computed tomography for CAC scoring. OPG, sclerostin, DKK1 and mineral metabolism markers including PTH and bone alkaline phosphatase were measured. Logistic regression analyses were used to study the relationships between CAC and these markers. RESULTS Decline in renal function was associated with a significant increase in OPG and sclerostin while a slight but significant decrease in DKK1 was observed. The main crude associations with presence of CAC were a high level of OPG [OR = 2.55 95% confidence interval (95% CI) (1.35-4.82) for a level ranging from 6.26 to 9.15 pmol/L and OR = 5.74 95% CI (2.87-11.5) for a level ≥9.15 pmol/L; P < 0.0001] and a high level of sclerostin [OR = 2.64 95% CI (1.39-5.00) for a level ranging from 0.748 to 1.139 ng/mL and OR = 3.78 95% CI (1.96-7.31) for a level ≥1.139 ng/mL; P = 0.0002]. A logistic regression model clearly showed that the risk to present CAC was significantly increased when both OPG (≥6.26 pmol/L) and sclerostin (≥0.748 ng/mL) levels were high [crude model: OR = 11.47 95% CI (4.54-29.0); P < 0.0001; model adjusted for age, gender, diabetes, body mass index and smoking habits: OR = 5.69 95% CI (1.76-18.4); P = 0.02]. No association between DKK1 and presence of CAC was observed. CONCLUSIONS Our results strongly suggest that bone turnover inhibitors, OPG and sclerostin, are independently associated with CAC with potential additive effects in ND-CKD 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.

Wall mechanics of the stented rabbit aorta: long-term study and correlation with histological findings.

Purpose: To evaluate long-term changes in arterial wall mechanics induced by stenting of the rabbit aorta. Methods: Eighteen New Zealand white rabbits had initial stent deployment (3×8 mm Multilink) at 110% of the pre-stenting abdominal aortic diameter. Group A (n=10) had no post-deployment stent expansion and group B (n=8) had 30% overdilation of the stent. A noninvasive B-mode ultrasound examination coupled with image processing allowed measurement of diameters at systole and diastole and the calculation of diameter compliance. Measurements were performed before stenting and compared to those recorded immediately after stenting and at 3 months at 3 locations: upstream from the stent, at the stent level, and downstream from the stent. Measurements were also compared among measurement sites. The pathological study included measurement of intimal thickening and calculation of an injury score. Results: At the stent level, diameter compliance was significantly lower after initial stenting and at 3 months than before stenting (group A: p<0.005; group B: p<0.001) and than downstream or upstream from the stent (group A: p<0.0001, group B: p<0.005). No significant difference in diameter compliance was found between groups A and B. In group B, intimal thickening and the injury score were greater than in group A (p<0.05 and p<0.0001, respectively). Conclusions: Endovascular stenting of the rabbit aorta impairs wall mechanics. Performing 30% overdilation of the stent does not worsen this impairment but induces greater in-stent intimal hyperplasia.

Validation of a newly developed B-mode image-processing technique versus wall-tracking ultrasound for the study of wall mechanics in small-calibre arteries

Purpose: To validate a newly developed image‐processing technique for the assessment of arterial wall compliance and distensibility from non‐invasive B‐mode ultrasound compared with the invasive wall‐tracking technique.

La lymphographie, modalité thérapeutique d'une plaie chirurgicale du canal thoracique : à propos d'un cas

e chylothorax est défini par la présence de chyle dans la cavité pleurale. La chirurgie et les traumatismes sont responsables pour moitié des chylothorax rencontrés en pratique clinique. L’autre moitié est liée à des étiologies médicales ; c’est-à-dire sans lésion du canal thoracique ; principalement représentées par des pathologies lymphoïdes dont notamment les lymphomes (1) et des pathologies mal connues de drainage du système lymphatique comme le syndrome des ongles jaunes et la lymphangioleïomyomatose (tableau I). Nous rapportons l’évolution d’un chylothorax post-chirurgical qui a régressé après lymphographie.

Experimental model for comparative evaluation of pharmacologically induced vasodilation of arterial wall mechanical properties.

&NA; Arterial wall compliance (C) and distensibility coefficient (DC) are key factors of pathologic physiology, especially in arteries less than 2 mm in diameter. The aim of this study was to design an experimental model allowing comparative measurement of C and DC during pharmacologically induced vasodilation on small‐diameter arteries. Both femoral arteries were exposed in eight New Zealand White rabbits. Diameter (d) and systolic/diastolic diameter changes (&dgr;d) were measured simultaneously, and C and DC were calculated before and after topical application of 1 mL of 4% papaverine on the right side and topical application of 1 mL of 1% lidocaine on the left side. Diameter measurements were performed by echo tracking with 20‐MHz implanted microprobes. After papaverine and lidocaine application, respectively, d increased from 1.36 mm to 2.23 mm (P < 0.0001) and from 1.45 mm to 2.4 mm (P < 0.0001), &dgr;d increased from 0.0568 mm to 0.0571 mm (P = 0.34) and from 0.064 mm to 0.077 mm (P < 0.01), C increased from 5.7 × 10‐3 mm/mm Hg to 6 × 10‐3 mm/mm Hg (P < 0.02) and from 6.23 × 10‐3 mm/mm Hg to 8.49 × 10‐3 mm/mm Hg (P < 0.01), and DC decreased from 4.22 × 10‐3 mm Hg‐1 to 2.61 × 10‐3 mm Hg ‐1 (P < 0.0004) and from 4.36 × 10‐3 mm/mm Hg to 3.46 × 10‐3 mm/mm Hg (P < 0.005). Papaverine‐ and lidocaine‐induced changes were significantly different for &dgr;d, C, and DC (P < 0.01). These results suggest that, unlike that with papaverine, lidocaine‐induced vasodilation leads the artery up to the nonlinear part of its pressure/diameter relationship, with decreased distensibility contrasting with increased diameter and compliance. Our experimental model may be useful to compare the effects of different vasoactive drugs at different concentrations on the mechanical properties of the arterial wall.

Prognostic Impact of Calcium Score after Transcatheter Aortic Valve Implantation Performed With New Generation Prosthesis

Calcium score (CS) is a well-known prognostic factor after transcatheter aortic valve implantation (TAVI) performed with first generation prosthesis but few data are available concerning new generation valves. The aim of this study was to evaluate if CS remains a prognostic factor after Sapien 3 and Evolut R valves implantation. Agatston CS was evaluated on multislice computed tomography before TAVI in 346 patients implanted with Sapien XT (n = 61), CoreValve (n = 57) devices, (group 1, n = 118), and with new generation Sapien 3 (n = 147), Evolut R (n = 81) prosthesis, (group 2, n = 228). Major adverse cardiovascular events and aortic regurgitation (AR) were evaluated at 1 month. The 2 groups were similar at baseline except for logistic Euroscore (20.1% in group 1 vs 15.0 % in group 2; p = 0.001), chronic renal failure (44.1% vs 37.2% respectively, p = 0.007) and preprocedural CS (4,092 ± 2,176 vs 3,682 ± 2,109 respectively, p = 0.022). In group 1, 28 patients (23.7%) had adverse clinical events vs 21 (9.2%) in group 2 (p <0.01). In multivariate analysis, a higher CS was predictive of adverse events in group 1 (5,785 ± 3,285 vs 3,565 ± 1,331 p <0.0001) but not in group 2 (p = 0.28). A higher CS was associated with AR in group 1 (6,234 ± 2711 vs 3,429 ± 1,505; p <0.001) and in patients implanted with an Evolut R device from group 2 (4,085 ± 3,645 vs 2,551 ± 1,356; p = 0.01). In conclusion, CS appears as an important prognostic factor of major events after TAVI with first generation valves but not with new generation devices. CS remains associated with AR only with new generation self-expandable Evolut R devices.