Cardiovascular Characteristics of Patients with Genetic Variation in Desmoplakin (DSP)

Background: Variants in the desmoplakin (DSP) gene have been recognized in association with the pathogenesis of arrhythmogenic right ventricular cardiomyopathy (ARVC) for nearly 20 years. More recently, genetic variation in DSP has also been associated with left-dominant arrhythmogenic cardiomyopathy. Data regarding the cardiac phenotypes associated with genetic variation in DSP have been largely accumulated from phenotype-first studies of ARVC. Methods: We aimed to evaluate the clinical manifestations of cardiac disease associated with variants in DSP through a genotype-first approach employed in the University of Pennsylvania Center for Inherited Cardiovascular Disease registry. We performed a retrospective study of 19 individuals with “pathogenic” or “likely pathogenic” variants in DSP identified by clinical genetic testing. Demographics and clinical characteristics were collected. Results: Among individuals with disease-causing variants in DSP, nearly 40% had left ventricular enlargement at initial assessment. Malignant arrhythmias were prevalent in this cohort (42%) with a high proportion of individuals undergoing primary and secondary prevention implantable cardioverter defibrillator implantation (68%) and ablation of ventricular arrhythmias (16%). Probands also experienced end-stage heart failure requiring heart transplantation (11%). Conclusions: Our data suggest DSP cardiomyopathy may manifest with a high burden of heart failure and arrhythmic events, highlighting its importance in the pathogenesis of dilated and arrhythmogenic cardiomyopathies. Targeted strategies for diagnosis and risk stratification for DSP cardiomyopathy should be investigated.

Validation of the local applicability of the ‘TIB’ Olfactory Test Device in the era of COVID-19

Objective To evaluate the validity and test–retest reliability of the novel ‘TIB’ Olfactory Test Device (TIB) and to determine its normative values. Methods The study stratified the study subjects into normosmic, hyposmic and anosmic groups according to their olfactory function. The olfactory function of the subjects was evaluated using both the traditional Chinese version of the University of Pennsylvania of Smell Identification Test (UPSIT-TC) and the TIB. The normosmic group was used to retest with the UPSIT-TC and TIB at an inter-test interval of at least 7 days. The cut-off scores of TIB among the three different groups were determined by receiver operating characteristic curve analysis. Results This study enrolled 180 subjects: 60 in each group. The mean scores of TIB were 44.1 for the normosmic group, 27.5 for the hyposmic group and 10.9 for the anosmic group. The TIB scores were significantly different across the three groups. There was a significant correlation between the first and second TIB tests ( r = 0.506). The cut-off scores were 41 for normosmic subjects and 24 for hyposmic subjects. Conclusion The validity and test–retest reliability results suggest that the TIB is an appropriate olfactory test for the Taiwanese population.