| 1. |
- Stokke, Mathis K, et al.
(författare)
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Absence of ECG task force criteria does not rule out structural changes in genotype positive ARVC patients
- 2020
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Ingår i: International Journal of Cardiology. - : Elsevier. - 0167-5273 .- 1874-1754. ; 317, s. 152-158
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: In Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), electrophysiological pathology has been claimed to precede morphological and functional pathology. Accordingly, an ECG without ARVC markers should be rare in ARVC patients with pathology identified by cardiac imaging. We quantified the prevalence of ARVC patients with evidence of structural disease, yet without ECG Task Force Criteria (TFC).METHODS AND RESULTS: We included 182 probands and family members with ARVC-associated mutations (40 ± 17 years, 50% women, 73% PKP2 mutations) from the Nordic ARVC Registry in a cross-sectional analysis. For echocardiography and cardiac MR (CMR), we differentiated between "abnormalities" and TFC. "Abnormalities" were defined as RV functional or structural measures outside TFC reference values, without combinations required to fulfill TFC. ECG TFC were used as defined, as these are not composite parameters. We found that only 4% of patients with ARVC fulfilled echocardiographic TFC without any ECG TFC. However, importantly, 38% of patients had imaging abnormalities without any ECG TFC. These results were supported by CMR data from a subset of 51 patients: 16% fulfilled CMR TFC without fulfilling ECG TFC, while 24% had CMR abnormalities without any ECG TFC. In a multivariate analysis, echocardiographic TFC were associated with arrhythmic events.CONCLUSION: More than one third of ARVC genotype positive patients had subtle imaging abnormalities without fulfilling ECG TFC. Although most patients will have both imaging and ECG abnormalities, structural abnormalities in ARVC genotype positive patients cannot be ruled out by the absence of ECG TFC.
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| 2. |
- Borgquist, Rasmus, et al.
(författare)
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The diagnostic performance of imaging methods in ARVC using the 2010 Task Force criteria.
- 2014
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Ingår i: European heart journal cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2412 .- 2047-2404. ; 15:11, s. 1219-1225
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Tidskriftsartikel (refereegranskat)abstract
- This study evaluates the agreement between echocardiographic and cardiac magnetic resonance (CMR) imaging data, and the impact a discrepancy between the two may have on the clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC).
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| 3. |
- Christensen, Alex Hörby, et al.
(författare)
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Genotype-phenotype correlation in arrhythmogenic right ventricular cardiomyopathy-risk of arrhythmias and heart failure.
- 2021
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Ingår i: Journal of medical genetics. - : BMJ PUBLISHING GROUP. - 1468-6244 .- 0022-2593.
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Tidskriftsartikel (refereegranskat)abstract
- Arrhythmogenic 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.The 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.We 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).In 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.
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| 4. |
- Christensen, Alex Horby, et al.
(författare)
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Genotype-phenotype correlation in arrhythmogenic right ventricular cardiomyopathy-risk of arrhythmias and heart failure
- 2022
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Ingår i: Journal of Medical Genetics. - : BMJ PUBLISHING GROUP. - 0022-2593 .- 1468-6244. ; 59:9, s. 858-864
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Tidskriftsartikel (refereegranskat)abstract
- Background Arrhythmogenic 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. Methods The 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. Results We 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). Conclusion In 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.
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| 5. |
- Haugaa, Kristina H, et al.
(författare)
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Management of patients with Arrhythmogenic Right Ventricular Cardiomyopathy in the Nordic countries.
- 2015
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 49:6, s. 299-307
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVES: Diagnostics of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) are complex, and based on the 2010 Task Force document including different diagnostic modalities. However, recommendations for clinical management and follow-up of patients with ARVC and their relatives are sparse. This paper aims to give a practical overview of management strategies, risk stratification, and selection of appropriate therapies for patients with ARVC and their family members.DESIGN: This paper summarizes follow-up and treatment strategies in ARVC patients in the Nordic countries. The author group represents cardiologists who are actively involved in the Nordic ARVC Registry which was established in 2009, and contains prospectively collected clinical data from more than 590 ARVC patients from Denmark, Norway, Sweden, and Finland.RESULTS: Different approaches of management and follow-up are required in patients with definite ARVC and in genetic-mutation-positive family members. Furthermore, ARVC patients with and without implantable cardioverter defibrillators (ICDs) require different follow-up strategies.CONCLUSION: Careful follow-up is required in patients with ARVC diagnosis to evaluate the need of anti-arrhythmic therapy and ICD implantation. Mutation-positive family members should be followed regularly for detection of early disease and risk stratification of ventricular arrhythmias.
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| 6. |
- Svensson, Anneli, 1972-, et al.
(författare)
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Genetic Variant Score and Arrhythmogenic Right Ventricular Cardiomyopathy Phenotype in Plakophilin-2 Mutation Carriers
- 2021
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Ingår i: Cardiology. - : S. Karger. - 0008-6312 .- 1421-9751. ; 146:6, s. 763-771
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Whether detailed genetic information contributes to risk stratification of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains uncertain. Pathogenic genetic variants in some genes seem to carry a higher risk for arrhythmia and earlier disease onset than others, but comparisons between variants in the same gene have not been done. Combined Annotation Dependent Depletion (CADD) score is a bioinformatics tool that measures the pathogenicity of each genetic variant. We hypothesized that a higher CADD score is associated with arrhythmic events and earlier age at ARVC manifestations in individuals carrying pathogenic or likely pathogenic genetic variants in plakophilin-2 (PKP2).METHODS: CADD scores were calculated using the data from pooled Scandinavian and North American ARVC cohorts, and their association with cardiac events defined as ventricular tachycardia/ventricular fibrillation (VT/VF) or syncope and age at definite ARVC diagnosis were assessed.RESULTS: In total, 33 unique genetic variants were reported in 179 patients (90 males, 71 probands, 96 with definite ARVC diagnosis at a median age of 35 years). Cardiac events were reported in 76 individuals (43%), of whom 53 had sustained VT/VF (35%). The CADD score was neither associated with age at cardiac events (HR 1.002, 95% CI: 0.953-1.054, p = 0.933) nor with age at definite ARVC diagnosis (HR 0.992, 95% CI: 0.947-1.039, p = 0.731).CONCLUSION: No correlation was found between CADD scores and clinical manifestations of ARVC, indicating that the score has no additional risk stratification value among carriers of pathogenic or likely pathogenic PKP2 genetic variants.
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| 7. |
- Svensson, Anneli, et al.
(författare)
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Natural Course of Electrocardiographic Features in Arrhythmogenic Right Ventricular Cardiomyopathy and Their Relation to Ventricular Arrhythmic Events.
- 2024
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 13:16
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Tidskriftsartikel (refereegranskat)abstract
- Electrocardiographic abnormalities are common in arrhythmogenic right ventricular cardiomyopathy and are included in the 2010 Task Force Criteria. Their time course, however, remains uncertain. In this retrospective observational study, we aimed to assess the long-term evolution of electrocardiographic characteristics and their relation to ventricular arrhythmias.Three hundred fifty-three patients with arrhythmogenic right ventricular cardiomyopathy as per the 2010 Task Force Criteria with 6871 automatically processed 12-lead digital ECGs were included. The relationship between the electrocardiographic parameters and the risk of ventricular arrhythmias was assessed at 10years from the first ECG. Electrocardiographic parameters were compared between the first contact ECG, the ECG at diagnosis, and the most recent ECG. Median time between the first and the latest ECG was 6 [interquartile range, 1-14] years. Reductions of QRS voltage, R- and T-wave amplitudes between the first, diagnostic, and the latest ECGs were observed across precordial and extremity leads. Mean QRS duration increased from 96 to 102ms (P<0.001), terminal activation duration (V1) from 47 to 52ms (P<0.001), and QTc from 419 to 432 ms (P<0.001). T-wave inversions in leads V3 to V6 and aVF at first ECG were associated with ventricular arrhythmias (adjusted hazard ratio [HRadj][V3], 2.03 [95% CI, 1.23-3.34] and HRadj[aVF], 1.87 [95% CI, 1.13-3.08]).Depolarization and repolarization parameters evolved over time in patients with arrhythmogenic right ventricular cardiomyopathy, supporting the progressive nature of arrhythmogenic right ventricular cardiomyopathy. Electrocardiographic abnormalities may be detected before diagnosis and might, although not fulfilling the 2010 Task Force Criteria, be markers of early disease. T-wave inversion in leads V3 or aVF before diagnosis was associated with ventricular arrhythmias during follow-up.
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