Vlas in Dogs
Vlas in Dogs
Vlas in Dogs
ment usually involves indexing the left atrium to the study because clinically irrelevant tricuspid valve re-
aorta to serve as an internal control because body gurgitation is common in dogs11 and does not affect
size varies widely among dogs. However, echocardio- LA size.
graphic assessment of LA size is not always a practical Dogs enrolled in the study were sedated with bu-
option owing to the limited availability and cost of torphanol (0.1 to 0.3 mg/kg [0.045 to 0.136 mg/lb], IV
echocardiography in many areas and the training and or IM) for radiographic and echocardiographic exam-
expertise necessary to acquire and interpret echocar- inations at the discretion of the attending clinician.
diographic assessments. Likewise, the medication regimens for individual
Thoracic radiography is recommended as part of dogs were adjusted between radiographic and echo-
the diagnostic evaluation for all dogs with suspect- cardiographic examinations as deemed necessary by
ed MMVD regardless of whether they have clinical the attending clinician. Myxomatous mitral valve dis-
signs.8 Compared with echocardiography, thoracic ease was diagnosed on the basis of echocardiograph-
radiography is widely available, cost-effective, and ic findings and was defined as the presence of valvu-
considered part of the gold-standard procedures for lar thickening, irregularity, and prolapse of the mitral
diagnosis of left-sided CHF. However, radiographic as- valve apparatus and evidence of mitral valve regurgi-
sessment of LA size is primarily subjective and prone tation during systole as determined by color Doppler
to error. Consequently, quantitative methods for ra- ultrasonography.12 Decompensated left-sided CHF
diographic estimation of LA size would be of clini- was diagnosed on the basis of radiographic evidence
cal value, particularly when echocardiography is not of pulmonary edema that was deemed cardiogenic
readily available. Studies in which radiographic esti- in origin by a cardiologist and the presence of respi-
mates of LA size have been compared with echocar- ratory difficulty that was responsive to furosemide
diographic measurements of LA size (gold standard administration.
for LA measurement) are limited. Investigators of 1
study9 concluded that measurement of the tracheal Thoracic radiography
bifurcation angle on dorsoventral thoracic radio- For each dog, right lateral, left lateral, and dorso-
graphs was not reliable for estimation of LA size. ventral radiographic images of the thorax were ob-
The purpose of the study reported here was to tained in a routine manner by use of a commercially
describe VLAS, a quantitative method to estimate LA available digital radiography system.a A digital caliperb
size radiographically, and to determine its diagnostic was used to determine the VLAS on both the right lat-
value for prediction of echocardiographic LA enlarge- eral and left lateral thoracic images. First, a line was
ment in dogs with MMVD of varying severity. We hy- drawn and measured (in arbitrary units) from the cen-
pothesized that VLAS would accurately predict the ter of the most ventral aspect of the carina to the most
presence of echocardiographic LA enlargement in a caudal aspect of the left atrium where it intersected
large and diverse sample of dogs with MMVD. with the dorsal border of the caudal vena cava. For the
purpose of this study, the carina was defined as the
Materials and Methods radiolucent circular or ovoid structure within the tra-
chea that represented the bifurcation of the left and
Animals right mainstem bronchi. Similar to the vertebral heart
All study procedures were reviewed and ap- size method,13 a second line that was equal in length
proved by the University of California-Davis Institu- to the first was drawn beginning at the cranial edge of
tional Animal Care and Use Committee. All dogs were T4 and extending caudally just ventral and parallel to
examined at the University of California-Davis Veteri- the vertebral canal (Figure 1). The VLAS was defined
nary Medical Teaching Hospital, and owner consent as the length of the second line expressed in vertebral-
was obtained for all dogs prior to study enrollment. body units to the nearest 0.1 vertebra.
Dogs with a left-sided systolic murmur that under- The same investigator (ELM) measured the
went a complete echocardiographic examination in VLAS on all lateral images. That investigator was
conventional imaging planes as described10 and had unaware of (blinded to) the clinical diagnosis of all
3-view thoracic radiographs obtained within 24 hours dogs and was also responsible for performing all
before or after the echocardiographic examination echocardiographic measurements. The investigator
as part of a routine diagnostic evaluation were pro- was not present when thoracic radiographs were
spectively enrolled in the study in a sequential man- obtained or echocardiographic examinations were
ner during the 7-month period from December 2015 performed. For each dog, radiographic measure-
to June 2016. Dogs were excluded from the study if ments were obtained before the echocardiographic
thoracic radiography revealed overt malpositioning measurements.
of the patient or the presence of thoracic vertebral
abnormalities (eg, hemivertebrae). Dogs that were Echocardiography
< 1 year old (eg, skeletally immature) and those with All echocardiographic examinationsc were per-
acute CHF secondary to chordae tendinae rupture formed by a board-certified veterinary cardiologist
were also excluded from the study. Dogs with tricus- or a cardiology resident under the supervision of a
pid valve regurgitation were not excluded from the board-certified veterinary cardiologist. All echocar-
diographic variables were measured from 2-D echo- Study group allocation
cardiographic images or views. Dogs with MMVD were allocated to 1 of 4 groups
A digital off-cart workstationd was used for all in accordance with American College of Veterinary
echocardiographic measurements and calculations. Internal Medicine guidelines.8 Dogs allocated to the
Measurements were determined by the same inves- control group had a left-sided physiologic or flow mur-
tigator (ELM) who performed all radiographic mea- mur but were free of echocardiographic abnormali-
surements. That investigator was trained to evaluate ties. Dogs allocated to the stage B1 group had MMVD
the echocardiographic imaging planes and calculate with hemodynamically irrelevant mitral valve regur-
the measurements evaluated in the study by a board- gitation as determined on the basis of an LA:AoSx
certified veterinary cardiologist (LCV). That training < 1.6 or LA:AoLx < 2.6. Dogs allocated to the stage
consisted of a one-on-one 3-day training period dur- B2 group had MMVD with hemodynamically relevant
ing which echocardiographic studies of several dogs mitral valve regurgitation as determined on the basis
were reviewed and measurements were demonstrat- of an LA:AoSx ≥ 1.6 and LA:AoLx ≥ 2.6 but without
ed. The investigator reviewed current literature on evidence of previous (compensated) or concurrent
the quantification of LA size in dogs, then performed (decompensated) CHF. Dogs allocated to the stage
the measurements under the direct supervision of C-D group had MMVD and evidence of compensated
the cardiologist. The cardiologist assessed the inves- or decompensated CHF.
tigator’s progress, and once the investigator’s ability
to perform the measurements closely matched that Determination of VLAS measurement
of the cardiologist, the training period was consid- agreement
ered complete and the measurements for the study To determine the intraobserver agreement of
were acquired. All echocardiographic measurements VLAS measurements, 1 investigator (ELM) measured
made by the investigator were reviewed for accuracy the VLAS on right and left lateral thoracic radiographic
by the cardiologist. A given variable was remeasured images for 20 dogs on 3 separate occasions. To deter-
when there was substantial disagreement between mine interobserver agreement of VLAS measurements,
the investigator and cardiologist. Each echocardio- 3 other investigators (LCV, KLP, and LRJ) individually
graphic variable was measured 3 times, and the mean measured the VLAS on right and left lateral thoracic
radiographic images for the same 20 dogs. All investi- Youden index (1 + [sensitivity – specificity]), which
gators were blinded to the clinical diagnosis for each reflected the optimal combination of sensitivity and
dog and the VLAS measurements determined by the specificity and minimized the amount of overlap be-
other investigators. tween affected and unaffected dogs. The area under
the ROC curve was used to assess the diagnostic ac-
Statistical analysis curacy and quantify the predictive value of VLAS.
Statistical analyses were performed with com- Values of P < 0.05 were considered significant for all
mercial software packages.f,g Descriptive statistics analyses.
were generated. The distribution of data for continu-
ous variables was assessed for normality by means Results
of the D’Agostino-Pearson test. None of the variables
were normally distributed, and results were reported Dogs
as the median and IQR unless otherwise specified. The study population consisted of 103 dogs, and
Continuous variables were compared among the descriptive data for each of the 4 study groups were
4 study groups by means of the Kruskal-Wallis test summarized (Table 1). The control group consisted
followed by the Dunn test for pairwise comparisons of 3 Chihuahuas and 1 dog from each of 12 other
when necessary. χ2 Tests were used to compare pro- breeds. The stage B1 group consisted of 8 mixed-
portions among groups. The Spearman rank-order breed dogs, 4 Shih Tzus, 3 Labrador Retrievers, 3 Chi-
correlation coefficient (rS) was calculated to deter- huahuas, 3 Toy Poodles, 3 Maltese, 2 Boston Terriers,
mine the strength of the association between VLAS 2 Pit Bull Terriers, 2 Cavalier King Charles Spaniels,
and echocardiographic indices of LA size (LA:AoSx 2 American Cocker Spaniels, and 1 dog from each of
and LA:AoLx). The VLAS as determined from the 8 other breeds. The stage B2 group consisted of 10
right lateral thoracic radiograph versus that deter- mixed-breed dogs, 4 Chihuahuas, 3 Dachshunds, 2
mined from the left lateral thoracic radiograph was Cavalier King Charles Spaniels, and 1 dog from each
compared with a Wilcoxon signed rank test and as- of 7 other breeds. The stage C-D group consisted of
sessed for bias and limits of agreement by means of 4 Cavalier King Charles Spaniels, 3 American Cocker
the Bland-Altman method. The extent of intraobserv- Spaniels, 2 Chihuahuas, 2 mixed-breed dogs, and 1
er and interobserver agreement for VLAS measure- dog from each of 11 other breeds.
ments was assessed by means of the ICC, and agree- The median age and left-sided murmur grade for
ment was considered high when the ICC was > 0.75. dogs with MMVD (ie, dogs in the stage B1, B2, and
Receiver operating characteristic analysis was used to C-D groups) were significantly greater than the corre-
assess the optimal cutoff value for VLAS (as measured sponding values for dogs in the control group (Table
on a right lateral thoracic radiograph) to predict LA 1). The sex distribution did not differ significantly (P
enlargement as determined on the basis of 3 sets of = 0.87) among the 4 study groups. The LA size for
criteria (LA:AoLx ≥ 2.6, LA:AoSx ≥ 1.6, and LA:AoLx dogs in the stage B2 and C-D groups was significantly
≥ 2.6 and LA:AoSx ≥ 1.6). For each set of criteria, the greater than that for dogs in the control and stage B1
optimal clinically relevant cutoff value for VLAS was groups regardless of the method (LA:AoSx, LA:AoLx,
defined as the measurement that yielded the highest or VLAS) used to assess LA size.
Table 1—Descriptive data for 103 dogs with a left-sided systolic murmur that underwent a complete echocardiographic
examination and had 3-view (right lateral, left lateral, and ventrodorsal) thoracic radiographs obtained as part of a routine diagnostic
evaluation at a veterinary teaching hospital from December 2015 through June 2016.
Study group
Variable Control Stage B1 Stage B2 Stage C-D P value
No. of dogs 15 40 26 22 —
Body weight (kg) 9.3 (5.4–27.2) 8.7 (5.7–27.3) 7.5 (5.4–13.2) 8.4 (4.8–10.9) 0.49
Age (y) 5.0 (2.4–11.0) 10.3 (8.5–13.3)* 11.1 (8.9–13.3)* 10.3 (7.7–11.8)* < 0.001
No. (%) of females 9 (60) 20 (50) 14 (54) 13 (59) 0.87
Murmur grade (scale, 1–6) 2 (1–2) 3 (2–4)* 4 (3–4)* 4 (4–5)*† < 0.001
LA:AoSx 1.3 (1.2–1.4) 1.4 (1.3–1.5) 2.0 (1.8–3.3)*† 2.6 (2.0–3.4)*† < 0.001
LA:AoLx 2.3 (2.1–2.4) 2.5 (2.2–2.6) 3.3 (2.9–3.7)*† 4.1 (3.6–4.8)*† < 0.001
VLAS (No. of vertebrae) 2.1 (1.8–2.3) 2.1 (2.0–2.4) 2.6 (2.3–2.9)*† 3.0 (2.7–3.6)*† < 0.001
Values represent the median (IQR) unless otherwise indicated. Dogs allocated to the control group had a left-sided physiologic or flow
murmur but were free of echocardiographic abnormalities. Dogs allocated to the stage B1 group had MMVD with hemodynamically irrelevant
mitral valve regurgitation as determined on the basis of an LA:AoSx < 1.6 or LA:AoLx < 2.6. Dogs allocated to the stage B2 group had MMVD with
hemodynamically relevant mitral valve regurgitation as determined on the basis of an LA:AoSx ≥ 1.6 and LA:AoLx ≥ 2.6 but without evidence of
previous (compensated) or concurrent (decompensated) CHF. Dogs allocated to the stage C-D group had MMVD and evidence of compensated
or decompensated CHF.
*Within a row, value differs significantly (P < 0.05) from that for the control group. †Within a row, value differs significantly (P < 0.05) from
that for the stage B1 group.
— = Not determined.
Of the 22 dogs in the stage C-D group, 12 (55%) received medications for the treatment of cardiac
had concurrent (decompensated) CHF and 10 (45%) disease between the radiographic and echocardio-
had compensated CHF owing to the administration of graphic examinations. All 10 of those dogs received
various medications. Ten dogs in the stage C-D group furosemide, IV, and 7 also received pimobendan, PO.
The medication regimens for the remaining 93 study
dogs were not modified between the radiographic
and echocardiographic examinations.
Correlation analyses
The VLAS was positively correlated with both
LA:AoSx (rS, 0.70; 95% CI, 0.59 to 0.80; P < 0.001)
and LA:AoLx (rS, 0.73; 95% CI, 0.63 to 0.81; P < 0.001;
Figure 2). When the 10 dogs in the stage C-D group
that received furosemide with or without pimoben-
dan were removed from the analyses, the correlation
between VLAS and LA:AoSx (rS, 0.73; 95% CI, 0.61 to
0.81) and LA:AoLx (rS, 0.76; 95% CI, 0.66 to 0.84) im-
proved slightly.
Table 2—Diagnostic accuracy of various LVAS cutoffs for radiographic prediction of LA enlargement when LA enlargement was
defined by each of 3 sets of echocardiographic criteria.
ROC analysis
Echocardiographic criteria AUC VLAS cutoff Sensitivity Specificity Youden
for LA enlargement (95% CI) P value (No. of vertebrae) Cutoff type (%) (%) index
LA:AoLx ≥ 2.6 0.84 (0.77–0.92) < 0.001 ≥ 1.9 Maximum sensitivity 100 20 20
≥ 2.3 Clinically relevant 87 67 53
≥ 3.0 Maximum specificity 36 100 36
LA:AoSx ≥ 1.6 0.84 (0.77–0.92) < 0.001 ≥ 1.9 Maximum sensitivity 100 21 21
≥ 2.5 Clinically relevant 67 84 50
≥ 2.8 Maximum specificity 49 100 49
LA:AoLx ≥ 2.6 and 0.88 (0.82–0.94) < 0.001 ≥ 1.9 Maximum sensitivity 100 16 16
LA:AoSx ≥ 1.6 ≥ 2.4 Clinically relevant 81 77 58
≥ 2.9 Maximum specificity 51 100 51
Data used for the analyses were obtained from the dogs of Table 1. The area under the ROC curve (AUC) was used to assess the diagnostic accuracy and
quantify the predictive value of VLAS. Three VLAS cutoff values were determined for each set of echocardiographic criteria for LA enlargement. One cutoff value
represented the most clinically relevant value for VLAS (ie, value with the highest Youden index). One cutoff value represented the VLAS that yielded maximum
sensitivity (ie, fewest false-negative results), and the remaining cutoff value represented the VLAS that yielded maximum specificity (ie, fewest false-positive results).
See Table 1 for remainder of key.
to 2.8 vertebrae). Bland-Altman analysis of the VLAS ments to determine LA size would increase the likeli-
acquired from right versus left lateral thoracic radio- hood of correctly diagnosing LA enlargement when
graphs revealed a mean ± SD bias of 0.02 ± 0.3 verte- it was present, and that comparison of VLAS with
brae (95% limits of agreement, –0.5 to 0.6 vertebrae). multiple echocardiographic measurements of LA size
The intraobserver and interobserver ICCs for VLAS would be more advantageous than comparison with
were high regardless of the lateral thoracic image only 1 echocardiographic measurement for assessing
(right or left) used for measurement. The intraobserv- its diagnostic value to detect LA enlargement. Also,
er ICC for VLAS was 0.93 and 0.89 when measured the echocardiographic criteria (LA:AoLx ≥ 2.6 and
on right and left lateral thoracic radiographs, respec- LA:AoSx ≥ 1.6) used to diagnose LA enlargement in
tively. The interobserver ICC for VLAS was 0.87 and the present study were purposely selected because
0.91 when measured on right and left lateral thoracic results of other studies4,5 indicate that dogs that meet
radiographs, respectively. those criteria likely have hemodynamically relevant
MMVD and require therapeutic intervention. There-
fore, accurate identification of those dogs, whether
Discussion by radiographic (VLAS) or echocardiographic means,
The purpose of the study reported here was to is clinically important for assessment of risks for CHF
describe how to measure VLAS, a new technique and anesthesia, development and modification of
for quantifying LA size on thoracic radiographs, and treatment regimens, and determining the prognosis.
determine its diagnostic value for predicting LA en- Results of the present study indicated that there was
largement in dogs with MMVD when compared with a significant positive correlation between VLAS and
echocardiographic measurement of LA size (gold both LA:AoSx and LA:AoLx, and VLAS cutoffs of 2.3
standard). Results indicated that VLAS is a highly re- to 2.5 vertebrae were associated with an LA:AoSx ≥
producible measurement that has a moderate positive 1.6 and LA:AoLx ≥ 2.6 (or both). Thus, a VLAS ≥ 2.3
correlation with echocardiographic measurements vertebrae can be used as a radiographic indicator of
of LA size. Thus, the VLAS provided a quantitative LA enlargement, and dogs with a VLAS ≥ 2.3 verte-
measurement of LA size that can be determined from brae likely have hemodynamically important MMVD.
right or lateral thoracic radiographs, which will be In the present study, we used linear echocar-
useful for veterinarians who do not have ready access diographic dimensions of the left atrium indexed to
to echocardiography. the aorta (LA:AoSx and LA:AoLx) to measure LA size
We believe that VLAS can provide valuable di- and serve as clinical gold standards. However, those
agnostic information for dogs with a left-sided apical measurements are simply surrogates for LA volume
systolic murmur in conjunction with clinical signs of estimates and do not represent a true gold standard
coughing or respiratory difficulty. Those signs often of LA size (ie, LA volume). An example of a true gold
create a clinical conundrum for veterinarians because standard is LA volume determined by multidetector
they can be caused by airway disease or cardiogenic CT,16 which is commonly measured in human medi-
pulmonary edema. Measurement of the VLAS could be cine. We chose to compare VLAS with LA:AoSx and
helpful for determining whether the LA is enlarged. In LA:AoLx because we believe most veterinarians use
our clinical experience, dogs with MMVD generally do those ratios to quantify LA size. Also, linear measure-
not develop signs of CHF without at least some degree ment ratios represent an efficient and practical meth-
(frequently moderate) of LA enlargement. The excep- od to estimate LA size. Alternate volumetrically based
tion to that observation is the rare dog with MMVD methods for quantification of LA size in dogs are less
that develops acute CHF secondary to rupture of a efficient and largely unavailable, lack reference inter-
major chordae tendinae; however, such dogs were ex- vals, or, in the case of CT, require anesthesia. Finally,
cluded from the present study. most of the veterinary literature regarding dogs with
The veterinary literature contains few studies MMVD use linear measurement ratios of LA size, par-
that describe quantitative radiographic measurement ticularly LA:AoSx, to help guide clinical decisions.2–7
of the LA size in dogs. In 1 study,9 the diagnostic The present study was not without limitations.
value of the tracheal bifurcation angle as determined The clinical value of the VLAS cutoffs determined in
from a dorsoventral thoracic radiograph for predict- this study is applicable only to dogs with left-sided
ing LA:AoSx was evaluated. Unfortunately, the results systolic murmurs and MMVD. Further research is
of that study9 indicate that there is extensive over- necessary to determine the diagnostic value of VLAS
lap between the tracheal bifurcation angles of clini- as a radiographic indicator of LA size for dogs with
cally normal dogs and dogs with varying degrees of other diseases or in other scenarios. Also, measure-
LA enlargement; therefore, the sensitivity of the tra- ment of the VLAS for a large number of healthy dogs
cheal bifurcation angle was insufficient to support of various breeds is necessary to establish reference
its use in clinical settings. In the present study, the intervals, as was done for vertebral heart size, a mea-
sensitivity and specificity of VLAS for detection of surement performed in a similar manner as VLAS.17–19
LA enlargement were calculated when 2 echocar- For dogs suspected of having MMVD, VLAS should
diographic measurements of LA size (LA:AoSx and be considered complementary rather than confirma-
LA:AoLx) were used as the gold standard. We be- tory information, and echocardiography should be
lieved that the use of 2 echocardiographic measure- performed whenever possible. In the present study,
without left atrial enlargement. Vet Radiol Ultrasound radiographic diagnosis of cardiac disease in dogs. Vet Rec
2002;43:568–575. 2001;148:707–711.
15. Rishniw M, Erb HN. Evaluation of four 2-dimensional echo- 19. Marin LM, Brown J, McBrien C, et al. Vertebral heart size
cardiographic methods of assessing left atrial size in dogs. in retired racing Greyhounds. Vet Radiol Ultrasound
J Vet Intern Med 2000;14:429–435. 2007;48:332–334.
16. Miyasaka Y, Tsujimoto S, Maeba H, et al. Left atrial volume 20. Häggström J, Lord PF, Höglund K, et al. Short-term hemo-
by real-time three-dimensional echocardiography: validation dynamic and neuroendocrine effects of pimobendan and
by 64-slice multidetector computed tomography. J Am Soc benazapril in dogs with myxomatous mitral valve disease
Echocardiogr 2011;24:680–686. and congestive heart failure. J Vet Intern Med 2013;27:1452–
17. Jepsen-Grant K, Pollard RE, Johnson LR. Vertebral heart 1462.
scores in eight dog breeds. Vet Radiol Ultrasound 21. Fine DM, Durham HE Jr, Rossi NF, et al. Echocardiograph-
2013;54:3–8. ic assessment of hemodynamic changes produced by two
18. Lamb CR, Wikeley H, Boswood A, et al. Use of breed-spe- methods of inducing fluid deficit in dogs. J Vet Intern Med
cific ranges for the vertebral heart scale as an aid to the 2010;24:348–353.
OBJECTIVE
To investigate cardiac structural and functional changes by tissue Doppler imaging (TDI) and
strain imaging in dogs with spontaneous type 1 diabetes mellitus.
ANIMALS October 2018
30 client-owned dogs, of which 10 had normotensive type 1 diabetes mellitus and 20 were healthy.
PROCEDURES
All dogs underwent physical examination, laboratory analyses, standard echocardiography, and TDI.
See the midmonth
RESULTS issues of JAVMA
On TDI and strain imaging, transmitral peak early diastolic velocity (E)-to-tissue Doppler–derived for the expanded
peak early diastolic velocity at basal segment (E′) of septum ratio, E:lateral E′ ratio, and septal tis-
sue Doppler–derived peak late diastolic velocity at basal segment (A′) were significantly higher table of contents
and the septal E′:A′ ratio and lateral longitudinal strain were significantly lower for diabetic dogs for the AJVR
than for control dogs. Furthermore, in diabetic dogs, serum glucose and fructosamine concentra-
tions after a 12-hour period of food withholding were positively correlated with regional systolic or log on to
functional variables (septal and lateral longitudinal strain) and left ventricular filling pressure indices avmajournals.avma.org
(E:septal E′ and E:lateral E′ ratios) but were negatively correlated with diastolic functional variables
(E:transmitral peak late diastolic velocity and septal and lateral E′:A′ ratios).
for access
CONCLUSIONS AND CLINICAL RELEVANCE to all the abstracts.
Results indicated that myocardial function in diabetic dogs may be altered before the development of
clinical heart-associated signs and that the change may be more readily detected by TDI and strain im-
aging than by conventional echocardiography. In addition, findings indicated that hyperglycemia could
have detrimental effects on myocardial function, independent of hypertension, other cardiac diseases,
and left ventricular hypertrophy, in dogs with type 1 diabetes. (Am J Vet Res 2018;79:1035–1043)