Diagnostic Criteria and Disease Staging for Desmoplakin Cardiomyopathy
Eric Smith1, Alessio Gasperetti2, Richard T Carrick2
1Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, USA.
Insights
New criteria for Desmoplakin (DSP) cardiomyopathy improve diagnosis and risk stratification. These gene-specific guidelines help identify patients at risk for heart failure and arrhythmias, aiding future gene-targeted treatments.
Area of Science:
- Cardiology
- Genetics
- Medical Diagnostics
Background:
- Desmoplakin (DSP) cardiomyopathy, a distinct subtype caused by DSP gene variants, lacks established diagnostic and staging criteria.
- Current understanding differentiates it from typical dilated or arrhythmogenic right ventricular cardiomyopathies.
Purpose of the Study:
- To develop specific diagnostic and disease staging criteria for Desmoplakin (DSP) cardiomyopathy.
- To utilize a large cohort of DSP cardiomyopathy patients and their genotype-positive family members for criterion development.
Main Methods:
- Enrolled 605 patients from the DSP-ERADOS Network with comprehensive rhythm monitoring, ECG, and cardiac MRI data.
- Assessed diagnostic criteria in probands and genotype-positive family members, integrating early disease features (preserved LVEF) into LVEF-based classifications.
- Evaluated criteria using time-event analyses for major ventricular arrhythmia and heart failure events.
Main Results:
- Identified key diagnostic features: premature ventricular contractions (>500/24hr), nonsustained ventricular tachycardia, LV late gadolinium enhancement (LGE), and reduced LVEF, achieving 97% sensitivity with a DSP pathogenic variant.
- Established criteria classified 77% of genotype-positive family members as clinically affected, with isolated right ventricular involvement rare (0.7%).
- Integrated criteria refined risk stratification for arrhythmia/heart failure events, with higher risk associated with lower LVEF and circumferential LGE.
Conclusions:
- Developed genotype-specific diagnostic and staging criteria for DSP cardiomyopathy, enhancing risk identification for heart failure and ventricular arrhythmias.
- These criteria represent a critical step toward refining diagnosis and staging for cardiomyopathy subtypes, particularly as gene-targeted therapies advance.
Background:
Desmoplakin (DSP) cardiomyopathy, caused by variants in the gene DSP, is a unique subtype of cardiomyopathy distinct from typical dilated or arrhythmogenic right ventricular cardiomyopathies. Specific diagnostic and disease staging criteria have yet to be developed for DSP cardiomyopathy.
Objective:
Utilizing a large cohort of DSP cardiomyopathy patients and their genotype-positive family members, this study aims to develop diagnostic and disease staging criteria for DSP cardiomyopathy.
Methods:
Patients from the DSP-ERADOS Network with complete rhythm monitoring, electrocardiogram and cardiac magnetic resonance imaging were enrolled. Diagnostic criteria were assessed in initially-presenting patients (probands) and their genotype-positive family members. Early disease criteria (with preserved left ventricular ejection fraction, LVEF) were integrated into standard LVEF-based classifications. Diagnostic and staging criteria were assessed by time-event analyses (major ventricular arrhythmia and heart failure events).
Results:
A total of 605 patients with complete diagnostic testing were included (mean age 40 yr, 60% female, 40% probands). The most prevalent disease features in probands were premature ventricular contractions (PVCs) >500/24hr (66%), nonsustained ventricular tachycardia (NSVT, 29%), LV late gadolinium enhancement (LGE, 53%), and reduced LVEF (44%). The presence of any one of these features was 97% sensitive for diagnosis (along with a DSP pathogenic variant) and were therefore considered as diagnostic criteria. Using these criteria, 77% of genotype-positive family members were considered clinically affected. Isolated right ventricular (RV) involvement occurred in only 0.7%. The absence of diagnostic criteria identified a low-risk group (composite event rate 0.8%/year, p<0.001). Integration of these criteria into LVEF-based classification improved identification of composite arrhythmia/heart failure events (early: diagnostic criteria with LVEF ≥50%, HR 2.7, p=0.04; intermediate: LVEF 41-49%, HR 3.7, p=0.009; advanced: LVEF ≤40% HR 10.3, p<0.001). LGE was mostly subepicardial (87%). Circumferential (ring-like) LGE was more frequent in intermediate or advanced vs early disease (66% vs 48%, p<0.001).
Conclusion:
This study identifies genotype-specific diagnostic and disease staging criteria for DSP cardiomyopathy that improve identification of risk for both heart failure and sustained ventricular arrhythmias. This work highlights how gene-specific criteria may be used to refine diagnosis and staging for cardiomyopathy subtypes - a critical step as gene-targeted treatments move toward clinical trials.
Related Concept Videos
01:30Cardiomyopathy II: Dilated Cardiomyopathy
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
01:29Cardiomyopathy IV: Restrictive Cardiomyopathy
01:23Mitral Stenosis II: Clinical features and Diagnostic Tests
01:25Cardiomyopathy I: Introduction and Classification
01:05Desmosomes