Marco Merlo

Ospedali Riuniti di Bergamo, Bérgamo, Lombardy, Italy

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Publications (84)387.44 Total impact

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    ABSTRACT: An important number of patients with idiopathic dilated cardiomyopathy have dramatically improved left ventricular function with optimal treatment; however, little is known about the evolution and long-term outcome of this subgroup, which shows apparent healing. This study assesses whether real healing actually exists in dilated cardiomyopathy . Persistent apparent healing was evaluated among 408 patients with dilated cardiomyopathy receiving tailored medical treatment and followed over the very long-term. Persistent apparent healing was defined as left ventricular ejection fraction ≥50% and indexed left ventricular end-diastolic diameter ≤33 mm/m(2) at both mid-term (19±4 months) and long-term (103±9 months) follow-up. At mid-term, 63 of 408 patients (15%) were apparently healed; 38 (60%; 9% of the whole population) showed persistent apparent healing at long-term evaluation. No predictors of persistent apparent healing were found. Patients with persistent apparent healing showed better heart transplant-free survival at very long-term follow-up (95% versus 71%; P=0.014) compared with nonpersistently normalized patients. Nevertheless, in the very long term, 37% of this subgroup experienced deterioration of left ventricular systolic function, and 5% died or had heart transplantation. Persistent long-term apparent healing was evident in a remarkable proportion of dilated cardiomyopathy patients receiving optimal medical treatment and was associated with stable normalization of main clinical and laboratory features. This condition can be characterized by a decline of left ventricular function over the very long term, highlighting the relevance of serial and individualized follow-up in all patients with dilated cardiomyopathy, especially considering the absence of predictors for long-term apparent healing. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
    Full-text · Article · Dec 2015 · Journal of the American Heart Association
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    ABSTRACT: Dilated Cardiomyopathy (DCM) is a primary heart muscle disease characterized by a progressive dilation and dysfunction of either the left or both ventricles. The management of DCM is currently challenging for clinicians. The persistent lack of knowledge about the etiology and pathophysiology of this disease continues to determine important fields of uncertainty in managing this condition. Molecular cardiology and genetics currently represents the most crucial horizon of increasing knowledge. Understanding the mechanisms underlying the disease allow clinicians to treat this disease more effectively and to further improve outcomes of DCM patients through advancements in etiologic characterization, prognostic stratification and individualized therapy. Left ventricular reverse remodeling predicts a lower rate of major cardiac adverse events independently from other factors. Optimized medical treatment and device implantation are pivotal in inducing left ventricular reverse remodeling. Newly identified targets, such as angiotensin-neprilysin inhibition, phosphodiesterase inhibition and calcium sensitizing are important in improving prognosis in patients affected by DCM.
    Preview · Article · Nov 2015 · Expert Review of Cardiovascular Therapy
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    ABSTRACT: Background: The titin gene (TTN) encodes the largest human protein, which plays a central role in sarcomere organization and passive myocyte stiffness. TTN truncating mutations cause dilated cardiomyopathy (DCM); however, the role of TTN missense variants in DCM has been difficult to elucidate because of the presence of background TTN variation. Methods and results: A cohort of 147 DCM index subjects underwent DNA sequencing for 313 TTN exons covering the N2B and N2BA cardiac isoforms of TTN. Of the 348 missense variants, we identified 44 "severe" rare variants by using a bioinformatic filtering process in 37 probands. Of these, 5 probands were double heterozygotes (additional variant in another DCM gene) and 7 were compound heterozygotes (2 TTN "severe" variants). Segregation analysis allowed the classification of the "severe" variants into 5 "likely" (cosegregating), 5 "unlikely" (noncosegregating), and 34 "possibly" (where family structure precluded segregation analysis) disease-causing variants. Patients with DCM carrying "likely" or "possibly" pathogenic TTN "severe" variants did not show a different outcome compared with "unlikely" and noncarriers of a "severe" TTN variant. However, the "likely" and "possibly" disease-causing variants were overrepresented in the C-zone of the A-band region of the sarcomere. Conclusions: TTN missense variants are common and present a challenge for bioinformatic classification, especially when informative families are not available. Although DCM patients carrying bioinformatically "severe" TTN variants do not appear to have a worse clinical course than noncarriers, the nonrandom distribution of "likely" and "possibly" disease-causing variants suggests a potential biological role for some TTN missense variants.
    Full-text · Article · Nov 2015 · Journal of the American Heart Association
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    ABSTRACT: Aims: Right ventricular (RV) dysfunction has been associated with a worse outcome in heart failure patients undergoing CRT. However, evidence on the RV response to CRT is controversial and there are no data regarding the early effects of CRT on RV function (RVF). We sought to investigate whether a CRT device favourably influences the RVF acutely after implantation, impacting on long-term outcomes. Methods and results: Patients who successfully underwent CRT device implantation from January 2005 to January 2014 were retrospectively analysed. RV dysfunction was defined by an RV fractional area change <35%. Post-procedural echocardiographic evaluation was performed at a median time of 2 days (interquartile range 1-6 days). The primary endpoint was a composite of all-cause mortality and urgent heart transplantation. A total of 194 patients with available pre- and post-procedural RVF assessment were included. Sixty-two (32%) presented an impaired RVF before the procedure. Of them, 32% showed prompt normalization of RVF following CRT. This occurred in parallel with a large improvement in pulmonary arterial pressure, mitral regurgitation, E/E' ratio, and diastolic function. Pre-implantation independent predictors of early RVF normalization were LBBB (P = 0.034) and higher systolic blood pressure (P = 0.026). Improvement in RVF was independently associated with a better long-term prognosis at multivariable analysis [hazard ratio 0.124; 95% confidence interval 0.016-0.966, P = 0.04). Conclusions: Acute normalization of RVF can be observed after CRT along with haemodynamic improvement, and therefore can be used as an independent predictor of transplant-free survival.
    No preview · Article · Nov 2015 · European Journal of Heart Failure
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    ABSTRACT: Background: Patients with dilated cardiomyopathy (DCM) may present with ventricular arrhythmias early in the disease course, unrelated to the severity of left ventricular dysfunction. These patients may be classified as having an arrhythmogenic DCM (AR-DCM). We investigated the phenotype and natural history of patients with AR-DCM. Methods and results: Two hundred eighty-five patients with a recent diagnosis of DCM (median duration of the disease 1 month, range 0 to 7 months) and who had Holter monitoring at baseline were comprehensively evaluated and followed for 107 months (range 29 to 170 months). AR-DCM was defined by the presence of ≥1 of the following: unexplained syncope, rapid nonsustained ventricular tachycardia (≥5 beats, ≥150 bpm), ≥1000 premature ventricular contractions/24 hours, and ≥50 ventricular couplets/24 hours, in the absence of overt heart failure. The primary end points were sudden cardiac death (SCD), sustained ventricular tachycardia (SVT), or ventricular fibrillation (VF). The secondary end points were death from congestive heart failure or heart transplantation. Of the 285 patients, 109 (38.2%) met criteria for AR-DCM phenotype. AR-DCM subjects had a higher incidence of SCD/SVT/VF compared with non-AR-DCM patients (30.3% vs 17.6%, P=0.022), with no difference in the secondary end points. A family history of SCD/SVT/VF and the AR-DCM phenotype were statistically significant and cumulative predictors of SCD/SVT/VF. Conclusions: One-third of DCM patients may have an arrhythmogenic phenotype associated with increased risk of arrhythmias during follow-up. A family history of ventricular arrhythmias in DCM predicts a poor prognosis and increased risk of SCD.
    Full-text · Article · Oct 2015 · Journal of the American Heart Association
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    ABSTRACT: Although the cause of myocarditis often remains unknown, a large variety of infections, systemic diseases, drugs and toxins have been associated with this disease. In most cases, myocarditis is induced by cardiotropic viruses and often evolves silently without discernible prognostic impact. However, in some patients, the lack of complete viral clearance and/or the association of a heart-specific inflammation can cause persistent myocyte damage, ultimately leading to progressive myocardial dilation and dysfunction or life-threatening arrhythmias. Spontaneous improvement of left ventricular function is described for 40-50% of patients. The diagnostic work-up and prognostic assessment of myocarditis should be multiparametric and all available resources should be employed, i.e. biomarkers of myocardial damage and ventricular dysfunction (troponin I, brain natriuretic peptide), advanced echocardiography, cardiac magnetic resonance and, in selected cases, endomyocardial biopsy (with histopathologic, immunohistochemical and virological analyses). These are the necessary prerequisites for an evidence-based and personalized management of myocarditis, which may require in some cases specific immunoactive treatments. However, controversial issues regarding diagnosis (such as role and timing of cardiac magnetic resonance imaging, role of endomyocardial biopsy) and therapy of myocarditis still remain unsolved. The purpose of this review is to analyze these crucial features in order to provide useful instructions for clinical practice.
    No preview · Article · Oct 2015 · Giornale italiano di cardiologia (2006)
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    ABSTRACT: Functional mitral regurgitation (FMR) is associated with reduced survival in dilated cardiomyopathy (DCM). Cardiac resynchronization therapy (CRT) can improve FMR. We sought to identify the predictors of FMR improvement after CRT in DCM. From January 2003 to December 2013, 430 DCM patients consecutively enrolled were retrospectively analysed. Inclusion criteria were successful CRT implantation in presence of conventional indications (i.e. left bundle-branch block, left ventricular ejection fraction (LVEF) ≤35%, NYHA functional class ≥II) and moderate to severe FMR at the time of procedure. Early echocardiographic evaluation after CRT-implantation (median 2.5 days) has been performed in each patient. Improvement in FMR (absent/absent) at mid-term (7 months; IQR 4-10) was considered as the primary study end-point. A total of 44 patients (10% of the overall cohort) were included. A significant reduction in FMR severity was observed in 21 patients (48%) at mid-term after CRT (median time 7 months). No pre-implantation variables predicted FMR evolution, but FMR improvement at mid-term was strongly predicted by an acute favorable hemodynamic response (persistence/persistence of normal right ventricular function and 10 mmHg decrease or normalization - ≤35 mmHg - of systolic pulmonary artery pressure) at post-implantation echocardiography (OR 13.7; 95% CI 1.27-42.8; p = 0.016). FMR improvement at mid-term was stable during follow-up and was associated with superior long-term transplant-free survival (p = 0.022). Stable FMR improvement frequently occurs after CRT-implantation in DCM and is associated with improved transplant-free survival. Echocardiographic evaluation of acute hemodynamic response to CRT is helpful to early identify the favourable FMR evolution. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · Aug 2015 · Pacing and Clinical Electrophysiology
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    ABSTRACT: The aim of the study was to assess the clinical and prognostic impact of early functional mitral regurgitation (FMR) improvement on the outcome of patients with idiopathic dilated cardiomyopathy (IDC). The prevalence and prognostic role of FMR improvement, particularly at early follow-up, in patients with IDC are still unclear. From 1988 to 2009, we enrolled 470 patients with IDC with available FMR data at baseline and after 6 ± 2 months. According to the evolution of FMR, patients were classified into 3 groups: stable absent-mild FMR, early FMR improvement (downgrading from moderate-severe to absent-mild), and persistence/early development of moderate-severe FMR. At baseline, 177 of 470 patients (38%) had moderate-severe FMR. Patients with early FMR improvement had significantly better survival rate-free from heart transplant with respect to those with persistence/early development of moderate-severe FMR (93%, 81%, and 66% vs 91%, 64%, and 52% at 1, 6, and 12 years, respectively; p = 0.044). At 6-month follow-up multivariate analysis, FMR improvement was associated with better prognosis (hazard ratio 0.78, 95% confidence interval [CI] 0.64 to 0.96, p = 0.02); the other independent predictors were male gender, heart failure duration, and early re-evaluation of the New York Heart Association class and left ventricle systolic function. This model provided more accurate risk stratification compared with the baseline model (Net Reclassification Index 80% at 12 months and 41% at 72 months). In conclusion, in a large cohort of patients with IDC receiving optimal medical treatment, early improvement of FMR was frequent (53%) and emerged as a favorable independent prognostic factor with an incremental short- and long-term power compared with the baseline evaluation. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Jan 2015 · The American Journal of Cardiology
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    ABSTRACT: Pulmonary artery aneurysm unassociated to congenital heart disease and pulmonary hypertension is exceedingly rare. Its pathogenesis and correct management remain unknown. Sarcoidosis is a systemic disease that can exceptionally involve large vessels, leading to stenosis and dilatation. Pulmonary artery aneurysm has never been described in association with sarcoidosis. Surgical approach should prevent aneurysm rupture, but it is not known when surgery should be preferred to strict medical follow-up. In this report we present a case of large pulmonary artery aneurysm associated to systemic sarcoidosis underlining problematic management of diseases 'forgotten' by evidence based medicine.
    No preview · Article · Jan 2015 · Journal of Cardiovascular Medicine
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    ABSTRACT: Heart Rate Variability (HRV) has been studied in a variety of clinical situations in order to quantify the modulations in the heart rate associated to different pathological conditions. Nevertheless, significant changes in spectral and some nonlinear parameters of the HRV were reported also in normal subjects, depending on age and gender. The aim of this work was to quantify the age-related differences in other nonlinear parameters, particularly in the fractal dimension, of the HRV of healthy subjects and to compare the results with the changes showed by spectral measures. The RR time series extracted by the Holter monitoring of 60 healthy subjects, divided into three groups similar for both age and gender, were accurately analyzed. The results only partially revealed age-related changes both in the spectral and fractal HRV measures, underlining the need to carefully examine the RR data selection and the pre-processing phases.
    No preview · Article · Jan 2015 · IFMBE proceedings
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    ABSTRACT: Heart rate variability (HRV) has been widely investigated in a variety of clinical conditions, but few studies have assessed the changes in the heart rate with regard to different congestive heart failure (CHF) etiologies. The aim of this work was to characterize the heart rate variability of patients affected by CHF caused by dilated cardiomyopathy, ischemic heart disease or other different CHF etiologies, in comparison to that of healthy subjects. The parameters adopted for analysis were the power spectral density in the very low, low and high frequency bands, the power-law β exponent and the SD1 and SD2 indexes of the Poincaré plot. Results showed significant changes related to etiology especially in the very low and high frequency bands and in the β exponent values, thus encouraging the future development of a classifier for the discrimination of the different CHF etiologies.
    No preview · Article · Jan 2015 · IFMBE proceedings
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    ABSTRACT: The aims of this study were to investigate the clinical outcomes of patients with low-gradient aortic stenosis despite preserved left ventricular ejection fraction and to assess reliable prognostic clinical-instrumental features in patients experiencing or not experiencing aortic valve replacement (AVR). Clinical-laboratory and echocardiographic data from 167 patients (median age 78 years, interquartile range 69 to 83) with aortic valve areas <1.0 cm(2), mean gradients ≤30 mm Hg, and preserved left ventricular ejection fraction (≥55%), enrolled from 2005 to 2010, were analyzed. During a mean follow-up period of 44 ± 23 months, 33% of patients died. On multivariate analysis, independent predictors of death were baseline New York Heart Association functional class III or IV (hazard ratio 2.16, p = 0.038) and atrial fibrillation (hazard ratio 2.00, p = 0.025). Conversely, AVR was protective (hazard ratio 0.25, p = 0.01). The magnitude of the protective effect of AVR seemed to be relatively more important in patients with atrial fibrillation than in those in sinus rhythm, independently of the severity of symptoms. Age >70 years showed a trend toward being a prognostic predictor (p = 0.082). In conclusion, in patients with low-gradient aortic stenosis despite a preserved left ventricular ejection fraction, AVR was strongly correlated with a better prognosis. Patients with atrial fibrillation associated with advanced New York Heart Association class had the worst prognosis if treated medically but at the same time a relative better benefit from surgical intervention.
    Full-text · Article · Sep 2014 · The American Journal of Cardiology

  • No preview · Conference Paper · Sep 2014
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    ABSTRACT: Background Genotype–phenotype correlations are poorly characterised in arrhythmogenic right ventricular cardiomyopathy (ARVC). We investigated whether carriers of rare variants in desmosomal genes (DC) and titin gene (TTN) display different phenotypes and clinical outcomes compared with non-carriers (NT-ND). Methods and results Thirty-nine ARVC families (173 subjects, 67 affected) with extensive follow-up (mean 9 years), prospectively enrolled in the International Familial Cardiomyopathy Registry since 1991, were screened for rare variants in TTN and desmosomal genes (DSP, PKP2, DSG2, DSC2). Multiple clinical and outcome variables were compared between three genetic groups (TTN, DC, NT-ND) to define genotype–phenotype associations. Of the 39 ARVC families, 13% (5/39) carried TTN rare variants (11 affected subjects), 13% (5/39) DC (8 affected), while 74% (29/39) were NT-ND (48 affected). When compared with NT-ND, DC had a higher prevalence of inverted T waves in V2-3 (75% vs 31%, p=0.004), while TTN had more supraventricular arrhythmias (46% vs 13%, p=0.013) and conduction disease (64% vs 6% p<0.001). When compared with the NT-ND group, the DC group experienced a worse prognosis (67% vs 11%, p=0.03) and exhibited a lower survival free from death or heart transplant (59% vs 95% at 30 years, and 31% vs 89% at 50 years, HR 9.66, p=0.006), while the TTN group showed an intermediate survival curve (HR 4.26, p=0.037). Conclusions TTN carriers display distinct phenotypic characteristics including a greater risk for supraventricular arrhythmias and conduction disease. Conversely, DC are characterised by negative T waves in anterior leads, severe prognosis, high mortality and morbidity.
    No preview · Article · Aug 2014 · Journal of Medical Genetics
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    Full-text · Article · Apr 2014 · Journal of the American College of Cardiology
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    ABSTRACT: Recent studies suggested that resting heart rate (RHR) might be an independent predictor of cardiovascular mortality and morbidity. Nonetheless, the interrelation between RHR and cardiovascular diseases is not clear. In order to resolve this puzzle, the importance of genetic determinants of RHR has been recently suggested, but it needs to be further investigated. The aim of this study was to estimate the contribution of common genetic variations on RHR using Genome Wide Association Study. We performed a Genome Wide Association Study in an isolated population cohort of 1737 individuals, the Italian Network on Genetic Isolates - Friuli Venezia Giulia (INGI-FVG). Moreover, a haplotype analysis was performed. A regression tree analysis was run to highlight the effect of each haplotype combination on the phenotype. A significant level of association (p<5×10(-8)) was detected for Single Nucleotide Polymorphisms (SNPs) in two genes expressed in the heart: MAML1 and CANX. Founding that the three different variants of the haplotype, which encompass both genes, yielded a phenotypic correlation. Indeed, a haplotype in homozygosity is significantly associated with the lower quartile of RHR (RHR≤58bpm). Moreover no significant association was found between cardiovascular risk factors and the different haplotype combinations. Mastermind-like 1 and Calnexin were found to be associated with RHR. We demonstrated a relation between a haplotype and the lower quartile of RHR in our populations. Our findings highlight that genetic determinants of RHR may be implicated in determining cardiovascular diseases and could allow a better risk stratification.
    No preview · Article · Mar 2014 · Gene
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    ABSTRACT: ACE-inhibitors, β-blockers, implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT) improved prognosis of heart failure. We sought to analyse the long-term prognostic impact of evidence-based integrated therapeutic strategies in patients with idiopathic dilated cardiomyopathy (IDCM). From 1978 to 2007, 853 IDCM patients (45 ± 15 years, 72% males) were enrolled and classified as follows: Group 1, 110 patients (12.8%) enrolled during 1978-1987; Group 2, 376 patients (44.1%) enrolled during 1988-1997; Group 3, 367 patients (43.1%) enrolled during 1998-2007. ACE-inhibitors/angiotensin receptor blockers were administered in 34%, 93%, and 93% (P <0.001), and β-blockers in 11%, 82%, and 86% (P <0.001) in Groups 1, 2, and 3, respectively; ICDs were implanted in 2%, 14%, and 13% (P = 0.005); mean time to device implantation was lower in Group 3. At 8 years, heart transplant (HTx)-free survival rates were 55%, 71%, and 87% in Groups 1, 2, and 3, respectively (P <0.001). Similar progressive improvement was found for pump-failure death (DHF)/HTx, while survival free from sudden death (SD) was significantly improved only in Group 3. Multivariable models considering competing risk indicated early diagnosis (i.e. a baseline less advanced disease stage) and tailored medical therapy (HR 0.44, CI 95% 0.19-0.98) as independent protectors against DHF/HTx. Concerning SD, lower left ventricular ejection fraction emerged as a predictor, while ICD was the only therapy with a protective role (HR 0.08, CI 95% 0.01-0.61). Treatment with digitalis emerged as a predictor of both DHF/HTx and SD. An effective management and evidence-based integrated therapeutic approach progressively and significantly improved the long-term prognosis of IDCM during the last three decades.
    No preview · Article · Mar 2014 · European Journal of Heart Failure
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    Full-text · Article · Jan 2014 · International journal of cardiology
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    ABSTRACT: Heart Rate Variability (HRV) has been widely studied both in healthy subjects and congestive heart failure (CHF) patients. Significant variations in the HRV patterns have been reported in cardiac patients and quantified both in time and spectral domain by various linear and nonlinear parameters which may be useful not only for the characterization of the autonomous nervous system but also for patients risk stratification. Nevertheless, the relationship between HRV measures and CHF aetiologies has not been completely investigated yet. The purpose of this work was to evaluate the spectral and fractal properties of HR V in patients with CHF caused by either dilated cardiomyopathy or ischemic heart disease, and to compare the results with those coming from normal subjects. Results revealed that changes in some of the examined parameters may lead to a possible separation of the CHF aetiologies.
    No preview · Article · Jan 2014
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    ABSTRACT: Purpose: With the advent of percutaneous transcatheter device closures in congenital heart defects and the emergence of percutaneous left atrial appendage closure, there is an increasingly important role for echocardiographic guidance and control of device position and function. Disc occluder devices frequently present as an unexplained ‘figure-of-8’ on echocardiography. The aim of this study was to clarify this ‘figure-of-8’ display and to relate its morphology to transducer position and device type. Methods: A mathematical model was developed to resemble disc occluder geometry and to allow a numerical simulation of the echocardiographic appearance. In addition, we developed an in vitro set-up for echocardiographic analysis of various disc occluders and various transducer positions. Results: In the mathematical model of an epitrochoid curve (closely resembling disc occluder geometry) a ‘figure-of-8’ display is obtained when emphasizing points with tangent vector perpendicular to the direction of ultrasound waves. Decreasing imaging depth results in a more asymmetric ‘figure-of-8’, with small upper part and wide lower part. Clinical and in vitro data are in close agreement with these results (Figure 1). Furthermore a ‘figure-of-8’ display is only obtained in a coronal imaging position, and is similar for different commercially available disc occluder types. Conclusions: The ‘figure-of-8’ display in the ultrasound image of a disc occluder is an imaging artifact due to the specific ‘epitrochoidal’ geometry of a deployed device and its interaction with ultrasound waves. The morphology of the ‘figure-of-8’ depends on transducer position, i.e. imaging depth, and is similar for different device types.
    Full-text · Poster · Dec 2013

Publication Stats

581 Citations
387.44 Total Impact Points

Institutions

  • 2010-2015
    • Ospedali Riuniti di Bergamo
      Bérgamo, Lombardy, Italy
  • 2008-2015
    • Università degli Studi di Trieste
      Trst, Friuli Venezia Giulia, Italy
  • 2005-2015
    • Azienda Ospedaliero - Universitaria "Ospedali Riuniti" Trieste
      Trst, Friuli Venezia Giulia, Italy