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New Frontiers in Arrhythmogenic Cardiomyopathies

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiology".

Deadline for manuscript submissions: closed (10 April 2022) | Viewed by 14089

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Special Issue Editor

Prof. Dr. Firat Duru

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Guest Editor

Department of Cardiology, University Heart Center Zurich, Zurich, Switzerland
Interests: ARVC; arrhythmogenic cardiomyopathies; atrial fibrillation; cardiac electrophysiology; catheter ablation

Special Issue Information

Dear Colleagues,

Arrhythmogenic cardiomyopathies (ACMs) are a group of cardiac diseases that are characterized by fibrofatty infiltration of the myocardium and increased risk of ventricular tachyarrhythmias. The disease is usually hereditary and often challenges clinicians since sudden cardiac death may be an early manifestation. In recent years, we have witnessed a constant increase in the number of preclinical and clinical research papers addressing various aspects of ACMs. In arrhythmogenic right ventricular cardiomyopathy (ARVC), which is the most typical and best described form of ACM, mutations in genes coding for desmosomal proteins account for most familial cases. The disease is usually progressive, causing left ventricular (LV) involvement and heart failure in later stages. However, there is now growing evidence demonstrating LV involvement even in earlier stages of ACM. Predominantly LV disease associated with early occurrence of ventricular arrhythmias has also been increasingly recognized. The nomenclature and classification of ACMs have been a matter of constant debate for experts in this field. Despite numerous publications in the medical literature in recent years, ACM still continues to be a challenging clinical entity. The aim of this Special Issue is to highlight recent advances in ACMs in the context of diagnosis, risk prediction, and therapy.

Prof. Dr. Firat Duru
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

Arrhythmogenic cardiomyopathy
ACM
Genetic testing
Desmosome
Diagnostic criteria
Risk stratification
Outcome

Published Papers (4 papers)

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Research

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16 pages, 3332 KiB

Open AccessArticle

Radial and Circumferential CMR-Based RV Strain Predicts Low R Wave Amplitude after ICD Implantation in Patients with Arrhythmogenic Cardiomyopathy

by Zhongli Chen, Yanyan Song, Liang Chen, Xuan Ma, Yan Dai, Shihua Zhao, Keping Chen and Shu Zhang

J. Clin. Med. 2023, 12(3), 886; https://doi.org/10.3390/jcm12030886 - 22 Jan 2023

Viewed by 1092

Abstract

Inadequate R wave amplitude (RWA) after implantable cardiac defibrillator (ICD) implantation in patients with arrhythmogenic cardiomyopathy (ACM) was suspected to relate to right ventricle impairment. However, little data-based evidence was provided to quantify the association. We retrospectively enrolled ACM patients receiving CMR examinations before transvenous ICD implantation from Fuwai Hospital. The RWA was obtained within 24 h and at 2–6-month follow-up after the operation. Structural, functional, as well as tissue characterization of the left ventricle (LV) and right ventricle (RV), were analyzed in relation to RWA. Among the 87 ACM patients (median RWA: 8.0 mV), 19 (21.8%) patients were found with low initial RWA (<5 mV) despite attempts in multiple positions. RV end diastolic diameter (RVEDD), (r = −0.44), RV ejection fraction (RVEF, r = 0.43), RV end diastolic volume index (RVEDVi, r = −0.49), RV end systolic volume index (RVESVi, r = −0.53), RV global circumferential (RVGCS, r = −0.64), and radial strain (RVGRS, r = 0.61, all p < 0.001) rather than LV metrics correlated strongly with initial RWA. RVGCS, RVESVi, and RVGRS were decent predictors of low RWA (areas under the curve AUC: 0.814, 0.769, 0.757, respectively) early after implantation and during 2–6-month follow-up. To summarize, low RWA of ICD lead in ACM patients was associated with RV abnormalities. The RVGCS, RVGRS, and RVESVi can be valuable predictors for identifying low RWA prior to ICD implantation. Full article

(This article belongs to the Special Issue New Frontiers in Arrhythmogenic Cardiomyopathies)

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15 pages, 1645 KiB

Open AccessArticle

A Novel Diagnostic Score Integrating Atrial Dimensions to Differentiate between the Athlete’s Heart and Arrhythmogenic Right Ventricular Cardiomyopathy

by Valentina A. Rossi, David Niederseer, Justyna M. Sokolska, Boldizsar Kovacs, Sarah Costa, Alessio Gasperetti, Corinna Brunckhorst, Deniz Akdis, Felix C. Tanner, Firat Duru, Christian M. Schmied and Ardan M. Saguner

J. Clin. Med. 2021, 10(18), 4094; https://doi.org/10.3390/jcm10184094 - 10 Sep 2021

Cited by 9 | Viewed by 3140

Abstract

Objective: The 2010 Task Force Criteria (TFC) have not been tested to differentiate ARVC from the athlete’s heart. Moreover, some criteria are not available (myocardial biopsy, genetic testing, morphology of ventricular tachycardia) or subject to interobserver variability (right ventricular regional wall motion abnormalities) in clinical practice. We hypothesized that atrial dimensions are useful and robust to differentiate between both entities and proposed a new diagnostic score based upon readily available parameters including echocardiographic atrial dimensions. Methods: In this observational study, 21 patients with definite ARVC were matched for age, gender and body mass index to 42 athletes. Based on ROC analysis, the following parameters were included in the score: indexed right/left atrial volumes ratio (RAVI/LAVI ratio), NT-proBNP, RVOT measurements (PLAX and PSAX BSA-corrected), tricuspid annular motion (TAM), precordial TWI and depolarization abnormalities according to TFC. Results: ARVC patients had a higher RAVI/LAVI ratio (1.76 ± 1.5 vs. 0.87 ± 0.2, p < 0.001), lower right ventricular function (fac: 29 ± 10.1 vs. 42.2 ± 5%, p < 0.001; TAM: 19.8 ± 5.4 vs. 23.8 ± 3.8 mm, p = 0.001) and higher serum NT-proBNP levels (345 ± 612 vs. 48 ± 57 ng/L, p < 0.001). Our score showed a good performance, which is comparable to the 2010 TFC using those parameters, which are available in routine clinical practice (AUC93%, p < 0.001 (95%CI 0.874–0.995) vs. AUC97%, p < 0.001 (95%CI 0.93–1.00). A score of 6/12 points yielded a specificity of 91% and an improved sensitivity of 67% for ARVC diagnosis as compared to a sensitivity of 41% for the abovementioned readily available 2010 TFC. Conclusions: ARVC patients present with significantly larger RA compared to athletes, resulting in a greater RAVI/LAVI ratio. Our novel diagnostic score includes readily available clinical parameters and has a high diagnostic accuracy to differentiate between ARVC and the athlete’s heart. Full article

(This article belongs to the Special Issue New Frontiers in Arrhythmogenic Cardiomyopathies)

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21 pages, 9640 KiB

Open AccessArticle

Altered Electrical, Biomolecular, and Immunologic Phenotypes in a Novel Patient-Derived Stem Cell Model of Desmoglein-2 Mutant ARVC

by Robert N. Hawthorne, Adriana Blazeski, Justin Lowenthal, Suraj Kannan, Roald Teuben, Deborah DiSilvestre, Justin Morrissette-McAlmon, Jeffrey E. Saffitz, Kenneth R. Boheler, Cynthia A. James, Stephen P. Chelko, Gordon Tomaselli and Leslie Tung

J. Clin. Med. 2021, 10(14), 3061; https://doi.org/10.3390/jcm10143061 - 10 Jul 2021

Cited by 20 | Viewed by 3917

Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive heart condition which causes fibro-fatty myocardial scarring, ventricular arrhythmias, and sudden cardiac death. Most cases of ARVC can be linked to pathogenic mutations in the cardiac desmosome, but the pathophysiology is not well understood, particularly in early phases when arrhythmias can develop prior to structural changes. Here, we created a novel human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) model of ARVC from a patient with a c.2358delA variant in desmoglein-2 (DSG2). These DSG2-mutant (DSG2^Mut) hiPSC-CMs were compared against two wildtype hiPSC-CM lines via immunostaining, RT-qPCR, Western blot, RNA-Seq, cytokine expression and optical mapping. Mutant cells expressed reduced DSG2 mRNA and had altered localization of desmoglein-2 protein alongside thinner, more disorganized myofibrils. No major changes in other desmosomal proteins were noted. There was increased pro-inflammatory cytokine expression that may be linked to canonical and non-canonical NFκB signaling. Action potentials in DSG2^Mut CMs were shorter with increased upstroke heterogeneity, while time-to-peak calcium and calcium decay rate were reduced. These were accompanied by changes in ion channel and calcium handling gene expression. Lastly, suppressing DSG2 in control lines via siRNA allowed partial recapitulation of electrical anomalies noted in DSG2^Mut cells. In conclusion, the aberrant cytoskeletal organization, cytokine expression, and electrophysiology found DSG2^Mut hiPSC-CMs could underlie early mechanisms of disease manifestation in ARVC patients. Full article

(This article belongs to the Special Issue New Frontiers in Arrhythmogenic Cardiomyopathies)

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Review

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12 pages, 4532 KiB

Open AccessReview

The 2020 “Padua Criteria” for Diagnosis and Phenotype Characterization of Arrhythmogenic Cardiomyopathy in Clinical Practice

by Francesca Graziano, Alessandro Zorzi, Alberto Cipriani, Manuel De Lazzari, Barbara Bauce, Ilaria Rigato, Giulia Brunetti, Kalliopi Pilichou, Cristina Basso, Martina Perazzolo Marra and Domenico Corrado

J. Clin. Med. 2022, 11(1), 279; https://doi.org/10.3390/jcm11010279 - 5 Jan 2022

Cited by 11 | Viewed by 4399

Abstract

Arrhythmogenic Cardiomyopathy (ACM) is a heredo-familial cardiac disease characterized by fibro-fatty myocardial replacement and increased risk of sudden cardiac death. The diagnosis of ACM can be challenging due to the lack of a single gold-standard test: for this reason, it is required to satisfy a combination of multiple criteria from different categories including ventricular morpho-functional abnormalities, repolarization and depolarization ECG changes, ventricular arrhythmias, tissue characterization findings and positive family history/molecular genetics. The first diagnostic criteria were published by an International Task Force (ITF) of experts in 1994 and revised in 2010 with the aim to increase sensitivity for early diagnosis. Limitations of the 2010 ITF criteria include the absence of specific criteria for left ventricle (LV) involvement and the limited role of cardiac magnetic resonance (CMR) as the use of the late gadolinium enhancement technique for tissue characterization was not considered. In 2020, new diagnostic criteria (“the Padua criteria”) were proposed. The traditional organization in six categories of major/minor criteria was maintained. The criteria for identifying the right ventricular involvement were modified and a specific set of criteria for identifying LV involvement was created. Depending on the combination of criteria for right and LV involvement, a diagnosis of classic (right dominant) ACM, biventricular ACM or left-dominant ACM is then made. The article reviews the rationale of the Padua criteria, summarizes the main modifications compared to the previous 2010 ITF criteria and provides three examples of the application of the Padua criteria in clinical practice. Full article

(This article belongs to the Special Issue New Frontiers in Arrhythmogenic Cardiomyopathies)

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