HYPERTROPHIC CARDIOMYOPATHY: RELATIONSHIP BETWEEN MYOCARDIAL ISCHEMIA,FIBROSIS AND CLINICAL STATUS

Hypertrophic cardiomyopathy (HCM) is a genetic disorder that is typically inherited in an autosomal dominant fashion. There are defects in several of the genes encoding for the sarcomeric proteins, such as myosin heavy chain, actin, tropomyosin, and titin. Multiple mutations have been identified, with genotype-specific risks for mortality and degree of hypertrophy. The disorder has a variable clinical presentation and carries a high incidence of sudden death. HCM is the leading cause of sudden cardiac death in young population. However, many patients may remain stable over long periods of time and then suddenly they may present adverse events: unexpected death, embolic stroke, and the consequences of heart failure. The disease is characterized by an inappropriate myocardial hypertrophy, often asymmetrical, and occurs with no obvious inciting hypertrophy stimulus. Hypertrophy can occur in any region of the left ventricle but frequently involves the interventricular septum, which sometimes results in an obstruction of flow through the left ventricular outflow tract (LVOT). At histology, myocardial disarray and islands of fibrosis are considered hallmarks of this disease. The systolic function of LV is preserved until the end-stage of the disease, but the thickened myocardium with fibrosis increases the stiffness of LV chamber causing impaired diastolic relaxation which produces atrial enlargement and may promote atrial fibrillation. At the end stage, the loss of myocites, replaced by gross scar, is sufficient to determine a manifest systolic LV dysfunction. Myocardial scars create a potentially arrhythmogenic substrate and may increase susceptibility to ventricular tachycardias/fibrillation. Indeed, gross macroscopic scarring is frequently present on post-mortem examination in HCM patients who died suddenly, suggesting a possible causal association between fibrosis and malignant arrhythmias. In most patients with HCM, dense focal myocardial fibrosis can also be visualized noninvasively with the use of gadolinium-enhanced cardiac magnetic resonance imaging (LGE-CMR). Recently, some studies demonstrated the prognostic role of fibrosis, expressed as late gadolinium enhancement (LGE), as predictor of myocardial death. In addiction is also possible to quantify extent of LGE in the myocardium of these patients. The diagnosis of HCM is usually performed at relatively young age when not significant stenosis are present in the main coronary arteries. Despite this, many studies showed the importance of myocardial ischemia, probably also due to microvascular disease, as cause of myocardial fibrosis and symptoms and as a trigger of ventricular arrhythmias. Infact the assessment of myocardial ischemia in selected patients with HCM (with preserved LV function) may represent a prognostic tool for identifying those patients at risk for profound disease progression. CMR also allows to evaluate myocardial perfusion and quantify non invasively myocardial blood flow. It’s now clear the importance to study both and individually myocardial fibrosis and ischemia, and to evaluate the relationship between myocardial scar, myocardial blood flow and clinical expression of the disease

Letter by Aquaro et al Regarding Article, "Intermediate-Signal-Intensity Late Gadolinium Enhancement Predicts Ventricular Tachyarrhythmias in Patients With Hypertrophic Cardiomyopathy"

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0483: Cardiac magnetic resonance imaging and left ventricular diastolic function in children with hypertrophic cardiomyopathy

BackgroundHypertrophic cardiomyopathy (HCM) has a variety of causes in children. In adult, Cardiac Magnetic Resonance imaging (CMR) is emerging as a unique tool particularly suited to define myocardial anatomy and fibrosis. The purpose of the study is to define the feasibility and the role of CMR in children with HCM as well as the influence of myocardial fibrosis on left ventricular (LV) diastolic function in children.MethodsCMR protocol included T2 weighted sequence in short axis view, TRIPLE IR FSE sequence, cine SSFP in short axis, two-chamber, three and four chamber view without contrast and perfusion analysis and late enhancement after injection of contrast agent. If left ventricular wall thickness seemed asymmetric, the size and location of relatively thickened segments were noted. Echocardiography analyzed LV diastolic function.ResultsA total of 60 patients were included in the study. Age at diagnosis was 3 years (range 1 day to 16 years). Mean age at CMR was 11 years (range 1-18 years). CMR was successfully performed in all patients, revealing a better performance in comparison to echocardiography to define precisely the anatomy of LV hypertrophy. Mean LV mass was estimated at 94±41gr/m2. LV hypertrophy was concentric in 32 patients, asymmetric in 28 patients, with evidence of LV non-compaction aspect in 7 patients. The right ventricle was affected in 7 cases. Presence of LV fibrosis was detected in 6 patients in LV septum. Perfusion defects were present in 5 patients in papillary muscles. LV function was reduced (LV ejection fraction < 55%) in 7 patients. While LV fibrosis was rare, LV diastolic dysfunction was found in the majority of children.ConclusionCMR in children with HCM is feasible and it contributes to anatomic definition and tissue analysis. LV diastolic function in pediatric HCM is common but is not related to fibrosis or perfusion defects. Prognostic value of fibrosis and perfusion defects have to be evaluated

Insulin resistance is a major determinant of myocardial blood flow impairment in anginal patients

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Hybrid Image Visualization Tool for 3D integration of CT coronary anatomy and quantitative myocardial perfusion PET

Purpose: Multimodal cardiac imaging by CTA and quantitative PET enables acquisition of patient-specific coronary anatomy and absolute myocardial perfusion at rest and during stress. In the clinical setting, integration of this information is performed visually or using coronary arteries distribution models. We developed a new tool for CTA and quantitative PET integrated 3D visualization, exploiting XML and DICOM clinical standards. Methods: The Hybrid Image Tool (HIT) developed in the present study included four main modules: (1) volumetric registration for spatial matching of CTA and PET datasets, (2) an interface to PET quantitative analysis software, (3) a derived DICOM generator able to build DICOM dataset from quantitative polar maps, and (4) a 3D visualization tool of integrated anatomical and quantitative flow information. The four modules incorporated in the HIT tool communicate by defined standard XML files: XML-transformation and XML MIST standards. Results: The HIT tool implements a 3D representation of CTA showing real coronary anatomy fused to PET derived quantitative myocardial blood flow distribution. The technique was validated on 16 datasets from EVINCI study population. The validation of the method confirmed the high matching between "original" and derived datasets as well as the accuracy of the registration procedure. Conclusions: Three-dimensional integration of patient-specific coronary artery anatomy provided by CTA and quantitative myocardial blood flow obtained from PET imaging can improve cardiac disease assessment. The HIT tool introduced in this paper may represent a significant advancement in the clinical use of this multimodal approach

Myocardial fibrosis as a key determinant of left ventricular remodeling in idiopathic dilated cardiomyopathy: a contrast-enhanced cardiovascular magnetic study

In idiopathic dilated cardiomyopathy, there are scarce data on the influence of late gadolinium enhancement (LGE) assessed by cardiovascular magnetic resonance on left ventricular (LV) remodeling

Role of Imaging in Cardiomyopathies

Imaging has a central role in the diagnosis, classification, and clinical management of cardiomyopathies. While echocardiography is the first-line technique, given its wide availability and safety, advanced imaging, including cardiovascular magnetic resonance (CMR), nuclear medicine and CT, is increasingly needed to refine the diagnosis or guide therapeutic decision-making. In selected cases, such as in transthyretin-related cardiac amyloidosis or in arrhythmogenic cardiomyopathy, the demonstration of histological features of the disease can be avoided when typical findings are observed at bone-tracer scintigraphy or CMR, respectively. Findings from imaging techniques should always be integrated with data from the clinical, electrocardiographic, biomarker, genetic and functional evaluation to pursue an individualised approach to patients with cardiomyopathy

Cardiovascular magnetic resonance imaging in hypertrophic cardiomyopathy:the importance of clinical context

In patients with suspected or established hypertrophic cardiomyopathy (HCM), cardiovascular magnetic resonance (CMR) is widely employed for clinical management, given its multimodality approach capable of providing unique information on cardiac morphology, function, and tissue characterization. Guidance regarding all aspects of HCM diagnosis and management is provided by the comprehensive 2014 European Society of Cardiology (ESC) guidelines on HCM. CMR should be performed in centres with recognized expertise in heart muscle diseases, by physicians who are familiar with the whole HCM disease spectrum, differential diagnoses, and pitfalls. Because CMR is usually performed and interpreted by physicians not directly involved in patient care, detailed, bidirectional, and standardized communication becomes essential to obtain best results and avoid misinterpretation. In order to maximize the potential of CMR, it is of paramount importance that reporting physicians are provided with the essential clinical information and that, in turn, referring physicians are given a core set of CMR morphological, functional, and tissue characterization results following the test. This article aims to summarize the current knowledge on the role of CMR in managing HCM and, in addition, to review the importance of the clinical context in which the report is provided, in both adult and paediatric population, highlighting implications for clinical research

Multicentre multi-device hybrid imaging study of coronary artery disease: results from the EValuation of INtegrated Cardiac Imaging for the Detection and Characterization of Ischaemic Heart Disease (EVINCI) hybrid imaging population

AIMS: Hybrid imaging provides a non-invasive assessment of coronary anatomy and myocardial perfusion. We sought to evaluate the added clinical value of hybrid imaging in a multi-centre multi-vendor setting. METHODS AND RESULTS: Fourteen centres enrolled 252 patients with stable angina and intermediate (20-90%) pre-test likelihood of coronary artery disease (CAD) who underwent myocardial perfusion scintigraphy (MPS), CT coronary angiography (CTCA), and quantitative coronary angiography (QCA) with fractional flow reserve (FFR). Hybrid MPS/CTCA images were obtained by 3D image fusion. Blinded core-lab analyses were performed for CTCA, MPS, QCA and hybrid datasets. Hemodynamically significant CAD was ruled-in non-invasively in the presence of a matched finding (myocardial perfusion defect co-localized with stenosed coronary artery) and ruled-out with normal findings (both CTCA and MPS normal). Overall prevalence of significant CAD on QCA (&gt;70% stenosis or 30-70% with FFR 640.80) was 37%. Of 1004 pathological myocardial segments on MPS, 246 (25%) were reclassified from their standard coronary distribution to another territory by hybrid imaging. In this respect, in 45/252 (18%) patients, hybrid imaging reassigned an entire perfusion defect to another coronary territory, changing the final diagnosis in 42% of the cases. Hybrid imaging allowed non-invasive CAD rule-out in 41%, and rule-in in 24% of patients, with a negative and positive predictive value of 88% and 87%, respectively. CONCLUSION: In patients at intermediate risk of CAD, hybrid imaging allows non-invasive co-localization of myocardial perfusion defects and subtending coronary arteries, impacting clinical decision-making in almost one every five subjects