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J Vet Intern Med 2006;20:104–110

Prognostic Indicators for Dogs with Dilated Cardiomyopathy Michele Borgarelli, Roberto A. Santilli, David Chiavegato, Gino D’Agnolo, Renato Zanatta, Alessandro Mannelli, and Alberto Tarducci The purpose of this study was to investigate the prognostic value of various clinical, ECG, echocardiographic, and Doppler echocardiographic variables in dogs with dilated cardiomyopathy. The relationship to survival of 11 variables was evaluated in 63 dogs. Studied variables were age at time of diagnosis, class of heart failure (HF), dyspnea, ascites, atrial fibrillation (AF), ejection fraction (EF), E-point septal separation, end-diastolic volume index, end-systolic volume index (ESV-I), and restrictive or nonrestrictive transmitral flow (TMF) pattern. Median survival time was 671 days (lower 95% confidence limit, 350 days). Survival curves showed that severity of HF, ascites, ESV-I greater than 140 mL/m2, EF less than 25%, and restrictive TMF pattern had a significant negative relation to survival time. Thirty-nine dogs with both sinus rhythm and AF presented adequate TMF recordings; in these dogs, after stratification by TMF pattern, the restrictive TMF pattern was the most important negative prognostic indicator. We conclude that in dogs with dilated cardiomyopathy the restrictive TMF pattern appears to represent a useful prognostic indicator. Class of HF, ascites, ESV-I, and EF are also useful indexes if an adequate TMF pattern is not recorded. Key words: Canine; Doppler echocardiography; Echocardiography; Heart.

diopathic dilated cardiomyopathy (DCM) is a cardiac muscle disease of unknown origin characterized by enlargement of the cardiac chambers and severe systolic dysfunction.1 The diagnosis of DCM is based on identification of myocardial (predominantly but not solely systolic) dysfunction and exclusion of other acquired or congenital cardiac diseases.2 Although there may be a long asymptomatic period, the disease eventually progresses into heart failure (HF), if this progression is not preempted by sudden death.3 Echocardiography is the standard imaging technique for the diagnosis of both preclinical and symptomatic DCM.2 Typical findings include increased left ventricular endsystolic dimension (ESD) and end-diastolic dimension (EDD), decreased fractional shortening (FS), and increased E-point septal separation (EPSS). Although Mmode and B-mode echocardiographic parameters are the most reliable way to diagnoses DCM, they poorly correlate with clinical signs, exercise capacity, and life expectancy.4–6 Human patients with DCM have been shown to have abnormal diastolic function and abnormal systolic function. It is clear that abnormalities of diastolic function play a major role in producing signs of disease in patients who present with HF.7 Pulsed Doppler echocardiographic evaluation of the transmitral flow

(TMF) and pulmonary venous flow has proven to be a rapid, repeatable, noninvasive method of assessing left ventricular filling in various cardiac diseases.7–9 Studies have recognized 2 different TMF patterns (restrictive and nonrestrictive) in patients with DCM.8–10 The restrictive pattern is the most common in patients with DCM. It is characterized by a short isovolumetric relaxation time, rapid filling in early diastole (E-wave) with a high E-wave and a short E-wave deceleration time (Edt), and minimal filling during atrial systole (reduced A-wave velocity). The nonrestrictive pattern (normal TMF, impaired relaxation, and pseudonormal pattern) is characterized by a lower E wave, higher A wave, lower E/A ratio, and longer Edt than in the restrictive pattern.7,11,12 The restrictive TMF pattern correlates well with high filling pressure and poor prognosis in people.8,10,13 In particular, a shortened Edt appears to be a powerful independent predictor of poor prognosis in symptomatic or asymptomatic patients with left ventricular dysfunction, even in patients with atrial fibrillation (AF).14,15 The purpose of this study was to investigate the prognostic value of various clinical, ECG, echocardiographic (B- or M-mode measurements), and Doppler echocardiographic variables in dogs with DCM by studying their relationship with survival.

From the Department Patologia Animale, Faculty Veterinary Medicine, Grugliasco, Italy (Borgarelli, Zanatta, Tarducci); Clinica Veterinaria Malpensa, Samarate, Italy (Santilli); Clinica Veterinaria, Padova, Italy (Chiavegato); Via Valdirivo, Trieste, Italy (D’Agnolo); and Department Produzioni Animali, Epidemiologia, Ecologia, Faculty Veterinary Medicine, Grugliasco, Italy (Mannelli). Preliminary results presented at the American College of Veterinary Medicine Conference, Seattle, WA, 2000. Reprint requests: Michele Borgarelli, DVM, Dipl. PhD, ECVIMCA, Department Patologia Animale, Faculty Veterinary Medicine, Via L. da Vinci 44, 10095 Grugliasco (To), Italy; e-mail: michele.borgarelli@unito.it. Submitted January 10, 2005; Revised March 23, 2005; Accepted June 3, 2005. Copyright E 2006 by the American College of Veterinary Internal Medicine 0891-6640/06/2001-0013/$3.00/0

Study Design

I

Materials and Methods The medical records of dogs examined at 4 different cardiology referral centers in Italy from 1998–2003 were retrospectively searched for cases of DCM. From these records, 76 dogs diagnosed as having DCM were reviewed. All dogs had been submitted for a cardiologic consultation for the presence of clinical signs compatible with a cardiovascular disorder (ie, dyspnea, exercise intolerance, arrhythmia) or for screening. The closing date of the study was December 31, 2003. Inclusion criteria were the recognition of left ventricular Mmode systolic dimension that exceeded 95% confidence intervals (CIs) for the individual based on regression equations or predicted reference values, or outside other established breed-specific reference ranges, an M-mode FS less than 20%, and a left ventricular ejection fraction (EF) less than 40%. To be included in the analysis, dogs had to have at least 2 of these abnormalities.


Dilated Cardiomyopathy Exclusion criteria were the presence of systemic hypertension, congenital heart diseases, other acquired cardiovascular disorders (ie, mitral valve disease, endocarditis), and systemic diseases that possibly affect the heart function (ie, hypothyroidism). Systolic blood pressure was noninvasively determined by Doppler sphygmomanometry,a and hypertension was defined as systolic arterial blood pressure above 180 mm Hg.16

Clinical Data Data extracted from each record included the presence or absence of heart murmur, gallop rhythm, dyspnea, pulmonary edema, and pleural effusion diagnosed by thoracic radiographs and ascites diagnosed by ultrasound examination. In each dog, HF was classified according to the International Small Animal Cardiac Health Council (ISACHC) recommendations.17

ECGs ECGs were performed with a standard 12-lead electrocardiograph.b The ECG recordings were analyzed with a 2-minute strip, and all ECGs were performed with the dog in right lateral recumbency. The following abnormalities were recorded from each tracing: supraventricular ectopic beats (SVB), AF, ventricular ectopic beats (VPC), and episodes of ventricular tachycardia.

Echocardiography and Echocardiographic Measurements All dogs underwent complete echocardiographic examination, including transthoracic, 2-dimensional, M-mode, spectral, and color flow Doppler echocardiography. Transducer arrays of 2.5– 3.5 MHz and 3.5–5.0 MHz were used.c Examinations were performed in conscious unsedated dogs. Right parasternal Mmode recordings were obtained from short-axis views with the dogs positioned in right lateral recumbency, and the 2-dimensional echocardiograms were obtained in accordance with techniques described elsewhere.18,19 All echocardiographic studies were recorded on videotape. All clinical, ECG, echocardiographic, and Doppler echocardiographic data were reviewed by a board-certified cardiologist (M.B.). Cardiac cycles were determined from a mean of 3 consecutive measurements in dogs with sinus rhythm and 5 consecutive measurements in dogs with AF. M-mode measurements were obtained according to the leading edge–to–leading edge method.20 M-mode measurements included the EDD and the ESD. The FS was calculated by the following formula: [(EDD 2 ESD)/ EDD] 3 100. End-diastolic volume (EDV) and end-systolic volume (ESV) were calculated by the Teicholz method: ESV 5 (ESD3 3 7)/(ESD + 2.4) and EDV 5 (EDD3 3 7)/(EDD + 2.4).21 Values were indexed to the body surface area to obtain the enddiastolic volume index (EDV-I) and the end-systolic volume index (ESV-I). The left atrial–aortic root ratio (LA/Ao) was obtained from the 2-dimensional short-axis view.22 Left ventricular EFs were obtained from whichever view optimizes left ventricular length and volume (right parasternal long-axis or left apical views) and was calculated by the area length method.23 The TMF was measured from the apical 4-chamber view with the sample volume placed between the tips of mitral valve leaflets. The following TMF variables were measured: peak E-wave velocity (early filling), peak A-wave velocity (atrial systole), Edt, and ratio of E-wave velocity to A-wave velocity (E/A ratio). In patients with sinus rhythm, grouping of Doppler TMF patterns into restrictive and nonrestrictive categories was first based on the E/A ratio, where an E/A ratio less than 1 was considered nonrestrictive and an E/A ratio of 2 or higher was considered restrictive. An E/A ratio of 1 or greater but less than 2 was considered nonrestrictive if Edt was greater than 80 milliseconds and restrictive if Edt was 80 milliseconds or

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less. In patients with AF, TMF flow was arbitrarily considered restrictive if the Edt was 80 milliseconds or less and nonrestrictive if it was more than 80 milliseconds. The cutoff value for Edt was defined in accordance with the range obtained from a control population of 55 normal dogs of all breeds (personal data) by the cutoff values that corresponded to the lower interquartile range. Mitral valve regurgitation was evaluated with color Doppler study from the right parasternal long-axis view. Presence and severity of mitral regurgitation were studied with both right parasternal and left apical views. Mitral regurgitation was classified as mild, moderate, or severe if it extended to the first third, middle portion, or roof of the left atrium, respectively. Dogs euthanized because they had refractory HF were counted as cardiac-related deaths. Sudden death was counted as cardiac related if no other cause of death was obvious. Dogs who died of causes other than HF or who were lost to follow-up were considered censored observations.

Statistical Analysis Statistical and graphical analyses were performed by the Survival package within the R software.24 Frequency of analyzed clinical findings, ECG variables, and thoracic radiographs findings was calculated. The relationship to survival of 11 clinical, ECG, echocardiographic, and Doppler echocardiographic variables (age at time of diagnosis, class of HF according to ISACHC classification,17 dyspnea, ascites, AF, EF ,25%, FS ,15%, EPSS .1.5 cm, EDV-I .200 mL/m2, ESV-I .140 mL/m2, and restrictive TMF pattern) was evaluated. To define classes of dogs with similar risk, we chose arbitrary cutoff points best able to discriminate between patient groups. Survival curves, median survival times, and 95% CIs were obtained by the Kaplan-Meier method. Differences between survival curves were tested by the log rank test (a 5 .05). Survival time was counted from the day of diagnosis of DCM at the referral center to either the day of death or closing time of the study. To verify if the effect of these predictors on survival time was attributable to TMF status and, therefore, to test for confounding by such a predictor, a stratified analysis was performed. Finally, differences for heart rate and systolic blood pressure between the restrictive and nonrestrictive groups were tested by the Wilcoxon 2-sample test.

Results Seventy-six dogs of 17 breeds met the diagnostic criteria for DCM during the period of this study. Thirteen dogs were eliminated from further evaluation because of incomplete records (n 5 4), systemic hypertension (n 5 4), hypothyroidism (n 5 3), or mitral valve disease with severe mitral regurgitation (n 5 2). Great Danes were the most common breed (46%), followed by St Bernard and Newfoundland (10% each), Doberman Pinchers (8%), Neapolitan Mastiff (5%), Rottweiler and Dogue de Bordeaux (3% each), Boxer, Leonberger, Labrador, Collie, Dalmatian, English Cocker Spaniel, German Shepherd, Greyhound, Irish Wolfhound, and mongrel (2% each). Ninety percent of the included dogs were males. All dogs were intact. Median age at the time of diagnosis was 5 years (range, 1–8 years). Mean 6 SD systolic blood pressure was 109 6 14 mm Hg. All dogs with ISACHC class 2 and 3 HF were treated with an angiotensin-converting enzyme inhibitor, furosemide, and digoxin, whereas 25 dogs also received


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Table 1. Clinical, ECG, and thoracic radiographic findings in dogs with dilated cardiomyopathy and restrictive or nonrestrictive transmitral flow pattern. No. of Dogs (N 5 39)

Frequency (%)

Variable

Restrictive (n 5 28)

Nonrestrictive (n 5 11)

Restrictive

Nonrestrictive

Male Female Dyspnea Heart murmur Gallop rhythm Ascites ISACHC class 1 HF ISACHC class 2 HF ISACHC class 3 HF Isolated SVB Isolated VPC Ventricular tachycardia Atrial fibrillation Pulmonary edema Pleural effusion

26 2 13 21 7 9 6 6 16 2 7 1 11 19 3

10 1 8 2 2 3 1 4 6 0 0 1 6 10 0

93 7 46 75 25 32 21 21 57 7 25 7 39 68 11

91 9 29 18 18 27 9 36 55 0 0 9 55 91 0

HF, heart failure; ISACHC, International Small Animal Cardiac Health Council; SVB, supraventricular ectopic beats; VPC, ventricular ectopic beats.

spironolactone and 10 dogs also received diltiazem. All dogs with ISACHC class 1 HF were not treated except 1, who received enalapril. The treatment regimen was not included in the analysis. Fifty-seven dogs (90%) were male and 6 (10%) were female. Forty-eight dogs (76%) had a heart murmur, 16 (25%) a gallop rhythm, 17 (27%) ascites, and 38 (60%) dyspnea. According to the severity of HF, 8 dogs (12%) had class 1 HF, 16 (25%) had class 2 HF, and 39 (62%) had class 3 HF. ECG showed isolated SVB in 2 (3%), isolated VPC in 8, and ventricular tachycardia in 3 dogs (5%). Thorax radiographs showed pulmonary edema in 50 (79%) and pleural effusion in 6 dogs (10%). The mean (SD) M-mode FS was 16.4% (7.7%), whereas the mean (SD) B-mode measure for EF was 27.7% (13.4%). All dogs had a subjectively hypokinetic left ventricle evaluated through both M- and B-mode measures. The mean (SD) La/Ao ratio was 2.1 (0.64). Forty-two dogs (66.6%) had atrial dilatation defined as Table 2. flow.

an LA/Ao ratio of more than 1.5.25 Mean (SD) calculated EDV-I and ESV-I were 220 (73) and 150 (57) mL/m2, respectively. Seventeen dogs had FS greater than 20%, but all these dogs had an EF less than 40% and an increased ESV-I. Adequate TMF profiles were obtained in 39 dogs; of these dogs, 22 had sinus rhythm and 17 had AF. Mean (SD) E-wave (n539) and A-wave (n522) peak velocities were 1.93 (0.73) and 0.57 (0.22) m/s, respectively. A restrictive left ventricular filling pattern (restrictive pattern) was found in 28 (72%) of 39 dogs in which the TMF pattern was obtained, and the nonrestrictive pattern was found in 11 (28%) of 39 dogs. Dogs with the restrictive TMF pattern presented more frequently with signs of severe HF (Table 1), whereas M-mode and B-mode echocardiographic variables were similar between the 2 groups (Table 2). Eleven dogs (17.5%) did not present any mitral regurgitations (MR) on color Doppler study, whereas 52 (82.5%) presented a mild MR.

Mean 6 SD echocardiographic findings of 39 dogs with dilated cardiomyopathy and adequate transmitral Transmitral Flow Pattern

Variable FS (%) EPSS (cm) EF (%) EDV-I (mL/m2) ESV-I (mL/m2) LA/Ao E-wave velocity (m/s) A-wave velocity (m/s) E/A ratio Edt (ms)

Restrictive (n 5 28) 14.6 2.2 21.8 210 152 2.1 1 0.6 1.9 68.3

6 6 6 6 6 6 6 6 6 6

7.5 0.7 7.9 69 61 0.7 0.3 0.2 (n 5 16) 0.8 (n 5 16) 20.5

Nonrestrictive (n 5 11) 21.8 2.2 25.3 226 159 1.8 1.1 0.7 1.3 92.8

6 6 6 6 6 6 6 6 6 6

7.9 0.7 8.4 60 34 0.4 0.3 0.1 (n 5 6) 0.2 (n 5 6) 13.0

E/A ratio, ratio of E-wave velocity to A-wave velocity; Edt, E-wave deceleration time; EDV-I, end-diastolic volume index; EF, ejection fraction; EPSS, E-point septal separation; ESV-I, end-systolic volume index; FS, fractional shortening; LA/Ao, left atrium–aorta ratio.


Dilated Cardiomyopathy

Fig 1. Survival curves of 63 dogs with dilated cardiomyopathy according to class of heart failure (HF). All dogs with class 1 HF survived during the observation time. Median survival time for dogs with class 2 HF was not determined (lower 95% confidence limit, 233 days). Median survival time for dogs with class 3 HF was 350 days (95% confidence interval, 93–193 days). P , .001 for class 1 (dashed line) vs class 2 (dotted line) and class 3 (continuous line). P , .05 for class 2 vs 3.

Altogether 25 dogs (39.7%) died of cardiac-related causes; of these, 2 dogs (3.2%) were euthanized because they had refractory HF and 15 dogs (23.8%) presented with sudden death. Two dogs (3.2%) were euthanized because they had other diseases (1 had renal failure and 1 had Wobbler syndrome). Thirty-two dogs (50.8%) were still alive by the end of the study, and 4 dogs (6.3%) were lost to follow-up. Survival time ranged from 2– 1,108 days (Fig 1). The median survival time was 671 days (lower 95% confidence limit, 350 days). Of the 8 variables that were used as predictors in Kaplan-Meier analysis, class of HF (Fig 1), ascites, ESV-I (Fig 2), EF, and restrictive TMF pattern (Fig 3) had a significant relation to survival time. Median survival time for dogs with ascites was 114 days (95% CI, 40–350 days), whereas more than 50% of dogs were alive at the end of the study (lower confidence limit). Median survival time for dogs with EFs of less than 25% was 365 days, which was significantly shorter (95% CI, 91–671) compared with dogs with EFs of 25% or higher

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Fig 3. Survival curve of 39 dogs with dilated cardiomyopathy with and without restrictive transmitral flow pattern (dashed line). The median survival time for the nonrestrictive group was not determined; the median survival time for the restrictive group was 114 days (95% confidence interval, 54–208 days; P , .001).

(median not determined; lower 95% confidence limit, 350 days; P , .05). The effects of these variables were, however, not significant after stratification by TMF pattern (restrictive and nonrestrictive). In fact, in dogs with adequate TMF recordings, restrictive TMF pattern was the most important negative prognostic indicator (Table 3). Only 1 dog in the nonrestrictive group died during the study period. No age difference was found between the 2 groups, whereas dogs with a restrictive pattern presented a significantly higher median heart rate (restrictive group: heart rate, 197 bpm; 95% CI, 120–230 bpm; nonrestrictive group: heart rate, 120 bpm; 95% CI, 80–210 bpm; P , .001) and decreased median blood pressure (restrictive group: blood pressure, 105 mm Hg; 95% CI, 100.5–109.1 mm Hg; nonrestrictive group: blood pressure, 110 mm Hg; 95% CI, 106.2– 121 mm Hg; P , .05).

Discussion DCM is the most common acquired myocardial disease in dogs.26 In people, indicators that predict poor prognosis in patients with left ventricular dysfunction Table 3. Effect of heart failure class, atrial fibrillation, end-systolic volume index, and ejection fraction on median survival time in 28 dogs with restrictive transmitral flow. Variable

Fig 2. Survival curve of 63 dogs with dilated cardiomyopathy with an end-systolic volume index (ESV-I) greater than or less than 140 mL/m2 (dashed line). Median survival time for dogs with an ESV-I less than 140 mL/m2 was not determined (lower 95% confidence limit, 458 days). Median survival time for dogs with an ESV-I greater than 140 mL/m2 was 208 days (95% confidence interval, 74–671 days; P , .001).

Ascites No ascites AF No AF Class 3 HF Class 2 HF ESV-I .140 mL/m2 ESV-I #140 mL/m2 EF $25% EF ,25%

Median (95% CI) (days) 58 164 58 164 80 114 58 114 80 114

(27–193) (74–208) (27–193) (74–208) (42–193) (74–208) (42–193) (74–208) (54–208) (11–233)

P Value .4 .4 .32 .15 .61

AF, atrial fibrillation; CI, confidence interval; EF, ejection fraction; ESV-I, end-systolic volume index; HF, heart failure.


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and congestive HF include age, etiology, left ventricular EF, functional class, exercise capacity, pulmonary arterial hypertension, increased concentration of plasma norepinephrine, and hyponatriemia.10,14 In dogs, few studies have been conducted to characterize prognostic indicators in those with DCM, with pulmonary edema, pleural effusion,4 age, dyspnea, ascites,5 AF, and bilateral HF6 representing the best independent parameters associated with significantly shorter survival times. Ascites also represented a useful clinical prognostic indicator in this study. However, the stratified analysis showed ascites has no effect on survival in dogs with a restrictive pattern. We did not find any effect of age and dyspnea on survival. Median survival time observed in the sample of dogs used in this study (671 days) was longer than those reported in other studies.4–6 One explanation for this finding is that we included dogs with asymptomatic or mildly symptomatic disease. Another possibility is that this population of dogs is different from what has been previously reported; because DCM could be considered, a familial diseases with breed-to-breed variability,2 the different population might have influenced these results. Functional class of HF is considered a prognostic indicator in people,27,28 and these results in dogs agree with such an observation, because no dog with class 1 disease died during the study period, whereas dogs with class 2 and 3 disease had significantly worse prognoses. Although the diagnosis of both presymptomatic and symptomatic DCM is based mainly on echocardiographic findings of decreased myocardial systolic function, such as decreased FS and increased EPSS, no effect of these parameters on longevity was found in this study. These findings agree with other studies in both dogs and people.4,5,29 EF appeared to significantly affect survival time in this study. Patients with DCM often have not only global systolic dysfunction but also a dyskinetic ventricle. Presence of mitral valve insufficiency may also increase FS because of increased septal movement.30 Therefore, EF evaluated by B-mode ultrasonography might represent a more accurate index of global myocardial function compared with FS. In fact, all 17 dogs who presented with FS of more than 20% had an EF less than 40% and an ESV-I of more than 60 mL/m2, indicating the presence of systolic dysfunction. An ESV-I of more than 140 mL/m2 also appeared to have an influence on survival in this series of patients. This index is considered a better indicator of systolic function because it only depends on afterload.25 However, stratified analysis to evaluate possible dependence between variables showed an effect of TMF on ESV-I , EF, and class of HF, suggesting, that in dogs with adequate TMF, the restrictive pattern represents the most important negative prognostic indicator. This finding agrees with studies in humans with DCM. In people, this TMF pattern has been found to correlate with high pulmonary wedge pressure and decreased myocardial compliance in patients with systolic dysfunction and reflects a severe diastolic dysfunction.10,13–15 These data suggest that diastolic dysfunction plays an important role in predicting cardiac mortality not only

in patients with DCM but also in dogs. In this study, we considered the presence of a restrictive or nonrestrictive filling pattern in dogs with AF based on the presence of a short Edt. A short Edt was found to represent the single most powerful indicator of poor prognosis in one study in people14 and also to correlate with increased pulmonary wedge pressure in patients with AF.15 Mitral Edt reflects time of pressure equilibration between left atrium and ventricle after early diastole.7 In DCM at the time the filling pressure increases, the decreased compliance of the ventricle induces a more rapid increase in diastolic pressure with a faster equilibration of left atrial and left ventricle pressure, resulting in rapid cessation of TMF and short Edt of rapid filling.14 The frequency of the restrictive TMF pattern in patients with ISACHC class 1 HF can be considered surprising. However, DCM is a progressive disease and changes of TMF reflect changes of diastolic function. It is possible that these changes occur before the onset of clinical signs. AF was found to represent a negative prognostic indicator in one study on Doberman Pinchers.6 In this study, there was a tendency for dogs without AF to survive longer than dogs with AF, although the difference was not significant at the 5% concentration. In fact, 63% of the dogs without AF were alive at the end of the observation period, compared with only 30% of the dogs with AF. Considering dogs with adequate evaluation of the TMF, stratified analysis revealed that AF has no effect on survival in dogs with a restrictive pattern. Loss of atrial contribution to the diastolic filling in patients with DCM can represent an important detrimental factor to the ventricular performance, because these patients need an adequate diastolic volume to maintain their cardiac output. Moreover, irregular and fast heart rate associated with AF may exert a further detrimental effect on cardiac function, decreasing cardiac output and increasing pulmonary wedge pressure.31–33 Potential limitations of this study include the inability to absolutely exclude concurrent other diseases (both systemic and cardiac) that could have affected outcome. Although we used recommended criteria for the diagnosis2 of the disease, it is still possible that other undefined systemic or metabolic conditions (ie, malignancies) could have affected myocardial function and favored the development of arrhythmias in some of these dogs. Moreover, it is possible that dogs with longstanding primary AF have been included in the study. It is well recognized that dogs with chronic lone AF might develop systolic dysfunction and signs of HF,34,35 and it can be difficult to differentiate these dogs from those with primary DCM. Another possible limitation concerns the evaluation of TMF. TMF can be affected by several factors, such as age, heart rate, systolic blood pressure, loading condition, degree of mitral valve regurgitation, and position of Doppler sample volume in people with increasing age, increased Edt, and decreased E/A ratio.36 However, in this study no differences concerning age have been found between dogs with restrictive, compared with nonrestrictive, TMF patterns. Tachycardia decreased


Dilated Cardiomyopathy

diastolic time and E-wave velocity, thereby decreasing the E/A ratio.37 In this study, dogs with the restrictive pattern had a significant increase in heart rate compared with dogs with the nonrestrictive pattern; therefore, it is unlikely that this could have affected the results. In addition, systolic blood pressure in the restrictive group was significantly lower. A previous experimental model on dogs has demonstrated that blood pressure has weak effects on TMF pattern.38 Severe mitral regurgitation increased E-wave velocity and the E/A ratio; however, all included dogs presented with only a mild mitral insufficiency. Finally, loading conditions can produce marked changes of TMF. An increase in preload increased the E-wave velocity and E/A ratio and decreased the Edt, whereas an increase in afterload may prolong relaxation time and decrease the E-wave velocity and E/A ratio.39 All dogs presented with normal blood pressure and mild mitral regurgitation. It is possible that other conditions, such as diuretic therapy, could have affected loading conditions. Diuretics that decrease preload might also decrease the E-wave velocity and E/A ratio. However, because all dogs with a restrictive pattern were taking diuretics, it is unlikely that this factor affected the study results. Other therapies, such as angiotensin-converting enzyme inhibitor, spironolactone, and diltiazem, which act on preload, afterload, ventricle remodeling, and heart rate, could affect the TMF pattern and long-term survival. For example, 25 dogs in this study were taking spironolactone, a drug that has been shown to exert a strong impact on survival in people.40 However, it was beyond the aim of this study to evaluate the impact of such therapies on survival, because dogs undergoing therapy were receiving different drugs at different dosages. Finally, to minimize the effects of Doppler sample volume, it was positioned at the tips of the mitral valve.41 The restrictive pattern of TMF appears to represent a useful prognostic indicator in both patients with AF and dogs with DCM. The findings of this study of dogs agree with findings previously reported in people. Class of HF, ESV-I, and EF can also be considered useful indexes if an inadequate TMF is recorded. Because some studies have shown that in patients with chronic HF42,43 changes of TMF patterns after long-term optimized therapy are associated with changes of prognosis and may provide some important prognostic information, a more extensive use of Doppler echocardiography parameters should be encouraged in the future to evaluate if such data can provide beneficial information on the management of dogs with DCM.

Footnotes a

Ultrasonic Doppler Flow detector model 811-B, Parks Medical Electronics, Alhoa, OR b P-80 Power, ESAOTE Biomedica, Florence, Italy c Caris, ESAOTE Biomedica, Florence, Italy

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32. Sisson D, Brown W, Riepe R. Hemodynamic effects of atrial fibrillation in dogs with experimental induced mitral regurgitation. J Vet Intern Med 1995;9:200. 33. Everett TH, Li H, Mangrum JM, et al. Electrical, morphological, and ultrastructural remodeling and reverse remodeling in a canine model of chronic atrial fibrillation. Circulation 2000;102:1454–1460. 34. Grogan M, Smith HC, Gersch BJ, Wood DL. Left ventricular dysfunction due to atrial fibrillation in patients initially believed to have dilated cardiomyopathy. Am J Cardiol 1992;69: 1570–1573. 35. Redfield MM, Kay GN, Jenkins LS, et al. Tachycardia related cardiomyopathy: A common cause of ventricular dysfunction in patients with atrial fibrillation referred for atrioventricular ablation. Mayo Clin Proc 2000;75:790–795. 36. Voutilainen S, Kupari M, Hippelainen M, et al. Factors influencing Doppler indexes of left ventricular filling in healthy persons. Am J Cardiol 1991;68:653–659. 37. Appleton CP, Hatle LK. The natural history of left ventricular filling abnormalities: Assessment by two-dimensional and Doppler echocardiography. Echocardiography 1992;9: 437–457. 38. Nishimura RA, Abel MD, Hatle LK, et al. Significance of Doppler indices of diastolic filling of the left ventricle: Comparison with invasive hemodynamics in a canine model. Am Heart J 1989;118:1248–1258. 39. Choong CY, Abascal VM, Thomas JD, et al. Combined influence of ventricular loading and relaxation on the transmitral flow velocity profile in dogs measured by Doppler echocardiography. Circulation 1988;78:672–683. 40. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999;341:709–717. 41. Schober KE, Fuentes VL. Effects of age, body weight, and heart rate on transmitral and pulmonary venous flow in clinically normal dogs. Am J Vet Res 2001;62:1447–1454. 42. Traversi E, Pozzoli M, Cioffi G, et al. Mitral flow velocity changes after 6 months of optimized therapy provide important hemodynamic and prognostic information in patients with chronic heart failure. Am Heart J 1996;132:809–819. 43. Pinamonti B, Zecchin M, Di Lenarda A, et al. Persistence of restrictive left ventricular filling pattern in dilated cardiomyopathy: An ominous prognostic sign. J Am Coll Cardiol 1997;29:604–612.


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Red Maple (Acer rubrum) Leaf Toxicosis in Horses: A Retrospective Study of 32 Cases Ashley Alward, Candice A. Corriher, Michelle H. Barton, Debra C. Sellon, Anthony T. Blikslager, and Samuel L. Jones Effects of Intravenously Administrated Omeprazole on Gastric Juice pH and Gastric Ulcer Scores in Adult Horses Frank M. Andrews, Nicholas Frank, Carla S. Sommardahl, Benjamin R. Buchanan, Sarah B. Elliott, and Vern A. Allen Allele Frequency and Likely Impact of the Glycogen Branching Enzyme Deficiency Gene in Quarter Horse and Paint Horse Populations M.L. Wagner, S.J. Valberg, E.G. Ames, M.M. Bauer, J.A. Wiseman, M.C.T. Penedo, H. Kinde, B. Abbitt, and J.R. Mickelson Successful Treatment and Polymerase Chain Reaction (PCR) Confirmation of Tyzzer’s Disease in a Foal and Clinical and Pathologic Characteristics of 6 Additional Foals (1986–2005) Angela Borchers, K. Gary Magdesian, Spring Halland, Nicola Pusterla, and W. David Wilson CASE REPORTS

1219 1224 1228 1232 1238 1241 1245 1248 1251 1256 1261 1264

Acute Encephalitis, Polyarthritis, and Myocarditis Associated with West Nile Virus Infection in a Dog Allison B. Cannon, Jennifer A. Luff, Aaron C. Brault, N. James MacLachlan, Joseph B. Case, Emily N.G. Green, and Jane E. Sykes Acute Conversion of Atrial Fibrillation in Two Dogs by Intravenous Amiodarone Administration Mark A. Oyama and Robert Prosek Canine Trichinosis Presenting with Syncope and AV Conduction Disturbance Meg M. Sleeper, Sally Bissett, and Linden Craig The Use of an Implantable Cardioverter Defibrillator in a Boxer Dog to Control Clinical Signs of Arrhythmogenic Right Ventricular Cardiomyopathy O. Lynne Nelson, Sunshine Lahmers, Terri Schneider, and Pam Thompson Dyskinesia Associated with Oral Phenobarbital Administration in a Dog Stephanie A. Kube, Karen M. Vernau, and Richard A. LeCouteur Cerebral Cholesterol Granuloma in a Cat Gaby Fluehmann, Martin Konar, Andre´ Jaggy, Alexandra Nicolier, and Marc Vandevelde Gastrin-Secreting Neoplasia in a Cat Jeremy S. Diroff, Nancy A. Sanders, Sean P. McDonough, and David E. Holt Factor-VIII Deficiency in a Newborn Alpaca Matt D. Miesner and David E. Anderson Lymphoma, Erythrocytosis, and Tumor Erythropoietin Gene Expression in a Horse Thomas G. Koch, Xin Wen, and Dorothee Bienzle Paraparesis in an Adult Alpaca with Discospondylitis Patrik Zanolari, Martin Konar, Ales Tomek, Stefan Hoby, and Mireille Meylan Aortic Thrombosis in Three Calves with Escherichia coli Sepsis Antonio D’Angelo, Claudio Bellino, Giovanni L. Alborali, Antonio Borrelli, Maria T. Capucchio, Cristina Casalone, Maria I. Crescio, Gianni L. Mattalia, and Andre Jaggy Program & Research Abstracts 18th Annual ECVN & ESVN Symposium, Munich, Germany, 23rd–24th September 2005

(continued from ix) Erratum ERRATUM. J Vet Intern Med 2006;20:104–110 ‘‘Prognostic indicators for dogs with dilated cardiomyopathy’’. There are errors in Table 1, a correct version of which is attached below. The mistake does not affect the survival and stratified analysis published, as both were completed using the correct data set. In addition, the sentence dealing with restrictive pattern in dogs with class 1 heart failure in the first paragraph of the second column on page 108 is retracted. The authors regret the errors.

No. of dogs (N539)

Frequency (%)

Variable

Restrictive (n527)

Nonrestrictive (n512)

Restrictive

Nonrestrictive

Male Female Dyspnea Heart murmur Gallop Rhythm Ascites ISACHC class 1 HF ISACHC class 2 HF ISACHC class 3 HF Isolated SVB Isolated VPC Atrial fibrillation Pulmonary edema Pleural effusion

25 2 13 21 7 9 0 8 19 2 7 11 19 3

11 1 8 2 2 3 7 2 3 0 0 6 10 0

96 7 48 78 26 33 0 30 70 7 26 41 70 11

92 8 67 17 17 25 58 17 25 0 0 50 83 0


DCM