Table 3.
Future directions: research priorities in ACM.
| Epidemiology and screening of ACM | Highly variable |
| Under-studied, underdiagnosed | |
| GWAS may be helpful to establish associations between patients’ genotype and phenotype; and to test existing genetic risk scores from other cardiac phenotypes with ACM phenotypes for associations. Moreover, this could be potentially developed into a screening test | |
| Clinical heterogeneity | Inter and intra-familial variability (even with some mutations) |
| Deep phenotyping with bipolar and unipolar voltage maps of RV, RVOT, LV, and with phenocopies | |
| Mechanisms of ACM | Pathophysiology and disease progression |
| Myocarditis as a possible trigger and predisposition to arrhythmias | |
| Animal models may be used to study the effect of protein mutations on ACM phenotypes, e.g., titin mutation and its link to heart failure | |
| Genetics | 40% undefined genetically |
| Genotype-phenotype correlation | |
| More precise definition of clinical phenotype | |
| GWAS and phenotype-genotype for effect modifiers? | |
| Desmosome | Study extra-cardiac desmosome expression such as buccal cells and skin |
| Inflammation and myocarditis | Investigate role of inflammation in animals and humans |
| Discern if ACM patients more susceptible to myocarditis | |
| Is inflammation primary or secondary? | |
| Is myocarditis a trigger for arrhythmogenicity? | |
| Is myocarditis an acute phase of ACM? | |
| Predicting SCD risk | Refine the criteria for ICD implantation in ACM patients e.g., balancing the benefits and risks of ICD, specifying the type of ICD (TV vs. SC) |
| Validation Hopkins Primary Prevention ARVC SCD risk calculator | |
| Evaluating blood biomarkers longitudinal studies | |
| Systematic follow-up of G+/P+, G+/P+, G−/P− understand evolution of arrhythmia | |
| Use of non-ICD therapies to manage arrhythmia risk | |
| Other therapies | Trials using standard anti-HF regimens in ACM (β-blockers, Angiotensin-converting enzyme, Angiotensin II receptor blocker, Mineralocorticoid receptor antagonist, Angiotensin receptor neprilysin inhibitor) |
| Disease-specific pathways to identify novel targets | |
| Skin and hair for testing novel therapies | |
| Precision medicine with the use of ‘avatars’ for testing therapies | |
| Establish trials with surrogate endpoints to expedite drug delivery |
GWAS = genome-wide association studies; G+ = genotype positive, G− = genotype negative, P+ = phenotype positive, P− = phenotype negative, HF = heart failure; RV = right ventricle; RVOT = right ventricular outflow tract; SC = subcutaneous; SCD = sudden cardiac death; TV = transvenous.