14
Abbreviations:
Ao aortic root diameter
CDMD degenerative mitral valvular disease
E/A early diastolic velocity/late diastolic velocity ratio
EF ejection fraction
FS fractional shortening
IVS thickness of interventricular septum LA left atrial diameter
LMB left cranial main stem bronchus LVED left ventricular dimension
LVFWd thickness of left ventricular free wall at end-diastole
MR mitral valve regurgitation
NYHA modified New York heart association functional classification RMB right cranial main stem bronchus
TB angle angle of tracheal bifurcation
TBC tracheobronchial collapse
TC tracheal collapse
TD tracheobronchial diameter
TI thoracic inlet distance
TR tricuspid regurgitation
VHS vertebral heart scale
15
Luminal diameters of trachea and bronchi in small breed dogs with and without chronic degenerative mitral valvular disease
Tzu-Chi Tai, Hui-Pi Huang
Department of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
Abstract
Background: Chronic degenerative mitral valvular disease (CDMD) and
tracheobronchial collapse (TBC) are common combination in small breed dogs.
Hypothesis: Trachea collapse (TC) is not one of the risk factors for development CDMD.
Animals: 54 clinically healthy dogs (control) and 133 dogs with CDMD.
Methods: Case-controlled, retrospective study. The angle of tracheal bifurcation (TB angle), ratio of tracheobronchial diameters to thoracic inlet distance (TD/TI) at six locations: cervical, thoracic inlet, thoracic, carina, right and left cranial main stem bronchi (RMB and LMB) were measured on radiographs; diagnosis of CDMD was based on echocardiographic characteristics and categorized based the modified New York heart association (NYHA) functional classification.
Results: The prevalence of TC prior to carina in control and CDMD were 28% and 29%, respectively (P=0.52). No significant differences in the TB angle and TD/TI were found among controls and groups of NYHA I and II; the TB angle, comparing to controls, TD/TI at carina and LMB of groups of NYHA III and IV were significantly different (P ≤ .001). In CDMD, VHS was negatively correlated to carina/TI, RMB/TI and LMB/TI (P ≤ .002); and left atrium/aorta root diameter ratio (LA/Ao) was
negatively correlated to carina/TI, RMB and LMB/TI (P ≤ .003). The TB angle was positively correlated to VHS and LA/Ao (P ≤ .009).
Conclusions: Development TC was not associated with CDMD in dogs. Narrowing of tracheobronchi in CDMD associated with the anatomical regions where directly contacted with the heart. Degree of TBC was associated with severity of CDMD.
Key words: dogs, tracheobronchial diameter, chronic degenerative mitral valvular disease
Part of the study was presented as a poster in the 21th European College of Veterinary Internal Medicine Congress, Seville, Spain. Sep. 8-10, 2011.
16
Background
Chronic degenerative mitral valvular disease (CDMD) and tracheobronchial collapse (TBC) are two of the most highly prevalent cardiopulmonary diseases in small breed dogs. The high rate of coexistence of two syndromes and similar clinical signs, such as coughing and panting, contributes to the diagnostic and therapeutic dilemma.1,2 In dogs, CDMD is the most common acquired cardiovascular disease.3 The prevalence of CDMD is strongly age and breed dependent: approximately 75% in dogs order than 16 years.3,4 Chronic degenerative mitral valvular disease is
characterized by chronic myxomatous mitral valve degeneration resulting in thickening and incomplete apposition of the valve leaflets during systole with secondary mitral valve regurgitation (MR).5,6 Several complications can occur concomitantly with MR worsening, including left- and then right-sided congestive heart failure secondary to elevated pulmonary artery pressure.7-10 Clinical signs are associated with the progress of CDMD and resulted from decompensated heart failure.11
Tracheobronchial collapse is defined either by narrowing of the lumen of the trachea and bronchi, prolapsed of the dorsal tracheal membrane, or combination of those abnormalities 12. Tracheobronchial narrowing is a multifactorial process that results from weakening of the tracheobronchial cartilage.13,14 Many dogs with tracheal collapse (TC) have collapse of both cervical and intrathoracic trachea.15 When
bronchial collapse is found in conjunction with tracheal collapse, this is termed tracheobronchial collapse.2,16 In some dogs, the principal bronchi are collapsed, with the right and left cranial lobar bronchi affected most commonly.16 The diagnosis of TBC is made by visual identification of > 25% reduction in luminal diameter of airway during tracheobronchoscopy in dogs.16,17 Although tracheobronchoscopy has been widely considered as the reference gold standard method for diagnosis and
17
staging TBC, it requires to be operated under general anesthesia.18 Thoracic radiographic examination is a routine and essential diagnosis for evaluation of tracheobronchial diameters and cardiac silhouette.19 The ratio of tracheobronchial diameters to thoracic inlet distance (TD/TI) on thoracic radiographs is a quantitative value for objective estimation of tracheobronchial diameters.20,21 In dogs with CDMD, the compressed left cranial mainstem bronchus (LMB) and associated clinical signs had been anecdotally attributed to the presence of severe left atrial enlargement.1,22 Determination of the TD/TI is a convenient and simple measurement for
tracheobronchial narrowing and compression by heart in dogs.20
The tracheal bifurcation angle (TB angle) is another supportively quantitative measurement to evaluate the enlargement of left atrium and it provide some information of the severity of heart failure in dogs with CDMD.23,24 Significant differences of the TB angle have also been observed between dogs with normal and increased left atrial size.23
Although the high comorbidity was observed between CDMD and TBC in small geriatric dogs, only few studies focused on the cardiac manifestations of respiratory disorders or the inverse relationship in the veterinary literatures and merely a limited population of TBC was included in these studies.2,25,26
This study aimed to estimate the prevalence of TBC in dogs with CDMD. The secondary aim of this study was to investigate the airway manifestations of heart failure in dogs with CDMD and to clarify whether a relationship between left atrial enlargement and airway collapse by comparing the angle of tracheal bifurcation and TD/TI ratio in clinically healthy small breed dogs and dogs with CDMD in different stages of heart failure.
18
Materials and Methods
Animals and clinical evaluation
One hundred eighty-seven client-owned small breed dogs (BW<10 kg) that presented to the National Taiwan University Veterinary Hospital between April 2009 and November 2011 were selected for this study.
Of the 187 dogs, 54 clinically healthy dogs without history of cardiopulmonary diseases were classified as healthy controls (Table 1). The age of these dogs was between 12 months and 8 years. The physical condition was evaluated by annual wellness check-ups and deemed as clinically healthy.
In group of CDMD, 133 dogs were included. The condition of CDMD was diagnosed echocardiographically. Through a medical record of clinical signs, findings of physical examinations and chest radiographs, condition of heart failure of these dogs were further classified based the modified New York heart association (NYHA) functional classification (Table 1).
Complete physical examination, systolic blood pressure measurement, chest radiography, electrocardiography (ECG), and echocardiography (two-dimensional, M-mode, and Doppler) were carried out in all dogs. The owner’s consent for each dog was obtained before enrollment in the study.
Thoracic radiographic measurements
All measurements were carried out using electronic calipers of the digital thoracic radiographic system.
The lateral thoracic radiograph:
1) Vertebral heart scale (VHS) was obtained using the method described by Buchanan and Bücheler. The reference range in this study was 9.2 to 10.2 vertebrae.27
19
2) Ratio of tracheobronchial diameters to thoracic inlet distance (TD/TI): TI was measured from the ventral aspect of the midpoint of the first thoracic vertebra to the dorsal surface of the manubrium at its minimal distance, whereas the
tracheobronchial intraluminal diameters (TD) were measured at six locations of trachea and bronchi (cervical, thoracic inlet, thoracic, carina, right and left cranial mainstem bronchi (RMB and LMB) and perpendicularly to the long axis of trachea (Fig 1).20 In this study, the ratio of TD/TI <0.16 at thoracic inlet, or the narrowest diameter of trachea prior to carina showing TD/TI <0.16 was considered collapsed trachea.18,20
The ventral dorsal radiographs
1) Tracheal bifurcation angle (TB angle) was determined by the intersection of lines positioned along the central axis of both stem bronchi in the left and right caudal lung lobs over their lengths (Fig 2).28
Echocardiography
Echocardiography examinations were performed in conscious status. All dogs were gently restrained in lateral recumbent positions using the 2D-guided M mode with ultrasound units equipped with 2-5 and 5-7.5 MHz transducersa.
Echocardiographic indices, including the left ventricular dimension at end-diastole (LVEDD) and end-systole (LVESD), the thickness of left ventricular free wall (LVFW) and interventricular septum (IVS) at end-diastole, left atrial/aortic root ratio (LA/Ao), ejection fraction (EF), and fractional shortening (FS), were measured from the standard views obtained from the right parasternal images. The inflow of
trans-mitral and trans-tricuspid, the flow of pulmonary artery and aortic flow were measured from the left apical location. Mitral and tricuspid regurgitation were also
20
evaluated by Doppler-derived echocardiography from the left apical location.
Statistical analysis
Data were expressed as the means ± standard deviations (SDs). The Kolmogorov-Smirnov and Shapiro-Wilk tests were used for testing normal
distribution of all data with commercial computer statistic softwareb. Differences in continuous variables between groups were evaluated by one-way analysis of variance (ANOVA), followed if necessary by Student’s t-test with Bonferroni correction.
Where the data were not normal distributed were analyzed by using Kruskal-Wallis test followed by the post-hoc Mann-Whitney U-test. Comparison of frequencies was using the Pearson chi-square or Fisher's exact test. The Pearson product-moment and Spearman rank order correlation coefficient (r) were used to assess the relationship between variables. All tests were two-tailed. Significance was defined as P-value
< .05.
Results
Patient characteristics
A total of 187 dogs of 13 different small breeds were enrolled in this study (Table 1).There was no statistical significance among five groups in sex distribution and body weight, but age of healthy controls was significantly lower compared with dogs affected with CDMD in different modified NYHA classes (P< .001) (Table 2).
Thoracic radiographic measurements
Results of the thoracic radiographic measurements are presented in Table 3. In right lateral radiographs, the VHS of group classified IV was significantly higher than healthy controls and groups of NYHA I, II and III (VHS: 12.0±1.2, P< .001) and the
21
VHS of groups NYHA II and III were significantly higher than healthy controls (P= .008 and P= .002, respectively).
The angle of tracheal bifurcation in NYHA IV group was significantly larger than other groups (TB angle: 93.2±6.4o, P< .001) and the angle of NYHA III group (TB angle: 79.0±10.8o) was significantly larger than healthy controls (TB angle:
65.7±8.7o, P< .001) and NYHA I group (TB angle: 66.7.0±7.9o, P= .005).
The prevalence of collapsed trachea defined at thoracic inlet in healthy controls and dogs affected with CDMD was 22% and 28%, respectively (P= .47); whereas the prevalence of collapsed trachea defined at the location prior to carina with TD/TI <
0.16 in healthy controls and dogs affected with CDMD was 28% and 29%,
respectively (P= .52). No significant differences in the TD/TI of cervical, thoracic inlet, thoracic, carina, right and left main stem bronchi were found among healthy controls, dogs with CDMD categorized in groups of NYHA I and II; whereas the TD/TI at carina and LMB of the dogs with CDMD categorized in group of NYHA III (carica/TI: 0.164±0.051; LMB/TI: 0.078±0.027) and IV (carica/TI: 0.152±0.043;
LMB/TI: 0.069±0.022) were significantly different (P= .001, P< .001, P= .001, P< .001, respectively) comparing to those of healthy controls.
No significant differences at the six locations of TD/TI of trachea and bronchi were found among the breeds of Chihuahuas, Maltese terriers, Miniature Poodles, Pomeranians, and Yorkshire Terriers of the healthy controls (P > .20); and there was no significant correlation between the age of the healthy controls and the TD/TI in the six locations of trachea and bronchi (P > .30).
In dog with CDMD, VHS was negatively correlated to carina/TI, RMB/TI and LMB/TI (r=-0.29, r=-0.31 and r=-0.24 respectively; P< .001, P< .001 and P= .002, respectively); and LA/Ao was negatively correlated to carina/TI, RMB and LMB/TI (r=-0.39, r=-0.48 and r=-0.45, respectively; P= .003, P= .001 and P= .001,
22
respectively). The angle of tracheal bifurcation was positively correlated to VHS and LA/Ao (r=0.26 and r=0.37 respectively; P= .002 and P= .009, respectively).
Echocardiography
Results of the two-dimensional echocardiographic indices are presented in Table 4. The left ventricular diameter and wall thickness, EF and FS were not significantly different among healthy controls and groups of four stages of NYHA classification.
However, the left ventricular diameter to aortic root diameter ratio (LVEDD /Ao) of dogs with CDMD categorized in modified NYHA IV was significantly higher as compared with dogs in other groups (P< .003). The LA/Ao of dogs in NYHA IV group was significantly higher than other groups (LA/Ao=2.54±0.37, P< .001). In NYHA III group, the LA/Ao was significantly higher than NYHA I and healthy controls (P= .041 and P= .026, respectively).
In Doppler hemodynamic assessment, no statistical significance of mitral E/A, tricuspid E/A, aortic and pulmonary artery flow velocity was found among healthy controls and dogs in groups of NYHA I to IV. The mitral and tricuspid regurgitation velocity was not significantly different among groups of NYHA I, II, III and IV.
Discussion
Chronic degenerative mitral valvular disease and TBC are common combination in small breed dogs, and the clinical signs of these two conditions are frequently overlapped 2. Chronic airflow limitation and the reduced lung function had been demonstrated as independently causal factors for cardiovascular diseases in many large-scale epidemiological studies of human patients.29-31 In this study, the
prevalence of TBC was higher in dogs with various severity of CDMD, however no significant difference was found between healthy controls and dogs with CDMD.
Tracheal collapse is common in small breed dog with a prevalence of 0.5 to
23
2.9%.32,33 In dogs with respiratory illness, the bronchoscopic prevalence of TBC and bronchial collapse were ranged 21% and 30%, respectively.16 The radiography have been reported as an effectively diagnostic modality in dogs with TC and collapse of the main bronchi, but the sensitivity and specificity were varied with the position of collapsed trachea and the degree of the dynamic tracheal luminal change during tidal respiration.19,34 In this study, TC was defined by TD/TI <0.16 radiographically.18,20 Cases with mild degree of tracheal luminal changes affected by respiratory pattern during the radiographs taken would be underestimated. Nevertheless, the prevalence of TC in clinically healthy dogs and dogs affected with CDMD was higher than the results reported by previous studies. The high prevalence of TC in both groups might simply reflects the popularity of the most predisposed breeds included in this area, such as Maltese terriers, Pomeranian, Yorkshire terrier, Shih Tzu, Chihuahuas, and Miniature Poodle, accounted for 89% of cases in this study.19,32
In this study, the TD/TI of cervical, thoracic inlet and thoracic levels were not significantly different between healthy controls and dogs with CDMD at all four NYHA classifications. No statistical correlation was found between the left
ventricular echocardiographic indices and the TD/TI of cervical, thoracic inlet, and thoracic levels. These findings suggested that TC was not associated with the higher prevalence and severity of CDMD in small breed dogs. However, TD/TI at carina and LMB in dogs with CDMD categorized in NYHA III and IV was significantly
decreased comparing to those of healthy controls. Both VHS and echocardiographic LA/Ao had significantly negative correlations with the carina/TI, RMB/TI and LMB/TI. And the TB angle in the groups of NYHA III and IV was significantly higher than those in the healthy controls. The TB angle was positively correlated to VHS and LA/Ao. Dorsal elevation of the trachea and carina, and dorsal displacement of the left mainstem bronchus by the enlarged left atrium and left ventricle on lateral
24
radiographs have been widely applied as indicators of CDMD.22,35-37 Compression of the bronchus in dogs with CDMD was believed to be associated with the enlarged left atrium and the degree of the compression was related to the severity of CDMD in our study.
Bronchoscopic evidence suggested that the left cranial bronchus was the most commonly affected location of bronchomalacia, i.e. bronchial collapse.16,38,39 Investigation on the development and location of bronchomalacia and in dogs with no/mild and moderate/severe left atrial enlargement caused by CDMD indicated that dorsal and ventral segments of the left cranial lobar bronchus were affected most commonly, followed by the left caudal and right middle lobar bronchi. However, no significant difference in site or severity of airway collapse between dogs affected with no/mild and moderate/severe left atrial enlargement.2 On the other hand,
bronchomalacia has been reported to occur in 87.5% brachycephalic dogs with respiratory distress and noisy breathing, generally at age less than three years. The prevalence of bronchial collapse in brachycephalic breeds has been found to be higher than the prevalence in other breeds (30%).16,39 Narrowing or compressed left cranial bronchi may also be contributed to other factors, such as ages, body weight, and inflammatory conditions.38,39 In the present study, there were no significant
differences in the TD/TI of trachea and bronchi among the five predisposed breeds in the controls and no significant correlation of the age in the healthy controls. The results in our study indicated that the anatomical link to the heart might be critical in the development of compression of and left bronchus.
There were limitations in our study, no bronchoscopic determinations of tracheobronchial diameters were applied to our dogs, all included dogs were
client-owned. The impact of TBC on heart functions may not be entirely elucidated using based conventional assessments of echocardiography, future studies regarding
25
evaluation of cardiac function using different echocardiographic analysis is warranted in dogs with respiratory disorders.
Conclusions
This study failed to identify an apparent increase in the prevalence of TBC in dogs with CDMD and did not find significant differences of the trachea diameters among healthy controls and dogs with CDMD in groups of NYHA I, II, III and IV despite the high comorbidity was subjectively observed between CDMD and TBC in small breed dogs. These results implied that the CDMD was not associated with TC in dogs. Compression of carina and bronchus in dogs with CDMD only developed where the anatomical regions directly contacted with the heart. Degree of carinal and
bronchial compression was associated with severity of CDMD.
Footnotes
a MyLabTM 50 Family, Esaote, Genova, Italy
b SPSS Version 12.0.1, Lead Technologies Inc., Charlotte, North Carolina, USA
26
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