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Echocardiographic and Tissue Doppler Imaging Alterations Associated with Spontaneous Canine Systemic Hypertension

Authors

  • C. Misbach,

    1. Unité de Cardiologie d'Alfort (UCA), Centre Hospitalier Universitaire Vétérinaire d'Alfort (CHUVA), Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort cedex, France
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  • V. Gouni,

    1. Unité de Cardiologie d'Alfort (UCA), Centre Hospitalier Universitaire Vétérinaire d'Alfort (CHUVA), Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort cedex, France
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  • R. Tissier,

    1. UMR INSERM U955, Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort cedex, France
    2. Unité de Pharmacie-Toxicologie, Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort cedex, France
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  • E. Trehiou-Sechi,

    1. Unité de Cardiologie d'Alfort (UCA), Centre Hospitalier Universitaire Vétérinaire d'Alfort (CHUVA), Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort cedex, France
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  • A.M.P. Petit,

    1. Unité de Cardiologie d'Alfort (UCA), Centre Hospitalier Universitaire Vétérinaire d'Alfort (CHUVA), Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort cedex, France
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  • C. Carlos Sampedrano,

    1. Unité de Cardiologie d'Alfort (UCA), Centre Hospitalier Universitaire Vétérinaire d'Alfort (CHUVA), Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort cedex, France
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  • J-L. Pouchelon,

    1. Unité de Cardiologie d'Alfort (UCA), Centre Hospitalier Universitaire Vétérinaire d'Alfort (CHUVA), Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort cedex, France
    2. UMR INSERM U955, Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort cedex, France
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  • V. Chetboul

    1. Unité de Cardiologie d'Alfort (UCA), Centre Hospitalier Universitaire Vétérinaire d'Alfort (CHUVA), Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort cedex, France
    2. UMR INSERM U955, Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort cedex, France
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  • Some of these results were presented as a short communication at the ECVIM congress in Toulouse, September 2010.

Corresponding author: V. Chetboul, DVM, PhD, Dipl-ECVIM-CA (Cardiology), Unité de Cardiologie d'Alfort (UCA), Centre Hospitalier Universitaire Vétérinaire d'Alfort (CHUVA), Ecole Nationale Vétérinaire d'Alfort, 7 avenue du général de Gaulle, 94704 Maisons-Alfort cedex, France; e-mail: vchetboul@vet-alfort.fr

Abstract

Background: Feline systemic arterial hypertension (SHT) is associated with a wide spectrum of left ventricular (LV) geometric patterns as well as diastolic, and to a lesser extent, systolic myocardial dysfunction. However, little is known about SHT-related cardiac changes in dogs.

Hypothesis: SHT in dogs is responsible for morphological and functional cardiac alterations.

Animals: Thirty dogs with spontaneous untreated SHT and 28 age- and body weight-matched healthy dogs as controls.

Methods: Prospective observational study. Conventional echocardiography and 2-dimensional color tissue Doppler imaging were performed in SHT dogs by trained observers and compared with controls.

Results: Forty-seven percent of SHT dogs (14/30) had diffuse concentric hypertrophy. None had left atrial dilatation and 10/30 (33%) had aortic insufficiency (AoI) associated with proximal aortic dilatation. Longitudinal diastolic left ventricular free wall (LVFW) motion was altered in all SHT dogs at the base (early to late diastolic wave ratio, E/A = 0.5 ± 0.1 versus 1.3 ± 0.3 for controls, P < .0001) and the apex (E/A = 1.6 ± 1.7 versus 3.9 ± 3.1, P < .05). Longitudinal motion of the interventricular septum at the base (E/A = 0.7 ± 0.4 versus 1.1 ± 0.1, P < .01) and radial LVFW motion in the subendocardium (E/A = 0.9 ± 0.5 versus 1.6 ± 0.3, P < .01) were also altered in dogs with SHT. Longitudinal LVFW systolic velocities and gradients were also significantly decreased (P < .05) in SHT dogs.

Conclusion and Clinical Importance: As in SHT in cats, SHT in dogs is associated with myocardial dysfunction independently of the presence of myocardial hypertrophy. However, unlike feline SHT, it results in a homogeneous LV geometric pattern with a relatively high prevalence of AoI.

Abbreviations:
2D

2-dimensional

ABP

arterial blood pressure

Ao

aorta

AoI

aortic insufficiency

HR

heart rate

IVCT

isovolumic contraction time

IVRT

isovolumic relaxation time

IVS

interventricular septum

LA

left atrium

LV

left ventricle

LVFW

left ventricular free wall

MVG

myocardial velocity gradient

PS

postsystolic

SABP

systolic arterial blood pressure

SHT

systemic arterial hypertension

TDI

tissue Doppler imaging

Systemic arterial hypertension (SHT) is defined as a sustained increase in arterial blood pressure (ABP) and may be primary or, more commonly, secondary to various disease processes, including renal diseases and endocrine disorders.1–7

Over the past 15 years, SHT has been increasingly recognized as a potential cause of severe irreversible organ lesions in dogs and cats, as in humans. The main damage to target organs includes renal lesions (glomerular sclerosis and interstitial fibrosis),8–12 ocular lesions (retinopathy and choroidopathy),13–15 as well as central nervous system16,17 and cardiovascular alterations.18–23 The risk of target organ damage has to be considered when the systolic arterial blood pressure (SABP) and diastolic ABP exceed 150 and 95 mmHg, respectively.3

Feline SHT is associated with various abnormal left ventricular (LV) geometric patterns, including concentric hypertrophic patterns (symmetric or asymmetric with predominant interventricular septum [IVS] or left ventricular free wall [LVFW] thickening), an eccentric hypertrophic pattern and a subaortic localized IVS hypertrophic pattern, with or without left atrial (LA) dilatation.19–23 LVFW dysfunction assessed by tissue Doppler imaging (TDI) has also been demonstrated in SHT cats, with alterations of radial and longitudinal diastolic velocities, as well as decreases in longitudinal systolic myocardial velocities and gradients, regardless of myocardial wall thickness.19

The 1st case series of dogs with spontaneous SHT was described in 1988.7 Since then a few single case reports have been published.24,25 Several studies have also been reported, but most of them focused on the association between SHT and kidney function (glomerular filtration rate, proteinuria, albuminuria) in renal8,9,11,26 and nonrenal diseases such as pheochromocytoma,27 hyperadrenocorticism,12 and diabetes mellitus.28 However, to the authors' knowledge, no studies have specifically focused on the cardiac morphological and functional alterations associated with SHT in dogs.

The aims of this prospective observational study were therefore (1) to describe conventional echo-Doppler alterations, and (2) to investigate radial and longitudinal myocardial function of the LVFW and IVS in dogs with spontaneous SHT in comparison to age- and body- weight-matched healthy dogs.

Material and Methods

Animals

Untreated hypertensive dogs (SHT group) from different breeds were prospectively recruited at the Cardiology Unit of Alfort (France) between November 2003 and March 2010. Owner's consent was obtained before enrollment in the study. Physical examination, ECG, ABP measurement, and conventional echo-Doppler examination were performed on all SHT animals. When possible (ie, in quiet dogs without panting), a 2-dimensional (2D) color TDI examination was also undertaken. A population of healthy dogs (control group) was investigated during the same period. These dogs were students' dogs or dogs coming for screenings or vaccinations, and were free of medication and had no history of heart or respiratory diseases. We decided to include dogs from different breeds as no specific canine breed is known to be spontaneously predisposed to SHT. These dogs were declared healthy on the basis of a complete physical examination, ABP measurement, ECG, and full conventional echo-Doppler examination.

SABP Measurement

SABP was indirectly measured in conscious dogs, in accordance with the ACVIM consensus statement,3 by the same observers (A.M.P.P., C.C.S., C.M., E.T., V.G.) by the Doppler methoda for dogs <15 kg and the oscillometricb method for dogs ≥15 kg. For both techniques, the dogs were held gently by the owner in sternal or lateral recumbency. An appropriate-size inflatable cuff c was placed on the tail for the Doppler method and on the right anterior limb for the oscillometric method, as described and validated previously.29 A period of acclimatization was allowed for each patient before measuring blood pressure. Several measurements were performed over 5–10 minutes to obtain a stable set of 5 values and the mean was used for statistical analyses. Dogs were considered as hypertensive if the average SABP exceeded 160 mmHg.3

Conventional Echocardiography and Doppler Examination

Standard transthoracic echo-Doppler examinations with continuous ECG monitoring were performed in all animals by the same trained observers (C.C.S., C.M., E.T., V.C., V.G.) with an ultrasound unitd equipped with 2.2–3.5 and 5.5–7.5 MHz phased-array transducers. All examinations were carried out in awake dogs gently restrained in the standing position, as described and validated previously.30 For each echocardiographic variable, a mean of 3 measurements was determined from 3 consecutive cardiac cycles on the same frame. Ventricular measurements were taken from the right parasternal transventricular short-axis view by 2D-guided M-mode according to the recommendations of the American Society of Echocardiography.31 Measurements were made of the LV end-diastolic and end-systolic diameters, LVFW thickness, and IVS thickness in diastole and in systole. The LV fractional shortening (%FS) was then calculated. Expected maximal thicknesses of the LVFW and IVS in diastole and systole as well as expected minimal LV diameters were also calculated by the method published by Cornell et al.32 In each case, the expected myocardial thicknesses corresponding to upper reference range (corresponding to the 97.5th percentile) and the expected diameters corresponding to lower reference range (corresponding to the 2.5th percentile) were derived from the dog's body weight.32 These values were used to calculate the percentage increase in myocardial thicknesses from expected values as follows: percentage increase = [100 × (observed thickness−expected upper normal thickness)/expected upper normal thickness]. The percentage decrease in LV diameters from expected values was similarly calculated. Additionally, myocardial wall thicknesses were compared with mean expected values (corresponding to the 50th percentile) calculated by the Cornell's method.32 Pathological hypertrophy was defined as diastolic LVFW (LVFWD) or IVS (IVSD) thicknesses greater than expected maximal values. Hypertrophy was defined as symmetric if the ratio IVSD/LVFWD was between 0.7 and 1.3, and as asymmetric with predominant IVS thickening or predominant LVFW thickening, if IVSD/LVFWD was >1.3 or <0.7, respectively.20 The aorta (Ao) and LA diameters were measured by a 2D method from a short-axis right-sided parasternal view obtained at the level of the aortic valve, as described and validated previously.33 The LA/Ao ratio was then calculated. Finally, the maximal systolic aortic velocities as well as maximal early (E) and late (A) diastolic mitral flow velocities were determined by pulsed-wave Doppler using the left apical 5- and 4-chamber views, respectively.

TDI Study

All 2D color TDI examinations were performed in awake standing dogs with continuous ECG monitoring by the same trained observers (C.C.S., E.T., V.C., V.G.) as for conventional echocardiography and with the same ultrasound units as described and validated previously by our group.34 Real-time color Doppler was superimposed on the gray scale with a high frame rate (>120 frames/s). Doppler receive gain was adjusted to maintain optimal coloring of the myocardium (ie, without any black spots), and the Doppler velocity range was set as low as possible to avoid aliasing. All digital images were stored and later analyzed with a specific software,e by a single trained observer (V.C.) who was blinded to the ABP values. A 2 × 2 mm sample was used, and a tissue-velocity profile displayed in each sample location. Myocardial velocities resulting from the radial LVFW motion were measured using the right parasternal ventricular short-axis view, and measurements were made between the 2 papillary muscles in subendocardial and subepicardial segments of the LVFW. Longitudinal velocities were measured using the standard left apical 4-chamber view in 3 locations: the LVFW at the base and apex, and IVS at the base. Radial myocardial velocity gradients (MVG, defined as the difference between subendocardial and subepicardial velocities) and longitudinal MVG (defined as the difference between basal and apical velocities) were also calculated for each phase of the cardiac cycle. Time indices, ie, TDI isovolumic relaxation time (IVRT) and isovolumic contraction time (IVCT), were also assessed on the same 3 consecutive cardiac cycles, with IVRT defined as the time interval between end of the TDI systolic wave (S) to onset of the TDI early diastolic wave (E) and IVCT as the time interval between end of the TDI late diastolic wave (A) to onset of the TDI S wave. To limit a potential heart rate (HR) effect on ICVT and IVRT, these 2 variables were also indexed to HR as follows: ICVTHR = IVCT/(HR/60,000) and IVRTHR = IVRT/(HR/60,000), where HR is heart rate in beats per minute. HR was calculated by ECG monitoring during each radial and longitudinal TDI examination from the same 3 cardiac cycles as those used for velocity measurements.

Statistical Analysis

Data are expressed as mean ± SD. A software programf was used to perform the statistical analysis. All variables were tested for normality by the Kolmogorov-Smirnov test. Most variables were normally distributed and were accordingly compared by a Student's t-test. For the nonnormally distributed variables (ie, body weight and %FS), a nonparametric Mann-Whitney analysis was used. Lastly, for all TDI parameters, data were compared among groups by an ANCOVA taking into account HR as a cofactor. In the SHT group, correlations between echocardiographic variables and SABP were examined by a Pearson correlation study. The level of significance was set at P < .05.

Results

Dogs

The whole population (n = 58) consisted of 2 groups of dogs from different breeds, ie, 30 dogs with untreated SHT and 28 age- and body-weight-matched healthy controls (Table 1).

Table 1.  Demographic characteristics of healthy (control group, n = 28) and hypertensive dogs (SHT group, n = 30).
Demographic CharacteristicsControl GroupSHT Group
  1. n, number of dogs; SHT, systemic arterial hypertension.

Sex
 Male17 (60%)15 (50%)
 Female11 (40%)15 (50%)
Age (years) (mean ± SD [range])8.6 ± 1.9 [6.1–10.0]9.6 ± 3.4 [0.9–13.0]
Body weight (kg) (mean ± SD [range])16.9 ± 12.9 [2.0–48.6]19.7 ± 11.2 [5.0–43.0]
Breed
 American Staffordshire Terrier1
 Basset Hound1
 Beagle5
 Beauceron1
 Bichon Maltese21
 Boxer3
 Brittany Spaniel1
 Cavalier King Charles and King Charles Spaniel2
 English and American Cocker Spaniel12
 English Setter1
 English Springer Spaniel1
 French Bulldog2
 Fox Terrier1 
 German and Belgian Shepherd72
 German Shorthaired Pointer2
 Jack Russel Terrier1
 Labrador and Golden Retriever2
 Lhassa Apso1
 Pinsher2
 Poodle1
 Pug1
 West Highland White Terrier11
 Whippet1
 Yorkshire Terrier22
 Cross-breed25

As expected, SABP was significantly higher (P < .0001) in the SHT group (198 ± 25 mm Hg [167–260 mmHg]) compared with the control group (136 ± 16 mm Hg [110–159 mmHg]).

Clinical findings in dogs with SHT at presentation included ocular, cardiac, neurologic, urinary, and gastrointestinal signs (Table 2).

Table 2.  Clinical findings in hypertensive dogs (SHT group, n = 30).
Clinical FindingsSHT Group (n[%])
  1. n, number of dogs; SHT, systemic arterial hypertension.

Left apical systolic heart murmur20 (66%)
Polyuria and polydypsia16 (53%)
Weight loss10 (33%)
Anorexia-lethargy9 (30%)
Vomiting8 (26%)
Neurological signs (seizure, ataxia)5 (16%)
Ocular signs (retinal hemorrhages and detachments, blindness)3 (10%)
Syncope2 (6%)
None0 (0%)

The origin of SHT could be confirmed in 24/30 dogs (80%) and remained unknown in 6/30 dogs (20%). Diagnosis in 63% of the SHT dogs (19/30) was consistent with chronic kidney disease (CKD). Regarding the International Renal Interest Society staging of CKD, only 1 of the 19 SHT dogs with CKD, (1/19; 5%) was in class 2 (ie, serum creatinine between 1.4 and 2.0 mg/dL), 9 dogs (9/19; 47%) were in class 3 (ie, serum creatinine between 2.1 and 5.0 mg/dL), and 9 dogs (9/19; 47%) were in class 4 (ie, serum creatinine upper 5.0 mg/dL). Five SHT dogs (5/30; 16%) had an adrenal gland disorder (ie, hyperadrenocorticism [n = 2] and noncortisol-secreting adrenal masses [n = 3] as confirmed by abdominal ultrasonography and low-dose dexamethasone suppression test).

Conventional Echocardiography and Doppler Examinations

Conventional echocardiography was performed on all dogs in the study population (Tables 3 and 4). All dogs with SHT had systolic and diastolic myocardial wall thicknesses upper expected mean values calculated by the Cornell's formula,32 and 47% (14/30) of them showed an abnormal LV geometric pattern in comparison with expected maximal diastolic values.32 This abnormal pattern consisted of diffuse concentric hypertrophy in all cases, and was symmetric for most of the dogs (10/14; 72%) and asymmetric with predominant IVS thickening in only 28% (4/14 cases). No asymmetric hypertrophy with predominant LVFW thickening was observed. LVFW and IVS thicknesses were significantly (P < .01) higher in the SHT group compared with the controls (Fig 1A,B). No correlation was found between SABP values and systolic and diastolic wall thicknesses or LV internal diameters.

Table 3.  Systolic arterial blood pressure, conventional echocardiography, and Doppler parameters in healthy dogs (control group, n = 28) and hypertensive dogs (SHT group, n = 30).
 Control GroupSHT Group
Mean ± SDMinimum-MaximumMean ± SDMinimum-Maximum
  • Data are expressed as mean ± SD and ranges as minimum-maximum values.

  • n, number of dogs; SHT, systemic arterial hypertension.

  • P < .05 versus control group.

  • *

    P < .01 versus control group.

  • P < .0001 versus control group.

Systolic arterial blood pressure (mmHg)136 ± 16110–159198 ± 25167–260
Two-dimensional echocardiographic variables
 Left atrium diameter (mm)17.0 ± 5.18.4–26.319.3 ± 4.88.8–27.5
 Aorta diameter (mm)20.1 ± 5.011.6–27.423.5 ± 6.111.2–33.6
 Left atrium/aorta0.84 ± 0.130.58–1.100.84 ± 0.160.55–1.27
M-Mode echocardiographic variables
 Left ventricular end-diastolic diameter (mm)33.1 ± 9.316.3–57.031.8 ± 8.916.6–48.1
 Left ventricular end-systolic diameter (mm)20.5 ± 6.76.2–37.418.2 ± 6.17.9–31.2
 Left ventricular end-diastolic free wall (mm)8.0 ± 2.64.8–16.610.2 ± 2.5*6.2–15.4
 Left ventricular end-systolic free wall (mm)12.4 ± 3.58.4–21.115.3 ± 3.5*8.8–24.3
 Interventricular end-diastolic septum (mm)8.7 ± 3.33.4–17.911.4 ± 2.6*6.8–16.6
 Interventricular end-systolic septum (mm)12.5 ± 3.87.0–21.516.1 ± 3.6*10.2–23.4
 Fractional shortening (%)37.8 ± 8.026.9–59.342.8 ± 7.929–63
Conventional Doppler variables
 Systolic maximum aortic velocity (m/s)1.27 ± 0.370.80–1.991.88 ± 1.460.84–1.65
 Mitral E wave assessed by pulsed wave Doppler (m/s)0.74 ± 0.170.41–1.371.04 ± 1.450.34–1.16
 Mitral A wave assessed by pulsed wave Doppler (m/s)0.58 ± 0.160.41–0.980.70 ± 0.130.45–0.97
 Mitral E/A ratio1.4 ± 0.70.50–5.01.59 ± 2.290.46–1.84
Table 4.  Percentage increase in myocardial wall thicknesses from expected maximal values (%) and percentage decrease in left ventricular diameters from expected minimal values (%) assessed in healthy (control group, n = 28) and hypertensive dogs (SHT group, n = 30) using M-mode echocardiography.
M-Mode echocardiographic variablesControl GroupSHT Group
Mean ± SDMinimum-MaximumMean ± SDMinimum-Maximum
  • Expected values were calculated using the method published by Cornell et al (a × body weightb, with a and b as covariables).32 Data are expressed as mean ± SD and ranges as minimum-maximum values.

  • IVSD and IVSS, interventricular septum thickness in diastole and systole, respectively; LVFWD and LVFWS, left ventricular free wall thickness in diastole and systole, respectively; LVIDD and LVIDS, left ventricular internal diameter in diastole and systole, respectively; SHT, systemic arterial hypertension.

  • P < .05 versus control group.

  • *

    P < .01 versus control group.

  • P < .0001 versus control group.

Diastole
 Percentage increase in IVSD from expected maximal values (%)−23.2 ± 16.2−51.8–18.9−0.9 ± 18.1−24.4–45.9
 Percentage decrease in LVIDD from expected minimal values (%)20.2 ± 10.515.7–56.59.4 ± 19.6−28.6–46.3
 Percentage increase in LVFWD from expected maximal values (%)−27.7 ± 12.3−47.6–12.3−10.4 ± 18.2−44.8–37.7
Systole
 Percentage increase in IVSS from expected maximal values (%)−15.8 ± 12.6−31.9–5.04.8 ± 16.4−23.4–33.4
 Percentage decrease in LVIDS from expected minimal values (%)24.9 ± 21.9−29.8–50.76.0 ± 26.6*−25.9–52.7
 Percentage increase in LVFWS from expected maximal values (%)−20.5 ± 13.9−47.0–8.5−4.7 ± 16.6−33.9–36.6
Figure 1.

 Box plots representing diastolic left ventricular free wall (LVFWD) and interventricular septum (IVSD) thicknesses in hypertensive (SHT) and control groups as assessed by conventional echocardiography.

%FS as well as mitral A wave were significantly (P < .05) higher in the SHT group as compared with the controls. However, no significant difference for systolic aortic flow velocity, mitral E wave, or mitral E/A ratio was observed between the 2 groups. No significant difference was found for the LA/Ao ratio, and none of the SHT dogs presented LA dilatation as compared with the reference ranges.35

Aortic insufficiency (AoI) was detected in 33% of the SHT dogs (10/30) using 2D and M-mode color-flow Doppler examination. All these AoI were related to a proximal aortic dilatation compared with reference ranges35 and were not associated with any cusp lesions. All of these regurgitations were considered mild (n = 6) to moderate (n = 2) according to the 2D or M-Mode color-flow Doppler examination.36 Maximal AoI velocities were only measured for the 2 moderate AoI (which, unlike the others, lasted throughout diastole) using continuous wave Doppler mode: the values were 5.54 and 5.87 m/s, corresponding to high diastolic pressure gradients of 123 and 138 mmHg, respectively. Finally, a mitral insufficiency was confirmed in all SHT dogs that presented a left apical systolic murmur (20/30; 66%) using color-flow Doppler mode.

TDI Examination

Radial LVFW Motion in the SHT Group Compared with the Control Group

Radial LVFW motion was assessed using the 2D color TDI technique in 45 animals (26 controls and 19 SHT dogs). Subendocardial and subepicardial systolic velocities as well as systolic MVG), E and A velocities, and E/A ratio in the subepicardial segment (Fig 2A) were similar in the 2 groups (Table 5). Conversely, several diastolic alterations were observed in the subendocardial segment (Fig 2B), the E velocity (P < .05), and E/A ratio (P < .01) being significantly lower, and the A velocity (P < .05) significantly higher in the SHT compared with controls. The radial early and late diastolic MVG were comparable between the 2 groups. Finally, the radial TDI times (IVCT, IVCTHR, IVRT, IVRTHR) were comparable between the 2 groups whereas HR was significantly higher (P < .0001) in the SHT group. Positive postsystolic (PS) waves, occurring after S waves and greater than the latter, were observed in 1/19 (5%) SHT dog in both subendocardial and subepicardial segments (with PS wave/S wave ratios of 1.3 and 2.3, respectively).

Figure 2.

 Box plots representing E/A ratio assessed in the hypertensive (SHT) and control groups using 2-dimensional color tissue Doppler imaging in different segments of the left ventricular free wall for the radial motion (subepicardial and subendocardial segments, A and B) and the longitudinal motion (basal and apical segments, C and D). E, early diastolic wave; A, late diastolic wave; NS, not significant.

Table 5.  Radial motion TDI variables in healthy (control group, n = 26) and hypertensive dogs (SHT group, n = 19).
 Control GroupSHT Group
Mean ± SDMinimum-MaximumMean ± SDMinimum-Maximum
  • Data are expressed as mean ± SD and ranges as minimum-maximum values.

  • n, number of dogs; SHT, systemic arterial hypertension; TDI, tissue Doppler imaging.

  • P < .05 versus control group.

  • *

    P < .01 versus control group.

  • P < .0001 versus control group.

Systolic velocities and gradient
 S wave in subendocardium (cm/s)6.0 ± 1.53.8–10.86.5 ± 1.54.5–10.4
 S wave in subepicardium (cm/s)3.3 ± 1.31.8–6.53.7 ± 1.21.2–5.9
 Gradient between subendocardium and subepicardium (cm/s)2.6 ± 0.61.9–4.42.8 ± 0.71.6–4.5
Diastolic velocities, ratios, and gradients
 E wave in subendocardium (cm/s)6.4 ± 2.13.4–12.44.5 ± 2.21.5–8.5
 E wave in subepicardium (cm/s)3.2 ± 1.30.9–6.02.6 ± 1.60.6–5.7
 A wave in subendocardium (cm/s)4.0 ± 1.12.3–6.25.1 ± 1.51.9–7.7
 A wave in subepicardium (cm/s)1.3 ± 0.70.4–3.22.1 ± 1.50.3–4.3
 E/A ratio in subendocardium1.6 ± 0.31.0–2.40.9 ± 0.5*0.2–2.0
 E/A ratio in subepicardium2.5 ± 1.71.0–5.62.1 ± 2.10.2–4.4
 E wave gradient between subendocardium and subepicardium (cm/s)2.2 ± 0.61.4–2.22.1 ± 1.31.0–7.3
 A wave gradient between subendocardium and subepicardium (cm/s)2.3 ± 0.61.3–3.93.0 ± 1.20.2–4.9
TDI time parameters
 Isovolumic contraction time in subendocardium (ms)54.1 ± 16.325.0–75.558.9 ± 14.339.7–78.9
 Isovolumic relaxation time in subendocardium (ms)43.1 ± 20.016.0–63.648.4 ± 23.117.2–87.3
 Heart rate during exam (beats/min)97 ± 2358–145129 ± 2698–175

Longitudinal LVFW Motion in the SHT Group Compared with the Control Group

Longitudinal LVFW TDI motion was assessed using the 2D color TDI technique in 45 animals (26 controls and 19 SHT dogs). Most longitudinal TDI variables were altered in the SHT group, with respect to the controls (Table 6). Regarding systolic function, systolic velocities at the base, but not the apex, as well as systolic MVG were significantly lower in the SHT group (P < .05). Regarding diastolic function, all variables ie, E and A waves, E/A ratio in the basal and apical segments (Fig 2C,D), as well as early and late diastolic MVG, differed significantly between the 2 groups. Positive PS waves were observed in basal and apical segments in 3/19 dogs (16%) with SHT (PS wave/S wave ratios of 2.6 ± 0.9 and 6.7 ± 8.8, respectively) but in no dog from the control group (Fig 3). These PS waves were markedly prolonged, leading to the absence of a longitudinal E wave in 1 dog. Lastly, the longitudinal TDI isovolumic times (IVCT and IVRT) were comparable between the 2 groups, with HR significantly higher (P < .0001) in the SHT group. However, longitudinal IVRTHR (but not IVCTHR) was significantly longer in the SHT group as compared with the control group (P < .05).

Table 6.  Longitudinal left ventricular free wall motion TDI variables in healthy (control group, n = 26) and hypertensive dogs (SHT group, n = 19).
 Control GroupSHT Group
Mean ± SDMinimum-MaximumMean ± SDMinimum-Maximum
  • Data are expressed as mean ± SD and ranges as minimum-maximum values.

  • n, number of dogs; SHT, systemic arterial hypertension; TDI, tissue Doppler imaging.

  • *

    P < .05 versus control group.

  • P < .01 versus control group.

  • P < .0001 versus control group.

Systolic velocities and gradients
 S wave in basal segment (cm/s)7.6 ± 2.63.5–14.36.0 ± 2.0*2.6–9.3
 S wave in apical segment (cm/s)3.1 ± 1.80.4–5.82.9 ± 1.80.6–5.2
 Gradient between basal and apical segments (cm/s)4.4 ± 2.22.0–8.63.3 ± 1.0*1.6–6.3
Diastolic velocities, ratios, and gradients
 E wave in basal segment (cm/s)7.9 ± 2.03.2–11.34.3 ± 1.71.8–8.4
 E wave in apical segment (cm/s)3.6 ± 2.10.7–8.62.2 ± 1.6*0.2–5.1
 A wave in basal segment (cm/s)5.8 ± 1.54.0–9.47.4 ± 2.4*3.5–14.3
 A wave in apical segment (cm/s)1.2 ± 0.80.2–2.52.5 ± 1.90.2–6.7
 E/A ratio in basal segment1.3 ± 0.30.4–2.00.5 ± 0.10.2–0.8
 E/A ratio in apical segment3.9 ± 3.10.5–5.71.6 ± 1.7*0.1–6.5
 E wave gradient between basal and apical segments (cm/s)4.2 ± 2.21.0–9.42.2 ± 1.4*0.8–5.8
 A wave gradient between basal and apical segments (cm/s)4.5 ± 1.61.8–7.84.9 ± 2.4*0.9–9.6
TDI time parameters
 Isovolumic contraction time in basal segment (ms)47.4 ± 17.925.2–89.851.7 ± 17.427.5–94.4
 Isovolumic relaxation time in apical segment (ms)71.4 ± 19.340.5–106.080.7 ± 15.561.2–105.9
 Heart rate during exam (beats/min)91 ± 1967–132126 ± 2495–174
Figure 3.

 Longitudinal myocardial velocity profiles of the left ventricular free wall (LVFW) obtained from a hypertensive dog (A) and a control dog (B) using 2-dimensional color tissue Doppler imaging. Simultaneous recordings of myocardial velocities are obtained in 2 segments of the LVFW (basal and apical segments, yellow and green curves, respectively). A typical severe longitudinal LVFW dysfunction is observed in the hypertensive dog (A). As compared with the healthy dog (B), this myocardial dysfunction is characterized in both segments by a small systolic wave (S), a large positive postsystolic (PS) wave and an inverted E/A ratio. A small systolic base-to-apex myocardial velocity gradient (MVGs, double arrow) is also present. E, early diastolic wave; A, late diastolic wave; AVC, aortic valve closure; AVO, aortic valve opening. These time markers (AVO and AVC) were obtained using the pulsed-wave Doppler trace of systolic aortic flow velocity with concomitant ECG tracing.

Longitudinal IVS Motion at the Base in the SHT Group Compared with the Control Group

Longitudinal IVS TDI motion was assessed using the 2D color TDI technique in 26 animals (14 controls and 12 SHT dogs). As shown in Table 7, no significant difference was found regarding systolic function of IVS at the base. Conversely, the E wave as well as E/A ratio (but not A wave) were significantly lower (P < .01) in the SHT group as compared with the controls. A PS wave occurred in 1/12 SHT dogs (8%, with a PS wave/S wave ratio of 1.6).

Table 7.  Longitudinal interventricular septum motion TDI variables in healthy (control group, n = 14) and hypertensive dogs (SHT group, n = 12).
 Control GroupSHT Group
Mean ± SDMinimum-MaximumMean ± SDMinimum-Maximum
  • Data are expressed as mean ± SD and ranges as minimum-maximum values.

  • n, number of dogs; SHT, systemic arterial hypertension; TDI, tissue Doppler imaging.

  • *

    P < .01 versus control group.

  • P < .0001 versus control group.

Systolic velocities and gradients
 S wave in basal segment (cm/s)5.8 ± 2.42.9–7.37.2 ± 1.74.7–9.6
Diastolic velocities, ratios, and gradients
 E wave in basal segment (cm/s)5.9 ± 1.64.2–8.53.6 ± 1.7*0.9–7.3
 A wave in basal segment (cm/s)5.1 ± 1.42.9–7.35.5 ± 2.11.8–10.3
 E/A ratio in basal segment1.1 ± 0.11.0–1.40.7 ± 0.4*0.1–1.5
TDI time parameters
 Heart rate during exam (beats/min)90 ± 2064–140127 ± 2585–171

SHT Dogs with Normal M-Mode Examination

Sixteen dogs (16/30; 53%) from the SHT group (mean age = 9.6 ± 3.5 years [1–13 years]; mean weight = 17.9 ± 11.1 kg [3.3–40.0 kg]) showed normal LVFW and IVS thicknesses as assessed by M-mode echocardiography despite a high SABP (197 ± 24.0 mm Hg [170–260 mm Hg]). Five dogs (5/16; 31%) presented with an AoI (4 mild and 1 moderate). Eight of these SHT dogs with normal M-mode underwent a TDI examination for the LVFW radial and longitudinal motion and 5 of them for the IVS longitudinal motion. All 8 had an inverted E/A ratio for the longitudinal LVFW motion at the base (E/A = 0.56 ± 0.21 [0.20–0.78]), and 4 of them (50%) showed an inverted E/A ratio for the radial motion of the subendocardial LVFW segment (E/A = 0.72 ± 0.20 [0.42–0.87]). Regarding the IVS, 4/5 dogs (80%) had an inverted E/A ratio at the base (E/A = 0.53 ± 0.27 [0.25–0.81]).

Discussion

This prospective study demonstrates that, as in feline SHT, cardiac and aortic morphology as well as myocardial function are commonly and severely impaired in dogs with untreated SHT with several special features, such as a relatively high prevalence of AoI and diffuse concentric hypertrophy of the LV.

In veterinary medicine, thoracic radiographs, echocardiography, TDI, and postmortem examinations have been used to document the cardiac changes and myocardial dysfunction associated in cats with SHT.19–23 Most cats with SHT that underwent an echocardiographic examination have an abnormal LV geometric pattern (85%), and significantly thicker diastolic and systolic IVS and LFVW, with reduced diastolic and systolic LV diameters, as compared with the healthy controls.20 A more recent retrospective study performed in 75 hypertensive cats confirmed this high prevalence of SHT-associated LV remodeling (79% using M-mode echocardiography).21 In the present study, cardiac remodeling was found in near half of SHT dogs (47%), and both diastolic and systolic LVFW and IVS thicknesses were significantly higher in dogs with SHT as compared with the controls. In humans, the prevalence of SHT-related cardiac remodeling, also called “hypertensive heart disease,” most commonly varies from 10 to 30% of unselected hypertensive adults.37–42 It can reach 90%, but only when patients with sustained severe or malignant SHT are considered.43 Such a high prevalence of LV hypertrophy in SHT cats and dogs, compared with that usually reported in human hypertensive patients, could be explained by a later diagnosis of the disease in small animals, and therefore more advanced target organ damage.

Although one might expect myocardial hypertrophy to increase proportionally with ABP values, in the feline study performed by our group, SABP did not differ significantly between SHT cats with different LV patterns, and no correlation was found either between SABP values and myocardial wall thicknesses or LV diameters.20 Other authors did not find any significant correlation between SHT severity and echocardiographic variables either.23 Similarly, in the present report, myocardial wall thicknesses and LV diameters were not correlated with SABP values. Although a period of acclimatization was given to each patient before measuring SABP, a “white coat effect” may have confounded our results, and an ambulatory 24-hour ABP recording, as used in human patients, would probably have documented the relationship between ABP values and echocardiographic variables more accurately. In humans, ABP values assessed by an ambulatory blood pressure profile have been shown to be well correlated with LV hypertrophy and LV geometric patterns,44,45 and a single 24-hour averaged ABP obtained by automatic noninvasive ambulatory monitoring is known to be a better predictor of myocardial wall thicknesses than the multiple office or single office average ABP.46

In human patients,47–49 SHT is associated with a wide spectrum of LV geometric patterns assessed by echocardiography including normal LV geometry, concentric remodeling, and lastly, concentric and eccentric LV hypertrophy. Several abnormal LV geometric patterns have also been described in SHT cats, including concentric hypertrophic patterns (symmetric or asymmetric with predominant IVS or LVFW thickening), and less commonly, the eccentric hypertrophic pattern and the subaortic localized IVS hypertrophic pattern (characterized by normal M-mode ventricular measurements and increased diastolic subaortic IVS). This broad spectrum of LV abnormalities has been confirmed in another retrospective study using M-mode echocardiography. The present study demonstrates that in hypertensive dogs, unlike cats and humans, and despite different levels of SHT severity (SABP = 167–260 mm Hg), cardiac morphological changes associated with SHT are homogenous, including only 1 abnormal pattern, ie, LV concentric hypertrophy (symmetric for most of the dogs [72%] and asymmetric with predominant IVS thickening in others). No asymmetric LV hypertrophy with predominant LVFW thickening and no eccentric or localized LV remodeling was observed in any SHT dog. A rational explanation for such a difference between species regarding SHT-related LV patterns is difficult to provide. Anyway, although there is strong evidence for a direct causal relationship between ABP (which increases wall stress) and LV mass, other factors (ie, hemodynamic, genetic, and humoral factors) may also influence LV geometry.48,49 Moreover, CKD, which was the main cause of SHT in the present study, may have contributed to LV hypertrophy and myocardial dysfunction to an unknown extent.50

Aortic root dilatation is reported as a common vascular alteration in both SHT human patients and SHT cats.22 In humans, aortic root dilatation is a major cause of aortic regurgitation. Its prevalence in hypertensive patients varies from 3.751 to 47%,52 according to studies and depending on the inclusion criteria for patients (treated or untreated) and the methods of aortic diameter measurement.53 In 1 study,22 SHT cats were evaluated for 4 different aortic root dimensions obtained from the right parasternal long-axis view, and the ratio between the proximal ascending Ao and the aortic annulus was shown to be helpful in differentiating SHT from healthy cats.22 In our study, aortic size did not differ significantly between the 2 groups (SHT versus control). However, the aortic diameter for each SHT dog was above the published reference ranges.35 Dilatation of the proximal Ao in SHT patients is related to a greater intra-aortic distending pressure,53 and may explain the high prevalence of AoI (33%) in the present study, as confirmed by continuous-wave and color-flow Doppler mode.

TDI is a relatively recent ultrasound technique that has been used for the noninvasive investigation of myocardial function associated with SHT in cats.19 In 1 study involving 108 cats, radial and, to a greater extent, longitudinal diastolic LVFW velocities were similarly altered in SHT cats and cats with hypertrophic cardiomyopathy, as compared with the controls.19 This myocardial dysfunction occurred independently of the presence of myocardial hypertrophy. Systolic dysfunction was shown to be an additional component of SHT-associated myocardial alteration, characterized by a decrease in longitudinal systolic velocities and gradients, and also by the presence of longitudinal PS waves. Similar results were obtained in the present study, again suggesting that SHT is associated with severe myocardial alteration and with a greater sensitivity to longitudinal fibers compared with radial ones as also shown in SHT human patients.54 Such a longitudinal alteration may be secondary to subendocardial longitudinal fiber lesions, to high wall stress, or to the hypertrophy itself.54 It also has more impact on diastolic function than on systolic function. However, a possible limitation of our study is that both control and SHT groups included dogs from different breeds, and a breed effect has been demonstrated by our group for several 2D color TDI variables.33

In the present study, positive PS waves, occurring after aortic valve closure and greater than S waves, were observed in 1 SHT dog in both subendocardial and subepicardial segments of the LVFW (radial motion), in 3 SHT dogs in both basal and apical segments of the LVFW (longitudinal motion), and in 1 dog in the IVS at the base (longitudinal motion). PS motion is a sensitive marker of segmental myocardial dysfunction and asynchrony,55 which has been shown to be a common and important feature of myocardial ischemia in both humans56 and animal models.57 It is also commonly found in humans and cats with hypertrophic cardiomyopathy and SHT, and in human patients with heart failure.19,55,58 However, the pathophysiology of PS motion is not yet fully resolved (active contraction or passive recoil) and its significance may be controversial, as PS waves (although not observed in the control dogs of the present study) are found in approximately one third of myocardial segments in healthy human subjects.59 Nevertheless it occurs more often (80%) and with a greater magnitude in patients with ischemic diseases.59

This study presents other limitations. First, only SABP was assessed. In the dog, SABP is known to be more variable than diastolic or mean ABP, and depends on several factors such as age, breed, and sex.60 However, recent studies in human medicine have shown that risks of target organ damages are more accurately attributed to SABP than to diastolic ABP, and regarding SHT-associated cardiac alterations, SABP better predicts strokes and coronary heart diseases than diastolic ABP.61 Similarly, LV mass is more closely related to SABP than diastolic ABP.45,62–64 Therefore, in SHT human patients, decreasing SABP is now considered as the primary focus of treatment prescriptions.61 Another limitation of the present study stems from the use of 2 different indirect methods to measure ABP (ie, oscillometric and Doppler techniques, in large- and small-breed dogs, respectively). Nevertheless, in a recent study performed by our group in awake healthy dogs, no statistically significant differences were observed between ABP values obtained by the 2 techniques.29 Additionally, several observers (n = 5) were in charge of SABP measurements, which could have interfere with SABP values. However, all these observers were trained to the procedures (at least 2 years of experience). In 1 recent study published by our group,29 the between-day coefficients of variation of SABP obtained by the less trained observer (1 hour of training only) were good (<15%, ie, 12.4 and 14.1% for the Doppler and oscillometric methods, respectively). Another limitation of the present study is that not all recruited dogs underwent a TDI examination (45/50; 78%). Nevertheless, this number of animals was sufficient to show statistical differences in TDI variables between the control and SHT groups.

In conclusion, as in cats, SHT in dogs is commonly associated with both LV remodeling and myocardial dysfunction. The latter occurs independently of the presence of myocardial hypertrophy, and is more pronounced in diastole particularly for the longitudinal motion of LVFW. However, unlike in cats, SHT in dogs results in a homogeneous LV geometric pattern with a relatively high prevalence of AoI. Further studies are now needed to determine the effects of antihypertensive drugs on such cardiovascular alterations. The impact of this hypertensive heart disease on prognosis and survival of SHT dogs should also be assessed.

Footnotes

a811-BL, Parks Medical Electronics Inc, Aloha, OR

bDinamap, Critikon Inc, Tampa, FL

cSoft-cuf, Ref 2525, 5 cm large; Ref 2523, 3 cm large; Ref 2422, 2 cm large, Parks Medical Electronics Inc

d Vivid 7, General Electric Medical System, Waukesha, WI

e Echopac Dimension, General Electric Medical System

f Systat, version 10.0, SPSS Inc, Chicago, IL

Acknowledgments

This study was supported by the PhD program of Novartis Animal Health.

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