Antonella Moreo

Influence of myocardial fibrosis on left ventricular diastolic function: noninvasive assessment by cardiac magnetic resonance and echo.

Background— Fibrosis is a common end point of many pathological processes affecting the myocardium and may alter myocardial relaxation properties. By measuring myocardial fibrosis with cardiac magnetic resonance and diastolic function with Doppler echocardiography, we sought to define the influence of fibrosis on left ventricular diastolic function. Methods and Results— Two hundred four eligible subjects from 252 consecutive subjects undergoing late postgadolinium myocardial enhancement (LGE) cardiac magnetic resonance and Doppler echocardiography were investigated. Subjects with normal diastolic function exhibited no or minimal fibrosis (median LGE score, 0; interquartile range, 0 to 0). In contrast, the majority of patients with cardiomyopathy (regardless of underlying cause) had abnormal diastolic function indices and substantial fibrosis (median LGE score, 3; interquartile range, 0 to 6.25). Prevalence of LGE positivity by diastolic filling pattern was 13% in normal, 48% in impaired relaxation, 78% in pseudonormal, and 87% in restrictive filling ( P <0.0001). Similarly, LGE score was significantly higher in patients with deceleration time <150 ms ( P <0.012), and it progressively increased with increasing left ventricular filling pressure estimated by tissue Doppler imaging–derived E/E′ ( P <0.0001). After multivariate analysis, LGE remained significantly correlated with degree of diastolic dysfunction ( P =0.0001). Conclusions— Severity of myocardial fibrosis by LGE significantly correlates with the degree of diastolic dysfunction in a broad range of cardiac conditions. Noninvasive assessment of myocardial fibrosis may provide valuable insights into the pathophysiology of left ventricular diastolic function and therapeutic response. Received November 25, 2008; accepted August 5, 2009. # CLINICAL PERSPECTIVE {#article-title-2}Background—Fibrosis is a common end point of many pathological processes affecting the myocardium and may alter myocardial relaxation properties. By measuring myocardial fibrosis with cardiac magnetic resonance and diastolic function with Doppler echocardiography, we sought to define the influence of fibrosis on left ventricular diastolic function. Methods and Results—Two hundred four eligible subjects from 252 consecutive subjects undergoing late postgadolinium myocardial enhancement (LGE) cardiac magnetic resonance and Doppler echocardiography were investigated. Subjects with normal diastolic function exhibited no or minimal fibrosis (median LGE score, 0; interquartile range, 0 to 0). In contrast, the majority of patients with cardiomyopathy (regardless of underlying cause) had abnormal diastolic function indices and substantial fibrosis (median LGE score, 3; interquartile range, 0 to 6.25). Prevalence of LGE positivity by diastolic filling pattern was 13% in normal, 48% in impaired relaxation, 78% in pseudonormal, and 87% in restrictive filling (P<0.0001). Similarly, LGE score was significantly higher in patients with deceleration time <150 ms (P<0.012), and it progressively increased with increasing left ventricular filling pressure estimated by tissue Doppler imaging–derived E/E′ (P<0.0001). After multivariate analysis, LGE remained significantly correlated with degree of diastolic dysfunction (P=0.0001). Conclusions—Severity of myocardial fibrosis by LGE significantly correlates with the degree of diastolic dysfunction in a broad range of cardiac conditions. Noninvasive assessment of myocardial fibrosis may provide valuable insights into the pathophysiology of left ventricular diastolic function and therapeutic response.

A new 2D-based method for myocardial velocity strain and strain rate quantification in a normal adult and paediatric population: assessment of reference values

BackgroundRecent advances in technology have provided the opportunity for off-line analysis of digital video-clips of two-dimensional (2-D) echocardiographic images.Commercially available software that follows the motion of cardiac structures during cardiac cycle computes both regional and global velocity, strain, and strain rate (SR).The present study aims to evaluate the clinical applicability of the software based on the tracking algorithm feature (studied for cardiology purposes) and to derive the reference values for longitudinal and circumferential strain and SR of the left ventricle in a normal population of children and young adults.Methods45 healthy volunteers (30 adults: 19 male, 11 female, mean age 37 ± 6 years; 15 children: 8 male, 7 female, mean age 8 ± 2 years) underwent transthoracic echocardiographic examination; 2D cine-loops recordings of apical 4-four 4-chamber (4C) and 2-chamber (2C) views and short axis views were stored for off-line analysis.Computer analyses were performed using specific software relying on the algorithm of optical flow analysis, specifically designed to track the endocardial border, installed on a Windows™ based computer workstation. Inter and intra-observer variability was assessed.ResultsThe feasibility of measurements obtained with tissue tracking system was higher in apical view (100% for systolic events; 64% for diastolic events) than in short axis view (70% for systolic events; 52% for diastolic events). Longitudinal systolic velocity decreased from base to apex in all subjects (5.22 ± 1.01 vs. 1.20 ± 0.88; p < 0.0001). Longitudinal strain and SR significantly increased from base to apex in all subjects (-12.95 ± 6.79 vs. -14.87 ± 6.78; p = 0.002; -0.72 ± 0.39 vs. -0.94 ± 0.48, p = 0.0001, respectively). Similarly, circumferential strain and SR increased from base to apex (-21.32 ± 5.15 vs. -27.02 ± 5.88, p = 0.002; -1.51 ± 0.37 vs. -1.95 ± 0.57, p = 0.003, respectively).Values of global systolic SR, both longitudinal and circumferential, were significantly higher in children than in adults (-1.3 ± 0.2, vs. -1.11 ± 0.2, p = 0.006; -1.9 ± 0.6 vs. -1.6 ± 0.5, p = 0.0265, respectively). No significant differences in longitudinal and circumferential systolic velocities were identified for any segment when comparing adults with children.ConclusionThis 2D based tissue tracking system used for computation is reliable and applicable in adults and children particularly for systolic events. Measured with this technology, we have established reference values for myocardial velocity, Strain and SR for both young adults and children.

Influence of CoreValve ReValving System Implantation on Mitral Valve Function: An Echocardiographic Study in Selected Patients

Objectives: The purpose of this study is to verify whether transcatheter aortic valve implantation (TAVI) determined changes in mitral valve (MV) function, in terms of mitral regurgitation (MR) and stenosis. Background: Little data is available regarding the effects of TAVI on global MV function, often derived from analysis primarily focused on clinical and aortic related outcomes. Methods: From May 2008 to March 2010, 73 patients with severe symptomatic aortic stenosis underwent TAVI with the CoreValve ReValving System. The study population consisted of 58 patients (27 males, mean age 82 ± 7 years) who underwent transthoracic echocardiography at least ≥1 month after implantation (mean follow‐up 7.8 ± 5.4 months). Results: In patients with a left ventricular dysfunction (ejection fraction, EF, <45%) at the baseline, EF significantly increased from 37 ± 6% to 48 ± 7% after TAVI (P = 0.003). Before TAVI, 42 patients had no or mild MR, 13 mild‐to‐moderate, and 3 moderate or moderate‐to‐severe. During follow‐up, the MR degree was unchanged in the majority of patients (55%), 12% reduced, and 33% worsened. Variables associated with worsening in MR were depth of aortic prosthesis (P = 0.02 for the distance between the ventricular end and the right coronary cusp; P = 0.04 for mean distance right‐left coronary cusps) and left atrium area at the baseline (P = 0.02). After TAVI, six patients (10%) developed mild or moderate mitral stenosis, often in a native valve with anterior calcifications. Conclusions: In the majority of patients no significant changes occurred in the degree of MR in native valve, but we found that if the aortic valve was deeply implanted in the left ventricle outflow tract, a worsening in MR can be observed. A mitral stenosis development must be sought in patients with heavy calcifications of the anterior leaflet.

Clinical ResearchCardiac ImagingComparison of Sulfur Hexafluoride Microbubble (SonoVue)-Enhanced Myocardial Contrast Echocardiography With Gated Single-Photon Emission Computed Tomography for Detection of Significant Coronary Artery Disease: A Large European Multicenter Study

OBJECTIVES The purpose of this study was to compare sulfur hexafluoride microbubble (SonoVue)-enhanced myocardial contrast echocardiography (MCE) with single-photon emission computed tomography (SPECT) relative to coronary angiography (CA) for assessment of coronary artery disease (CAD). BACKGROUND Small-scale studies have shown that myocardial perfusion assessed by SonoVue-enhanced MCE is a viable alternative to SPECT for CAD assessment. However, large multicenter studies are lacking. METHODS Patients referred for myocardial ischemia testing at 34 centers underwent rest/vasodilator SonoVue-enhanced flash-replenishment MCE, standard (99m)Tc-labeled electrocardiography-gated SPECT, and quantitative CA within 1 month. Myocardial ischemia assessments by 3 independent, blinded readers for MCE and 3 readers for SPECT were collapsed into 1 diagnosis per patient per technique and were compared to CA (reference standard) read by 1 independent blinded reader. RESULTS Of 628 enrolled patients who received SonoVue (71% males; mean age: 64 years; >1 cardiovascular [CV] risk factor in 99% of patients) 516 patients underwent all 3 examinations, of whom 161 (31.2%) had ≥70% stenosis (131 had single-vessel disease [SVD]; 30 had multivessel disease), and 310 (60.1%) had ≥50% stenosis. Higher sensitivity was obtained with MCE than with SPECT (75.2% vs. 49.1%, respectively; p < 0.0001), although specificity was lower (52.4% vs. 80.6%, respectively; p < 0.0001) for ≥70% stenosis. Similar findings were obtained for patients with ≥50% stenosis. Sensitivity levels for detection of SVD and proximal disease for ≥70% stenosis were higher for MCE (72.5% vs. 42.7%, respectively; p < 0.0001; 80% vs. 58%, respectively; p = 0.005, respectively). CONCLUSIONS SonoVue-enhanced MCE demonstrated superior sensitivity but lower specificity for detection of CAD compared to SPECT in a population with a high incidence of CV risk factors and intermediate-high prevalence of CAD. (A phase III study to compare SonoVue® enhanced myocardial echocardiography [MCE] to single photon emission computerized tomography [ECG-GATED SPECT], at rest and at peak of low-dose Dipyridamole stress test, in the assessment of significant coronary artery disease [CAD] in patients with suspect or known CAD using Coronary Angiography as Gold Standard-SonoVue MCE vs SPECT; EUCTR2007-003492-39-GR).

Safety, feasibility, and diagnostic accuracy of accelerated high-dose dipyridamole stress echocardiography

Protocols for dipyridamole stress testing have evolved in the last 16 years in the neverending quest of optimal diagnostic accuracy and user friendliness. Higher dipyridamole dose in a shorter infusion time provides higher sensitivity, but concern over safety is still controversial. An accelerated high-dose (0.84 mg/kg in 6 minutes without atropine) dipyridamole stress test was performed on 1,295 patients in 2 echocardiographic laborotories: Institute of Clinical Physiology of Pisa and Niguarda Hospital of Milan. During testing, there were no deaths and no patients had ventricular fibrillation. Major adverse reactions occurred in 3 cases (1 every 431 studies): 1 myocardial infarction, 1 brief cardiac asystole, and 1 transient ischemic attack. Overall feasibility was 97%. In 66 patients with normal function at rest who were evaluated off therapy, with coronary angiography performed independently of test results, the accelerated high-dose protocol showed a sensitivity of 85% (confidence interval [CI] 73% to 92%) and a specificity of 93% (CI 83% to 97%) for angiographically assessed coronary artery disease (quantitatively assessed diameter reduction > or = 50%). Diagnostic accuracy of the accelerated high dose was 89% (CI 79% to 95%). Thus, accelerated high-dose dipyridamole stress echocardiography was reasonably safe and well tolerated. This protocol is especially appealing for its excellent diagnostic accuracy coupled with the short imaging time and no need for drug cocktails.

Clinical and echocardiographic correlations of exercise-induced pulmonary hypertension in systemic sclerosis: A multicenter study

BACKGROUND Patients with systemic sclerosis (SSc) are at risk for developing pulmonary hypertension, which is associated with a poor prognosis. Exercise Doppler echocardiography enables the identification of exercise-induced increase in pulmonary artery systolic pressure (PASP) and may provide a thorough noninvasive hemodynamic evaluation. AIM The aim of this study was to evaluate the clinical and echocardiographic determinants of exercise-induced increase in PASP in a large population of patients with SSc. METHODS We selected 164 patients with SSc (age 58 ± 13 years, 91% female) with normal resting PASP (<40 mm Hg) who underwent a comprehensive 2-dimensional and Doppler echocardiography and graded bicycle semisupine exercise Doppler echocardiography. Pulmonary artery systolic pressure, cardiac output, and pulmonary vascular resistance (PVR) were estimated noninvasively. Cutoff values of PASP ≥50 mm Hg and PVR ≥3.0 Wood Units at peak exercise were considered a significant exercise-induced increase in PASP and PVR, respectively. RESULTS Sixty-nine (42%) patients showed a significant exercise-induced increase in PASP. Among them, peak PVR ≥3 Wood Units was present only in 11% of patients, about 5% of the total population. Univariate analysis showed that age, presence of interstitial lung disease, and both right and left diastolic dysfunction are predictors of peak PASP ≥50 mm Hg, but none of these parameters predict elevated peak PVR. CONCLUSIONS Exercise-induced increase in PASP occurs in almost one-half of patients with SSc with normal resting PASP. Peak exercise PASP is affected by age, interstitial lung disease, and right and left ventricular diastolic dysfunction and, only in 5% of the patients, is associated with an increase in PVR during exercise, suggesting heterogeneity of the mechanisms underlying exercise-induced pulmonary hypertension in SSc.

Clinical impact and evolution of mitral regurgitation following transcatheter aortic valve replacement: a meta-analysis

Objectives Mitral regurgitation (MR) is a common entity in patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR), but its influence on outcomes remains controversial. The purpose of this meta-analysis was to assess the clinical impact of and changes in significant (moderate–severe) MR in patients undergoing TAVR, overall and according to valve design (self-expandable (SEV) vs balloon-expandable (BEV)). Methods All national registries and randomised trials were pooled using meta-analytical guidelines to establish the impact of moderate–severe MR on mortality after TAVR. Studies reporting changes in MR after TAVR on an individual level were electronically searched and used for the analysis. Results Eight studies including 8015 patients (SEV: 3474 patients; BEV: 4492 patients) were included in the analysis. The overall 30-day and 1-year mortality was increased in patients with significant MR (OR 1.49, 95% CI 1.16 to 1.92; HR 1.32, 95% CI 1.12 to 1.55, respectively), but a significant heterogeneity across studies was observed (p<0.05). The impact of MR on mortality was not different between SEV and BEV in meta-regression analysis for 30-day (p=0.360) and 1-year (p=0.388) mortality. Changes in MR over time were evaluated in nine studies including 1278 patients. Moderate–severe MR (SEV: 326 patients; BEV: 192 patients) improved in 50.5% of the patients at a median follow-up of 180 (30–360) days after TAVR, and the degree of improvement was greater in patients who had received a BEV (66.7% vs 40.8% in the SEV group, p=0.001). Conclusions Concomitant moderate–severe MR was associated with increased early and late mortality following TAVR. A significant improvement in MR severity was detected in half of the patients following TAVR, and the degree of improvement was greater in those patients who had received a BEV.

Incorrect echocardiographic diagnosis in patients with mechanical prosthetic valve dysfunction : Correlation with surgical findings

PURPOSE To identify the rate of occurrence and type of incorrect echocardiographic diagnoses in patients with mechanical valve prostheses. PATIENTS AND METHODS We studied 170 consecutive patients (73 women and 97 men) with a total of 208 prostheses who underwent surgery for mitral (n = 136) or aortic (n = 72) valve dysfunction between January 1991 and December 1997. Preoperative echocardiographic data were compared with surgical findings. Any major discrepancy between the echocardiographic reports and surgery was judged to be unconfirmed when the preoperative echocardiographic diagnosis was not confirmed at surgery, but the prosthesis was found to be dysfunctioning; and was judged to be erroneous when the preoperative echocardiographic diagnosis was not confirmed, and surgical inspection failed to reveal any other prosthetic abnormality. RESULTS There were 25 (12%) diagnostic errors. Of the 136 mitral prostheses, there were 9 unconfirmed diagnoses of paravalvular regurgitation (6 had a fibrous tissue overgrowth, 1 had a thrombus with fibrous tissue overgrowth, 1 had endocarditis vegetations, and 1 had a ball variance) and 5 erroneous diagnoses. Eleven diagnostic errors were made in the 72 aortic prostheses: there were 9 unconfirmed diagnoses (paravalvular regurgitation was diagnosed as transvalvular in 7, and transvalvular regurgitation as paravalvular in 2 cases), and 2 erroneous diagnoses. CONCLUSIONS Although echocardiography has gained great credibility among clinicians, special care should be taken when assessing patients in whom prosthetic valve dysfunction is suspected.

Aortic valve sclerosis as a marker of coronary artery atherosclerosis; a multicenter study of a large population with a low prevalence of coronary artery disease

UNLABELLED There are no studies analyzing the association between aortic valve sclerosis (AVS) and coronary artery disease (CAD) in a large and multicenter patient population with an overall low prevalence of CAD. We hypothesized that AVS could predict the presence and degree of CAD in patients with severe organic mitral regurgitation. METHODS We retrospectively analyzed consecutive patients with flail mitral leaflet who had coronary angiography for pre-surgical screening and not because suspect of CAD. End-points were considered: 1) any degree of CAD (stenosis>20%) and 2) obstructive CAD (stenosis>75% of at least one coronary artery). AVS was defined as focal areas of increased echogenicity and thickening of the leaflets. Traditional clinical risk factors were considered: age, male gender, hypertension (>140/90 mmHg or medical therapy), hypercholesterolemia (total cholesterol>200 mg/dl or statin), diabetes, family history of CAD and smoking habit. RESULTS 675 patients (mean age: 64±12; 27% female) formed the study population. Among patients with AVS, 60% and 39% had any-CAD and ob-CAD respectively, on the opposite among patients without AVS 12% and 7% had any-CAD and ob-cad. After adjustment for clinical risk factors, AVS was associated with a 22.7 fold increased risk of any degree of CAD (95% CI 8.1 63.6 p<0.0001) and with a 21.8 fold increased risk of obstructive-CAD (95% CI 6.6 71.9; p<0.0001). CONCLUSION In a large and multicenter sample of patient with flail mitral leaflet, AVS was strongly associated with the presence and degree of CAD independently of clinical risk factors.

Clinical epidemiology in Italian Registry of Infective Endocarditis (RIEI): Focus on age, intravascular devices and enterococci.

INTRODUCTION The epidemiology of infective endocarditis (IE) is changing due to a number of factors, including aging and health related comorbidities and medical procedures. The aim of this study is to describe the main clinical, epidemiologic and etiologic changes of IE from a large database in Italy. METHODS We prospectively collected episodes of IE in 17 Italian centers from July 2007 to December 2010. RESULTS We enrolled 677 patients with definite IE, of which 24% health-care associated. Patients were male (73%) with a median age of 62 years (IQR: 49-74) and 61% had several comorbidities. One hundred and twenty-eight (19%) patients had prosthetic left side IE, 391 (58%) native left side IE, 94 (14%) device-related IE and 54 (8%) right side IE. A predisposing cardiopathy was present in 50%, while odontoiatric and non odontoiatric procedures were reported in 5% and 21% of patients respectively. Symptoms were usually atypical and precocious. The prevalent etiology was represented by Staphylococcus aureus (27%) followed by coagulase-negative staphylococci (CNS, 21%), Streptococcus viridans (15%) and enterococci (14%). CNS and enterococci were relatively more frequent in patients with intravascular devices and prosthesis and S. viridans in left native valve. Diagnosis was made by transthoracic and transesophageal echocardiography in 62% and 94% of cases, respectively. The in-hospital mortality was 14% and 1-year mortality was 21%. CONCLUSION The epidemiology is changing in Italy, where IE more often affects older patients with comorbidities and intravascular devices, with an acute onset and including a high frequency of enterococci. There were few preceding odontoiatric procedures.