Letizia Bacchi Reggiani

Importance of dural ectasia in phenotypic assessment of M arfan's syndrome

BACKGROUND Early identification of Marfans syndrome is fundamental in the prevention of aortic dilatation, but the wide phenotypic expression of the disorder makes the clinical diagnosis very difficult. Dural ectasia has been classified as a major diagnostic criterion; however, its prevalence is not known. We aimed to identify the true prevalence of dural ectasia in Marfans syndrome, and to investigate its relation to aortic pathology. METHODS A magnetic-resonance-imaging (MRI) study of the thoracic aorta and of the lumbosacral spine was done in an inclusive series of 83 patients with Marfans syndrome to assess the presence and degree of dural ectasia and aortic involvement; 12 patients were younger than 18 years. 100 individuals who underwent MRI of the lumbar spine for routine clinical indications represented the control group; none of them had any potential causes for dural ectasia. FINDINGS Dural ectasia was identified in 76 (92%) patients and none of the control group. The severity of dural ectasia was related to age; the mean (SD) age of patients with mild dural ectasia was 26 years (14) whereas that of those with severe disease (meningocele) was 36 years (9) (p=0.038). 11 of 12 patients younger than 18 years had dural ectasia. No association was found between aortic dilatation and dural ectasia. INTERPRETATION Dural ectasia is a highly characteristic sign of Marfans syndrome, even at an early age.

Stent Thrombosis With Everolimus-Eluting Stents Meta-Analysis of Comparative Randomized Controlled Trials

Background— Some but not all studies have reported reduced rates of stent thrombosis (ST) with everolimus-eluting stents (EES) compared with other drug-eluting stents (DES). All of these studies were insufficiently powered to reliably detect differences in ST. We therefore performed a meta-analysis of randomized controlled trials comparing the risk of 2-year definite ST between EES and other DES. Methods and Results— Randomized controlled trials comparing EES versus other DES were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. Information on study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted. Eleven randomized controlled trials (16 775 patients) were analyzed, including 5 trials (n=7113) of EES versus paclitaxel-eluting stents, 5 trials (n=7370) of EES versus sirolimus-eluting stents, and 1 trial (n=2292) of EES versus zotarolimus-eluting stents. By 2 years definite ST with EES compared with pooled DES occurred in 0.5% versus 1.3% patients, respectively (relative risk, 0.38; 95% CI, 0.24–0.59; P<0.0001). Similar results were observed when the broader definition of definite/probable ST was considered (relative risk, 0.46; 95% CI, 0.33–0.66; P<0.0001). EES compared with other DES reduced the relative risk of early ST (within 30 days), late ST (31 days to 1 year), cumulative 1-year ST, and very late ST (1–2 years). The reduced rate of definite ST observed with EES was consistent across all DES comparators with no interactions apparent during any time interval. Conclusions— EES compared with a pooled group of paclitaxel-eluting stents, sirolimus-eluting stents, and zotarolimus-eluting stents is associated with a significant reduction of definite ST, an effect that appears early and increases in magnitude through at least 2 years.

Risk of Stroke With Coronary Artery Bypass Graft Surgery Compared With Percutaneous Coronary Intervention

OBJECTIVES This study sought to determine whether coronary artery bypass graft (CABG) surgery is associated with an increased risk of stroke compared with percutaneous coronary intervention (PCI). BACKGROUND Some, but not all, randomized trials have reported increased rates of stroke with CABG compared with PCI. However, all these studies were powered insufficiently to examine differences in the risk of stroke reliably. METHODS We performed a meta-analysis of 19 trials in which 10,944 patients were randomized to CABG versus PCI. The primary end point was the 30-day rate of stroke. We also determined the rate of stroke at the midterm follow-up and investigated whether there was an interaction between revascularization type and the extent of coronary artery disease on the relative risk of stroke. RESULTS The 30-day rate of stroke was 1.20% after CABG compared with 0.34% after PCI (odds ratio: 2.94, 95% confidence interval: 1.69 to 5.09, p < 0.0001). Similar results were observed after a median follow-up of 12.1 months (1.83% vs. 0.99%, odds ratio: 1.67, 95% confidence interval: 1.09 to 2.56, p = 0.02). The extent of coronary artery disease (single vessel vs. multivessel vs. left main) did not affect the relative increase in the risk of stroke observed with CABG compared with PCI at either 30 days (p = 0.57 for interaction) or midterm follow-up (p = 0.08 for interaction). Similar results were observed when the outcomes in 33,980 patients from 27 observational studies were analyzed. CONCLUSIONS Coronary revascularization by CABG compared with PCI is associated with an increased risk of stroke at 30 days and at the mid-term follow-up.

Three, six, or twelve months of dual antiplatelet therapy after DES implantation in patients with or without acute coronary syndromes: an individual patient data pairwise and network meta-analysis of six randomized trials and 11 473 patients.

Aim We sought to determine whether the optimal dual antiplatelet therapy (DAPT) duration after drug-eluting stent (DES) placement varies according to clinical presentation. Methods and Results We performed an individual patient data pairwise and network meta-analysis comparing short-term (⩽6-months) versus long-term (1-year) DAPT as well as 3-month vs. 6-month vs 1-year DAPT. The primary study outcome was the 1-year composite risk of myocardial infarction (MI) or definite/probable stent thrombosis (ST). Six trials were included in which DAPT after DES consisted of aspirin and clopidogrel. Among 11 473 randomized patients 6714 (58.5%) had stable CAD and 4758 (41.5%) presented with acute coronary syndrome (ACS), the majority of whom (67.0%) had unstable angina. In ACS patients, ⩽6-month DAPT was associated with non-significantly higher 1-year rates of MI or ST compared with 1-year DAPT (Hazard Ratio (HR) 1.48, 95% Confidence interval (CI) 0.98–2.22; P = 0.059), whereas in stable patients rates of MI and ST were similar between the two DAPT strategies (HR 0.93, 95%CI 0.65–1.35; P = 0.71; Pinteraction = 0.09). By network meta-analysis, 3-month DAPT, but not 6-month DAPT, was associated with higher rates of MI or ST in ACS, whereas no significant differences were apparent in stable patients. Short DAPT was associated with lower rates of major bleeding compared with 1-year DAPT, irrespective of clinical presentation. All-cause mortality was not significantly different with short vs. long DAPT in both patients with stable CAD and ACS. Conclusions Optimal DAPT duration after DES differs according to clinical presentation. In the present meta-analysis, despite the fact that most enrolled ACS patients were relatively low risk, 3-month DAPT was associated with increased ischaemic risk, whereas 3-month DAPT appeared safe in stable CAD. Prolonged DAPT increases bleeding regardless of clinical presentation. Further study is required to identify the optimal duration of DAPT after DES in individual patients based on their relative ischaemic and bleeding risks.

Role of Statins in the Management of Dyslipidemia After Cardiac Transplant: Randomized Controlled Trial Comparing the Efficacy and the Safety of Atorvastatin with Pravastatin

BACKGROUND Cardiac transplant patients are at increased risk of dyslipidemia, a known pathogenetic factor in chronic rejection. The aim of this study was to compare the efficacy and the safety of treatment with atorvastatin (AT) and treatment with pravastatin (PV) in a population of dyslipidemic transplant patients. METHODS Thirty-nine transplant patients were randomized to receive a 4-month cycle of therapy with AT or PV, in a cross-over sequence. We analyzed the effects on their lipid profiles using Student t-test for paired data. RESULTS AND CONCLUSION Atorvastatin was significantly more effective than PV in reducing total cholesterol (33% vs 21%, p < 0.001), LDL cholesterol (45% vs 30%, p = 0.001), and triglycerides (24% vs 7.7%, p < 0.001), at lower doses and with comparable tolerability and safety.

Spleen stiffness measurement can predict clinical complications in compensated HCV-related cirrhosis: A prospective study

BACKGROUND & AIMS Hepatic venous pressure gradient (HVPG) measurement represents the best predictor of clinical decompensation (CD) in cirrhotic patients. Recently data show that measurement of spleen stiffness (SS) has an excellent correlation with HVPG levels. Aim of the present prospective study was to assess SS predictive value for CD compared to HVPG, liver stiffness (LS), and other non-invasive tests for portal hypertension in a cohort of patients with HCV-related compensated cirrhosis. METHODS From an initial cohort of 124 patients, 92 underwent baseline LS, SS, HVPG measurements and upper gastrointestinal endoscopy at enrolment and then followed-up for 2 years or until the occurrence of the first CD. Univariate and multivariate logistic regression models were used for determining judgement criteria associated parameters. Accuracy of predictive factors was evaluated using c statistic. The final model was internally validated using the bootstrap method. RESULTS During follow-up, 30 out 92 (32.6%) patients developed CD. At univariate analysis varices at enrolment, all non-invasive parameters, HVPG, and model for end-stage liver disease (MELD) resulted clinical predictors of CD. At multivariate analysis only SS (p=0.0001) and MELD (p=0.014) resulted as predictive factors. A decision algorithm based on the results of a predictive model was proposed to detect patients with low risk of decompensation. CONCLUSIONS This study shows that in compensated cirrhotic patients a SS and MELD predictive model represents an accurate predictor of CD with accuracy at least equivalent to that of HVPG. If confirmed by further studies, SS and MELD could represent valid alternatives to HVPG as prognostic indicator of CD in HCV-related cirrhosis.

A randomised study comparing the antiplatelet and antinflammatory effect of clopidogrel 150 mg/day versus 75 mg/day in patients with ST-segment elevation acute myocardial infarction and poor responsiveness to clopidogrel: Results from the DOUBLE study

INTRODUCTION The antiplatelet effect of standard or increased clopidogrel doses in patients with ST- segment elevation acute myocardial infarction (STEMI) has never been studied. In this study we compared the antiplatelet effect of a 75 mg daily maintenance dose of clopidogrel with 150 mg in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). MATERIALS AND METHODS Fifty-four patients with STEMI undergoing PCI were randomly allocated to receive either 75 mg/day clopidogrel (group 1) or 150 mg/day (group 2) for 1 month. Platelet function, measured by 5 different assays, was determined at 3 time points: 38+/-8 hours after the procedure, 1 week and 1 month after randomization. RESULTS In group 1, mean +/- SD platelet reactivity index (PRI) measured with the VASP assay was 57.7+/-15.7% and 46.9+/-15.7% at 1 week and 1 month, respectively, compared to 38.8+/-15.7% and 34.9+/-12.6% in group 2 (p=0.0001). Same results were observed for light transmittance aggregometry, whole blood aggregometry and VerifyNow, but not for thromboelastometry. In contrast to what may be expected, the 75 mg daily maintenance dose took longer than 1-week to provide the full clopidogrel antiplatelet effect. Furthermore, patients in group 2 had a nearly 50% reduction in C-reactive protein levels both at 1 week and 1 month. CONCLUSION In patients with STEMI and poor responsiveness to clopidogrel a 150 mg daily maintenance dose of clopidogrel is associated with a significant reduction of platelet aggregation and a trend towards reduced inflammation.

Assessment of restrictive cardiomyopathy of amyloid or idiopathic etiology by magnetic resonance imaging.

This study was designed to assess the role of magnetic resonance imaging in the differential diagnosis of amyloid and idiopathic etiology of cardiomyopathy. This technique demonstrated the capability to differentiate the 2 forms, providing high-resolution evaluation of the myocardial wall and detecting the infiltrative pathology by tissue characterization.

Non-invasive detection of coronary artery stenosis: a comparison among power-Doppler contrast echo, 99Tc-sestamibi SPECT and echo wall-motion analysis

Background Power‐Doppler imaging is a recently developed method for myocardial contrast echocardiography (MCE). It can selectively evaluate the signal coming from an ultrasound contrast agent, allowing myocardial perfusion studies. Objective To compare the ability of power‐Doppler MCE with stress‐echo wall‐motion and nuclear scan imaging (SPECT) to assess myocardial ischaemia during pharmacological stress, using coronary angiography as reference. Methods In 25 patients the three non‐invasive imaging modalities were acquired during a single dipyridamole stress test (so as to avoid stress variations). Power‐Doppler MCE was acquired using continuous intravenous infusion of Levovist. Echo wall‐motion was acquired too. At peak stress 99Tc‐Sestamibi was injected; stress SPECT images were acquired 30 min after injection. Results Power‐Doppler MCE and SPECT showed 84% concordance (21 of 25 patients; &kgr; = 0.67) for detection of ischaemia. Concordance based on coronary artery territories for normal perfusion versus fixed defects versus reversible defects was 92% (69 of 75; &kgr; = 0.81), with 100% for left anterior descending, 92% for right coronary artery and 84% for circumflex. Power‐Doppler MCE had lower sensitivity than SPECT (89 versus 100%) but higher specificity (100 versus 88%) for identification of stenotic (≥ 70%) coronary arteries as assessed by angiography. Echo wall‐motion analysis showed the lowest sensitivity (68%) with 100% specificity. Accuracy was 94% for both power‐Doppler MCE and SPECT, and 83% for wall‐motion analysis. Conclusion Power‐Doppler MCE is a sensitive and specific method for identification of myocardial perfusion during pharmacological stress. Accuracy of power‐Doppler MCE for stenotic coronary arteries appears to be slightly higher than stress‐echo wall‐motion and similar to SPECT. Coron Artery Dis 14:239‐245

Magnetic Resonance Imaging Evaluation of Aortic Elastic Properties as Early Expression of Marfan Syndrome

In Marfan syndrome, early identification and treatment of aortic involvement could improve prognosis, but clinical diagnosis may be difficult at a young age, before aortic dilation occurs. The aim of this study was to evaluate biomechanical aortic properties in Marfan patients and in their relatives to identify an early index of aortic involvement. A magnetic resonance imaging (MRI) morphologic and functional study of the thoracic aorta was performed in 20 Marfan patients, 15 family members, and 14 healthy volunteers as a control group. The aorta was imaged in the oblique sagittal plane by spin-echo sequence. A high-resolution gradient-echo sequence was then applied in the axial plane at the level of ascending supravalvular aorta to evaluate aortic distensibility. Aortic distensibility (mm Hg(-1) was significantly different in the three groups (ANOVA, p = 0.0001). Aortic distensibility was sensibly reduced in Marfan patients (0.0085 +/- 0.006 vs. 0.025 +/- 0.006 control group, p < 0.05). No significant correlation was found between aortic area and distensibility. Aortic distensibility was reduced also in family members (0.016 +/- 0.011 vs. 0.025 +/- 0.006 control group, p < 0.05). Among them, 4 subjects showed aortic diameters to the upper limit of the normal range, whereas the other 11 presented normal aortic diameters. Intraobserver and interobserver reproducibility for diastolic measurement was 1.2% and 0.4%, respectively, and 1.1% and 0.3%, respectively, for systolic measurement. MRI is an accurate technique in detecting abnormal aortic elastic properties in Marfan patients. Abnormal ascending aorta distensibility may constitute an index of early aortic involvement before dilation occurs.