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

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

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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

Cardiac T1 Mapping and Extracellular Volume (ECV) in clinical practice: a comprehensive review.

Cardiovascular Magnetic Resonance is increasingly used to differentiate the aetiology of cardiomyopathies. Late Gadolinium Enhancement (LGE) is the reference standard for non-invasive imaging of myocardial scar and focal fibrosis and is valuable in the differential diagnosis of ischaemic versus non-ischaemic cardiomyopathy. Diffuse fibrosis may go undetected on LGE imaging. Tissue characterisation with parametric mapping methods has the potential to detect and quantify both focal and diffuse alterations in myocardial structure not assessable by LGE. Native and post-contrast T1 mapping in particular has shown promise as a novel biomarker to support diagnostic, therapeutic and prognostic decision making in ischaemic and non-ischaemic cardiomyopathies as well as in patients with acute chest pain syndromes. Furthermore, changes in the myocardium over time may be assessed longitudinally with this non-invasive tissue characterisation method

Effect of cellular and extracellular pathology assessed by T1 mapping on regional contractile function in hypertrophic cardiomyopathy

Background Regional contractile dysfunction is a frequent finding in hypertrophic cardiomyopathy (HCM). We aimed to investigate the contribution of different tissue characteristics in HCM to regional contractile dysfunction. Methods We prospectively recruited 50 patients with HCM who underwent cardiovascular magnetic resonance (CMR) studies at 3.0 T including cine imaging, T1 mapping and late gadolinium enhancement (LGE) imaging. For each segment of the American Heart Association model segment thickness, native T1, extracellular volume (ECV), presence of LGE and regional strain (by feature tracking and tissue tagging) were assessed. The relationship of segmental function, hypertrophy and tissue characteristics were determined using a mixed effects model, with random intercept for each patient. Results Individually segment thickness, native T1, ECV and the presence of LGE all had significant associations with regional strain. The first multivariable model (segment thickness, LGE and ECV) demonstrated that all strain parameters were associated with segment thickness (P < 0.001 for all) but not ECV. LGE (Beta 2.603, P = 0.024) had a significant association with circumferential strain measured by tissue tagging. In a second multivariable model (segment thickness, LGE and native T1) all strain parameters were associated with both segment thickness (P < 0.001 for all) and native T1 (P < 0.001 for all) but not LGE. Conclusion Impairment of contractile function in HCM is predominantly associated with the degree of hypertrophy and native T1 but not markers of extracellular fibrosis (ECV or LGE). These findings suggest that impairment of contractility in HCM is mediated by mechanisms other than extracellular expansion that include cellular changes in structure and function. The cellular mechanisms leading to increased native T1 and its prognostic significance remain to be established

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

Cost-effectiveness analysis of stand-alone or combined non-invasive imaging tests for the diagnosis of stable coronary artery disease: results from the EVINCI study

Aim: This study aimed at evaluating the cost-effectiveness of different non-invasive imaging-guided strategies for the diagnosis of obstructive coronary artery disease (CAD) in a European population of patients from the Evaluation of Integrated Cardiac Imaging in Ischemic Heart Disease (EVINCI) study.Methods and results: Cost-effectiveness analysis was performed in 350 patients (209 males, mean age 59 ± 9 years) with symptoms of suspected stable CAD undergoing computed tomography coronary angiography (CTCA) and at least one cardiac imaging stress-test prior to invasive coronary angiography (ICA) and in whom imaging exams were analysed at dedicated core laboratories. Stand-alone stress-tests or combined non-invasive strategies, when the first exam was uncertain, were compared. The diagnostic end-point was obstructive CAD defined as > 50% stenosis at quantitative ICA in the left main or at least one major coronary vessel. Effectiveness was defined as the percentage of correct diagnosis (cd) and costs were calculated using country-specific reimbursements. Incremental cost-effectiveness ratios (ICERs) were obtained using per-patient data and considering “no-imaging” as reference. The overall prevalence of obstructive CAD was 28%. Strategies combining CTCA followed by stress ECHO, SPECT, PET, or stress CMR followed by CTCA, were all cost-effective. ICERs values indicated cost saving from − 969€/cd for CMR-CTCA to − 1490€/cd for CTCA-PET, − 3,09 €/cd for CTCA-SPECT and − 3776€/cd for CTCA-ECHO. Similarly when considering early revascularization as effectiveness measure.Conclusion: In patients with suspected stable CAD and low prevalence of disease, combined non-invasive strategies with CTCA and stress-imaging are cost-effective as gatekeepers to ICA and to select candidates for early revascularization.</p

Role of cardiac imaging in heart failure

Heart failure is the leading cause of mortality and rehospitalization in Western countries. With the development of new technologies applied to medical diagnostic pathways, cardiovascular imaging has rapidly gained ground. Therefore, the clinical cardiologist has to keep updated on the management of such innovative diagnostic tools which were once the exclusive domain of radiologists. The need to understand a new language is fundamental for the selection of diagnostic and therapeutic strategies in patients with heart failure, which is often the final destination for many cardiovascular diseases. Alongside standard diagnostic techniques such as chest radiography two-dimensional ultrasound and cardiac color Doppler, all of which are indispensable in daily practice, innovative tools have been defining their incremental role in cardiovascular imaging. Cardiac magnetic resonance (CMR), cardiac computed tomography (CT), speckle tracking, 3D echocardiography, new applications in nuclear medicine (SPECT MIBG), and "cardiac hybrid imaging" are emerging for research and are also playing a pivotal role in the clinical scenario. These techniques are useful the for non-invasive acquisition of diagnostic and prognostic information in heart failure. Whether the radiological and economic impact of these new technologies is sustainable is a question the clinical cardiologist will need to answer when considering the cost/benefit of the diagnostic tool selected among these methods