Cardiogenetics

11 pages, 1039 KiB

Open AccessEditor’s ChoiceArticle

MYH7 Genotype–Phenotype Correlation in a Cohort of Finnish Patients

by Teemu Vepsäläinen, Tiina Heliö, Catalina Vasilescu, Laura Martelius, Sini Weckström, Juha Koskenvuo, Anita Hiippala and Tiina Ojala

Cardiogenetics 2022, 12(1), 122-132; https://doi.org/10.3390/cardiogenetics12010013 - 16 Mar 2022

Cited by 4 | Viewed by 5812

Abstract

Cardiomyopathies (CMPs) are a heterogeneous group of diseases, frequently genetic, affecting the heart muscle. The symptoms range from asymptomatic to dyspnea, arrhythmias, syncope, and sudden cardiac death. This study is focused on MYH7 (beta-myosin heavy chain), as this gene is commonly mutated in [...] Read more.

Cardiomyopathies (CMPs) are a heterogeneous group of diseases, frequently genetic, affecting the heart muscle. The symptoms range from asymptomatic to dyspnea, arrhythmias, syncope, and sudden cardiac death. This study is focused on MYH7 (beta-myosin heavy chain), as this gene is commonly mutated in cardiomyopathy patients. Due to the high combined prevalence of MYH7 variants and severe health outcomes, it is one of the most frequently tested genes in clinical settings. We analyzed the clinical presentation and natural history of 48 patients with MYH7-related cardiomyopathy belonging to a cohort from a tertiary center at Helsinki University Hospital, Finland. We made special reference to three age subgroups (0–1, 1–12, and >12 years). Our results characterize a clinically significant MYH7 cohort, emphasizing the high variability of the CMP phenotype depending on age. We observed a subgroup of infants (0–1 years) with MYH7 associated severe DCM phenotype. We further demonstrate that patients under the age of 12 years have a similar symptom burden compared to older patients. Full article

(This article belongs to the Special Issue Genetic Diagnostics in Inherited Cardiomyopathies)

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10 pages, 1157 KiB

Open AccessReview

Clinical and Molecular Characteristics of Patients with PLN R14del Cardiomyopathy: State-of-the-Art Review

by Emanuele Monda, Ettore Blasi, Antonio De Pasquale, Alessandro Di Vilio, Federica Amodio, Martina Caiazza, Gaetano Diana, Michele Lioncino, Alessia Perna, Federica Verrillo, Maria Luigia Martucci, Orlando Munciguerra, Andrea Vergara and Giuseppe Limongelli

Cardiogenetics 2022, 12(1), 112-121; https://doi.org/10.3390/cardiogenetics12010012 - 2 Mar 2022

Viewed by 5398

Abstract

The deletion of the arginine 14 codon (R14del) in the phospholamban (PLN) gene is a rare cause of arrhythmogenic cardiomyopathy (ACM) and is associated with prevalent ventricular arrhythmias, heart failure, and sudden cardiac death. The pathophysiological mechanism which culminates in the [...] Read more.

The deletion of the arginine 14 codon (R14del) in the phospholamban (PLN) gene is a rare cause of arrhythmogenic cardiomyopathy (ACM) and is associated with prevalent ventricular arrhythmias, heart failure, and sudden cardiac death. The pathophysiological mechanism which culminates in the ACM phenotype is multifactorial and mainly based on the alteration of the endoplasmic reticulum proteostasis, mitochondrial dysfunction and compromised Ca²⁺ cytosolic homeostasis. The symptoms of this condition are usually non-specific and consist of arrhythmia-related or heart failure-related manifestation; however, some peculiar diagnostic clues were detected, such as the T-wave inversion in the lateral leads, low QRS complexes voltages, mid-wall or epicardial fibrosis of the inferolateral wall of the left ventricle, and their presence should raise the suspicion of this condition. The risk stratification for sudden cardiac death is mandatory and several predictors were identified in recent years. However, the management of affected patients is often challenging due to the absence of specific prediction tools and therapies. This review aims to provide the current state of the art of PLN R14del cardiomyopathy, focusing on its pathophysiology, clinical manifestation, risk stratification for sudden cardiac death, and management. Full article

(This article belongs to the Section Molecular Genetics)

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3 pages, 148 KiB

Open AccessEditorial

Publisher’s Note: We Changed Page Numbers to Article Numbers for Articles Published in Cardiogenetics Volume 1–Volume 10, Issue 1

by Cardiogenetics Editorial Office

Cardiogenetics 2022, 12(1), 109-111; https://doi.org/10.3390/cardiogenetics12010011 - 25 Feb 2022

Viewed by 2297

Abstract

Previously, Cardiogenetics [1] was published by PAGEPress from Volume 1 (2011) to Volume 10, Issue 1 (2020) [...] Full article

7 pages, 3114 KiB

Open AccessCase Report

Diagnosis of Fabry Disease in a Patient with a Surgically Repaired Congenital Heart Defect: When Clinical History and Genetics Make the Difference

by Marta Rubino, Emanuele Monda, Martina Caiazza, Giuseppe Palmiero, Michele Lioncino, Annapaola Cirillo, Adelaide Fusco, Federica Verrillo, Alessia Perna, Gaetano Diana, Federica Amodio, Arturo Cesaro, Giovanni Duro, Berardo Sarubbi, Maria Giovanna Russo, Paolo Calabrò and Giuseppe Limongelli

Cardiogenetics 2022, 12(1), 102-108; https://doi.org/10.3390/cardiogenetics12010010 - 25 Feb 2022

Cited by 1 | Viewed by 3308

Abstract

Fabry disease (FD) is a multiorgan disease, which can potentially affect any organ or tissue, with the heart, kidneys, and central nervous system representing the major disease targets. FD can be suspected based on the presence of specific red flags, and the subsequent [...] Read more.

Fabry disease (FD) is a multiorgan disease, which can potentially affect any organ or tissue, with the heart, kidneys, and central nervous system representing the major disease targets. FD can be suspected based on the presence of specific red flags, and the subsequent evaluation of the α-Gal A activity and GLA sequencing, are required to confirm the diagnosis, to evaluate the presence of amenable GLA mutation, and to perform a cascade program screening in family members. An early diagnosis is required to start an etiological treatment and to prevent irreversible organ damage. Here, we describe a case of a 37-years-old patient, with a surgically repaired congenital heart defect in his childhood, who had a late diagnosis of FD based on the clinical history and targeted genetic evaluation. This case highlights the importance to perform a correct phenotyping and definite diagnosis of FD, to start an early and appropriate treatment in the index patient, and a cascade clinical and genetic screening to identify other family members at risk, which may benefit from specific treatment and/or a close follow-up. Full article

(This article belongs to the Section Rare Disease-Genetic Syndromes)

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12 pages, 1034 KiB

Open AccessArticle

Genetic Diagnostics Contribute to the Risk Stratification for Major Arrhythmic Events in Pediatric Patients with Long QT Syndrome Type 1–3

by Tobias Burkard, Dominik Sebastian Westphal, Franziska Markel, Roman Antonin Gebauer, Gabriele Hessling and Cordula Maria Wolf

Cardiogenetics 2022, 12(1), 90-101; https://doi.org/10.3390/cardiogenetics12010009 - 21 Feb 2022

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Abstract

Long QT syndrome (LQTS) is an inherited arrhythmic disorder associated with sudden cardiac death (SCD). This study aimed to identify the clinical and molecular genetic risk factors that contribute to major arrhythmic events (MAEs) in patients with genetically confirmed childhood onset LQTS 1–3. [...] Read more.

Long QT syndrome (LQTS) is an inherited arrhythmic disorder associated with sudden cardiac death (SCD). This study aimed to identify the clinical and molecular genetic risk factors that contribute to major arrhythmic events (MAEs) in patients with genetically confirmed childhood onset LQTS 1–3. This study was a retrospective double-center study. An MAE was defined as the occurrence of SCD, aborted SCD, appropriate implantable cardioverter defibrillator discharge, or sustained ventricular tachycardia. During a median follow-up of 4.6 years (range 0.1–24.3 years), MAEs occurred in 18 (17.8%) of 101 patients diagnosed with LQTS at a median of 7.7 years (range 0.0–18.0 years) despite the use of beta-blockers in 91.6% of patients at the last follow-up. A multivariate analysis identified a genetic diagnosis of LQTS2 and LQTS3 and variants within the KCNH2 S5-loop-S6 pore region as independent risk factors for MAEs, independent of the QTc value or a history of syncope detected from a univariate analysis. MAEs occur frequently in childhood onset LQTS despite beta-blocker treatment. A detailed molecular genetic diagnosis can contribute to the arrhythmia risk stratification and optimize the use of preventive measures in this vulnerable patient population. Full article

(This article belongs to the Special Issue Cardiogenetics: Feature Papers 2021)

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1 pages, 148 KiB

Open AccessEditorial

Acknowledgment to Reviewers of Cardiogenetics in 2021

by Cardiogenetics Editorial Office

Cardiogenetics 2022, 12(1), 89; https://doi.org/10.3390/cardiogenetics12010008 - 17 Feb 2022

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Abstract

Rigorous peer-reviews are the basis of high-quality academic publishing [...] Full article

9 pages, 906 KiB

Open AccessCase Report

Pharmacogenomics of Pediatric Cardiac Arrest: Cisplatin Treatment Worsened by a Ryanodine Receptor 2 Gene Mutation

by Angela Maggio, Sandra Mastroianno, Giuseppe Di Stolfo, Stefano Castellana, Pietro Palumbo, Maria Pia Leone, Anita Spirito, Domenico Rosario Potenza, Saverio Ladogana, Marco Castori, Massimo Carella, Massimo Villella and Mauro Pellegrino Salvatori

Cardiogenetics 2022, 12(1), 80-88; https://doi.org/10.3390/cardiogenetics12010007 - 7 Feb 2022

Cited by 1 | Viewed by 3099

Abstract

In thelast few decades, the roles of cardio-oncology and cardiovascular geneticsgained more and more attention in research and daily clinical practice, shaping a new clinical approach and management of patients affected by cancer and cardiovascular disease. Genetic characterization of patients undergoing cancer treatment [...] Read more.

In thelast few decades, the roles of cardio-oncology and cardiovascular geneticsgained more and more attention in research and daily clinical practice, shaping a new clinical approach and management of patients affected by cancer and cardiovascular disease. Genetic characterization of patients undergoing cancer treatment can support a better cardiovascular risk stratification beyond the typical risk factors, suchas contractile function and QT interval duration, uncovering a possible patient’s concealed predisposition to heart failure, life threatening arrhythmias and sudden death. Specifically, an integrated cardiogenetic approach in daily oncological clinical practice can ensure the best patient-centered healthcare model, suggesting, also the adequate cardiac monitoring timing and alternative cancer treatments, reducing drug-related complications. We report the case of a 14-month-old girl affected by neuroblastoma, treated by cisplatin, complicated by cardiac arrest. We described the genetic characterization of a Ryanodine receptor 2 (RYR2) gene mutation and subsequent pharmacogenomic approach to better shape the cancer treatment. Full article

(This article belongs to the Special Issue Cardiogenetics: Feature Papers 2021)

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17 pages, 767 KiB

Open AccessEditor’s ChoiceReview

Genetics of Heritable Thoracic Aortic Disease

by Efstathios Papatheodorou, Dimitrios Degiannis and Aris Anastasakis

Cardiogenetics 2022, 12(1), 63-79; https://doi.org/10.3390/cardiogenetics12010006 - 4 Feb 2022

Cited by 6 | Viewed by 5984

Abstract

Genetic testing plays an increasing diagnostic and prognostic role in the management of patients with heritable thoracic aortic disease (HTAD). The identification of a specific variant can establish or confirm the diagnosis of syndromic HTAD, dictate extensive evaluation of the arterial tree in [...] Read more.

Genetic testing plays an increasing diagnostic and prognostic role in the management of patients with heritable thoracic aortic disease (HTAD). The identification of a specific variant can establish or confirm the diagnosis of syndromic HTAD, dictate extensive evaluation of the arterial tree in HTAD with known distal vasculature involvement and justify closer follow-up and earlier surgical intervention in HTAD with high risk of dissection of minimal or normal aortic size. Evolving phenotype–genotype correlations lead us towards more precise and individualized management and treatment of patients with HTAD. In this review, we present the latest evidence regarding the role of genetics in patients with HTAD. Full article

(This article belongs to the Special Issue Cardiogenetics: Feature Papers 2021)

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14 pages, 6228 KiB

Open AccessEditor’s ChoiceReview

The Roles of Platelet-Activating Factor and Magnesium in Pathophysiology of Hypertension, Atherogenesis, Cardiovascular Disease, Stroke and Aging

by Nilank Shah, Roshni Sethi, Sachin Shah, Komail Jafri, Jonah Duran, Yong Chang, Chirag Soni and Hanna Wollocko

Cardiogenetics 2022, 12(1), 49-62; https://doi.org/10.3390/cardiogenetics12010005 - 2 Feb 2022

Cited by 5 | Viewed by 4755

Abstract

Hypertension and atherosclerosis are debilitating diseases that affect millions each year. Long-term consequences include but are not limited to stroke, myocardial infarction, and kidney failure. Platelet-activating factor (PAF) is a proinflammatory mediator synthesized from a subclass of phosphatidylcholines that increases platelet activation, leukocyte [...] Read more.

Hypertension and atherosclerosis are debilitating diseases that affect millions each year. Long-term consequences include but are not limited to stroke, myocardial infarction, and kidney failure. Platelet-activating factor (PAF) is a proinflammatory mediator synthesized from a subclass of phosphatidylcholines that increases platelet activation, leukocyte adhesion, infiltration of macrophages, and intracellular lipid accumulation, thereby contributing to atherosclerosis. Magnesium, a key micronutrient and free radical scavenger, is a water-soluble mineral that regulates peripheral vasodilation and calcium, phosphate, and hydroxyapatite homeostasis. Magnesium’s antihypertensive ability stems from its role as a natural calcium antagonist and promoter of vasodilatory mediators, such as nitric oxide. Platelet-activating factor and magnesium share an inverse relationship, and elevated magnesium levels have been shown to have protective effects against plaque formation as well as antihypertensive and antiarrhythmic effects, all of which allow for healthier aging. The purpose of this literature review is to investigate the role of platelet-activating factor and magnesium in the pathophysiology of hypertension, atherosclerosis, cardiovascular disease, stroke, and aging. Since the pathophysiology of the platelet-activating factor biomolecule is underexplored, further research studies are warranted in order to navigate the putative signaling pathways involved in the cardioprotective effects of dietary magnesium as a natural anti-PAF agent. Full article

(This article belongs to the Special Issue Cardiogenetics: Feature Papers 2021)

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12 pages, 275 KiB

Open AccessReview

An Overview of Therapy Guidelines for Cardiac Arrest and the Potential Benefits of Hemoglobin-Based Oxygen Carriers

by Brian M. Wollocko, Bardia Papian-Gorji, Winston Yen, Urooj Zahid, Nilank Shah, Kenneth Steier and Hanna Wollocko

Cardiogenetics 2022, 12(1), 37-48; https://doi.org/10.3390/cardiogenetics12010004 - 20 Jan 2022

Viewed by 3508

Abstract

Currently, there is an unmet therapeutic need for the medical management of cardiac arrest, as is evident from the high mortality rate associated with this condition. These dire outcomes can be attributed to the severe nature and poor prognosis of this disorder. However, [...] Read more.

Currently, there is an unmet therapeutic need for the medical management of cardiac arrest, as is evident from the high mortality rate associated with this condition. These dire outcomes can be attributed to the severe nature and poor prognosis of this disorder. However, the current treatment modalities, while helping to augment survival, are limited and do not offer adequate improvements to outcomes. Treatment modalities are particularly lacking when considering the underlying pathophysiology of the metabolic phase of cardiac arrest. In this study, we explore the three phases of cardiac arrest and assess the factors related to positive clinical outcomes and survival for these events. Furthermore, we evaluate the present guidelines for resuscitation and recovery, the issues related to ischemia and tissue reperfusion, and the benefit of oxygen-delivery therapeutic methods including blood transfusion therapy and synthetic hemoglobins (HBOCs). The current therapy protocols are limited specifically by the lack of an efficient method of oxygen delivery to address the metabolic phase of cardiac arrest. In this article, we investigate the next generation of HBOCs and review their properties that make them attractive for their potential application in the treatment of cardiac arrest. These products may be a viable solution to address complications associated with ischemia, reperfusion injury, and organ damage. Full article

(This article belongs to the Special Issue Cardiogenetics: Feature Papers 2021)

13 pages, 2595 KiB

Open AccessEditor’s ChoiceArticle

Cardiovascular Characteristics of Patients with Genetic Variation in Desmoplakin (DSP)

by Nosheen Reza, Alejandro de Feria, Jessica L. Chowns, Lily Hoffman-Andrews, Laura Vann, Jessica Kim, Amy Marzolf and Anjali Tiku Owens

Cardiogenetics 2022, 12(1), 24-36; https://doi.org/10.3390/cardiogenetics12010003 - 6 Jan 2022

Cited by 8 | Viewed by 5164

Abstract

Background: Variants in the desmoplakin (DSP) gene have been recognized in association with the pathogenesis of arrhythmogenic right ventricular cardiomyopathy (ARVC) for nearly 20 years. More recently, genetic variation in DSP has also been associated with left-dominant arrhythmogenic cardiomyopathy. Data regarding [...] Read more.

Background: Variants in the desmoplakin (DSP) gene have been recognized in association with the pathogenesis of arrhythmogenic right ventricular cardiomyopathy (ARVC) for nearly 20 years. More recently, genetic variation in DSP has also been associated with left-dominant arrhythmogenic cardiomyopathy. Data regarding the cardiac phenotypes associated with genetic variation in DSP have been largely accumulated from phenotype-first studies of ARVC. Methods: We aimed to evaluate the clinical manifestations of cardiac disease associated with variants in DSP through a genotype-first approach employed in the University of Pennsylvania Center for Inherited Cardiovascular Disease registry. We performed a retrospective study of 19 individuals with “pathogenic” or “likely pathogenic” variants in DSP identified by clinical genetic testing. Demographics and clinical characteristics were collected. Results: Among individuals with disease-causing variants in DSP, nearly 40% had left ventricular enlargement at initial assessment. Malignant arrhythmias were prevalent in this cohort (42%) with a high proportion of individuals undergoing primary and secondary prevention implantable cardioverter defibrillator implantation (68%) and ablation of ventricular arrhythmias (16%). Probands also experienced end-stage heart failure requiring heart transplantation (11%). Conclusions: Our data suggest DSP cardiomyopathy may manifest with a high burden of heart failure and arrhythmic events, highlighting its importance in the pathogenesis of dilated and arrhythmogenic cardiomyopathies. Targeted strategies for diagnosis and risk stratification for DSP cardiomyopathy should be investigated. Full article

(This article belongs to the Special Issue Genetic Diagnostics in Inherited Cardiomyopathies)

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12 pages, 461 KiB

Open AccessReview

Nanoparticle-Based Modification of the DNA Methylome: A Therapeutic Tool for Atherosclerosis?

by Ana Cristina Márquez-Sánchez, Lino Sánchez-Segura, Gertrud Lund and Silvio Zaina

Cardiogenetics 2022, 12(1), 12-23; https://doi.org/10.3390/cardiogenetics12010002 - 6 Jan 2022

Viewed by 3216

Abstract

Cardiovascular epigenomics is a relatively young field of research, yet it is providing novel insights into gene regulation in the atherosclerotic arterial wall. That information is already pointing to new avenues for atherosclerosis (AS) prevention and therapy. In parallel, advances in nanoparticle (NP) [...] Read more.

Cardiovascular epigenomics is a relatively young field of research, yet it is providing novel insights into gene regulation in the atherosclerotic arterial wall. That information is already pointing to new avenues for atherosclerosis (AS) prevention and therapy. In parallel, advances in nanoparticle (NP) technology allow effective targeting of drugs and bioactive molecules to the vascular wall. The partnership of NP technology and epigenetics in AS is just beginning and promises to produce novel exciting candidate treatments. Here, we briefly discuss the most relevant recent advances in the two fields. We focus on AS and DNA methylation, as the DNA methylome of that condition is better understood in comparison with the rest of the cardiovascular disease field. In particular, we review the most recent advances in NP-based delivery systems and their use for DNA methylome modification in inflammation. We also address the promises of DNA methyltransferase inhibitors for prevention and therapy. Furthermore, we emphasize the unique challenges in designing therapies that target the cardiovascular epigenome. Lastly, we touch the issue of human exposure to industrial NPs and its impact on the epigenome as a reminder of the undesired effects that any NP-based therapy must avoid to be apt for secondary prevention of AS. Full article

(This article belongs to the Special Issue Cardiogenetics: Feature Papers 2021)

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11 pages, 868 KiB

Open AccessEditor’s ChoiceArticle

Transthyretin Gene Variants and Associated Phenotypes in Danish Patients with Amyloid Cardiomyopathy

by Torsten B. Rasmussen, Bertil T. Ladefoged, Anne M. Dybro, Tor S. Clemmensen, Rikke H. Sørensen, Astrid J. Terkelsen, Henning Mølgaard, Henrik Vase and Steen H. Poulsen

Cardiogenetics 2022, 12(1), 1-11; https://doi.org/10.3390/cardiogenetics12010001 - 4 Jan 2022

Cited by 1 | Viewed by 3432

Abstract

Genotyping divides transthyretin cardiac amyloidosis (ATTR-CA) in hereditary (ATTRv) and wild type (ATTRwt) forms. This study investigated the prevalence and clinical presentation of ATTRv in a contemporary cohort of consecutive ATTR-CA patients diagnosed at a tertiary Danish amyloidosis center. Age at diagnosis, clinical- [...] Read more.

Genotyping divides transthyretin cardiac amyloidosis (ATTR-CA) in hereditary (ATTRv) and wild type (ATTRwt) forms. This study investigated the prevalence and clinical presentation of ATTRv in a contemporary cohort of consecutive ATTR-CA patients diagnosed at a tertiary Danish amyloidosis center. Age at diagnosis, clinical- and echocardiographic data, and transthyretin (TTR) genotype were recorded. Relatives of ATTRv patients underwent clinical phenotyping and predictive gene testing. Genetic testing in 102 patients identified four TTR variant carriers: p.Pro63Ser, p.Ala65Ser (n = 2) and p.Val142Ile. The mean age of ATTRv index patients was significantly lower compared to ATTRwt patients: 70.2 ± 1.2 versus 80.0 ± 6.2, p-value: 0.005. Evaluation of ATTRv families identified seven TTR variant carriers with a median age of 65 years (range 48–76) and three were diagnosed with ATTR-CA by DPD-scintigraphy. Family members with ATTR-CA were all asymptomatic and had normal levels of cardiac biomarkers. In conclusion, the prevalence of ATTRv in a contemporary Danish ATTR-CA cohort is 4%. ATTRv index patients were significantly younger age at diagnosis than ATTRwt patients. Non-p.Leu131Met TTR variants have reduced penetrance at the age of 65 years in which approximately half of variant carriers have asymptomatic ATTR-CA with normal LV systolic function and cardiac biomarker analyses. Full article

(This article belongs to the Special Issue Cardiogenetics: Feature Papers 2021)

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Cardiogenetics, Volume 12, Issue 1 (March 2022) – 13 articles

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