Cardiogenetics

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Open AccessReview

Cardiovascular Magnetic Resonance in Rare Systemic Diseases

by Antonello D’Andrea, Marianna Fontana, Rosangela Cocchia, Raffaele Calabrò, Maria Giovanna Russo and James C. Moon

Cardiogenetics 2013, 3(1), e8; https://doi.org/10.4081/cardiogenetics.2013.e8 - 24 Dec 2013

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Abstract

The heart may be involved in a number of systemic syndromes. The pericardium, myocardium, heart valves, and coronary arteries may be involved either singly or in various combinations. In most cases the cardiac manifestations are not the dominant feature, but in some it [...] Read more.

The heart may be involved in a number of systemic syndromes. The pericardium, myocardium, heart valves, and coronary arteries may be involved either singly or in various combinations. In most cases the cardiac manifestations are not the dominant feature, but in some it is the primary determinant of symptoms and survival. Both the early identification of cardiac involvement and the etiology underneath is of paramount importance, as some causes require specific treatment and may be correctable. In this respect non-invasive imaging plays a central role especially in the context of rare cardiac disease, where specific imaging features can help to make the appropriate diagnosis on a substantial proportion of them, enabling the physician to choose the best management strategy tailored to the disease. Whereas echocardiography is the firstline investigation for detecting a cardiac involvement in systemic disease, cardiovascular magnetic resonance (CMR) provides additional incremental data allowing in addition to a detailed examination of cardiac structure and function also the tissue characterization. The aim of this review is therefore to delineate the role of CMR in detecting cardiac involvement in patients with rare systemic diseases and delineate the specific imaging features of the different etiologies. Full article

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Open AccessEditorial

Imaging in Rare Disease: A Roadmap for Diagnosis

by Giovanni Di Salvo and Giuseppe Limongelli

Cardiogenetics 2013, 3(1), e10; https://doi.org/10.4081/cardiogenetics.2013.e10 - 24 Dec 2013

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Abstract

Rare diseases are a heterogeneous group of conditions including genetic syndromes, inherited metabolic diseases, and neuromuscular disorders with various expression and different organ involvement. [...] Full article

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Open AccessReview

Muscular Dystrophies: Key Elements for Everyday Diagnosis and Management

by Alberto Palladino, Gerardo Nigro and Luisa Politano

Cardiogenetics 2013, 3(1), e9; https://doi.org/10.4081/cardiogenetics.2013.e9 - 20 Dec 2013

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Abstract

Muscular dystrophies are a heterogeneous group of inherited disorders that share similar clinical features and dystrophic changes on muscle biopsy, associated with progressive weakness. Weakness may be noted at birth or develop in late adult life. In recent years, cardiac involvement has been [...] Read more.

Muscular dystrophies are a heterogeneous group of inherited disorders that share similar clinical features and dystrophic changes on muscle biopsy, associated with progressive weakness. Weakness may be noted at birth or develop in late adult life. In recent years, cardiac involvement has been observed in a growing number of genetic muscle diseases, and considerable progress has been made in understanding the relationships between disease skeletal muscle and cardiac muscle disease. This review will focus on the skeletal muscle diseases most commonly associated with cardiac complications that can be diagnosed by echocardiography, such as dystrophinopathies including Duchenne (DMD) and Becker (BMD) muscular dystrophies, cardiomyopathy of DMD/BMD carriers and X-L dilated cardiomyopathy. Full article

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Open AccessReview

High-Density Lipoproteincholesterol, Reverse Cholesterol Transport, and Cardiovascular Risk: A Tale of Genetics?

by Giovanni Cimmino, Chiara D’Amico, Giovanni Ciccarelli, Marco Golino, Alberto Morello, Saverio D’Elia, Valeria Marchese and Paolo Golino

Cardiogenetics 2013, 3(1), e7; https://doi.org/10.4081/cardiogenetics.2013.e7 - 15 Oct 2013

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Abstract

Cholesterol deposition plays a central role in atherogenesis. The accumulation of lipid material is the result of an imbalance between the influx and efflux of cholesterol within the arterial wall. High levels of plasma low-density lipoprotein-cholesterol are considered the major mechanism responsible for [...] Read more.

Cholesterol deposition plays a central role in atherogenesis. The accumulation of lipid material is the result of an imbalance between the influx and efflux of cholesterol within the arterial wall. High levels of plasma low-density lipoprotein-cholesterol are considered the major mechanism responsible for the influx and accumulation of cholesterol in the arterial wall, while high-density lipoprotein (HDL)- cholesterol seems responsible for its efflux. The mechanism by which cholesterol is removed from extra-hepatic organs and delivered to the liver for its catabolism and excretion is called reverse cholesterol transport (RCT). Epidemiological evidence has associated high levels of HDL-cholesterol/ApoA-I with protection against atherosclerotic disease, but the ultimate mechanism(s) responsible for the beneficial effect is not well established. HDLs are synthesized by the liver and small intestine and released to the circulation as a lipid-poor HDL (nascent HDL), mostly formed by ApoA-I and phospholipids. Through their metabolic maturation, HDLs interact with the ABCA1 receptor in the macrophage surface increasing their lipid content by taking phospholipids and cholesterol from macrophages becoming mature HDL. The cholesterol of the HDLs is transported to the liver, via the scavenger receptor class B, type I, for further metabolization and excretion to the intestines in the form of bile acids and cholesterol, completing the process of RCT. It is clear that an inherited mutation or acquired abnormality in any of the key players in RCT mat affect the atherosclerotic process. Full article

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Open AccessArticle

Atrial Fibrillation Is Poorly Tolerated by Patients with Hypertrophic Concentric Cardiomyopathy Caused by Mitochondrial tRNA^{Leu (UUR)} Mutations

by Tiina M. Heliö, Alexandra Götz, Janne Rapola, Sari Kiuru-Enari, Sari Kivistö, Terttu Heikinheimo and Anu Suomalainen

Cardiogenetics 2013, 3(1), e6; https://doi.org/10.4081/cardiogenetics.2013.e6 - 28 Jun 2013

Cited by 2 | Viewed by 1

Abstract

Knowledge on the molecular background of mitochondrial disorders has accumulated during the past two decades, but clinical and molecular features of mitochondrial cardiomyopathies (CMPs) are only starting to be characterized. We studied the detailed cardiologic phenotype of patients with adult-onset CMPs associated with [...] Read more.

Knowledge on the molecular background of mitochondrial disorders has accumulated during the past two decades, but clinical and molecular features of mitochondrial cardiomyopathies (CMPs) are only starting to be characterized. We studied the detailed cardiologic phenotype of patients with adult-onset CMPs associated with mitochondrial DNA (mtDNA) mutations and their relatives, from three families. We identified a pathogenic T3258C point mutation of mtDNA tRNA^Leu(UUR) in an adult patient with mitochondrial myopathy and CMP, with acute manifestation of dyspnea and elevated plasma N-terminal pro-B-type natriuretic peptide concentration. Two other families with maternally segregated CMP, fatal in three patients, had the A3243G mutation in tRNA^Leu(UUR) of mtDNA. Many of the mutation carriers, even if oligosymptomatic, had concentric, non-obstructive hypertrophic CMP with diastolic dysfunction or restrictive hemodynamics, or depression of systolic function especially at times when patients had lactic acidosis. Atrial fibrillation led to manifest heart failure in four patients, fatal in one. In conclusion, tRNA^Leu(UUR) mutations in mtDNA may underlie mitochondrial non-obstructive, sometimes fatal, hypertrophic CMPs of adult age. Such CMPs are characterized by left ventricular hypertrophy and poor tolerance of atrial arrhythmias, often leading to rapidly deteriorating systolic function and heart failure. These patients benefit of rapid intervention of tachyarrhythmias. These patients may not have neurological symptoms, and may therefore remain underdiagnosed. Our observations emphasize that patients with tRNA^Leu(UUR) mutations need cardiologic evaluation and follow- up. tRNA^Leu(UUR) mutations should be screened of patients with hypertrophic CMP and metabolic acidosis, especially if atrial arrhythmia provoked cardiac decompensation. Full article

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Open AccessReview

Echocardiography in Fabry Disease

by Markus Niemann and Frank Weidemann

Cardiogenetics 2013, 3(1), e3; https://doi.org/10.4081/cardiogenetics.2013.e3 - 13 Jun 2013

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Abstract

Fabry disease is an X-linked lysosomal storage disorder caused by alpha-galactosidase A deficiency. The genetic defect leads to progressive intracellular accumulation of Gl3 in various tissues, including heart, kidney, vascular endothelium and the nervous system. Cardiac involvement is frequent and since renal transplantation [...] Read more.

Fabry disease is an X-linked lysosomal storage disorder caused by alpha-galactosidase A deficiency. The genetic defect leads to progressive intracellular accumulation of Gl3 in various tissues, including heart, kidney, vascular endothelium and the nervous system. Cardiac involvement is frequent and since renal transplantation therapy became standard most Fabry patients die due to cardiac reasons. Left ventricular hypertrophy is the morphological hallmark of the disease. Hypertrophy can be accompanied by various other cardiac findings, which can be visualized using echocardiography. Especially the left ventricular geometry and the regional myocardial function can show major alterations during disease progression. This review provides echocardiographic guidance in Fabry disease and highlights possible alterations of the hearts components visualizable with echocardiography. The main findings are summarized in the Take home message sections. Full article

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Open AccessReview

Myocardial Deformation Imaging and Rare Cardiomyopathies with Hypertrophic Phenotype: A Review Focused on Fabry Disease, Friedreich Ataxia and Amyloidosis

by Bahaa Fadel, Luca Baldini, Valeria Pergola, Ziad Al Bulbul and Giovanni Di Salvo

Cardiogenetics 2013, 3(1), e4; https://doi.org/10.4081/cardiogenetics.2013.e4 - 10 Jun 2013

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Abstract

Tissue Doppler and deformation imaging, including Doppler-derived strain and speckle tracking, have significantly improved our understanding of cardiac mechanics in both physiological and pathological states. The various modes of left ventricular deformation (longitudinal, circumferential, radial and twist) leading to systolic contraction can nowadays [...] Read more.

Tissue Doppler and deformation imaging, including Doppler-derived strain and speckle tracking, have significantly improved our understanding of cardiac mechanics in both physiological and pathological states. The various modes of left ventricular deformation (longitudinal, circumferential, radial and twist) leading to systolic contraction can nowadays be quantified. One of the best applications of deformation imaging is in the area of hypertrophic cardiomyopathies. Deformation imaging allows the evaluation of global and regional myocardial performance and the noninvasive characterization of abnormal intramural myocardial mechanics. In this review, we discuss the role of myocardial deformation imaging derived by echocardiography in the assessment of rare hypertrophic phenotype including Fabry disease, Friedreich ataxia and amyloidosis. Deformation imaging allows for early identification of myocardial dysfunction in many hypertrophic disorders, at an earlier stage than that provided by standard imaging or echocardiographic techniques. This allows for the implementation of appropriate therapy before significant disease progression has occurred and prior to the development of advanced myocardial fibrosis. Thus therapy would likely be more effective and may potentially lead to improvement in patient outcome. Additionally strain imaging allows to better monitoring the efficacy of therapy by assessing the progression and regression of myocardial involvement. Finally, findings on strain imaging carry important prognostic information in many hypertrophic disorders. Full article

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Open AccessReview

J Wave Syndromes as a Cause of Sudden Arrhythmic Death

by Charles Antzelevitch

Cardiogenetics 2013, 3(1), e2; https://doi.org/10.4081/cardiogenetics.2013.e2 - 5 Jun 2013

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Abstract

Accentuated J waves have been associated with idiopathic ventricular tachycardia and fibrillation (VT/VF) for nearly three decades. Prominent J waves characterize both Brugada and early repolarization syndromes leading to their designation as J wave syndromes. An early repolarization (ER) pattern, characterized by J [...] Read more.

Accentuated J waves have been associated with idiopathic ventricular tachycardia and fibrillation (VT/VF) for nearly three decades. Prominent J waves characterize both Brugada and early repolarization syndromes leading to their designation as J wave syndromes. An early repolarization (ER) pattern, characterized by J point elevation, slurring of the terminal part of the QRS and ST segment elevation was considered to be a totally benign electrocardiographic manifestation until a decade ago. Recent casecontrol and population-based association studies have advanced evidence that an ER pattern in the inferior or infero-lateral leads is associated with increased risk for life-threatening arrhythmias, named early repolarization syndrome (ERS). ERS and Brugada syndrome (BrS) share similar electrocardiogram features, clinical outcomes, risk factors as well as a common arrhythmic platform related to amplification of I_to-mediated J waves. Although BrS and ERS differ with respect to the magnitude and lead location of abnormal J wave manifestation, they are thought to represent a continuous spectrum of phenotypic expression, termed J wave syndromes. A classification scheme for ERS has been proposed: type 1, displaying an ER pattern predominantly in the lateral precordial leads, is considered to be largely benign; type 2, displaying an ER pattern predominantly in inferior or infero-lateral leads, is associated with a higher level of risk; whereas type 3, displaying an ER pattern globally in inferior, lateral and right precordial leads, is associated with the highest level of risk for development of malignant arrhythmias and is often associated with VF storms. Full article

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Open AccessArticle

Cost-Effectiveness of Genetic Studies in Inherited Heart Diseases

by María Sabater-Molina, Esperanza García-Molina, Isabel Tovar, Francisco Ruiz-Espejo, Juan Ramón Gimeno and Mariano Valdés

Cardiogenetics 2013, 3(1), e5; https://doi.org/10.4081/cardiogenetics.2013.e5 - 23 May 2013

Cited by 5 | Viewed by 1

Abstract

There is a need to evidence the cost of genetic testing and know their profitability in order to establish criteria for priorizing access to genetic testing for these diseases. We determinated the cost per positive genotyping in 234 index cases with diagnosis of [...] Read more.

There is a need to evidence the cost of genetic testing and know their profitability in order to establish criteria for priorizing access to genetic testing for these diseases. We determinated the cost per positive genotyping in 234 index cases with diagnosis of hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), long-QT syndrome (LQTS), or Brugada syndrome (BS). The genetic tests of the most prevalent genes and the estimation of the costs of periodical screening in wildtype relatives (WT) were calculated. A total of 738 individuals (517 HCM, 76 ARVC, 71 LQTS and 74 BS) from 234 probands were genotyped. The savings made by not having to perform the clinical testing of WT relatives exceeded the cost of genotyping for HCM families € +220,710, ARVC families € +9405 and LQTS families € +8362. The balance in BS was negative (€ –25,112). Our data suggests that individuals with conclusive clinical diagnostic of HCM should have a priority to access genetic testing. A positive overall benefit was also demonstrated in ARVC and LQTS. Full article

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Open AccessArticle

Lamin A/C Mutation Affecting Primarily the Right Side of the Heart

by Laura Ollila, Johanna Kuusisto, Keijo Peuhkurinen, Satu Kärkkäinen, Petri Tuomainen, Maija Kaartinen, Olayinka Raheem, Bjarne Udd, Jarkko Magga, Janne Rapola, Annukka M. Lahtinen, Eero Lehtonen, Miia Holmström, Sari Kivistö, Elisabeth Widén, Markku Saksa and Tiina Heliö

Cardiogenetics 2013, 3(1), e1; https://doi.org/10.4081/cardiogenetics.2013.e1 - 15 Apr 2013

Cited by 2 | Viewed by 2

Abstract

LMNA mutations are amongst the most important causes of familial dilated cardiomyopathy. The most important cause of arrhythmogenic right ventricular cardiomyopathy (ARVC) is desmosomal pathology. The aim of the study was to elucidate the role of LMNA mutations among Finnish cardiomyopathy patients. We [...] Read more.

LMNA mutations are amongst the most important causes of familial dilated cardiomyopathy. The most important cause of arrhythmogenic right ventricular cardiomyopathy (ARVC) is desmosomal pathology. The aim of the study was to elucidate the role of LMNA mutations among Finnish cardiomyopathy patients. We screened 135 unrelated cardiomyopathy patients for LMNA mutations. Because of unusual phenotype, two patients were screened for the known Finnish ARVC-related mutations of desmosomal genes, and their Plakophilin-2b gene was sequenced. Myocardial samples from two patients were examined by immunohistochemical plakoglobin staining and in one case by electron microscopy. We found a new LMNA mutation Phe237Ser in a family of five affected members with a cardiomyopathy affecting primarily the right side of the heart. The phenotype resembles ARVC but does not fulfill the Task Force Criteria. The main clinical manifestations of the mutation were severe tricuspid insufficiency, right ventricular enlargement and failure. Three of the affected patients died of the heart disease, and the two living patients received heart transplants at ages 44 and 47. Electron microscopy showed nuclear blebbing compatible with laminopathy. Immunohisto - chemical analysis did not suggest desmosomal pathology. No desmosomal mutations were found. The Phe237Ser LMNA mutation causes a phenotype different from traditional cardiolaminopathy. Our findings suggest that cardiomyopathy affecting primarily the right side of the heart is not always caused by desmosomal pathology. Our observations highlight the challenges in classifying cardiomyopathies, as there often is significant overlap between the traditional categories. Full article

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Cardiogenetics, Volume 3, Issue 1 (April 2013) – 10 articles

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