scholarly journals Impact of Genetic Variant Reassessment on the Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy Based on the 2010 Task Force Criteria

2020 ◽  
Author(s):  
Sarah Costa ◽  
Argelia Medeiros-Domingo ◽  
Alessio Gasperetti ◽  
Deniz Akdis ◽  
Wolfgang Berger ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Genetic Variants ◽  
Genetic Variant ◽  
Task Force ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Accurate Determination ◽  
Disease Status ◽  
Ventricular Cardiomyopathy ◽  
Genetic Test Results ◽  
The Impact

Background - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy, which is associated with life-threatening ventricular arrhythmias. Approximately 60% of patients carry a putative disease-causing genetic variant, but interpretation of genetic test results can be challenging. The aims of this study were to systematically reclassify genetic variants in patients with ARVC and to assess the impact on ARVC diagnosis. Methods - This study included patients from the Multicenter Zurich ARVC Registry who hosted a genetic variant deemed to be associated with the disease. Reclassification of pathogenicity was performed according to the modified 2015 American College of Medical Genetics (ACMG) criteria. ARVC diagnosis (categories: definite, borderline, possible) based on the 2010 Task Force Criteria (TFC) was reclassified after genetic re-adjudication. Results - In 79 patients bearing 80 unique genetic variants, n=47 (58.8%) genetic variants were reclassified, and reclassification was judged to be clinically relevant in n=33 (41.3%). Variants in plakophilin-2 ( PKP2 ) were shown to reclassify less frequently as compared to other genes ( PKP2 , n=1, 8.3%; desmosomal non- PKP2 , n=20, 66.7%; non-desmosomal, n=26, 68.4%) (p=0.001 for overall comparison; PKP2 vs desmosomal non- PKP2 , p=0.001; PKP2 vs non-desmosomal, p< 0.001). Genetic reclassification impacted ARVC diagnosis. Eight patients (10.1%) were downgraded from definite to borderline/possible disease at the time of initial genetic testing as well as last follow-up, respectively. Separate genetic reclassification in family members led to downgrading of n=5 (38.5%) of variants. Conclusions - Given that approximately half of genetic variants were reclassified, with 10.1% of patients losing their definite disease status, accurate determination of variant pathogenicity is of utmost importance in the diagnosis of ARVC.

scholarly journals Characteristics of Patients With Arrhythmogenic Left Ventricular Cardiomyopathy

2020 ◽  
Vol 13 (12) ◽  
Author(s):  
Michela Casella ◽  
Alessio Gasperetti ◽  
Rita Sicuso ◽  
Edoardo Conte ◽  
Valentina Catto ◽  
...  
Keyword(s):  
Late Gadolinium Enhancement ◽  
Right Ventricular ◽  
Genetic Variants ◽  
Task Force ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Left Ventricular ◽  
Ventricular Cardiomyopathy ◽  
Gadolinium Enhancement ◽  
Voltage Mapping ◽  
Fatty Replacement

Background: Arrhythmogenic left ventricular cardiomyopathy (ALVC) is an under-characterized phenotype of arrhythmogenic cardiomyopathy involving the LV ab initio. ALVC was not included in the 2010 International Task Force Criteria for arrhythmogenic right ventricular cardiomyopathy diagnosis and data regarding this phenotype are scarce. Methods: Clinical characteristics were reported from all consecutive patients diagnosed with ALVC, defined as a LV isolated late gadolinium enhancement and fibro-fatty replacement at cardiac magnetic resonance plus genetic variants associated with arrhythmogenic right ventricular cardiomyopathy and of an endomyocardial biopsy showing fibro-fatty replacement complying with the 2010 International Task Force Criteria in the LV. Results: Twenty-five patients ALVC (53 [48–59] years, 60% male) were enrolled. T wave inversion in infero-lateral and left precordial leads were the most common ECG abnormalities. Overall arrhythmic burden at study inclusion was 56%. Cardiac magnetic resonance showed LV late gadolinium enhancement in the LV lateral and posterior basal segments in all patients. In 72% of the patients an invasive evaluation was performed, in which electroanatomical voltage mapping and electroanatomical voltage mapping-guided endomyocardial biopsy showed low endocardial voltages and fibro-fatty replacement in areas of late gadolinium enhancement presence. Genetic variants in desmosomal genes (desmoplakin and desmoglein-2) were identified in 12/25 of the cohort presenting pathogenic/likely pathogenic variants. A definite/borderline 2010 International Task Force Criteria arrhythmogenic right ventricular cardiomyopathy diagnosis was reached only in 11/25 patients. Conclusions: ALVC presents with a preferential involvement of the lateral and postero-lateral basal LV and is associated mostly with variants in desmoplakin and desmoglein-2 genes. An amendment to the current International Task Force Criteria is reasonable to better diagnose patients with ALVC.

Arrhythmias right ventricular cardiomyopathy and sports activity: from molecular pathways in diseased hearts to new insights into the athletic heart mimicry

2020 ◽  
Author(s):  
Alessio Gasperetti ◽  
Cynthia A James ◽  
Marina Cerrone ◽  
Mario Delmar ◽  
Hugh Calkins ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Task Force ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Phenotypic Expression ◽  
Disease Diagnosis ◽  
Inherited Disease ◽  
Ventricular Cardiomyopathy ◽  
Sports Activity ◽  
Clinical Consequences ◽  
The Impact

Abstract Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease associated with a high risk of sudden cardiac death. Among other factors, physical exercise has been clearly identified as a strong determinant of phenotypic expression of the disease, arrhythmia risk, and disease progression. Because of this, current guidelines advise that individuals with ARVC should not participate in competitive or frequent high-intensity endurance exercise. Exercise-induced electrical and morphological para-physiological remodelling (the so-called ‘athlete’s heart’) may mimic several of the classic features of ARVC. Therefore, the current International Task Force Criteria for disease diagnosis may not perform as well in athletes. Clear adjudication between the two conditions is often a real challenge, with false positives, that may lead to unnecessary treatments, and false negatives, which may leave patients unprotected, both of which are equally inacceptable. This review aims to summarize the molecular interactions caused by physical activity in inducing cardiac structural alterations, and the impact of sports on arrhythmia occurrence and other clinical consequences in patients with ARVC, and help the physicians in setting the two conditions apart.

Impact of genetic reclassification on ARVC diagnosis based on the 2010 task force criteria

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Costa ◽  
A Gasperetti ◽  
D Akdis ◽  
G Suna ◽  
A Medeiros Domingo ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Genetic Variant ◽  
Task Force ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Significant Proportion ◽  
Clinical Information ◽  
University Hospital ◽  
Funding Source ◽  
Cascade Screening ◽  
The Impact

Abstract Introduction Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is an inherited condition, which is associated with potentially life-threatening ventricular arrhythmias in the young. Approximately 60% of patients carry a possibly disease-causing genetic variant. Purpose The aim of this study was to investigate the impact of the 2015 American College of Medical Genetics (ACMG) Criteria on ARVC diagnosis based on the 2010 Modified Task Force Criteria (TFC). Methods The study included 79 patients from the Swiss ARVC Registry who harbored a genetic variant deemed to be associated with the disease at initial screening, and classified them as definite, borderline or possible ARVC. Every variant found was re-classified on Varsome Genetics, based on the 2015 ACMG Criteria. Clinical information was then assessed at last available follow-up of every patient and ARVC diagnosis was reclassified based on the newest genetic evidence available. Results In 42 out of 79 patients (53.2%), genetic variants were reclassified. Out of these, 33 variants (41.8%) were downgraded from pathogenic (P) / likely pathogenic (LP) to either variants of unknown significance (VUS) or benign (B) / likely benign (LB). Three patients (3.8%) were upgraded from VUS / LP to P. Out of the 12 variants initially classified as VUS, 9 (75%) were reclassified as B or LB. Overall, 13 patients (16.5%) were downgraded from their initial diagnosis (11 from definite to borderline and 2 from borderline to possible). Conclusion A significant proportion of patients with ARVC diagnosed based on the 2010 TFC were reclassified when the 2015 ACMG Criteria were taken into consideration. These findings may have clinical consequences, particularly for genetic cascade screening of family members of ARVC patients and necessitate reassessment of genetic variants of index patients who were previously diagnosed with ARVC. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): University Hospital Zurich

Quality of life metrics in arrhythmogenic right ventricular cardiomyopathy patients: The impact of age, shock and sex

2017 ◽  
Vol 248 ◽  
pp. 216-220 ◽  
Author(s):  
Ashley C. Rhodes ◽  
Brittney Murray ◽  
Crystal Tichnell ◽  
Cynthia A. James ◽  
Hugh Calkins ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Right Ventricular ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Ventricular Cardiomyopathy ◽  
The Impact

scholarly journals Frequency of genetic variants associated with arrhythmogenic right ventricular cardiomyopathy in the genome aggregation database

2018 ◽  
Vol 26 (9) ◽  
pp. 1312-1318 ◽  
Author(s):  
Charlotte L Hall ◽  
Henry Sutanto ◽  
Chrysoula Dalageorgou ◽  
William John McKenna ◽  
Petros Syrris ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Genetic Variants ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Ventricular Cardiomyopathy

Abstract 15314: Left Ventricular Dysfunction in Children and Adolescents With Arrhythmogenic Right Ventricular Cardiomyopathy

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Paweena Chungsomprasong ◽  
Robert Hamilton ◽  
Wietske Luining ◽  
Shi-Joon Yoo ◽  
Meena Fatah ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Task Force ◽  
Myocardial Dysfunction ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Myocardial Strain ◽  
Young Patients ◽  
Left Ventricular ◽  
Lv Function ◽  
Ventricular Cardiomyopathy ◽  
End Diastolic Volume

Background: Involvement of the left ventricle (LV) is increasingly recognized in adults with arrhythmogenic right ventricular cardiomyopathy (ARVC) but it is unclear whether LV function is compromised in children with this condition. The aim of this study was examine myocardial contractility in pediatric patients with suspected ARVC. Methods: For this retrospective study, patients with a work-up for ARVC were classified into ‘no’, ‘possible’, ‘borderline’ or ‘definite’ ARVC according to the revised Task Force Criteria (rTFC). Ventricular size and function as well as LV myocardial strain and torsion were measured by cardiac magnetic resonance (CMR). Results: A total of 142 patients were enrolled, of whom 58 (41%) had no, 32 (23%) possible, 29 (20%) borderline and 23 (16%) definite ARVC. The groups were similar in age at CMR. With higher rTFC score, z scores (Z) of right ventricular (RV) ejection fraction (EF) were lower (p<0.001) while z-RV end diastolic volume (EDV) and z-LV EDV were larger (p=0.002 and 0.013, respectively). LV EF did not differ between rTFC categories. Global circumferential strain (GCS) of the LV was lower in patients in higher rTFC categories (p=0.018). Z-LVEDV correlated with z-RVEDV (r2 = 0.69, p<0.001) and z- LVEF correlated with z-RVEF (r2 = 0.55, p <0.001). Z-LVEF and z-RVEF correlated with LV GCS (r2 = 0.48, p<0.001 and r2 = 0.46, p<0.001, respectively) and torsion (r2 = 0.21, p=0.032 for both). Forty-two patients had a follow-up CMR, after a median interval of 2.6 years (0.4- 8.4). The rate of deterioration of LV or RV EF or EDV did not differ between rTFC categories. A more rapid increase of z-RVEDV was associated with a faster decline in z-RVEF (r2 = -0.383, p=0.004) and z-LVEF (r2 = -0.45, p=0.001). A decline of z-LVEF over time correlated with that of z-RVEF (r2 = 0.60, p<0.001) and z-LVEDV increase correlated with z-RVEDV increase (r2 = 0.84, p<0.001). Conclusion: LV myocardial dysfunction is present in young patients with suspected or confirmed ARVC. Quantification of myocardial mechanics with CMR may be a useful tool to detect early LV involvement in ARVC. Progressive LV dysfunction and enlargement appear to parallel those of the RV.

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