Control group and reference intervals
There was no significant difference between CTs of the 2 healthy dog populations (P=.87), so data from the 21 dogs were merged with data from the 37 healthy dogs used in a preliminary study to achieve the control group of 58 dogs. These dogs ranged in age from 6 months to 13 years, represented 17 breeds, and included 2 intact females, 23 spayed females, 4 intact males, and 27 neutered males. One female and 1 male dog had unknown neuter status.
CTs for the 58 control dogs ranged from 48 to 79 seconds (Figure 1) (mean±SD, 57.6±5.9 seconds; median, 56.5 seconds). CVs ranged from 0% to 10% (3.79±2.66%, median 3.00%). A CT reference interval of 48–77 seconds was calculated.
Figure 1. Closure times in 58 healthy dogs determined by the PFA-100 analyzer. Mean±SD, 57.6±5.9 seconds; median, 56.5 seconds; range, 48–79 seconds.
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Dogs with cardiac disease
Fifty-five dogs with cardiac disease were initially sampled. Sixteen dogs were excluded due to low vWF:Ag results (n=6), medication histories with exclusionary drugs (n=6), low HCT (n=3), or a combination of low vWF:Ag and drugs (n=1). All dogs with cardiac murmurs that had plasma vWF:Ag analysis performed (33/39) had vWF:Ag concentrations >55%. Six dogs with cardiac murmurs that did not have vWF:Ag analysis performed had CTs within the reference interval. The 39 dogs included in the study were 8 intact females, 9 spayed females, 4 intact males, and 16 neutered males that ranged in age from 4 to 168 months and ranged in weight from 4.6 to 56.8 kg. No significant differences in CT were found between gender groups (P=.989). Twenty-three breeds were represented, including 6 CKCS, 4 Golden Retrievers, 3 Boxers, 3 mixed breed, 2 of each Border Collie, Bichon Frise, Bull Mastiff, and Boston Terrier, and 1 of each Cocker Spaniel, Dachshund, Miniature Poodle, Shih Tzu, West Highland White Terrier, Australian Shepherd, Bull Terrier, German Shepherd, Greyhound, Labrador Retriever, English Springer Spaniel, Pomeranian, Afghan, Beagle, and Newfoundland.
The CT for dogs with cardiac murmurs ranged from 48 to 187 seconds (79.6±24.1 seconds; median, 74.0 seconds). Of the 39 dogs with cardiac disease, 21 had CTs within the reference interval and 18 had CTs above the upper limit. A significantly longer median CT was found in the group of dogs with cardiac murmurs compared with controls (P<.001) (Figure 2). In subgroup analysis, a significant difference in median CT was found in both the valvular insufficiency (n=23; P<.001) and subaortic stenosis (n=9; P=.007) subgroups when compared with controls (n=58) (Figure 2). CT was not significantly different between the 2 cardiac subgroups (P=.227). For the 23 dogs with valvular insufficiency, correlation between CT and ATJ, ATJ:AA, and ATJ:Ao was poor (r2<.12; data not shown). For the 9 dogs with subaortic stenosis and the 1 dog with pulmonic stenosis, correlations between CT and velocity (r2=.46) and CT and pressure gradient (r2=.44) were also weak. While CTs tended to be longer with increasing murmur grade, no significant differences in CT were found between murmur grades.
Figure 2. Closure times (CTs) for dogs with cardiac murmurs compared with control dogs. Median CTs differ significantly in dogs with various types of cardiac murmurs (overall cardiac group; n=39; P<.001), dogs with valvular insufficiency (VI; n=23; P<.001), and dogs with subaortic stenosis (SS; n=9; P=.007), compared with control dogs (n=58). Crosshair symbols indicate median CT, dashed lines indicate lower and upper reference limits, and asterisks indicate outliers.
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The remaining 7 dogs with a murmur that were not included in either of the subgroups had various cardiac conditions that included physiological murmurs (n=3, CT 63, 72, and 94.5 seconds, murmur grades I/VI, II/VI, and IV/VI, respectively), ventricular septal defects (n=2, CT 48 and 118 seconds, murmur grades III/VI and V/V, respectively), and patent ductus arteriosus (PDA) (n=2, CT 74 and 111, murmur grades IV/VI and V/VI, respectively). One dog with valvular insufficiency had, in addition to congenital mitral valve dysplasia, a ventricular septal defect, and PDA. This dog had the longest CT observed (187 seconds) and a murmur grade of V/VI.
Three of the dogs with cardiac disease had CTs recorded both pre- and postsurgical intervention. These included 1 dog with PDA, 1 dog with PDA and mitral valve dysplasia, and 1 dog with valvular pulmonic stenosis and a ventricular septal defect. The dog with PDA had an initial CT of 110 seconds and CTs of 65 and 66 seconds, 2 and 3 days after complete surgical ligation of the patent ductus, respectively. No murmur was auscultable postoperatively and color-flow Doppler echocardiography results indicated an absence of turbulence. The dog with PDA and mitral valve dysplasia had an initial CT of 111 seconds and a CT of 187 seconds at 2 months postoperatively. Surgical correction had been attempted by thoracotomy but the lesions were not safely correctable and the patient was discharged without a change in cardiac status. Cardiac evaluation 2 months postoperatively showed worsening turbulence with color-flow Doppler echocardiography and the dog died of congestive heart failure 8 months postoperatively. The dog with valvular pulmonic stenosis and a ventricular septal defect had an initial CT of 93.5 seconds, with a CT of 118 seconds at 2 months postsurgical correction with thoracotomy and partial instrument dilation of the stenotic pulmonic valve and no treatment of the septal defect.
To ensure breed bias was not a confounding factor, statistical analyses were performed excluding the 6 CKCS dogs. Statistically significant differences were found between the remaining dogs with cardiac murmurs (n=23) and dogs with valvular insufficiency (n=17) compared with controls (for both groups, P<.001).