Critical role of cardiac magnetic resonance in the diagnosis of left-dominant arrhythmogenic cardiomyopathy: A paradigmatic case in a recreational middle-aged athlete.
Ontology highlight
ABSTRACT:
SUBMITTER: de la Guia-Galipienso F
PROVIDER: S-EPMC8283542 | biostudies-literature | 2021 Jul
REPOSITORIES: biostudies-literature
Publications
Critical role of cardiac magnetic resonance in the diagnosis of left-dominant arrhythmogenic cardiomyopathy: A paradigmatic case in a recreational middle-aged athlete.
de la Guía-Galipienso Fernando F Feliu-Rey Eloísa E Raso-Raso Rafael R Quesada-Dorador Aurelio A Meyer-Josten Christoph C Lavie Carl J CJ Morin Daniel P DP Sanchis-Gomar Fabian F
HeartRhythm case reports 20210409 7
Similar Datasets
Project description:A 74-year-old man had abnormal left ventricular (LV) function according to a perioperative test at a local hospital and was transferred to our institution for further evaluation and treatment. His electrocardiogram demonstrated the presence of premature ventricular contraction with a QRS complex of the right bundle branch block type and superior axis. His echocardiography showed systolic dysfunction of the LV (LV ejection fraction, 44.6%). Cardiac computed tomography imaging revealed banded and patchy densities observed frequently from the middle to epicardial layer of the LV wall. Cardiac magnetic resonance imaging showed fat signals on fat-selective images and late gadolinium enhancement in the mid-wall to subepicardial layers in the LV myocardium. Endomyocardial biopsy revealed the histological presence of fibrofatty replacement. A genetic analysis revealed a nonsense mutation in the desmoplakin gene. Thus, he was diagnosed with left-dominant arrhythmogenic cardiomyopathy. To prevent fatal ventricular arrhythmias, an implantable cardioverter defibrillator was successfully implanted.
| S-EPMC7524242 | biostudies-literature
Project description:The case of a 49-year-old man with acute onset of heart failure is presented. The initial work-up showed a dilated cardiomyopathy with severely reduced left ventricular ejection fraction. In the differential diagnostic process, hypertensive, ischaemic, and valvular aetiologies were discarded. Subsequently, a cardiac magnetic resonance revealed global hypokinesis and inferior and anterior subepicardial fibrosis. Once differential diagnoses of subepicardial fibrosis (myocarditis, sarcoidosis, and Chagas disease) were discarded, a genetic panel was performed, resulting in a heterozygous mutation of desmoplakin (DSP) gene c.6697_6698del. A left-dominant DSP arrhythmogenic cardiomyopathy mutation was diagnosed. Structural myocardial abnormalities and ventricular arrhythmias characterize arrhythmogenic cardiomyopathy. Up to 50% of cases are associated with mutations in DSP genes (JUP, DSP, and PKP2). DSP is the fundamental component of the desmosome structure and provides structural support through intercellular adhesion. Therefore, when frequent differential diagnoses are discarded, genetic studies for dilated cardiomyopathy and DSP mutation should be considered.
| S-EPMC10567658 | biostudies-literature
Project description:BackgroundThe diagnosis of left dominant arrhythmogenic cardiomyopathy (LDAC) is sometimes complex. The Padua group recently published a document with criteria to identify patients with LDAC, requiring a compatible genetic variant for diagnosis. Due to the gaps in the knowledge of the role of genetics in its pathogenesis, our objective is to describe the findings of the genetic test in patients with LDAC in our center and its prognostic impact.MethodsSingle-center prospective cohort study, in which we recruited 77 patients diagnosed with LDAC or biventricular arrhythmogenic cardiomyopathy according to the criteria of Sen-Chowdhry et al.ResultsWe obtained a positive result in the genetic test in 53.2 %. The desmoplakin gene was the most affected (16.9 %). The mean value of left ventricular (LV) ejection fraction was 45.6 ± 13.1 %, with no significant differences in the severity of the dysfunction according to genetics (p = 0.187). Among the patients with positive genetics there was a greater number of segments in the LV affected by fibrosis (p = 0.043). Regarding fatty infiltration in the LV and number of affected segments, there were no significant differences between groups (p = 0.144). MACE was recorded in 23 patients (29.9 %). The positive result in the genetic test was not significantly associated with the occurrence of MACE (p = 0.902).ConclusionIn our study, we did not find mutations responsible for the disease in practically half of the cases. Despite the existence of a high proportion of MACE during follow-up, there were no prognostic differences according to the result of the genetic test.
| S-EPMC10907150 | biostudies-literature
Project description:BackgroundDesmosomes are specialized intercellular adhesive junctions of cardiac and epithelial cells that provide intercellular mechanical coupling through glycoproteins, one of which is desmoglein (DSG). DSG-2 mutations are frequently associated with biventricular arrhythmogenic cardiomyopathy (ACM). We report a case of left-dominant ACM in a patient who initially was misclassified as dilated cardiomyopathy (DCM).Case summaryA 28-year-old-woman was found to have a moderately reduced left ventricular (LV) systolic function and frequent premature ventricular contractions (PVCs). Targeted genetic testing revealed a heterozygous likely pathogenic variant associated with ACM in exon 15 of the DSG-2 gene (c.3059_3062del; p.Glu1020Alafs*18). Subsequent cardiac magnetic resonance (CMR) imaging showed epicardial and mid-myocardial fatty infiltration involving multiple LV wall segments, multiple areas of mid-myocardial fibrosis/scar, regional dyskinesis involving both ventricles, and an overall reduced left ventricular ejection fraction. The patient's right ventricular (RV) cavity size and overall RV systolic function were normal. Based on the patient's frequent PVCs, family history, fibrofatty myocardial replacement in multiple LV segments, and dyskinetic motion of multiple ventricular wall segments (predominantly affecting the LV), the patient was diagnosed with left-dominant ACM.DiscussionIdentifying a likely pathogenic mutation associated with ACM in a patient with ventricular arrhythmias and a family history of sudden cardiac death increased the possibility of ACM. Subsequent CMR imaging confirmed the diagnosis of left-dominant ACM by demonstrating regional biventricular dyskinesia and a characteristic pattern of fibrofatty myocardial replacement. Our case highlights the importance of targeted genetic testing and advanced cardiac imaging in distinguishing left-dominant ACM from DCM.
| S-EPMC8274644 | biostudies-literature
Project description: Not available
| S-EPMC8134784 | biostudies-literature
Project description:Background Left ventricular (LV) involvement is frequently observed in arrhythmogenic cardiomyopathy (ACM). We investigated the association of LV myocardial assessment using cardiac magnetic resonance (CMR) with clinical outcomes including heart failure (HF)-related events in ACM. Methods and Results We retrospectively analyzed 60 patients with ACM between 2005 and 2020 according to the 2010 Task Force Criteria and assessed HF-related events (HF hospitalization, heart transplantation, and cardiac death) and ventricular tachycardia events. We analyzed CMR findings including late gadolinium enhancement (LGE) in all subjects and obtained mapping values (native T1, extracellular volume, and T2) on 30 (50%) patients out of them. Among the study population (mean age 49 years, 77% male), 41 (68%) patients had LV LGE. During a median follow-up of 34 months, there were 13 (22%) HF-related events, and 20 (30%) ventricular tachycardia events. Kaplan-Meier survival analysis revealed that HF-related events occurred only in patients with LV LGE (+) (versus LV LGE (-), log-rank P=0.006), and the events were not significantly different regarding right ventricular LGE (log-rank P>0.999). When categorized by median value for each mapping parameter, HF-related events occurred more in patients with higher native T1 (versus lower native T1, log-rank P=0.002), and higher T2 (versus lower T2, log-rank P=0.002), higher extracellular volume (versus lower extracellular volume, log-rank P=0.002). However, regarding ventricular tachycardia events, there were no significant differences according to these CMR markers. Conclusions LV myocardial assessment using CMR with LGE imaging and native T1, T2, and extracellular volume markers were significantly associated with HF-related event risk in patients with ACM.
| S-EPMC9075293 | biostudies-literature
Project description:Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disorder associated with arrhythmias and sudden death. A recessive mutation in the gene encoding plakoglobin has been shown to cause Naxos disease, a cardiocutaneous syndrome characterized by ARVC and abnormalities of hair and skin. Here, we report, for the first time, a dominant mutation in the gene encoding plakoglobin in a German family with ARVC but no cutaneous abnormalities. The mutation (S39_K40insS) is predicted to insert an extra serine residue at position 39 in the N-terminus of plakoglobin. Analysis of a biopsy sample of the right ventricle from the proband showed markedly decreased localization of plakoglobin, desmoplakin, and connexin43 at intercalated discs in cardiac myocytes. A yeast-two-hybrid screen revealed that the mutant protein established novel interactions with histidine-rich calcium-binding protein and TGF beta induced apoptosis protein 2. Immunoblotting and confocal microscopy in human embryonic kidney 293 (HEK293) cell lines transfected to stably express either wild-type or mutant plakoglobin protein showed that the mutant protein was apparently ubiquitylated and was preferentially located in the cytoplasm, suggesting that the S39_K40insS mutation may increase plakoglobin turnover via proteasomal degradation. HEK293 cells expressing mutant plakoglobin also showed higher rates of proliferation and lower rates of apoptosis than did cells expressing the wild-type protein. Electron microscopy showed smaller and fewer desmosomes in cells expressing mutant plakoglobin. Taken together, these observations suggest that the S39_K40insS mutation affects the structure and distribution of mechanical and electrical cell junctions and could interfere with regulatory mechanisms mediated by Wnt-signaling pathways. These results implicate novel molecular mechanisms in the pathogenesis of ARVC.
| S-EPMC2265660 | biostudies-literature
Project description:BackgroundArrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disease characterized by fibrofatty replacement of ventricular myocardium. Ventricular arrhythmia and sudden cardiac death (SCD) are the main clinical manifestations. ACM was previously called arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). However, recent studies have shown that this disease is not limited to the right ventricle; biventricular involvement occurs in 50% of ACM patients. The left-dominant subtype was subsequently identified, which supported the adoption of the broader term "ACM". The clinical literature includes more extensive reports on ARVC, but reports on arrhythmogenic left ventricular cardiomyopathy (ALVC), which is likely to be underrecognized, are limited.Case descriptionIn this report, we describe a case of secondary syncope in a patient with ALVC who developed right bundle branch block with ventricular tachycardia (RBBB-VT), with VT originating in the left ventricle (LV). Cardiac magnetic resonance (CMR) revealed significant enlargement of the LV, with LV dysfunction. Late gadolinium enhancement (LGE) and fat sequencing revealed that most of the free wall of the LV was replaced by fibrofatty tissue.ConclusionsThis report could help improve the understanding of this rare disease, and its management. CMR plays a key role in the diagnosis of ACM.
| S-EPMC11759933 | biostudies-literature
Project description:BackgroundCardiovascular magnetic resonance (CMR) is commonly used in patients with suspected arrhythmogenic right ventricular cardiomyopathy (ARVC) based on ECG, echocardiogram and Holter. However, various diseases may present with clinical characteristics resembling ARVC causing diagnostic dilemmas. The aim of this study was to explore the role of CMR in the differential diagnosis of patients with suspected ARVC.Methods657 CMR referrals suspicious for ARVC in a single tertiary referral centre were analysed. Standardized CMR imaging protocols for ARVC were performed. Potential ARVC mimics were grouped into: 1) displacement of the heart, 2) right ventricular overload, and 3) non ARVC-like cardiac scarring. For each, a judgment of clinical impact was made.ResultsTwenty patients (3.0%) fulfilled imaging ARVC criteria. Thirty (4.6%) had a potential ARVC mimic, of which 25 (3.8%) were considered clinically important: cardiac displacement (n=17), RV overload (n=7) and non-ARVC like myocardial scarring (n=4). One patient had two mimics; one patient had dual pathology with important mimic and ARVC. RV overload and scarring conditions were always thought clinically important whilst the importance of cardiac displacement depended on the degree of displacement from severe (partial absence of pericardium) to epiphenomenon (minor kyphoscoliosis).ConclusionsSome patients referred for CMR with suspected ARVC fulfil ARVC imaging criteria (3%) but more have otherwise unrecognised diseases (4.6%) mimicking potentially ARVC. Clinical assessment should reflect this, emphasising the assessment and/or exclusion of potential mimics in parallel with the detection of ARVC major and minor criteria.
| S-EPMC3599618 | biostudies-literature
Project description:The aim of this study was to investigate left ventricular (LV) global myocardial strain and LV involvement characteristics in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and to evaluate their predictive value of adverse cardiac events. Sixty consecutive ARVD/C patients with a definite diagnosis of ARVD/C who underwent CMR examination and thirty-four healthy controls were enrolled retrospectively. The CMR images were analyzed for LV myocardial strain and the presence of LV involvement. The endpoint was defined as a composite of sustained ventricular tachycardia or fibrillation, cardiac death, resuscitated cardiac arrest, heart transplantation, and appropriate implantable cardioverter-defibrillator shock. LV global longitudinal (GLS), circumferential (GCS), and radial strain (GRS) were significantly impaired in ARVC/D patients compared to healthy controls (GLS: -13.89 ± 3.26% vs. -16.68 ± 2.74%, GCS: -15.65 ± 3.40% vs. -19.20 ± 2.23%, GRS: 34.57 ± 11.98% vs. 49.92 ± 12.59%; P < 0.001 for all). Even in ARVC/D patients with preserved LVEF, LV GLS, GCS and GRS were also significantly reduced than in controls. During a mean follow-up period of 4.10 ± 1.77 years, the endpoint was reached in 17 patients. LV GLS >-12.65% (HR, 3.58; 95%CI, 1.14 to 11.25; p = 0.029) and history of syncope (HR, 4.99; 95%CI, 1.88 to 13.24; p = 0.001) were the only independent predictors of cardiac outcomes. The LV myocardial deformation derived from FT CMR was significantly impaired in ARVD/C patients, and this alteration can occur before the impairment of LVEF. LV GLS >-12.65% and history of syncope were the only independent prognostic markers of adverse cardiac outcomes.
| S-EPMC6775112 | biostudies-literature