scholarly journals Two Novel Variants in Genes of Arrhythmogenic Right Ventricular Cardiomyopathy – a Case Report

2021 ◽  
Vol 28 (1) ◽  
pp. 1
Author(s):  
Dovilė Gabartaitė ◽  
Dovilė Jančauskaitė ◽  
Violeta Mikštienė ◽  
Eglė Preikšaitienė ◽  
Rimvydas Norvilas ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Structural Changes ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Right Ventricular Ejection Fraction ◽  
Left Ventricular ◽  
Ventricular Cardiomyopathy ◽  
Ventricular Ejection Fraction ◽  
Variant Of Uncertain Significance ◽  
Novel Variants ◽  
The Right

 Background. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable cardiomyopathy, characterized by fibrofatty replacement of myocytes in the right ventricular, left ventricular or both ventricles. It is caused by pathogenic variants of genes encoding desmosomal (JUP, DSP, PKP2, DSG2, DSC2) and non-desmosomal proteins, and is one of the most common causes of sudden cardiac death in young athletes. Therefore, early identification, correct prevention and treatment can prevent adverse outcomes.Case report. Our case presents a 65-years-old man with recurrent ventricular tachycardia. The ischemic cause was the first to rule out. Echocardiography revealed right ventricular structural and functional abnormalities. After suspicion of ARVC, magnetic resonance imaging was performed showing reduced right ventricular ejection fraction with local aneurysms, structural changes ir the right and left myocardium. Subsequently performed genetic testing identified a novel ARVC likely pathogenic variant in DSC2 gene and variant of uncertain significance in RYR2 gene.Conclusions. Diagnostic evaluation of ARVC is challenging and requires multidisciplinary team collaboration. Further functional tests for elucidation of the clinical significance of the two novel variants of ARVC-associated genes could be suggested.

scholarly journals Sudden Cardiac Death Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC): A Multinational Collaboration

2020 ◽  
Author(s):  
Julia Cadrin-Tourigny ◽  
Laurens P. Bosman ◽  
Weijia Wang ◽  
Rafik Tadros ◽  
Aditya Bhonsale ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Right Ventricular ◽  
Cardiac Death ◽  
Cox Regression ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Right Ventricular Ejection Fraction ◽  
Ventricular Cardiomyopathy ◽  
Clinical Predictors ◽  
Ventricular Ejection Fraction

Background - Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is associated with ventricular arrhythmias (VA) and sudden cardiac death (SCD). A model was recently developed to predict incident sustained VA in ARVC patients. However, since this outcome may overestimate the risk for SCD, we aimed to specifically predict life-threatening VA (LTVA) as a closer surrogate for SCD. Methods - We assembled a retrospective cohort of definite ARVC cases from 15 centers in North America and Europe. Association of 8 pre-specified clinical predictors with LTVA (SCD, aborted SCD, sustained or ICD treated VT>250 bpm) in follow-up was assessed by Cox regression with backward selection. Candidate variables included age, sex, prior sustained VA (≥30s, hemodynamically unstable or ICD treated VT; or aborted SCD), syncope, 24-hour premature ventricular complexes (PVC) count, the number of anterior and inferior leads with T-wave inversion (TWI), left and right ventricular ejection fraction. The resulting model was internally validated using bootstrapping. Results - A total of 864 definite ARVC patients (40±16 years; 53% male) were included. Over 5.75 years [IQR 2.77, 10.58] of follow-up, 93 (10.8%) patients experienced LTVA including 15 with SCD/aborted SCD (1.7%). Of the 8 pre-specified clinical predictors, only 4 (younger age, male sex, PVC count and number of leads with TWI) were associated with LTVA. Notably, prior sustained VA did not predict subsequent LTVA (p=0.850). A model including only these 4 predictors had an optimism-corrected C-index of 0.74 (95% CI:0.69-0.80) and calibration slope of 0.95 (95% CI:0.94-0.98) indicating minimal over-optimism. Conclusions - LTVA events in patients with ARVC can be predicted by a novel simple prediction model using only 4 clinical predictors. Prior sustained VA and the extent of functional heart disease are not associated with subsequent LTVA events.

Arrhythmogenic Right Ventricular Cardiomyopathy with Left Ventricular Involvement: A Novel Splice Site Mutation in the DSG2 Gene

Cardiology ◽  
2015 ◽  
Vol 130 (3) ◽  
pp. 159-161 ◽  
Author(s):  
Marina Pereira Fernandes ◽  
Olga Azevedo ◽  
Vitor Pereira ◽  
Lucy Calvo ◽  
António Lourenço
Keyword(s):  
Right Ventricular ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Splice Site Mutation ◽  
Left Ventricular ◽  
Transthoracic Echocardiogram ◽  
Ventricular Cardiomyopathy ◽  
Site Mutation ◽  
Electrocardiographic Monitoring ◽  
History Of ◽  
The Right

We report the case of a 37-year-old male patient admitted to the cardiac intensive care unit for acute pulmonary edema. He had a history of excessive alcoholic consumption and had had a viral syndrome in the preceding 10 days. A transthoracic echocardiogram revealed severe biventricular dysfunction, mild dilatation of the left heart chambers, and severe dilatation of the right chambers. Nonsustained ventricular tachycardia with a left bundle branch block morphology was detected during electrocardiographic monitoring. In the follow-up, he underwent a contrast-enhanced transthoracic echocardiogram and a cardiac resonance which were compatible with the diagnosis of arrhythmogenic right ventricular cardiomyopathy with biventricular involvement. Molecular analysis detected the mutation c.1423+2T>G (IVS10 ds +2T>G) in intron 10 of the gene DSG2 (desmoglein-2) in heterozygosity. To our knowledge, this mutation has not been previously described in arrhythmogenic right ventricular cardiomyopathy.

Genotype–phenotype correlation in arrhythmogenic right ventricular cardiomyopathy—risk of arrhythmias and heart failure

2021 ◽  
pp. jmedgenet-2021-107911
Author(s):  
Alex Hørby Christensen ◽  
Pyotr G Platonov ◽  
Henrik Kjærulf Jensen ◽  
Monica Chivulescu ◽  
Anneli Svensson ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Carrier Status ◽  
Ventricular Cardiomyopathy ◽  
Ventricular Ejection Fraction ◽  
Male Sex ◽  
The Impact

BackgroundArrhythmogenic right ventricular cardiomyopathy (ARVC) is predominantly caused by desmosomal genetic variants, and clinical hallmarks include arrhythmias and systolic dysfunction. We aimed at studying the impact of the implicated gene(s) on the disease course.MethodsThe Nordic ARVC Registry holds data on a multinational cohort of ARVC families. The effects of genotype on electrocardiographic features, imaging findings and clinical events were analysed.ResultsWe evaluated 419 patients (55% men), with a mean follow-up of 11.2±7.4 years. A pathogenic desmosomal variant was identified in 62% of the 230 families: PKP2 in 41%, DSG2 in 13%, DSP in 7% and DSC2 in 3%. Reduced left ventricular ejection fraction (LVEF) ≤45% on cardiac MRI was more frequent among patients with DSC2/DSG2/DSP than PKP2 ARVC (27% vs 4%, p<0.01). In contrast, in Cox regression modelling of patients with definite ARVC, we found a higher risk of arrhythmias among PKP2 than DSC2/DSG2/DSP carriers: HR 0.25 (0.10–0.68, p<0.01) for atrial fibrillation/flutter, HR 0.67 (0.44–1.0, p=0.06) for ventricular arrhythmias and HR 0.63 (0.42–0.95, p<0.05) for any arrhythmia. Gene-negative patients had an intermediate risk (16%) of LVEF ≤45% and a risk of the combined arrhythmic endpoint comparable with DSC2/DSG2/DSP carriers. Male sex was a risk factor for both arrhythmias and reduced LVEF across all genotype groups (p<0.01).ConclusionIn this large cohort of ARVC families with long-term follow-up, we found PKP2 genotype to be more arrhythmic than DSC2/DSG2/DSP or gene-negative carrier status, whereas reduced LVEF was mostly seen among DSC2/DSG2/DSP carriers. Male sex was associated with a more severe phenotype.

Arrhythmogenic right ventricular cardiomyopathy: contemporary challenges of diagnosis and management

2019 ◽  
Vol 14 (12) ◽  
pp. 1-14
Author(s):  
Liam Driver
Keyword(s):  
Right Ventricular ◽  
Cardiac Death ◽  
Ventricular Arrhythmias ◽  
Structural Changes ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Ventricular Cardiomyopathy ◽  
Device Therapy ◽  
Score System ◽  
To Come ◽  
The Right

Arrhythmogenic right ventricular cardiomyopathy is a rare but potentially lethal condition that predominantly affects the right ventricle although a left or biventricular form is now recognised. The condition can present in a variety of ways from palpitations to aborted sudden cardiac death. It is characterised by the replacement of healthy myocardium with fatty infiltrates and is progressive in nature. There is no single test for this condition and diagnosis can be difficult – relying on a diagnostic criteria to aid diagnosis. This score system uses criteria based on ECG findings, evidence of arrhythmia, structural changes detected on echocardiogram and MRI, histopathology and family history. Treatment is initially medicine based, to suppress ventricular arrhythmias; however, patients may require device therapy, ablation or cardiac transplantation. There are recognised psychological implications for patients with arrhythmogenic right ventricular tachycardia and they may require support to come to terms with the changes that a diagnosis can bring.

scholarly journals Possibly Late-Onset Arrhythmogenic Right Ventricular Cardiomyopathy: Unique Triglyceride Deposition by Analysis of Lipid Contents

2019 ◽  
Vol 12 ◽  
pp. 117954761982871
Author(s):  
Kentaro Yamamoto ◽  
Xin Guo ◽  
Ken-ichi Mizutani ◽  
Nozomu Kurose ◽  
Motona Kumagai ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Late Onset ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Ventricular Myocardium ◽  
Cholesterol Content ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Ventricular Cardiomyopathy ◽  
Lipid Contents ◽  
The Right

We presented an unusual arrhythmogenic right ventricular cardiomyopathy (ARVC) case of a late-60s elderly man’s death, due to severe pericardial/pleural effusion and ascites, and arrhythmic events, with unique pathological features. The hypertrophic heart grossly displayed yellowish to yellow-whitish predominantly in the variably thinned wall of the dilated right ventricle. Microscopic findings showed diffuse fatty/fibrofatty replacement in not only the right but left ventricular myocardium, together with an outer lymphoplasmacytic infiltrate. According to the lipid contents analysis, the triglyceride content, but not the cholesterol content, in our patient’s right and left ventricular cardiac muscle was much higher than that in the control subject. We propose that this unique triglyceride deposition in our possibly late-onset ARVC case might be one of new clues to understand its enigmatic cause. Further prospective studies are needed to validate the presence and significance of a greater volume of triglyceride deposit, after collecting and investigating a larger number of early and late-onset ARVC cases examined.

scholarly journals Arrhythmogenic left ventricular cardiomyopathy

2020 ◽  
Vol 6 (1) ◽  
pp. 20190079
Author(s):  
Seyedeh Mojdeh Mirmomen ◽  
Andrew Jay Bradley ◽  
Andrew Ernest Arai ◽  
Arlene Sirajuddin
Keyword(s):  
Right Ventricular ◽  
Cardiac Death ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Ventricular Cardiomyopathy ◽  
Cardiotoxic Effect ◽  
Life Threatening ◽  
Muscle Disorder ◽  
The Right

Arrhythmogenic ventricular cardiomyopathy (AVC) is a heritable heart muscle disorder characterized by fibrofatty infiltration of the myocardium. Intramyocardial fat deposition is considered arrhythmogenic and predisposes patients to life-threatening arrhythmias and sudden cardiac death. The classic subtype of AVC is characterized by fibrofatty replacement of the right ventricular myocardium (i.e. arrhythmogenic right ventricular cardiomyopathy). In advanced cases of arrhythmogenic right ventricular cardiomyopathy, the left ventricle may be involved as well. Predominantly left ventricular involvement by AVC is exceedingly rare and lack of specific diagnostic criteria as well as its potential cardiotoxic effect make its diagnosis challenging and of high importance.

scholarly journals Pathogenic variants in plakophilin-2 gene (PKP2) are associated with better survival in arrhythmogenic right ventricular cardiomyopathy

2021 ◽  
Author(s):  
Elżbieta K. Biernacka ◽  
Karolina Borowiec ◽  
Maria Franaszczyk ◽  
Małgorzata Szperl ◽  
Alessandra Rampazzo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Right Ventricular ◽  
Heart Transplant ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Cardiomyopathy ◽  
Ventricular Ejection Fraction ◽  
Pathogenic Variants ◽  
Plakophilin 2

AbstractArrhythmogenic right ventricular cardiomyopathy (ARVC) is mainly caused by mutations in genes encoding desmosomal proteins. Variants in plakophilin-2 gene (PKP2) are the most common cause of the disease, associated with conventional ARVC phenotype. The study aims to evaluate the prevalence of PKP2 variants and examine genotype–phenotype correlation in Polish ARVC cohort. All 56 ARVC patients fulfilling the current criteria were screened for genetic variants in PKP2 using denaturing high-performance liquid chromatography or next-generation sequencing. The clinical evaluation involved medical history, electrocardiogram, echocardiography, and follow-up. Ten variants (5 frameshift, 2 nonsense, 2 splicing, and 1 missense) in PKP2 were found in 28 (50%) cases. All truncating variants are classified as pathogenic/likely pathogenic, while the missense variant is classified as variant of uncertain significance. Patients carrying a PKP2 mutation were younger at diagnosis (p = 0.003), more often had negative T waves in V1–V3 (p = 0.01), had higher left ventricular ejection fraction (p = 0.04), and were less likely to present symptoms of heart failure (p = 0.01) and left ventricular damage progression (p = 0.04). Combined endpoint of death or heart transplant was more frequent in subgroup without PKP2 mutation (p = 0.03). Pathogenic variants in PKP2 are responsible for 50% of ARVC cases in the Polish population and are associated with a better prognosis. ARVC patients with PKP2 mutation are less likely to present left ventricular involvement and heart failure symptoms. Combined endpoint of death or heart transplant was less frequent in this group.

P5694Outcomes of patients with arrhythmogenic right ventricular cardiomyopathy after ventricular tachycardia ablation without an implantable cardioverter-defibrillator: a multicenter international study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Gandjbakhch ◽  
M Laredo ◽  
A Berruezo ◽  
J B Gourraud ◽  
R Martins ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Right Ventricular ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Cardiomyopathy ◽  
Ventricular Ejection Fraction

Abstract Background In arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), implantable cardioverter-defibrillators (ICD) after an episode of sustained monomorphic ventricular tachycardia (MVT) are currently recommended in most situations. However, radiofrequency catheter ablation (RCA) is effective in reducing recurrent VT and whether MVT is a surrogate of sudden cardiac death is debated when other risk factors are lacking. Purpose To report the outcomes of patients with ARVC/D who underwent RCA of well-tolerated MVT without a back-up ICD. Methods Patients with a definite ARVC/D diagnosis according to the 2010 Task Force revised criteria who underwent RCA of well-tolerated MVT at 9 tertiary centers across 5 countries, without an ICD prior to RCA and in the 3 following months were retrospectively included. Patients presenting with syncope or electrical storm, and patients with left ventricular ejection fraction <50% were excluded. Similar patients implanted with an ICD prior or without RCA in the same period served as controls. Results Sixty-five patients [median age 46.1 years, range (19.5–73.8), 75% males] underwent RCA of MVT between 2003 and 2016. Familial history of ARVC/D was found in 11% of patients. Epsilon-waves were present in 19% and T-waves inversion beyond V2 in 43%. A right ventricular (RV) ejection fraction ≤40% or fractional area change ≤33% was found in 14 (25%) patients. Median left ventricular ejection fraction was 61% (50–70). Clinical presentation was palpitations in 81% of patients and near-syncope in 14%. Prior to RCA, patients were on beta-blockers alone in 18%, class I drugs in 37% and amiodarone in 9%, while 15% of patients were free any antiarrhythmic medication. Only 1 patient (2%) had >1 clinical VT morphology. Median VT rate was 180 (110–270). An epicardial approach was used in 31% patients. The clinical VT was inducible in 84% of patients. The median number of targeted RV site was 1 (1–3) (RV outflow tract in 72%). Full acute success defined inability to induce any VT was achieved in 72% of patients. During a median follow-up time of 49 month (1.4–162), there was no death or aborted cardiac arrest. Survival without VT recurrence was estimated at 82%, 71% and 60%, 12-, 36- and 60-months after RCA. No VT recurrence was observed among patient who had undergone an epicardial ablation. Among patients with VT recurrence, 6 (35%) did not receive an ICD, and 14 (70%) underwent redo RCA. An ICD was implanted in 10 patients, including 5 for VT recurrence. Fifty-eight patients constituted the control group, and 64% had appropriate ICD interventions during follow-up. Conclusions Despite a significant rate of VT recurrence, selected patients with ARVC/D who underwent RCA for stable MVT without an ICD did not experience any arrhythmic death. Further prospective studies are mandatory to precise the respective places of ICD and RCA in the management of ARVC/D patients with well-tolerated MVT. Acknowledgement/Funding None

scholarly journals The utility of the 1994 versus the revised 2010 arrhythmogenic right ventricular cardiomyopathy (ARVC) task force diagnostic criteria for identifying mutation-positive probands with ARVC

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Lukhna ◽  
S Kraus ◽  
N Ntusi
Keyword(s):  
Right Ventricular ◽  
Task Force ◽  
Diagnostic Yield ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Left Ventricular ◽  
Ventricular Cardiomyopathy ◽  
Significant Difference ◽  
Diagnostic Panel ◽  
The Mean ◽  
The Right

Abstract Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disorder characterised by structural and functional abnormalities of the right ventricle with or without left ventricular involvement. In 1994, Task Force criteria (TFC) were proposed for the diagnosis of ARVC and were found to be highly specific but lacked sensitivity. In 2010, revised TFC were proposed to increase sensitivity and facilitate diagnosis in those with subtle phenotypes. Purpose To compare the utility of the 1994 vs the 2010 TFC for the diagnosis of mutation-positive probands with ARVC in the IMHOTEP (The African Cardiomyopathy and Myocarditis Registry Program) study. Method 162 participants with the suspicion of ARVC were referred between May 2003 and May 2018. After the exclusion of 12 participants lacking sufficient clinical data, 150 cases were reviewed and classified using both 1994 and 2010 TFC by a diagnostic panel in an hospital. Results 82 participants were found to have an alternative diagnosis or insufficient criteria and were excluded. 68 participants were diagnosed with ARVC by the diagnostic panel and included; 14/68 participants with ARVC were found to be mutation-positive. Mutation-positive probands presented at a significantly younger age compared to the mutation-negative group (29±14 years vs 39±13 years, p=0.009), suggesting an earlier onset of ARVC. Common reasons for presentation in the mutation-positive cohort included palpitations (79%) and presyncope (64%), with twice the number of participants presenting with sustained ventricular tachycardia compared to mutation-negative participants (79% vs 47%, p=0.036). The diagnostic yield of the 2010 vs 1994 TFC in participants with ARVC (n=68) revealed more participants with a definite diagnosis (77% vs 69%, p=0.267). A 67% change in diagnosis from 1994 borderline to 2010 definite was observed. Mutation-positive participants had a higher yield for definite ARVC compared to mutation-negative participants (100% vs 86%). When comparing the mean number of task force (TF) major and minor criteria according to mutation status, we found a significant difference in the mean number of 2010 TF major criteria between mutation-positive and mutation-negative groups, even with the exclusion of gene mutation as a criterion (2.50±0.86 vs 1.74±0.85, p=0.005). We assessed each diagnostic modality's contribution to the 2010 TF major criteria in mutation-positive definite participants and found cardiac magnetic resonance contribution statistically significant, p=0.021. Conclusion Mutation-positive ARVC probands were found to be younger, more likely to present with sustained VT, and fulfilled a significantly higher number of 2010 TF major criteria than mutation-negative probands. The evolution in classification between the 2010 and 1994 TFC suggests that reclassifying participants recruited in traditional ARVC registries according to updated criteria is worthwhile. Funding Acknowledgement Type of funding source: None

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