Journal Description
Cardiogenetics
Cardiogenetics
is an international, scientific, peer-reviewed, open access journal, published quarterly online by MDPI (from Volume 10 Issue 2 - 2020).
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within ESCI (Web of Science), Embase, and other databases.
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 43.2 days after submission; acceptance to publication is undertaken in 5.9 days (median values for papers published in this journal in the first half of 2024).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names published annually in the journal.
Impact Factor:
0.5 (2023)
Latest Articles
Unusual Mild Phenotype Presentation in an Elderly Patient with Homozygous Tangier Disease
Cardiogenetics 2024, 14(4), 198-203; https://doi.org/10.3390/cardiogenetics14040015 - 25 Oct 2024
Abstract
Tangier disease (TD) is an extremely rare inherited disorder involving lipoprotein metabolism and high-density lipoprotein (HDL) recycling in particular. TD is linked with a mutation of the ABCA1 gene codifying for the transport protein ABCA1 which, in normal conditions, enables the efflux of
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Tangier disease (TD) is an extremely rare inherited disorder involving lipoprotein metabolism and high-density lipoprotein (HDL) recycling in particular. TD is linked with a mutation of the ABCA1 gene codifying for the transport protein ABCA1 which, in normal conditions, enables the efflux of cholesterol through the cell membrane to HDL and apolipoprotein A1. As such, early cardiovascular events and neuropathy are common in these patients, mostly in homozygous carriers. Here, we describe the unique case of a homozygous TD patient whose diagnosis was made in later life. He was affected by the A1046D protein mutation and suffered from mild neurological symptoms and asymptomatic atherosclerosis.
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(This article belongs to the Section Rare Disease-Metabolic Diseases)
Open AccessEditor’s ChoiceArticle
Circulating Cell-Free Nuclear DNA Predicted an Improvement of Systolic Left Ventricular Function in Individuals with Chronic Heart Failure with Reduced Ejection Fraction
by
Tetiana Berezina, Oleksandr O. Berezin, Michael Lichtenauer and Alexander E. Berezin
Cardiogenetics 2024, 14(4), 183-197; https://doi.org/10.3390/cardiogenetics14040014 - 1 Oct 2024
Abstract
Background: Patients with heart failure (HF) with improved ejection fraction (HFimpEF) demonstrate better clinical outcomes when compared with individuals without restoration of cardiac function. The identification of predictors for HFimpEF may play a crucial role in the individual management of HF with reduced
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Background: Patients with heart failure (HF) with improved ejection fraction (HFimpEF) demonstrate better clinical outcomes when compared with individuals without restoration of cardiac function. The identification of predictors for HFimpEF may play a crucial role in the individual management of HF with reduced ejection fraction (HFrEF). Cell-free nuclear (cf-nDNA) DNA is released from damaged cells and contributes to impaired cardiac structure and function and inflammation. The purpose of the study was to elucidate whether cf-nDNA is associated with HFimpEF. Methods: The study prescreened 1416 patients with HF using a local database. Between October 2021 and August 2022, we included 452 patients with chronic HFrEF after prescription of optimal guideline-based therapy and identified 177 HFimpEF individuals. Circulating biomarkers were measured at baseline and after 6 months. Detection of cf-nDNA was executed with real-time quantitative PCR (qPCR) using NADH dehydrogenase, ND2, and beta-2-microglobulin. Results: We found that HFimpEF was associated with a significant decrease in the levels of cf-nDNA when compared with the patients from persistent HFrEF cohort. The presence of ischemia-induced cardiomyopathy (odds ration [OR] = 0.75; p = 0.044), type 2 diabetes mellitus (OR = 0.77; p = 0.042), and digoxin administration (OR = 0.85; p = 0.042) were negative factors for HFimpEF, whereas NT-proBNP ≤ 1940 pmol/mL (OR = 1.42, p = 0.001), relative decrease in NT-proBNP levels (>35% vs. ≤35%) from baseline (OR = 1.52; p = 0.001), and cf-nDNA ≤ 7.5 μmol/L (OR = 1.56; p = 0.001) were positive predictors for HFimpEF. Conclusions: We established that the levels of cf-nDNA ≤ 7.5 μmol/L independently predicted HFimpEF and improved the discriminative ability of ischemia-induced cardiomyopathy, IV NYHA class, and single-measured NT-proBNP and led to a relative decrease in NT-proBNP levels ≤35% from baseline in individuals with HFrEF.
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(This article belongs to the Section Biomarkers)
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Open AccessEditor’s ChoiceReview
Review of p.(Val429Met), a Variant of LDLR That Is Associated with Familial Hypercholesterolemia
by
Eric F. Jotch and Mark S. Kindy
Cardiogenetics 2024, 14(4), 170-182; https://doi.org/10.3390/cardiogenetics14040013 - 29 Sep 2024
Abstract
Patients affected by familial hypercholesterolemia possess elevated low-density lipoprotein cholesterol and therefore have greater risk for cardiovascular disease. About 90% of familial hypercholesterolemia cases are associated with aberrant LDLR. Over 3500 LDLR variants have been identified, 15% of which are considered “pathogenic.”
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Patients affected by familial hypercholesterolemia possess elevated low-density lipoprotein cholesterol and therefore have greater risk for cardiovascular disease. About 90% of familial hypercholesterolemia cases are associated with aberrant LDLR. Over 3500 LDLR variants have been identified, 15% of which are considered “pathogenic.” Given the genetic diversity of LDLR variants, specific variants rarely receive attention. However, investigators have proposed the critical evaluation of individual variants as a method to clarify knowledge and to resolve discrepancies in the literature. This article reviews p.(Val429Met) (rs28942078) in the areas of pathology, epidemiology, lipid-lowering therapy, and genetic testing. The p.(Val429Met) variant is associated with a missense point substitution in exon 9 of chromosome 19. Biochemical studies have found severely reduced low-density lipoprotein receptor protein in autologous and heterologous expression systems. Additionally, there are inconsistencies regarding the functional classification of p.(Val429Met). Considered to be of European origin, p.(Val429Met) is found in extant populations due to founder effects. Evidence from clinical trials have also demonstrated variable responses to newer lipid-lowering therapies in patients with a p.(Val429Met) variant. Proper clinical detection and adequate genetic testing have been shown to greatly improve outcomes. Future research may be aimed at resolving discrepancies to better comprehend the implications of familial hypercholesterolemia.
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(This article belongs to the Section Molecular Genetics)
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Open AccessReview
Beyond the Beat: Understanding Inherited Risk and Therapeutic Opportunities in Cardiovascular Diseases with Emphasis on Inherited Cardiomyopathies and Inherited Arrhythmic Syndromes
by
Antea Krsek, Lara Baticic and Vlatka Sotosek
Cardiogenetics 2024, 14(3), 149-169; https://doi.org/10.3390/cardiogenetics14030012 - 2 Sep 2024
Abstract
Over the past three decades, significant progress has been made in elucidating the intricate connection between genetic predispositions and cardiovascular diseases (CVDs). Through extensive investigation, numerous genetic variants linked to various cardiovascular conditions have been discovered, shedding crucial light on the underlying biological
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Over the past three decades, significant progress has been made in elucidating the intricate connection between genetic predispositions and cardiovascular diseases (CVDs). Through extensive investigation, numerous genetic variants linked to various cardiovascular conditions have been discovered, shedding crucial light on the underlying biological mechanisms and pathways. These discoveries have not only revolutionized risk assessment for patients but have also paved the way for personalized treatment strategies, allowing healthcare providers to tailor interventions according to individual genetic profiles. Furthermore, genetic testing has facilitated cascade screening, enabling the early identification and intervention of potential cardiovascular issues among at-risk biological family members. This review aims to comprehensively summarize the current state of knowledge regarding inherited risk and novel insights from human genome and epigenome research, as well as therapeutic opportunities in CVDs with special emphasis on inherited cardiomyopathies and inherited arrhythmic syndromes. The newest translational trials for CVDs and pharmaceutical approaches are discussed, including gene therapy options for heart failure and cardiomyopathies.
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(This article belongs to the Section Cardiovascular Genetics in Clinical Practice)
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Open AccessEditor’s ChoiceReview
Gene Therapy for Inherited Arrhythmia Syndromes
by
Cameron J. Leong, Sohat Sharma, Jayant Seth, Archan Dave, Abdul Aziz Abdul Ghafoor and Zachary Laksman
Cardiogenetics 2024, 14(3), 132-148; https://doi.org/10.3390/cardiogenetics14030011 - 2 Aug 2024
Abstract
The emergence of gene therapy offers opportunities for treating a myriad of genetic disorders and complex diseases that previously had limited or no treatment options. The key basic strategies for gene therapy involve either the addition, inhibition, or introduction of a new gene,
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The emergence of gene therapy offers opportunities for treating a myriad of genetic disorders and complex diseases that previously had limited or no treatment options. The key basic strategies for gene therapy involve either the addition, inhibition, or introduction of a new gene, with a crucial component being the use of a delivery vector to effectively target cells. Particularly promising is the application of gene therapy for the treatment of inherited arrhythmia syndromes, conditions associated with significant mortality and morbidity that have limited treatment options, and a paucity of disease modifying therapy. This review aims to summarize the utility of gene therapy for the treatment of inherited arrhythmia syndromes by exploring the current state of knowledge, limitations, and future directions.
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(This article belongs to the Special Issue Genetics of Inherited Arrhythmogenic Syndromes Associated with Sudden Death)
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Open AccessEditor’s ChoiceArticle
Genetic Testing for Patients with Cardiomyopathies: The INDACO Study—Towards a Cardiogenetic Clinic
by
Matteo Bianco, Noemi Giordano, Valentina Gazzola, Carloalberto Biolè, Giulia Nangeroni, Maurizio Lazzero, Giulia Margherita Brach del Prever, Fiorenza Mioli, Giulia Gobello, Amir Hassan Mousavi, Monica Guidante, Silvia Deaglio, Daniela Francesca Giachino and Alessandra Chinaglia
Cardiogenetics 2024, 14(3), 122-131; https://doi.org/10.3390/cardiogenetics14030010 - 22 Jul 2024
Abstract
Cardiomyopathies have evolved from being considered rare and idiopathic to being increasingly linked to genetic factors. This shift was enabled by advancements in understanding genetic variants and the widespread use of next generation sequencing (NGS). Current guidelines emphasize the importance of evidence-based gene
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Cardiomyopathies have evolved from being considered rare and idiopathic to being increasingly linked to genetic factors. This shift was enabled by advancements in understanding genetic variants and the widespread use of next generation sequencing (NGS). Current guidelines emphasize the importance of evidence-based gene panels that can offer “clinically actionable results”, which provide diagnostic and prognostic insights. They also advise against indiscriminate family screening after finding variants of uncertain significance (VUS) and recommend collaboration among multidisciplinary teams for an accurate variant pathogenicity assessment. This article presents an innovative “cardiogenetic clinic” approach involving cardiologists and medical geneticists to provide genetic testing and family screening. This study attempts to improve the diagnostic process for suspected genetic cardiomyopathies; this includes direct patient recruitment during cardiology appointments, NGS analysis, and combined consultations with cardiologists and geneticists to assess the results and screen the families. The study cohort of 170 patients underwent genetic testing, which identified 78 gene variants. Positive results (C4 or C5 variants) occurred in 20 (19.8%) cases, with rates varying by cardiomyopathy phenotype, while 57 (73.1%) of the variants found were classified as C3-VUS, causing a significant management issue. This model shortened the time to results, increased patient adherence, and improved patients’ diagnoses. Family screening was pondered depending on the relevance of the detected variants, showing this method’s potential to impact patient management.
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(This article belongs to the Section Cardiovascular Genetics in Clinical Practice)
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Open AccessEditor’s ChoiceReview
Exploring the Role of Genetics in Sarcoidosis and Its Impact on the Development of Cardiac Sarcoidosis
by
Sanjay Sivalokanathan
Cardiogenetics 2024, 14(2), 106-121; https://doi.org/10.3390/cardiogenetics14020009 - 3 Jun 2024
Abstract
Sarcoidosis is a multifaceted and multisystemic inflammatory disorder, the etiology of which remains unknown. However, it has been suggested that an intricate interplay between genetic, environmental, and inflammatory factors may contribute to the development and progression of sarcoidosis. Although 30–50% of patients demonstrate
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Sarcoidosis is a multifaceted and multisystemic inflammatory disorder, the etiology of which remains unknown. However, it has been suggested that an intricate interplay between genetic, environmental, and inflammatory factors may contribute to the development and progression of sarcoidosis. Although 30–50% of patients demonstrate extra-pulmonary manifestations, cardiac involvement is rare, affecting only 2–5% of cases. Diagnosis is often challenging, relying on the careful application of clinical judgment, histopathological evidence, and imaging biomarkers. In this literature review, we aim to provide a comprehensive overview of the current understanding of the genetic basis of sarcoidosis, the contribution to the pathogenesis of the disorder, and discuss the potential link between certain genetic variants and the development of cardiac sarcoidosis.
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(This article belongs to the Special Issue Cardiogenetics: Feature Papers 2024)
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Open AccessEditor’s ChoiceArticle
Gene Polymorphisms LEP, LEPR, 5HT2A, GHRL, NPY, and FTO-Obesity Biomarkers in Metabolic Risk Assessment: A Retrospective Pilot Study in Overweight and Obese Population in Romania
by
Ovidiu Nicolae Penes, Bernard Weber, Anca Lucia Pop, Mihaela Bodnarescu-Cobanoglu, Valentin Nicolae Varlas, Aleksandru Serkan Kucukberksun, Dragos Cretoiu, Roxana Georgiana Varlas and Cornelia Zetu
Cardiogenetics 2024, 14(2), 93-105; https://doi.org/10.3390/cardiogenetics14020008 - 20 May 2024
Cited by 1
Abstract
Genome-wide association studies (GWAS) have successfully revealed numerous susceptibility loci for obesity. The PREDATORR study (2014) shows that in Romania, 346% of adults aged 20–79 y/o are overweight, and 31.4% are obese with a high risk of cardiometabolic complications, a number that puts
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Genome-wide association studies (GWAS) have successfully revealed numerous susceptibility loci for obesity. The PREDATORR study (2014) shows that in Romania, 346% of adults aged 20–79 y/o are overweight, and 31.4% are obese with a high risk of cardiometabolic complications, a number that puts almost 67% of Romania’s population in the abnormal weight group. Our study aims to investigate the current status of the genetic foundation in metabolic disease associated with obesity, applied to a pilot group of patients specifically examining the impact of known polymorphisms and their haplotype of six food intake-regulating genes, namely leptin (LEP), leptin receptor (LEP-R), serotonin receptor (5HTR2A), ghrelin (GHRL), neuropeptide Y (NPY), and fat-mass and obesity-associated protein (FTO) with the following polymorphisms: LEP A-2548G, LEPR A-223G, 5HTR2A G-1439A, GHRL G-72T, NPY T-29063C, FTO A-T, and body mass index (BMI). A notable link between the LEP-2548 rs7799039 gene’s AG genotype and the risk of obesity was observed, particularly pronounced in males aged 40–49, with an approximately seven-fold increased likelihood of obesity. The 5HTR2A rs6311 AA genotype was associated with a higher BMI, which was not statistically significant. The FTO rs9939609 gene’s AA genotype emerged as a significant predictor of obesity risk. Besides these significant findings, no substantial associations were observed with the LEPR, 5HTR2A, GHRL, and NPY genes. Haplotype association analysis showed a suggestive indication of GRGMLA (rs7799039, rs1137101, rs6311, rs696217, rs16139, rs9939609 sequence) haplotype with a susceptibility effect towards obesity predisposition. Linkage disequilibrium (LD) analysis showed statistically significant associations between LEP and LEPR gene (p = 0.04), LEP and GHRL gene (p = 0.0047), and GHRL and FTO gene (p = 0.03). Our study, to the best of our knowledge, is one of the very few on the Romanian population, and aims to be a starting point for further research on the targeted interventional strategies to reduce cardiometabolic risks.
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(This article belongs to the Special Issue Metabolic and Genetic Bases of Cardiovascular Diseases)
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Open AccessCase Report
A Single Nucleotide Variant in Ankyrin-2 Influencing Ventricular Tachycardia in COVID-19 Associated Myocarditis
by
Erin Haase, Chandana Kulkarni, Peyton Moore, Akash Ramanathan and Mohanakrishnan Sathyamoorthy
Cardiogenetics 2024, 14(2), 84-92; https://doi.org/10.3390/cardiogenetics14020007 - 6 May 2024
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Introduction: This paper explores the potential influence of a single nucleotide variant in the ANK-2 gene on COVID-19 myocarditis-related ventricular tachycardia. Case Description: A 53-year-old female with a history of Crohn’s disease and asthma developed COVID-19. Shortly after infection, she experienced
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Introduction: This paper explores the potential influence of a single nucleotide variant in the ANK-2 gene on COVID-19 myocarditis-related ventricular tachycardia. Case Description: A 53-year-old female with a history of Crohn’s disease and asthma developed COVID-19. Shortly after infection, she experienced symptoms of chest pressure, palpitations, and shortness of breath, leading to the eventual diagnosis of myocarditis complicated by recurrent ventricular tachycardia. Treatment with mechanistically driven anti-arrhythmic therapy and beta-blockers suppressed this highly symptomatic ventricular tachycardia. Genetic testing to further risk stratify and influence long term care identified a single nucleotide variant in the ANK-2 gene, which is known to be associated with arrhythmic risk. Discussion: This case study highlights the use of rationally selected anti-arrhythmic therapy, mexiletine, in the management of ventricular tachycardia associated with COVID-19 myocarditis and the presence of a single nucleotide variant in ANK-2, raising the possibility of its contribution to VT susceptibility and severity. Our patient demonstrated significant improvement with administered therapeutics, including the resolution of myocarditis and ventricular tachycardia. The normalization of the QT interval during the resolution phase further supports the potential influence of the genetic variant in ANK-2 on potassium channel activity.
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Open AccessCase Report
Anderson–Fabry Disease Homozygosity: Rare Case of Late-Onset Variant
by
Gabriela Dostalova, Jaroslav Januska, Michaela Veselá, Petra Reková, Anna Taborska, Martin Pleva, David Zemanek and Aleš Linhart
Cardiogenetics 2024, 14(2), 74-83; https://doi.org/10.3390/cardiogenetics14020006 - 7 Apr 2024
Cited by 1
Abstract
Anderson–Fabry Disease (AFD) is a rare, X-linked lysosomal storage disorder caused by a mutation in the α-Galactosidase A gene resulting in α-Galactosidase A enzyme (α-Gal A) deficiency. The metabolic defect leads to the progressive accumulation of glycosphingolipids and the structural and functional impairment
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Anderson–Fabry Disease (AFD) is a rare, X-linked lysosomal storage disorder caused by a mutation in the α-Galactosidase A gene resulting in α-Galactosidase A enzyme (α-Gal A) deficiency. The metabolic defect leads to the progressive accumulation of glycosphingolipids and the structural and functional impairment of affected organs. Due to the inheritance pattern, male patients are hemizygous with more severe manifestations of the disease as compared to females who, in most cases, are heterozygous with delayed and variable clinical presentation caused by uneven X-chromosome inactivation. Fabry disease cases are often identified by targeted screening programs in high-risk groups, such as in patients with end-stage renal disease, premature stroke, or unexplained cardiomyopathy. Here, we describe a unique case of a homozygous female patient identified by a nationwide screening program in hypertrophic cardiomyopathy patients. Before the systematic screening, the patient had a diagnosis of hypertrophic obstructive cardiomyopathy and was treated accordingly, including with alcohol septal ablation to reduce the obstructive gradient. The confirmation of Fabry disease led to the discovery of the same variant in several members of her family. The identified variant was c.644A>G, p.Asn215Ser (p.N215S), which is known to cause predominant cardiac involvement with late onset of the disease. This variant is amenable to oral therapy with the small-molecule chaperone migalastat, which was started and then interrupted due to the recurrence of the patient’s migraine and then re-initiated again after two years. During this period, the patient received enzyme replacement therapy with agalsidase beta but developed progressively worsening venous access. Our case illustrates the importance of the systematic screening of patients with clinical evidence of hypertrophic cardiomyopathy in whom the routine diagnostic process fails to discover Fabry disease, in particular variants with late-onset cardiac manifestations. Many of the late-onset variants are amenable to orally active therapy with migalastat, which significantly improves the comfort of the treatment. Its long-term results are being analyzed by a large international “Follow-me” registry, which was designed to verify the validity of pivotal trials with migalastat in Fabry disease.
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(This article belongs to the Special Issue Metabolic and Genetic Bases of Cardiovascular Diseases)
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Open AccessEditor’s ChoiceReview
Consideration of the Medical Economics of Cardiac Genetics, Focusing on the Cost-Effectiveness of P2Y12 Inhibitor Selection Based on the CYP2C19 Loss-of-Function Allele: A Semi-Systematic Review
by
Tomoyuki Takura
Cardiogenetics 2024, 14(2), 59-73; https://doi.org/10.3390/cardiogenetics14020005 - 3 Apr 2024
Abstract
Medical economics is essential in cardiac genetics for the clinical application and development of research results. However, related economic evaluations are unclear, and limited systematic reviews are available on the cost-effectiveness of drug selection based on the CYP2C19 LOF allele. This review analyzed
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Medical economics is essential in cardiac genetics for the clinical application and development of research results. However, related economic evaluations are unclear, and limited systematic reviews are available on the cost-effectiveness of drug selection based on the CYP2C19 LOF allele. This review analyzed research in the MEDLINE database from January 2012 to June 2023 using more evidence than a well-designed cohort study, owing to the lack of relevant research in the database. For example, cost-effectiveness analyses are often reported as simulation assays, and were included in this analysis. No conditions related to patient background or antiplatelet drug therapy were selected. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (2020). Twenty-one cardiac genetic studies were selected, of which nineteen involved antiplatelet therapy after PCI. A universal group consisting of clopidogrel and other drugs was used as the baseline and compared with the drug selection groups based on the CYP2C19 LOF allele. The incremental cost–effectiveness ratio was generally below 50,000 (US$/Qaly), and drug selection based on the CYP2C19 LOF allele was the most cost-effective, followed by universal clopidogrel. Although cardiac genetic and economic data are rudimentary, this review indicates that antiplatelet therapy (drug selection based on the CYP2C19 LOF allele) after PCI is generally cost-effective.
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(This article belongs to the Section Cardiovascular Genetics in Clinical Practice)
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Open AccessPerspective
COVID-19 and the Heart: Lessons Learned and Future Research Directions
by
Tetz Cheng-Che Lee, Alaa Mabrouk Salem Omar and Jonathan N. Bella
Cardiogenetics 2024, 14(1), 51-58; https://doi.org/10.3390/cardiogenetics14010004 - 19 Mar 2024
Abstract
It has become evident that acute COVID-19 infection can lead to cardiovascular complications. While the exact mechanisms by which COVID-19 affects the cardiovascular system have yet to be fully elucidated, several mechanisms have been proposed, including direct myocardial effects on the virus and
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It has become evident that acute COVID-19 infection can lead to cardiovascular complications. While the exact mechanisms by which COVID-19 affects the cardiovascular system have yet to be fully elucidated, several mechanisms have been proposed, including direct myocardial effects on the virus and systemic inflammation as an indirect result. The cardiovascular complications of COVID-19 have been characterized and described using noninvasive cardiac imaging. The impact of COVID-19 on the cardiovascular system extends beyond the acute phase of the infection and well beyond recovery or the convalescent period. However, the underlying mechanisms of post-viral long-COVID symptoms have yet to be elucidated. It is evident that COVID-19 has become endemic and is here to stay. Future studies are needed (1) to understand the long-term effects of the cardiovascular complications of COVID-19, future cardiovascular events and the impact of mutating variants on cardiovascular complications through data collection and analysis, (2) to identify the most important diagnostic criteria for prognosis of COVID-19 and to understand the disease mechanism through biomarkers and advanced cardiac imaging, including echocardiography and (3) to develop novel strategies to manage and treat these cardiovascular complications using the knowledge gained.
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Open AccessFeature PaperEditor’s ChoiceArticle
Risk of Cardiac Arrhythmias in Patients with Late-Onset Pompe Disease—Results from a Long Follow-Up in a Group of 12 Patients and Review of Literature
by
Alberto Palladino, Luigia Passamano, Marianna Scutifero, Salvatore Morra, Esther Picillo, Andrea Antonio Papa, Gerardo Nigro and Luisa Politano
Cardiogenetics 2024, 14(1), 38-50; https://doi.org/10.3390/cardiogenetics14010003 - 12 Feb 2024
Abstract
Background. Pompe disease is a rare, severe, autosomal recessive genetic disorder caused by GAA gene mutations, which cause α-1,4-glucosidase enzyme deficiency. There are two forms of Pompe disease based on the age of onset, the infantile and the adult form (LOPD). Cardiac
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Background. Pompe disease is a rare, severe, autosomal recessive genetic disorder caused by GAA gene mutations, which cause α-1,4-glucosidase enzyme deficiency. There are two forms of Pompe disease based on the age of onset, the infantile and the adult form (LOPD). Cardiac involvement, previously recognized only in infantile cases, is now also reported in adults. Cardiomyopathy remains an exceptional finding while heart rhythm disorders appear to be more frequent. Methods. We retrospectively evaluated cardiac involvement in 12 patients with late-onset Pompe disease (LOPD) followed for an overall period of 143 years (mean 12.7 ± 7.7) using ECG, Holter ECG, and echocardiography. Results. The mean age of patients (M8:F4) at the first visit was 40.7 ± 16.1 (range 14–63) and 53.7 ± 16.9 (range 21–76) at last visit. Conduction delay was present in three patients; one patient developed ascending aorta ectasia but had a history of hypertension, and one patient showed right heart enlargement on echocardiography, probably due to pulmonary hypertension. No patient died during the FU, nor developed cardiomyopathy. Ectopic supraventricular beats and repeated episodes of ablation-resistant atrial fibrillation were observed in only one patient (8.3%) who required PMK implantation. Conclusions. Benefitting from the long follow-up, this study allows us to state that primary myocardial involvement is rare in patients with LOPD, while rhythm disorders are more frequent and require monitoring to avoid the risk of possible life-threatening complications.
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(This article belongs to the Section Rare Disease-Neuromuscular Diseases)
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Open AccessEditor’s ChoiceReview
Hypertrophic Cardiomyopathy and Chronic Kidney Disease: An Updated Review
by
Sheefah Dhuny, Henry H. L. Wu, Manova David and Rajkumar Chinnadurai
Cardiogenetics 2024, 14(1), 26-37; https://doi.org/10.3390/cardiogenetics14010002 - 12 Jan 2024
Abstract
The links between chronic kidney disease (CKD) and cardiac conditions such as coronary heart disease or valvular disease are well established in the literature. However, the relationship between hypertrophic cardiomyopathy (HCM) and CKD is not as frequently described or researched. HCM is the
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The links between chronic kidney disease (CKD) and cardiac conditions such as coronary heart disease or valvular disease are well established in the literature. However, the relationship between hypertrophic cardiomyopathy (HCM) and CKD is not as frequently described or researched. HCM is the most common form of inherited cardiac disease. It is mainly transmitted in an autosomal dominant fashion and caused by mutations in genes encoding sarcomere proteins. HCM is estimated to affect 0.2% of the general population and has an annual mortality rate of between approximately 0.5 and 1%. Our review article aims to summarize the genetics of HCM; discuss the potential clinical mimics that occur concurrently with HCM and CKD, potential interlinks that associate between these two conditions, the role of renal dysfunction as a poor prognostic indicator in HCM; and based on currently available evidence, recommend a management approach that may be suitable when clinicians are faced with this clinical scenario.
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(This article belongs to the Section Cardiovascular Genetics in Clinical Practice)
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Open AccessArticle
Gene-Specific Discriminative Echocardiogram Findings in Hypertrophic Cardiomyopathy Determined Using Artificial Intelligence: A Pilot Study
by
Mila Glavaški, Aleksandra Ilić and Lazar Velicki
Cardiogenetics 2024, 14(1), 1-25; https://doi.org/10.3390/cardiogenetics14010001 - 25 Dec 2023
Abstract
Hypertrophic cardiomyopathy (HCM) is among the most common forms of cardiomyopathies, with a prevalence of 1:200 to 1:500 people. HCM is caused by variants in genes encoding cardiac sarcomeric proteins, of which a majority reside in MYH7, MYBPC3, and TNNT2.
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Hypertrophic cardiomyopathy (HCM) is among the most common forms of cardiomyopathies, with a prevalence of 1:200 to 1:500 people. HCM is caused by variants in genes encoding cardiac sarcomeric proteins, of which a majority reside in MYH7, MYBPC3, and TNNT2. Up to 40% of the HCM cases do not have any known HCM variant. Genotype–phenotype associations in HCM remain incompletely understood. This study involved two visits of 46 adult patients with a confirmed diagnosis of HCM. In total, 174 genes were analyzed on the Next-Generation Sequencing platform, and transthoracic echocardiography was performed. Gene-specific discriminative echocardiogram findings were identified using the computer vision library Fast AI. This was accomplished with the generation of deep learning models for the classification of ultrasonic images based on the underlying genotype and a later analysis of the most decisive image regions. Gene-specific echocardiogram findings were identified: for variants in the MYH7 gene (vs. variant not detected), the most discriminative structures were the septum, left ventricular outflow tract (LVOT) segment, anterior wall, apex, right ventricle, and mitral apparatus; for variants in MYBPC3 gene (vs. variant not detected) these were the septum, left ventricle, and left ventricle/chamber; while for variants in the TNNT2 gene (vs. variant not detected), the most discriminative structures were the septum and right ventricle.
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(This article belongs to the Section Cardiovascular Genetics in Clinical Practice)
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Open AccessEditorial
Inherited Arrhythmogenic Syndromes
by
Georgia Sarquella-Brugada and Oscar Campuzano
Cardiogenetics 2023, 13(4), 173-174; https://doi.org/10.3390/cardiogenetics13040016 - 4 Dec 2023
Abstract
Inherited arrhythmogenic syndromes (IASs) are a heterogeneous group of rare cardiac entities of genetic origin [...]
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(This article belongs to the Special Issue Genetics of Inherited Arrhythmogenic Syndromes Associated with Sudden Death)
Open AccessEditor’s ChoiceReview
From Natural History to Contemporary Management of Aortic Diseases: A State-of-the-Art Review of Thoracic Aortic Aneurysm
by
Yuliya Paulenka, Christopher Lee, Mays Tawayha, Sam Dow, Kajal Shah, Stanislav Henkin and Wassim Mosleh
Cardiogenetics 2023, 13(4), 154-172; https://doi.org/10.3390/cardiogenetics13040015 - 29 Nov 2023
Abstract
Thoracic aortic aneurysms (TAAs) are commonly seen in cardiovascular practice. Acquired and genetic conditions contribute to TAA formation. The natural history of genetically mediated TAA underscores the importance of early detection, regular monitoring, and prompt treatment to prevent complications, including dissection or rupture.
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Thoracic aortic aneurysms (TAAs) are commonly seen in cardiovascular practice. Acquired and genetic conditions contribute to TAA formation. The natural history of genetically mediated TAA underscores the importance of early detection, regular monitoring, and prompt treatment to prevent complications, including dissection or rupture. The prognosis is poor in the event of acute dissection, with high rates of in-hospital mortality. Healthcare providers need to remain vigilant in their efforts to identify and surveil TAA to reduce the risk of complications. In this manuscript, we review the natural history of TAA, discuss the most common causes leading to the development of TAA, assess the value and limitations of diagnostic modalities, and review the management and long-term surveillance of patients with aortic disease.
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(This article belongs to the Special Issue Advanced Research on Inherited Aortic Diseases)
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Open AccessCase Report
Sudden Cardiac Death in Biventricular Arrhythmogenic Cardiomyopathy: A New Undescribed Variant of the MYH6 Gene
by
Pedro Garcia Brás, Isabel Cardoso, José Viegas, Diana Antunes and Sílvia Aguiar Rosa
Cardiogenetics 2023, 13(4), 145-153; https://doi.org/10.3390/cardiogenetics13040014 - 23 Oct 2023
Abstract
Arrhythmogenic cardiomyopathy (ACM) may present with sudden cardiac arrest (SCA), and demonstration of a pathogenic variant in ACM-related genes is crucial for its definitive diagnosis. A 42-year-old female patient with family history of sudden cardiac death (SCD) was referred to the cardiomyopathy clinic
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Arrhythmogenic cardiomyopathy (ACM) may present with sudden cardiac arrest (SCA), and demonstration of a pathogenic variant in ACM-related genes is crucial for its definitive diagnosis. A 42-year-old female patient with family history of sudden cardiac death (SCD) was referred to the cardiomyopathy clinic after two episodes of aborted SCA. In the second episode, the patient was transported under cardiopulmonary resuscitation (downtime of 57 min) until extracorporeal membrane oxygenation was implanted. A thorough diagnostic work-up led to a diagnosis of biventricular ACM. Genetic testing revealed a previously undescribed variant in ACM patients in the MYH6 gene, c.3673G>T p.(Glu 1225*), which inserts a premature stop codon. This was considered a possible pathogenic variant originating a truncated protein, previously undescribed in ACM. The patient’s 23-year-old daughter was positive for the MYH6 variant and had ECG abnormalities suggestive of ACM. This case details the complex differential diagnosis of SCA and explores the current recommendations for the diagnosis of biventricular ACM. The identification of a MYH6 variant in a patient with ACM, recurrent SCA, and family history of SCD appears to support the hypothesis of the pathogenicity of MYH6 variants in ACM, in which the association of phenotype with sarcomere variants is still unclear.
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(This article belongs to the Section Cardiovascular Genetics in Clinical Practice)
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Open AccessCase Report
A Family with a Single LMNA Mutation Illustrates Diversity in Cardiac Phenotypes Associated with Laminopathic Progeroid Syndromes
by
Anna-Gaëlle Giguet-Valard, Astrid Monfort, Hugues Lucron, Helena Mosbah, Franck Boccara, Camille Vatier, Corinne Vigouroux, Pascale Richard, Karim Wahbi, Remi Bellance, Elisabeth Sarrazin and Jocelyn Inamo
Cardiogenetics 2023, 13(4), 135-144; https://doi.org/10.3390/cardiogenetics13040013 - 26 Sep 2023
Abstract
The likely pathogenic variant c.407A>T p.Asp136Val of the LMNA gene has been recently described in a young woman presenting with atypical progeroid syndrome, associated with severe aortic valve stenosis. We further describe the cardiovascular involvement associated with the syndrome in her family. We
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The likely pathogenic variant c.407A>T p.Asp136Val of the LMNA gene has been recently described in a young woman presenting with atypical progeroid syndrome, associated with severe aortic valve stenosis. We further describe the cardiovascular involvement associated with the syndrome in her family. We identified seven members with a general presentation suggestive of progeroid syndrome. All of them presented heart conduction abnormalities: degenerative cardiac diseases such as coronary artery disease (two subjects) and aortic stenosis (three subjects) occurred in the 3rd–5th decade, and a young patient developed a severe dilated cardiomyopathy, leading to death at 15 years of age. The likely pathogenic variant was found in all the patients who consented to carry out the genetic test. This diverse family cardiologic phenotype emphasizes the complex molecular background at play in lamin-involved cardiac diseases, and the need for early and thorough cardiac evaluations in patients with laminopathic progeroid syndromes.
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(This article belongs to the Section Rare Disease-Genetic Syndromes)
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Open AccessEditor’s ChoiceArticle
Functional Characterization of the A414G Loss-of-Function Mutation in HCN4 Associated with Sinus Bradycardia
by
Arie O. Verkerk and Ronald Wilders
Cardiogenetics 2023, 13(3), 117-134; https://doi.org/10.3390/cardiogenetics13030012 - 4 Aug 2023
Cited by 1
Abstract
Patients carrying the heterozygous A414G mutation in the HCN4 gene, which encodes the HCN4 protein, demonstrate moderate to severe bradycardia of the heart. Tetramers of HCN4 subunits compose the ion channels in the sinus node that carry the hyperpolarization-activated ‘funny’ current (If
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Patients carrying the heterozygous A414G mutation in the HCN4 gene, which encodes the HCN4 protein, demonstrate moderate to severe bradycardia of the heart. Tetramers of HCN4 subunits compose the ion channels in the sinus node that carry the hyperpolarization-activated ‘funny’ current (If), also named the ‘pacemaker current’. If plays an essential modulating role in sinus node pacemaker activity. To assess the mechanism by which the A414G mutation results in sinus bradycardia, we first performed voltage clamp measurements on wild-type (WT) and heterozygous mutant HCN4 channels expressed in Chinese hamster ovary (CHO) cells. These experiments were performed at physiological temperature using the amphotericin-perforated patch-clamp technique. Next, we applied the experimentally observed mutation-induced changes in the HCN4 current of the CHO cells to If of the single human sinus node cell model developed by Fabbri and coworkers. The half-maximal activation voltage V1/2 of the heterozygous mutant HCN4 current was 19.9 mV more negative than that of the WT HCN4 current (p < 0.001). In addition, the voltage dependence of the heterozygous mutant HCN4 current (de)activation time constant showed a −11.9 mV shift (p < 0.001) compared to the WT HCN4 current. The fully-activated current density, the slope factor of the activation curve, and the reversal potential were not significantly affected by the heterozygous A414G mutation. In the human sinus node computer model, the cycle length was substantially increased, almost entirely due to the shift in the voltage dependence of steady-state activation, and this increase was more prominent under vagal tone. The introduction of a passive atrial load into the model sinus node cell further reduced the beating rate, demonstrating that the bradycardia of the sinus node was even more pronounced by interactions between the sinus node and atria. In conclusion, the experimentally identified A414G-induced changes in If can explain the clinically observed sinus bradycardia in patients carrying the A414G HCN4 gene mutation.
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(This article belongs to the Section Molecular Genetics)
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