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- Author or Editor: Joshua A. Stern x
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Abstract
Objective—To sequence the exonic and splice site regions of the 4 desmosomal genes associated with the human form of familial arrhythmogenic right ventricular cardiomyopathy (ARVC) in Boxers with ARVC and identify a causative mutation.
Animals—10 unrelated Boxers with ARVC and 2 unaffected Labrador Retrievers (control dogs).
Procedures—Exonic and splice site regions of the 4 genes encoding the desmosomal proteins plakophilin-2, plakoglobin, desmoplakin, and desmoglein-2 were sequenced. Sequences were compared for nucleotide sequence changes between affected dogs and the published sequences for clinically normal dogs and between affected dogs and the control dogs. Base-pair changes were considered to be causative for ARVC if they were detected in an affected dog but not in unaffected dogs, and if they involved a conserved amino acid and changed that amino acid to one of a different polarity, acid-base status, or structure.
Results—A causative mutation for ARVC in Boxers was not identified, although single nucleotide polymorphisms were detected in some affected dogs within exon 3 of the plakophilin-2 gene; exon 3 of the plakoglobin gene; exons 3 and 7 of the desmoglein-2 gene; and exons 6, 14, 15, and 24 of the desmoplakin gene. None of these changed the amino acid of the respective protein.
Conclusions and Clinical Relevance—Mutations within the desmosomal genes associated with the development of ARVC in humans do not appear to be causative for ARVC in Boxers. Genomewide scanning for genetic loci of interest in dogs should be pursued.
Abstract
Objective—To identify Doppler echocardiographic (DE) variables that correlate with left ventricular filling pressure (LVFP).
Animals—7 healthy dogs (1 to 3 years old).
Procedures—Dogs were anesthetized and instrumented to measure left atrial pressure (LAP), left ventricular pressures, and cardiac output. Nine DE variables of LVFP derived from diastolic time intervals, transmitral and pulmonary venous flow, and tissue Doppler images were measured over a range of hemodynamic states induced by volume loading and right atrial pacing. Associations between simultaneous invasive measures of LVFP and DE measures of LVFP were determined by use of regression analysis. Receiver operating characteristic analysis was used to predict increases in mean LAP on the basis of DE variables.
Results—Mean LAP was correlated with several DE variables: the ratio between peak velocity during early diastolic transmitral flow and left ventricular isovolumic relaxation time (peak E:IVRT) during sinus rhythm and during right atrial pacing, IVRT, the ratio between late diastolic transmitral flow velocity and pulmonary venous flow duration, and the interval between onset of early diastolic mitral annulus motion and onset of early diastolic transmitral flow. Cutoff values of 2.20 and 2.17, for peak E:IVRT in dogs with sinus rhythm and atrial pacing predicted increases in mean LAP (≥ 15 mm Hg) with sensitivities of 90% and 100% and specificities of 92% and 100%, respectively.
Conclusions and Clinical Relevance—Doppler echocardiography can be used to predict an increase in LVFP in healthy anesthetized dogs subjected to volume loading.
Abstract
OBJECTIVE
To evaluate the frequency of variants in the pyruvate kinase dehydrogenase 4 (PDK4) and titin (TTN) genes in a group of Doberman Pinschers with dilated cardiomyopathy (DCM) and to determine whether there were unique clinical attributes to each variant.
ANIMALS
48 Doberman Pinschers with DCM.
PROCEDURES
Doberman Pinschers with recently diagnosed DCM were identified, and genomic DNA from each was genotyped with a PCR assay for detection of PDK4 and TTN genetic variants. Dogs were grouped on the basis of whether they had the TTN variant alone, PDK4 variant alone, both variants, or neither variant. Descriptive statistics were compiled for dog age, body weight, and left ventricular dimensions and fractional shortening and for the presence of ventricular and supraventricular arrhythmias and heart failure. Results were compared across groups.
RESULTS
Of the 48 dogs, 28 had the TTN variant alone, 10 had both variants, 6 had neither variant, and 4 had the PDK4 variant alone. The mean age was younger for dogs with the PDK4 variant alone, compared with other dogs. However, the number of dogs with the PDK4 variant alone was very small, and there was an overlap in age across groups. No other meaningful differences were detected across groups, and independent genotype-phenotype relationships were not identified.
CONCLUSIONS AND CLINICAL RELEVANCE
Although findings indicated that the TTN variant was most common, 6 dogs had neither variant, and this fact supported the concept of ≥ 1 other genetic contributor to DCM in Doberman Pinschers. Future studies are warranted to evaluate genotype-phenotype relationships in Doberman Pinschers with DCM.
Abstract
Objective—To determine the prevalence of ventricular arrhythmias in clinically normal adult Boxers.
Design—Prospective cross-sectional study.
Animals—301 Boxers (181 females and 120 males) > 1 year old with echocardiographically normal systolic function and no history of syncope or congestive heart failure.
Procedures—Physical examination, which included echocardiography, was performed on all dogs. A 24-hour ambulatory ECG was performed on each dog, and results were evaluated to assess ventricular arrhythmias. Statistical evaluation was performed to determine correlations between the total number of ventricular premature complexes (VPCs)/24 h, grade of ventricular arrhythmia, and age of the dogs.
Results—Age of dogs ranged from 1 to 16 years (median, 4 years). Number of VPCs/24 h in each dog ranged from 0 to 62,622 (median, 6 VPCs/24 h). Grade of arrhythmias ranged from 0 to 3 (median, 1). Age was correlated significantly with number of VPCs/24 h (r = 0.43) and with grade of arrhythmia (r = 0.37). Number of VPCs/24 h was significantly correlated with grade of arrhythmia (r = 0.82).
Conclusions and Clinical Relevance—Clinically normal adult Boxers generally had < 91 VPCs/24 h and an arrhythmia grade < 2. Boxers with > 91 VPCs/24 h were uncommon and may have represented dogs with arrhythmogenic right ventricular cardiomyopathy or other disease processes that could have resulted in the development of ventricular arrhythmias.
