J Vet Intern Med 2010;24:13751382

As ses sment of Left Ventricular Sys tolic Function by S tr ain Imaging E chocardiography in V arious Stages of Feline Hypertrophic Cardiomyopathy
G. Wess, R. Sarkar, and K. Hartmann
Background: Diastolic dysfunction occurs in many cats with hypertrophic cardiomyopathy (HCM). Less is known about systolic function in various stages of HCM. Myocardial strain analysis by tissue Doppler imaging (TDI) is a noninvasive echocardiographic method to assess systolic function that has not been reported previously in cats. Objectives: To evaluate systolic function in various stages of feline HCM by measurement of myocardial strain. Animals: Two hundred and sixty-three cats. Methods: Cats were classied by echocardiography into one of the following groups: clinically healthy (control) group (n 5 160), mild HCM (n 5 22), moderate HCM (n 5 39), and severe HCM (n 5 42). Peak myocardial strain, measured by TDI in the basal and midventricular segment of the interventricular septal wall (IVS) and the left ventricular posterior wall (LVPW), was compared among different HCM and control groups. Results: Whereas conventional echocardiography demonstrated an apparently normal or supernormal contractile state based on percentage of fractional shortening, myocardial strain in all HCM groups was signicantly decreased compared with the control group (P o .001). There was a signicant correlation between strain values and wall thickness (P o .001). Reproducibility of strain analysis was 6.3% in the IVS and 9.7% in the LVPW. Conclusions and Clinical Importance: Myocardial strain analysis is a new, valuable, and reproducible method in cats. This method allows noninvasive detection of abnormal systolic deformation in cats with HCM despite apparently normal left ventricular systolic function as assessed by conventional echocardiography. The abnormal systolic deformation already was present in mild HCM and increased with progressive left ventricular concentric hypertrophy. Key words: Cardiology; Cats; Myocardial function; Tissue Doppler imaging.

eline hypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by left ventricular (LV) concentric hypertrophy, interstitial brosis, and myocardial disarray. Autosomal dominant inheritance with a heterogeneous disease outcome has been documented in a family of Maine Coon cats.1,2 The disease is characterized by increased left ventricular concentric hypertrophy which occurs symmetrically or asymmetrically. Papillary muscle hypertrophy is almost always present and can lead to end-systolic obliteration of the left ventricular cavity.3 Concentric hypertrophy results in diastolic dysfunction leading to left-sided congestive heart failure. Sudden cardiac death also is associated with this disease in cats as well as in humans.4 Abnormalities in diastolic function using mitral valve inow proles have been well characterized.5,6 However, systolic as well as diastolic function is highly inuenced by preload and afterload.713 Tissue Doppler imaging (TDI) overcomes some of these problems. It is the method of choice for noninvasive assessment of regional myocardial function in humans,1317 and is increasingly used in veterinary medicine.1824 The 1st Doppler method used for the assessment of myocardial function was pulsed wave tissue

Abbreviations:
EF FS HCM IVSd LA/AO LV LVPWd SR TDI TVI ejection fraction fractional shortening hypertrophic cardiomyopathy interventricular septal wall in diastole left atrium/aorta ratio left ventricle left ventricular posterior wall in diastole strain rate tissue Doppler imaging tissue velocity imaging

From the Clinic of Small Animal Medicine, LMU University, Munich, Germany. Corresponding author: Gerhard Wess, DVM, Dipl. ACVIM (Cardiology), Dipl. ECVIM-CA (Cardiology and Internal Medicine), Clinic of Small Animal Medicine, LMU University, Veterinaerstr. 13, Munich 80539, Germany; e-mail: gwess@lmu.de.

Submitted January 25, 2010; Revised April 8, 2010; Accepted July 9, 2010.
Copyright r 2010 by the American College of Veterinary Internal Medicine 10.1111/j.1939-1676.2010.0586.x

velocity imaging (TVI) followed by color-coded Doppler TDI to measure myocardial TVI.19,23,2529 In cats with HCM, indices of diastolic function measured by TVI are different from those of healthy cats and similar to values reported in human beings with HCM and restrictive cardiomyopathy.19,20,23,24,2932 By color-coded TDI, strain and strain rate (SR) measurements were later introduced into clinical practice to evaluate regional myocardial deformation magnitude and rate, respectively. Doppler-based strain and SR were validated both experimentally with ultrasonic crystals and clinically by tagged magnetic resonance imaging (MRI), and are considered to be less affected by tethering, translational artifacts, and traction than Doppler measurements of myocardial velocities.3335 The application of TDI in human beings with HCM has shown that in contrast to traditional echocardiographic techniques, which consider diastolic dysfunction as the main abnormality of the disease, systolic

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Wess, Sarkar, and Hartmann wall measurement results, independent if only 1 segment or only 1 wall was hypertrophied. Color Doppler images of the myocardium were acquired with a 601751 sector size and 180300 frames per second for the IVS and LVPW using the left apical 4-chamber view as single wall images. Complete digital data from 3 heart cycles were stored in cine loop format and transferred to a computer workstation for subsequent myocardial strain analysisb in the basal and midventricular segment of the IVS and LVPW using the left apical 4-chamber view. The mean value of at least 3 peak myocardial strain measurements in each segment was calculated. To avoid any artifact from aliasing, the velocity range was adjusted to allow interrogation of the maximal velocity of the myocardium. Wall lters and gain settings also were optimized for myocardial color saturation for each subject. Hyperthyroidism and hypertension were excluded as secondary causes of concentric hypertrophy by measurement of basal T4 and blood pressure by Doppler technique.c Blood pressure was considered normal if systolic blood pressure was o150 mmHg. Cats with evidence of systemic disease or hyperthyroidism were not included in the study. Measurement reliability of the echocardiographic examination was determined for systolic and diastolic LV chamber diameter and for diastolic wall thickness of the LVPW and IVS as well as for the strain measurements. Ten digitally stored echocardiograms were randomly selected to be subjected to 3 repeated analyses within 1 week by 1 investigator (G.W.) to determine intraobserver measurement variability. The investigator was unaware of the results of the prior echocardiographic analyses.

impairment also is evident, despite the apparently normal or supernormal contractile state of the LV based on percentage of fractional shortening (FS) and percentage of ejection fraction (EF).36 Abnormal systolic function also has been found in cats with HCM using TVI measurements, but only as a group, and not in various disease stages.19,20,30 Noninvasive evaluation of regional systolic function can be performed by measuring myocardial strain.14,33,37 In humans, strain in particular has been proposed as a sensitive tool to detect early systolic function abnormalities in patients with HCM.38,39 However, longitudinal myocardial strain measurement has neither been evaluated in healthy cats nor used to assess systolic function in various stages of feline HCM. The hypothesis of this study was that cats with HCM would have decreased systolic function assessed by longitudinal myocardial strain measurement that is undetected by conventional echocardiography, possibly even in early stages of HCM. Therefore, the objective of this prospective study was to evaluate longitudinal myocardial strain to assess systolic function in healthy cats and in various stages of feline HCM.

Materials and Methods

Animals
A total of 263 cats (male, 151; female, 112) of various breeds were included in this prospective study. The following breeds were represented: European short hair (n 5 151), Maine Coon (n 5 53), Persian (n 5 18), Norwegian Forest Cats (n 5 10), and 31 cats of other breed with o3 cats per group. All cats belonged to owners living in Germany, Switzerland, or Austria and were patients presented to the cardiology service of the Clinic of Small Animal Medicine, or were cats owned by faculty or students.

Statistical Analysis
Data are reported as mean SD. All echocardiographic data were visually inspected and tested for normality by the KolmogorovSmirnov test. A general linear mixed model with Bonferroni adjustment was performed to compare myocardial strain of each segment (basal and midventricular), in each myocardial wall (IVS and LVPW), among the HCM groups (mild, moderate, and severe HCM) and with the control group. Sex, age, concentric hypertrophy presence in the selected segment (present or absent in regional HCM), and heart rate were analyzed as covariates in the general linear mixed model with multivariate analysis and stepwise backward regression analysis. To determine whether functional regional abnormalities were related to structural abnormalities, myocardial strain was compared with IVS and LVPW thickness by linear regression analysis. The intraobserver coefcients of variations (CV) were calculated by a variance component analysis. The CV were obtained by dividing the root of the variance error by the mean of the repeated measurements multiplied by 100. A commercially available software program was used for analysis.d Signicance was dened as P o .05.

Examinations
In all cats, clinical examination, echocardiography, and blood pressure measurements were performed. All echocardiographic studies were performed by 1 experienced examiner (G.W.), using an ultrasound unit equipped with a 7.0 (3.5/6.9) MHz phased-array transducer.a Ultrasound examinations were performed without sedation in gently restrained cats in lateral recumbency. Standard echocardiographic views were obtained in right and left lateral recumbency.40 Two-dimensional images were used for LV measurements. End-diastolic wall thickness of the interventricular septum (IVS) and the left ventricular posterior wall (LVPW) were measured in the basal and midventricular segment of the respective myocardial wall using the right parasternal long-axis view. The left atrium to aorta ratio (LA/AO) was measured in the short-axis view. At least 3 measurements were performed in each segment of the LVPW and IVS and the mean value of the measurements was calculated for each segment. HCM was dened as regional or generalized concentric hypertrophy with a diastolic wall thickness !6 mm of the LVPWd or of the IVSd. The cats were classied according to echocardiography into one of the following groups: control group (LVPWd and IVSd o5.5 mm; LA/ Ao o 1.5), mild HCM (focal or generalized concentric hypertrophy with LVPWd, IVSd, or both 6.06.5 mm and LA/Ao o 1.5), moderate HCM (focal or generalized concentric hypertrophy with LVPWd, IVSd, or both 6.57.0 mm and LA/Ao o 1.8; or LVPWd, IVSd, or both 6.06.5 mm and LA/Ao 1.51.8), and severe HCM (focal or generalized concentric hypertrophy with LVPWd, IVSd, or both 47.0 mm; or LVPWd, IVSd, or both 46.0 mm and LA/Ao 4 1.8). Cats were classied into the HCM groups according to their maximal

Results
Baseline characteristics of the study population are shown in Table 1. The majority of cats in the mild HCM group had a regional, asymmetric HCM form, in which the concentric hypertrophy was present either in the LVPW (n 5 5) or the IVS (n 5 11). In most cats in the moderate and severe HCM groups, both walls were hypertrophied. The mean values of the IVSd and LVPWd are displayed in Table 1. In the HCM groups the table includes measurements o6 mm in some cases, because HCM was present in these cases only regionally and affected the other myocardial wall (IVS or LVPW, respectively). As expected, wall thickness of the IVS and LVPW were signicantly different among all groups (P o .001). The LV diameters in systole and diastole

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Table 1.

Characteristics of the control and various HCM groups.

Control and HCM Groups Healthy N 5 160 Mild N 5 22 11 5 6 4.04 (0.56) 2.175.41 3.97 (0.67) 2.465.78 1.35 (0.12) 41.42 (7.94) 15.26 (2.36) 8.93 (1.82) 59 (48) 12205 83 47 7 7 16 5.99 (0.51) 4.696.43 6.02 (0.53) 4.736.65 1.40 (0.20) 57.62 (7.21) 13.19 (1.61) 5.61 (1.28) 114 (52) 26215 11 2 3 1 5 Moderate N 5 39 4 5 30 6.50 (0.48) 4.876.98 6.46 (0.50) 4.946.99 1.52 (0.19) 54.00 (8.11) 13.94 (2.04) 6.46 (1.67) 118 (55) 18222 27 2 5 1 4 Severe N 5 42 2 2 38 7.61 (1.14) 4.1110.94 7.84 (1.40) 6.0010.94 1.99 (0.64) 48.00 (13.30) 14.23 (2.47) 7.32 (2.01) 111 (54) 10183 30 2 3 1 6

Affected wall Only IVSd 4 6 mm Only LVPWd 4 6 mm Both walls 4 6 mm IVSd Mean (std.) Range LVPWd Mean (std.) Range LA/Ao Mean (std.) FS (%) Mean (std.) LVIDd Mean (std.) LVIDs Mean (std.) Age (month) Mean (std.) Range Breeds European short hair Maine Coon cats Persian Norwegian Forest Other breed cats

IVSd, interventricular septal wall in diastole; LVPWd, left ventricular posterior wall in diastole; LA/AO, ratio left atrium to aorta; FS, fractional shortening; LVIDd, left ventricular internal diameter in diastole; LVIDs, left ventricular internal diameter in systole; std, standard. The maximum value of the respective wall (IVS or LVPW) is displayed, independent from which segment (basal or midventricular segment) the maximum measurement was obtained. Some cats had only a regional hypertrophy of the wall, which explains why some measurements in the HCM groups are below the respective classication value.

were signicantly smaller in the HCM groups compared with the control group (P o .001). The LA/Ao ratio was signicantly higher in the moderate and severe HCM groups compared with the mild HCM and control group and the FS was signicantly higher in all HCM groups compared with the control group (P o .001). Cats in the control group were signicantly (P o .001) younger than those in the HCM groups, but this inuence was accounted for using the general linear model. Heart rate was not different among the groups (P 5 .67). More than 3,120 strain measurements were performed in 260 cats (4 segments, minimum of 3 strain measurements per segment). Myocardial strain was signicantly lower in all HCM groups compared with the control group (P o .001). Median and interquartile ranges for the different groups are shown in Figure 1, separately displayed for each of the myocardial segments. Mean strain in the basal segment of the IVS was 22.0 (4.8), 15.9 (3.9), 14.6 (5.3), 11.4 (4.6) in the control, mild, moderate, and severe groups, respectively. Mean strain in the midventricular segment of the IVS was 22.2 (5.7), 17.0 (5.4), 15.6 (6.6), 12.6 (5.1) in the control, mild, moderate, and severe groups, respectively. In the basal

segment of the LVPW, the mean peak systolic strain was 18.3 (3.8) in the control group, 8.9 (4.9) in the mild HCM group, 9.0 (4.3) in the moderate HCM group, and 6.2 (2.7) in the severe HCM group. In the midventricular segment of the LVPW, the mean peak systolic strain was 18.6 (4.3) in the control group, 11.5 (7.4) in the mild HCM group, 8.4 (4.4) in the moderate HCM group, and 7.1 (3.4) in the severe HCM group. Age, heart rate, sex, breed, and type of concentric hypertrophy (regional or generalized HCM) did not inuence the myocardial strain measurements, only disease stage (HCM group) remained signicant in the stepwise backward regression analysis using the general linear mixed model in all segments of the IVS and LVPW. The severe HCM group had signicantly lower strain values than the moderate HCM group (P 5 .017), mild HCM group (P 5 .003), and control group (P o .001). No signicant difference in strain values was found between the mild and moderate HCM groups, but results in both HCM groups were signicantly lower than in the control group (P o .001). A positive strain value was found in 7 cats in the severe HCM group. These values were censored from the analysis, because

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Wess, Sarkar, and Hartmann

Fig 1. Distribution of systolic myocardial strain analysis results of 263 cats in different stages of hypertrophic cardiomyopathy and a control group in different myocardial segments (basal and midventricular) in the interventricular septal wall (IVS) and left ventricular posterior wall (LVPW). All hypertrophic cardiomyopathy (HCM) groups were signicantly lower (less negative) than control. Among the HCM groups only the severe stage was lower than the other HCM groups. For each plot, the box represents the inter quartile range (IQR), the horizontal line in the middle of the box represents the median, and the whiskers denote the range. Outlier values between 1.5 and 3 times the IQR are indicated by a circle. Cases with values more than 3 box lengths from the upper or lower edge of the box are shown with an asterisk.

they would have decreased mean strain values (which are negative values) even further. There was a signicant correlation (P o .001) between strain values and LV wall thickness (Fig 2). The correlation between combined strain values (basal and midventricular) and LV wall thickness was similar in the IVS (R 5 0.59) and in the LVPW (R 5 0.69). Results of the echocardiographic repeatability study were acceptable: CV was 3.3% for diastolic LVPW, 2.6% for diastolic IVS, 2.0% for diastolic LV diameter, and 4.2% for systolic LV diameter.

CV for the myocardial strain was better in the IVS (6.3%) compared with the LVPW (9.7%).

Discussion
The present study is the 1st to evaluate systolic function by TDI strain analysis in various stages of feline HCM. The study shows that strain analysis is a feasible and repeatable method in cats, and that longitudinal systolic myocardial deformation decreased in cats with

Fig 2. Linear regression scatter diagrams to compare combined basal and midventricular strain of the interventricular septal wall (IVS), and of the left ventricular posterior wall (LVPW), with IVS and LVPW thickness in diastole (n 5 260 cats).

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HCM, despite normal echocardiographic indices of global LV systolic function, suggesting the presence of subclinical systolic dysfunction that is not detectable by conventional echocardiographic methods. Recently, new echocardiographic techniques such as TVI and strain imaging have become clinically available. Strain and SR in particular provide direct quantitative information on regional systolic and diastolic myocardial function without using geometrical assumptions. Strain imaging has been shown to be a sensitive method to quantify regional systolic myocardial function in a variety of cardiac diseases.22,4144 It enables the evaluation of regional myocardial deformation in different myocardial segments in the radial, longitudinal, or circumferential directions and therefore is ideal to characterize heterogeneity in myocardial function in cardiomyopathies.41 Myocardial strain analysis assessed by color TDI is a sensitive tool to detect early systolic function abnormalities in human patients with HCM.38,39 The present study shows that strain analysis can be used in cats and that the repeatability of strain measurements is good in both LV myocardial walls. The CV was better in the IVS, possibly because it is more difcult to align the LVPW with the ultrasound beam (compared with the IVS). The present study demonstrates that systolic myocardial strain is already decreased in mild forms of HCM and decreases more in more severe HCM stages. Decreased systolic myocardial tissue velocity previously has been demonstrated in cats with HCM, but not in various stages of HCM and not using myocardial strain.19,20,30 From a clinical perspective, HCM is considered to be predominantly a diastolic disorder with relaxation abnormalities in the early stages that can progress toward a more restrictive physiology later in the disease process.20,21,23,30,45,46 In patients with HCM, diastolic dysfunction is thought to precede systolic dysfunction.4749 A recent study in humans by TDI showed that both diastolic and longitudinal systolic abnormalities are present in HCM despite normal EF. That study proposed that diastolic dysfunction is an early consequence of sarcomere mutations, whereas systolic dysfunction results from mutations combined with subsequent pathological remodeling.50 Our study demonstrates that decreased regional systolic function is already present in cats with mild HCM. These ndings are in agreement with transgenic mice models of HCM in which sarcomere length, systolic shortening, and shear strains were lower in hypertrophied segments with myober disarray.51 In a recent study in human carriers of HCM mutations that had normal LV wall thickness, peak systolic strain was deceased.52 Similarly, magnetic resonance tagging data suggest that myocardial shortening and thickening are heterogeneously decreased and inversely correlated with end-diastolic wall thickness in HCM patients.53,54 An MRI tagging study to evaluate regional myocardial function found a marked reduction in longitudinal deformation in all myocardial segments, which was more pronounced in the more hypertrophied septum.55 There are discrepancies between measures of regional and global myocardial function assessed by conventional echocardiography (FS or EF) and myocardial strain

analysis for several reasons. First, endocardial indices of LV function such as FS and EF are known to overestimate systolic function in the presence of LV concentric hypertrophy.5660 Normally, endocardial wall thickening is higher than epicardial wall thickening and this difference becomes more pronounced with greater degrees of concentric hypertrophy. For this reason, one should be cautious when using endocardial indices in the setting of increased wall thickness. Secondly, patients with HCM have smaller end-diastolic diameter and increased wall thickness, resulting in decreased ventricular afterload.57 The load dependency of both FS and EF is a well-known shortcoming of these indices. In the presence of substantial concentric hypertrophy, higher values of FS and EF are seen, despite decreased wall thickening.5860 Therefore, the commonly used echocardiographic measures of systolic function (ie, EF and FS) might not reliably reect intrinsic myocardial contractile function in the presence of remodeled hearts such as that occurring in HCM.50,56,57,61,62 Studies in humans patients with HCM have identied decreased longitudinal and circumferential strain by TDI and MRI, respectively.38,39,41,50,61,6367 Interestingly, the present study showed decreased strain in both hypertrophied and nonhypertrophied regions, a nding in accordance with studies in humans.50,68,69 Hence, strain analysis appears to be a more sensitive index of myocardial function than standard LV function assessment, emphasizing the diffuse nature of the disease.50,61,63,70 The reduction in systolic strain correlates with the degree of concentric hypertrophy in a linear fashion. Different factors explain this relationship. HCM is a disorder characterized by LV concentric hypertrophy, interstitial brosis, and myocardial disarray. Myocardial structural abnormalities with more pronounced ber disarray are present in the more severely hypertrophied myocardial segments.63 When bers are not geometrically arranged in a coherent direction but are randomly structured, contraction of these bers will not result in an organized deformation pattern.51,71 Fibrosis and wall thickness were both multivariate predictors of lower segmental longitudinal strain in a human HCM study.63,71,72 Myocardial brosis was associated with impaired longitudinal strain in patients with HCM.71,72 Additionally, changes in passive mechanical characteristics caused by brosis and altered collagen deposition also affect deformation when active force is developed within a myocardial segment.73 Finally, increased concentric hypertrophy can cause an imbalance between oxygen demand and delivery exceeding regional coronary ow reserve, potentially resulting in regional ischemia.74 A recent study showed that left ventricular diastolic dysfunction, systolic dysfunction, or both at follow-up are relatively frequent in HCM and are associated with a poor prognosis.75 Thus, myocardial strain measurements in cats might be useful to detect early or progressive systolic dysfunction at follow-up examinations. The use of positive inotropic drugs in humans or cats with HCM has not been evaluated and studies on that subject are necessary before such drugs can be recommended. A limitation of the present study was the noninvasive study design. The study was carried out on pet animals

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Wess, Sarkar, and Hartmann 3. Kittleson MD. Hypertrophic cardiomyopathy. In: Kittleson MD, Kienle RD, eds. Small Animal Cardivascular Medicine. St Louis: Mosby Inc; 1998:347362. 4. Kittleson MD. Feline myocardial disease. In: Ettinger EJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. St Louis: Elsevier; 2005:10821103. 5. Bright JM, Herrtage ME, Schneider JF. Pulsed Doppler assessment of left ventricular diastolic function in normal and cardiomyopathic cats. J Am Anim Hosp Assoc 1999;35:285291. 6. Ferasin L. Feline myocardial disease 2: Diagnosis, prognosis and clinical management. J Feline Med Surg 2009;11:183194. 7. Moise NS, Horne WA, Flanders JA, et al. Repeatability of the M-mode echocardiogram and the effects of acute changes in heart rate, cardiac contractility, and preload in healthy cats sedated with ketamine hydrochloride and acepromazine. Cornell Vet 1986;76:241258. 8. Jacobs G, Mahjoob K. Inuence of alterations in heart rate on echocardiographic measurements in the dog. Am J Vet Res 1988;49:548552. 9. Fox PR, Bond BR, Peterson ME. Echocardiographic reference values in healthy cats sedated with ketamine hydrochloride. Am J Vet Res 1985;46:14791484. 10. Jacobs G, Knight DH. Change in M-mode echocardiographic values in cats given ketamine. Am J Vet Res 1985;46:17121713. 11. Suzuki K, Aoyagi S, Koie H, et al. The effect of 7.2% hypertonic saline solution on m-mode echocardiographic indices in normovolemic dogs. J Vet Med Sci 2006;68:749751. 12. Suzuki K, Otake M, Saida Y, et al. The effect of 7.2% hypertonic saline solution with 6% dextran 70 on cardiac contractility as observed by an echocardiography in normovolemic and anesthetized dogs. J Vet Med Sci 2008;70:8994. 13. Dalsgaard M, Snyder EM, Kjaergaard J, et al. Isovolumic acceleration measured by tissue Doppler echocardiography is preload independent in healthy subjects. Echocardiography 2007; 24:572579. 14. Greenberg NL, Firstenberg MS, Castro PL, et al. Dopplerderived myocardial systolic strain rate is a strong index of left ventricular contractility. Circulation 2002;105:99105. 15. Nagueh SF, Middleton KJ, Kopelen HA, et al. Doppler tissue imaging: A noninvasive technique for evaluation of left ventricular relaxation and estimation of lling pressures. J Am Coll Cardiol 1997;30:15271533. 16. Oh JK, Appleton CP, Hatle LK, et al. The noninvasive assessment of left ventricular diastolic function with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 1997;10:246270. 17. Bruch C, Schmermund A, Bartel T, et al. Tissue Doppler imaging: A new technique for assessment of pseudonormalization of the mitral inow pattern. Echocardiography 2000;17:539546. 18. Chetboul V, Athanassiadis N, Carlos C, et al. Quantication, repeatability, and reproducibility of feline radial and longitudinal left ventricular velocities by tissue Doppler imaging. Am J Vet Res 2004;65:566572. 19. Carlos Sampedrano C, Chetboul V, Gouni V, et al. Systolic and diastolic myocardial dysfunction in cats with hypertrophic cardiomyopathy or systemic hypertension. J Vet Intern Med 2006;20:11061115. 20. Koffas H, Dukes-McEwan J, Corcoran BM, et al. Pulsed tissue Doppler imaging in normal cats and cats with hypertrophic cardiomyopathy. J Vet Intern Med 2006;20:6577. 21. MacDonald KA, Kittleson MD, Garcia-Nolen T, et al. Tissue Doppler imaging and gradient echo cardiac magnetic resonance imaging in normal cats and cats with hypertrophic cardiomyopathy. J Vet Intern Med 2006;20:627634. 22. Chetboul V, Gouni V, Sampedrano CC, et al. Assessment of regional systolic and diastolic myocardial function using tissue Doppler and strain imaging in dogs with dilated cardiomyopathy. J Vet Intern Med 2007;21:719730.

without any invasively determined hemodynamic data to which the results of strain analysis could be compared. Furthermore, classication of different HCM groups was based on morphological rather than pathological criteria. This may have resulted in falsely including affected animals in the normal group and affected animals with cardiac diseases other than HCM in the affected group. Additionally, classication into different HCM groups was quite arbitrary, based on LV wall thickness and LA/Ao ratio, which may explain why there was no statistical difference between mild and moderate HCM groups because disease progression is a continuous process. Furthermore, it was impossible to blind the observer concerning the presence or absence of concentric hypertrophy of the myocardial wall while performing the TDI analysis. This might have caused a potential bias, but TDI results are displayed by the software automatically and were not manipulated by the investigator. Because the study was not performed in a longitudinal fashion and because diastolic dysfunction was not assessed in this study, no conclusion can be drawn about whether or not diastolic dysfunction precedes systolic dysfunction. In summary, this study demonstrates that strain analysis is a feasible and repeatable method to assess systolic function in cats. Strain analysis is a valuable new echocardiographic method and provides useful additional information in cats with HCM. The present study shows that systolic TDI strain measurement allows noninvasive detection of abnormal systolic deformation in cats with HCM, despite an apparent normal or supernormal contractile state of the LV based on percentage of FS. The abnormal systolic deformation already was present in mild HCM and increased with progressive LV concentric hypertrophy. Hence, strain analysis appears to be a more sensitive index of global myocardial function than standard LV function assessment, emphasizing the diffuse nature of the disease. The results of the present study provide not only new insights into the pathophysiology of feline HCM, but challenge the concept that diastolic dysfunction precedes systolic dysfunction.

Footnotes
a

Vivid 7 dimension, General Electric Medical System, Waukesha, WI b EchoPac PC, Version 6.0, General Electric Medical System c Parks 811-BT, Parks Medical Electronics Inc, Aloha, OR d SPSS for Windows, Version 13.0, SPSS Inc, Chicago, IL

References
1. Kittleson MD, Meurs KM, Munro MJ, et al. Familial hypertrophic cardiomyopathy in Maine Coon cats: An animal model of human disease. Circulation 1999;99:31723180. 2. Meurs KM, Sanchez X, David RM, et al. A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy. Hum Mol Genet 2005;14:35873593.

Myocardial Strain in Feline HCM 23. Gavaghan BJ, Kittleson MD, Fisher KJ, et al. Quantication of left ventricular diastolic wall motion by Doppler tissue imaging in healthy cats and cats with cardiomyopathy. Am J Vet Res 1999;60:14781486. 24. MacDonald KA, Kittleson MD, Kass PH, et al. Tissue Doppler imaging in Maine Coon cats with a mutation of myosin binding protein C with or without hypertrophy. J Vet Intern Med 2007;21:232237. 25. Chetboul V, Sampedrano CC, Gouni V, et al. Quantitative assessment of regional right ventricular myocardial velocities in awake dogs by Doppler tissue imaging: Repeatability, reproducibility, effect of body weight and breed, and comparison with left ventricular myocardial velocities. J Vet Intern Med 2005;19:837844. 26. Chetboul V, Sampedrano CC, Concordet D, et al. Use of quantitative two-dimensional color tissue Doppler imaging for assessment of left ventricular radial and longitudinal myocardial velocities in dogs. Am J Vet Res 2005;66:953961. 27. Chetboul V, Athanassiadis N, Carlos C, et al. Assessment of repeatability, reproducibility, and effect of anesthesia on determination of radial and longitudinal left ventricular velocities via tissue Doppler imaging in dogs. Am J Vet Res 2004;65:909915. 28. Carlos Sampedrano C, Chetboul V, Mary J, et al. Prospective echocardiographic and tissue Doppler imaging screening of a population of Maine Coon cats tested for the A31P mutation in the myosin-binding protein C gene: A specic analysis of the heterozygous status. J Vet Intern Med 2009;23:9199. 29. Chetboul V, Blot S, Sampedrano CC, et al. Tissue Doppler imaging for detection of radial and longitudinal myocardial dysfunction in a family of cats affected by dystrophin-decient hypertrophic muscular dystrophy. J Vet Intern Med 2006;20:640647. 30. Koffas H, Dukes-McEwan J, Corcoran BM, et al. Colour M-mode tissue Doppler imaging in healthy cats and cats with hypertrophic cardiomyopathy. J Small Anim Pract 2008;49:330338. 31. Simpson KE, Gunn-Moore DA, Shaw DJ, et al. Pulsed-wave Doppler tissue imaging velocities in normal geriatric cats and geriatric cats with primary or systemic diseases linked to specic cardiomyopathies in humans, and the inuence of age and heart rate upon these velocities. J Feline Med Surg 2009;11:293304. 32. MacDonald KA, Kittleson MD, Kass PH, et al. Effect of spironolactone on diastolic function and left ventricular mass in Maine Coon cats with familial hypertrophic cardiomyopathy. J Vet Intern Med 2008;22:335341. 33. Urheim S, Edvardsen T, Torp H, et al. Myocardial strain by Doppler echocardiography. Validation of a new method to quantify regional myocardial function. Circulation 2000;102:11581164. 34. Edvardsen T, Gerber BL, Garot J, et al. Quantitative assessment of intrinsic regional myocardial deformation by Doppler strain rate echocardiography in humans: Validation against three-dimensional tagged magnetic resonance imaging. Circulation 2002;106:5056. 35. Chetboul V, Serres F, Gouni V, et al. Radial strain and strain rate by two-dimensional speckle tracking echocardiography and the tissue velocity based technique in the dog. J Vet Cardiol 2007;9:6981. 36. Cardim N, Castela S, Cordeiro R, et al. Tissue Doppler imaging assessment of long axis left ventricular function in hypertrophic cardiomyopathy. Rev Port Cardiol 2002;21:953985. 37. Heimdal A, Stoylen A, Torp H, et al. Real-time strain rate imaging of the left ventricle by ultrasound. J Am Soc Echocardiogr 1998;11:10131019. 38. Yang H, Sun JP, Lever HM, et al. Use of strain imaging in detecting segmental dysfunction in patients with hypertrophic cardiomyopathy. J Am Soc Echocardiogr 2003;16:233239. 39. Serri K, Reant P, Latte M, et al. Global and regional myocardial function quantication by two-dimensional strain: Application in hypertrophic cardiomyopathy. J Am Coll Cardiol 2006;47:11751181. 40. Kittleson MD. Echocardiography. In: Kittleson MD, Kienle RD, eds. Small Animal Cardiovascular Medicine. St Louis: Mosby Inc; 1998:95117.

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41. Ganame J, Mertens L, Eidem BW, et al. Regional myocardial deformation in children with hypertrophic cardiomyopathy: Morphological and clinical correlations. Eur Heart J 2007;28:28862894. 42. Flachskampf FA, Breithardt OA, Daniel WG. Diagnostic value of tissue Doppler parameters in the early diagnosis of cardiomyopathies. Herz 2007;32:8996. 43. Arita T, Sorescu GP, Schuler BT, et al. Speckle-tracking strain echocardiography for detecting cardiac dyssynchrony in a canine model of dyssynchrony and heart failure. Am J Physiol Heart Circ Physiol 2007;293:H735H742. 44. Rajdev S, Nanda NC, Patel V, et al. Tissue Doppler assessment of longitudinal right and left ventricular strain and strain rate in pulmonary artery hypertension. Echocardiography 2006;23:872879. 45. Nagueh SF, Kopelen HA, Lim DS, et al. Tissue Doppler imaging consistently detects myocardial contraction and relaxation abnormalities, irrespective of cardiac hypertrophy, in a transgenic rabbit model of human hypertrophic cardiomyopathy. Circulation 2000;102:13461350. 46. Nagueh SF, Lakkis NM, Middleton KJ, et al. Doppler estimation of left ventricular lling pressures in patients with hypertrophic cardiomyopathy. Circulation 1999;99:254261. 47. Severino S, Caso P, Galderisi M, et al. Use of pulsed Doppler tissue imaging to assess regional left ventricular diastolic dysfunction in hypertrophic cardiomyopathy. Am J Cardiol 1998;82:13941398. 48. Maron BJ, Spirito P, Green KJ, et al. Noninvasive assessment of left ventricular diastolic function by pulsed Doppler echocardiography in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 1987;10:733742. 49. Vinereanu D, Ionescu AA, Fraser AG. Assessment of left ventricular long axis contraction can detect early myocardial dysfunction in asymptomatic patients with severe aortic regurgitation. Heart 2001;85:3036. 50. Ho CY, Carlsen C, Thune JJ, et al. Echocardiographic strain imaging to assess early and late consequences of sarcomere mutations in hypertrophic cardiomyopathy. Circ Cardiovasc Genet 2009;2:314321. 51. Karlon WJ, McCulloch AD, Covell JW, et al. Regional dysfunction correlates with myober disarray in transgenic mice with ventricular expression of ras. Am J Physiol Heart Circ Physiol 2000;278:H898H906. 52. Germans T, Russel IK, Gotte MJ, et al. How do hypertrophic cardiomyopathy mutations affect myocardial function in carriers with normal wall thickness? Assessment with cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2010;12:110. 53. Dong SJ, MacGregor JH, Crawley AP, et al. Left ventricular wall thickness and regional systolic function in patients with hypertrophic cardiomyopathy. A three-dimensional tagged magnetic resonance imaging study. Circulation 1994;90:12001209. 54. Kramer CM, Reichek N, Ferrari VA, et al. Regional heterogeneity of function in hypertrophic cardiomyopathy. Circulation 1994;90:186194. 55. Young AA, Kramer CM, Ferrari VA, et al. Three-dimensional left ventricular deformation in hypertrophic cardiomyopathy. Circulation 1994;90:854867. 56. Connelly KA, Prior DL, Kelly DJ, et al. Load-sensitive measures may overestimate global systolic function in the presence of left ventricular hypertrophy: A comparison with load-insensitive measures. Am J Physiol Heart Circ Physiol 2006;290:H1699H1705. 57. Hirota Y, Furubayashi K, Kaku K, et al. Hypertrophic nonobstructive cardiomyopathy: A precise assessment of hemodynamic characteristics and clinical implications. Am J Cardiol 1982;50:990997. 58. Shimizu G, Hirota Y, Kita Y, et al. Left ventricular midwall mechanics in systemic arterial hypertension. Myocardial function is depressed in pressure-overload hypertrophy. Circulation 1991;83: 16761684. 59. Palmon LC, Reichek N, Yeon SB, et al. Intramural myocardial shortening in hypertensive left ventricular hypertrophy with normal pump function. Circulation 1994;89:122131.

1382

Wess, Sarkar, and Hartmann 68. Mishiro Y, Oki T, Iuchi A, et al. Regional left ventricular myocardial contraction abnormalities and asynchrony in patients with hypertrophic cardiomyopathy evaluated by magnetic resonance spatial modulation of magnetization myocardial tagging. Jpn Circ J 1999;63:442446. 69. Liu Y, Deng Y, Li X, et al. Assessment of left ventricular longitudinal regional myocardial systolic function by strain imaging echocardiography in patients with hypertrophic cardiomyopathy. J Huazhong Univ Sci Technolog Med Sci 2005;25:703705. 70. Saccheri MC, Cianciulli TF, Lax JA, et al. Impaired myocardial function in hypertrophic cardiomyopathy. Echocardiography 2009;26:657664. 71. Tseng WY, Dou J, Reese TG, et al. Imaging myocardial ber disarray and intramural strain hypokinesis in hypertrophic cardiomyopathy with MRI. J Magn Reson Imaging 2006;23:18. 72. Popovic ZB, Kwon DH, Mishra M, et al. Association between regional ventricular function and myocardial brosis in hypertrophic cardiomyopathy assessed by speckle tracking echocardiography and delayed hyperenhancement magnetic resonance imaging. J Am Soc Echocardiogr 2008;21:12991305. 73. Shirani J, Pick R, Roberts WC, et al. Morphology and signicance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death. J Am Coll Cardiol 2000;35:3644. 74. Basso C, Thiene G, Corrado D, et al. Hypertrophic cardiomyopathy and sudden death in the young: Pathologic evidence of myocardial ischemia. Hum Pathol 2000;31:988998. 75. Pinamonti B, Merlo M, Nangah R, et al. The progression of left ventricular systolic and diastolic dysfunctions in hypertrophic cardiomyopathy: Clinical and prognostic signicance. J Cardiovasc Med (Hagerstown) 2010;11:669677.

60. Aurigemma GP, Silver KH, Priest MA, et al. Geometric changes allow normal ejection fraction despite depressed myocardial shortening in hypertensive left ventricular hypertrophy. J Am Coll Cardiol 1995;26:195202. 61. Sun JP, Stewart WJ, Yang XS, et al. Differentiation of hypertrophic cardiomyopathy and cardiac amyloidosis from other causes of ventricular wall thickening by two-dimensional strain imaging echocardiography. Am J Cardiol 2009;103:411415. 62. Nesbitt GC, Mankad S. Strain and strain rate imaging in cardiomyopathy. Echocardiography 2009;26:337344. 63. Ghio S, Revera M, Mori F, et al. Regional abnormalities of myocardial deformation in patients with hypertrophic cardiomyopathy: Correlations with delayed enhancement in cardiac magnetic resonance. Eur J Heart Fail 2009;11:952957. 64. Kato TS, Izawa H, Komamura K, et al. Heterogeneity of regional systolic function detected by tissue Doppler imaging is linked to impaired global left ventricular relaxation in hypertrophic cardiomyopathy. Heart 2008;94:13021306. 65. Kato TS, Noda A, Izawa H, et al. Discrimination of nonobstructive hypertrophic cardiomyopathy from hypertensive left ventricular hypertrophy on the basis of strain rate imaging by tissue Doppler ultrasonography. Circulation 2004;110: 38083814. 66. Minoshima M, Noda A, Nishizawa T, et al. Endomyocardial radial strain imaging and left ventricular relaxation abnormalities in patients with hypertrophic cardiomyopathy or hypertensive left ventricular hypertrophy. Circ J 2009;73:22942299. 67. Paraskevaidis IA, Farmakis D, Papadopoulos C, et al. Twodimensional strain analysis in patients with hypertrophic cardiomyopathy and normal systolic function: A 12-month follow-up study. Am Heart J 2009;158:444450.