Publications (28) View all
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Article: Cardiac transplantation in arrhythmogenic right ventricular dysplasia/cardiomyopathy.
Journal of the American College of Cardiology 01/2012; 59(3):289-90. · 14.16 Impact Factor -
Article: Shared desmosome gene findings in early and late onset arrhythmogenic right ventricular dysplasia/cardiomyopathy.
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ABSTRACT: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited form of cardiomyopathy with low penetrance and variable expressivity. Dominant mutations and rare polymorphisms in desmosome genes are frequently identified. We reasoned that individuals with earlier onset disease would have more frequent desmosome gene mutations and rare polymorphisms. Three groups were compared: Young with symptoms attributable to ARVD/C or a diagnosis of ARVD/C at age of 21 years or earlier, Middle with first symptoms or diagnosis age of 22-49 years, and Late with first symptoms or diagnosis at age of 50 or more years. deoxyribonucleic acid (DNA) sequence analysis was performed on five cardiac desmosome genes, and the presence of mutations and rare missense polymorphisms was compared among the three groups. In the entire Young cohort, 20 (67%) had one or more cardiac desmosome gene mutations. The prevalence of cardiac desmosome gene mutations was similar in the Middle (48%) and Late (53%) cohorts (P = 0.23). Similar numbers of individuals in each cohort had more than one desmosome gene mutation, although the numbers are too small for statistical comparisons. The prevalence of certain rare missense DNA variants was not different among the cohorts (P = 0.71), yet these rare missense alleles were more prevalent in the overall study cohort of 112 ARVD/C participants compared to 100 race-matched controls (P = 0.027). The presence of these variants did not associate with the age of onset of ARVD/C or ventricular tachycardia. These findings highlight the complex interplay of environmental and genetic factors contributing to this condition.Journal of Cardiovascular Translational Research 12/2010; 3(6):663-73. · 2.61 Impact Factor -
Article: Reader- and instrument-dependent variability in the electrocardiographic assessment of arrhythmogenic right ventricular dysplasia/cardiomyopathy.
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ABSTRACT: Despite the use of standardized definitions, widely varying prevalence estimates of electrocardiographic (ECG) features related to arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) have been reported in different cohorts. This study was aimed at examining the variability in the ECG interpretation resulting from the same reader, different readers, and using different ECG-resolutions. Blinded to other clinical data, 2 readers examined quantitative and qualitative ECG features of 20 (10 ARVD/C) randomly selected individuals. ECGs were recorded at standard-speed (SS) and double-speed-double-amplitude (DS) settings. The SS ECGs were scanned, magnified 4×, and evaluated using electronic calipers (EL). One reader repeated all measurements. For both readers, the intraclass correlation coefficient (ICC) for the measurement of QRS duration was good between conventional and electronic evaluation [DS vs EL: Reader 1--0.64 (0.52-0.73); Reader 2--0.67 (0.55-0.76)][SS vs EL: Reader 1--0.60 (0.47-0.70); Reader 2--0.60 (0.47-0.70)]. Using the same resolution, the intrareader ICC was good for SS [0.70 (0.59-0.78)], DS [0.85 (0.80-0.90)], and EL [0.70 (0.69-0.83)] resolutions, but deteriorated for interreader comparisons [0.50 (0.36-0.62), 0.75 (0.66-0.82), and 0.75 (0.66-0.82), respectively]. For qualitative parameters, the intra- and interreader agreement was inconsistent for all but 2 parameters. Both readers were in perfect agreement while interpreting right precordial T-wave inversion [κ= 1] and right bundle branch block morphology (RBBB) [κ= 0.83 (0.5-1.0)] even when using SS resolution. Right precordial t-wave inversion and RBBB are the only ECG parameters that can be detected consistently even using the conventionally used ECG-resolution. The substantial variability in evaluation of other parameters is not improved even with the use of higher resolutions.Journal of Cardiovascular Electrophysiology 11/2010; 22(5):561-8. · 3.06 Impact Factor -
Article: Comprehensive desmosome mutation analysis in north americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy.
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ABSTRACT: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited disorder typically caused by mutations in components of the cardiac desmosome. The prevalence and significance of desmosome mutations among patients with ARVD/C in North America have not been described previously. We report comprehensive desmosome genetic analysis for 100 North Americans with clinically confirmed or suspected ARVD/C. In 82 individuals with ARVD/C and 18 people with suspected ARVD/C, DNA sequence analysis was performed on PKP2, DSG2, DSP, DSC2, and JUP. In those with ARVD/C, 52% harbored a desmosome mutation. A majority of these mutations occurred in PKP2. Notably, 3 of the individuals studied have a mutation in more than 1 gene. Patients with a desmosome mutation were more likely to have experienced ventricular tachycardia (73% versus 44%), and they presented at a younger age (33 versus 41 years) compared with those without a desmosome mutation. Men with ARVD/C were more likely than women to carry a desmosome mutation (63% versus 38%). A mutation was identified in 5 of 18 patients (28%) with suspected ARVD. In this smaller subgroup, there were no significant phenotypic differences identified between individuals with a desmosome mutation compared with those without a mutation. Our study shows that in 52% of North Americans with ARVD/C a mutation in one of the cardiac desmosome genes can be identified. Compared with those without a desmosome gene mutation, individuals with a desmosome gene mutation had earlier-onset ARVD/C and were more likely to have ventricular tachycardia.Circulation Cardiovascular Genetics 10/2009; 2(5):428-35. · 6.11 Impact Factor -
Article: Prevalence and pathophysiologic attributes of ventricular dyssynchrony in arrhythmogenic right ventricular dysplasia/cardiomyopathy.
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ABSTRACT: This study sought to investigate the prevalence and mechanisms underlying right ventricular (RV) dyssynchrony in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) using tissue Doppler echocardiography (TDE). An ARVD/C is characterized by fibrofatty replacement of RV myocardium and RV dilation. These pathologic changes may result in electromechanical dyssynchrony. Echocardiography, both conventional and TDE, was performed in 52 ARVD/C patients fulfilling Task Force criteria and 25 control subjects. The RV end-diastolic and -systolic areas, right ventricular fractional area change (RVFAC), and left ventricular (LV) volumes and function were assessed. Mechanical synchrony was assessed by measuring differences in time-to-peak systolic velocity (T(SV)) between the RV free wall, ventricular septum, and LV lateral wall. An RV dyssynchrony was defined as the difference in T(SV) between the RV free wall and the ventricular septum, >2 SD above the mean value for control subjects. The mean difference in RV T(SV) was higher in ARVD/C compared with control subjects (55 +/- 34 ms vs. 26 +/- 15 ms, p < 0.001). Significant RV dyssynchrony was not noted in any of the control subjects. Based on a cutoff value of 56 ms, significant RV dyssynchrony was present in 26 ARVD/C patients (50%). Patients with RV dyssynchrony had a larger RV end-diastolic area (22 +/- 5 cm(2) vs. 19 +/- 4 cm(2), p = 0.02), and lower RVFAC (29 +/- 8% vs. 34 +/- 8%, p = 0.03) compared with ARVD/C patients without RV dyssynchrony. No differences in QRS duration, LV volumes, or function were present between the 2 groups. An RV dyssynchrony may occur in up to 50% of ARVD/C patients, and is associated with RV remodeling. This finding may have therapeutic and prognostic implications in ARVD/C.Journal of the American College of Cardiology 08/2009; 54(5):445-51. · 14.16 Impact Factor
