Magnetic Resonance Imaging of Right Ventricular Morphology and Function in Boxer Dogs with Arrhythmogenic Right Ventricular Cardiomyopathy

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a myocardial disease characterized by fibrofatty replacement of the right ventricle and ventricular tachyarrhythmias, reported most commonly in the Boxer dog. Although ARVC is characterized as a myocardial disease, the impact of the disease on the function of the right ventricle has not been well studied.
Objective: To noninvasively evaluate the function and anatomy of the right ventricle in Boxer dogs with ARVC.
Animals: Five adult Boxer dogs with ARVC and 5 healthy size-matched hound dogs.
Methods: Magnetic resonance imaging was performed on an ECG-gated conventional 1.5-T scanner using dark blood imaging and cine acquisitions. Images were evaluated by delineation of endocardial right and left ventricular contours in the end-diastolic and end-systolic phases of each slice. Right and left end-systolic and end-diastolic volumes were generated using Simpson's rule and ejection fraction was calculated. Images were evaluated for right ventricular (RV) aneurysms and wall motion abnormalities. Spin echo images were reviewed for the presence of RV myocardial fatty replacement or scar.
Results: RV ejection fraction was significantly lower in Boxers with ARVC compared with the controls (ARVC 34%± 11 control 53%± 10, P < .01). There was an RV aneurysm in 1 dog with ARVC but not in any of the controls. RV myocardial gross fatty changes were not observed in dogs of either group.
Conclusions and Clinical Importance: These findings could be interpreted to suggest that arrhythmias and myocardial dysfunction precede the development of morphological abnormalities in dogs with ARVC.     

Echocardiographic ratio indices in overtly healthy Boxer dogs screened for heart disease

BACKGROUND: Boxer dogs are routinely screened by echocardiography to exclude congenital and acquired heart disease. Individuals of a given breed may span a large range of body sizes, potentially invalidating linear regression of M-mode measurements against body weight. Echocardiographic ratio indices (ERIs) provide a novel method of characterizing echocardiographic differences between Boxers and other dog breeds. HYPOTHESIS: ERIs obtained from overtly healthy Boxer dogs presented for cardiac screening will be different from ERIs established for normal non-Boxer dogs, and those differences will be unrelated to aortic velocity or systolic blood pressure. ANIMALS: Eighty-one Boxers with no outward clinical signs of heart disease were studied. METHODS: All dogs were examined by 2-dimensional, M-mode, and Doppler echocardiography. M-mode measurements were used to perform ERI calculations, and the indices in Boxers were compared between Boxers with varying severity of arrhythmia and those of normal non-Boxer dogs. RESULTS: Differences in weight-based ERIs, which reflect increased thickness of the left ventricular free wall (LVW) and interventricular septum (IVS) and smaller aortic size, were found in overtly healthy Boxer dogs compared with normal non-Boxer dogs. ERIs of left atrial and LV cavity size in overtly healthy Boxers were not significantly different from those of non-Boxer dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Boxer dogs may have an increased relative thickness of the LVW and IVS that is independent of aortic size, aortic velocity, or arterial blood pressure, and this morphology should be taken into consideration when screening Boxers by echocardiography.     

Association of Tricuspid Annular Plane Systolic Excursion with Survival Time in Boxer Dogs with Ventricular Arrhythmias

Background

Tricuspid annular plane systolic excursion (TAPSE) is a useful estimate of right ventricular function in humans. Reference intervals for dogs have been generated, but the value of measuring TAPSE in other diseases, or investigating the association between TAPSE and outcome, is unknown.

Hypothesis

TAPSE is lower in Boxer dogs with ≥50 VPCs/24 h on Holter than in dogs with fewer ventricular ectopics, and lower TAPSE is associated with a shorter survival time.

Animals

Fifty Boxer dogs that presented for investigation of syncope or suspected arrhythmogenic right ventricular cardiomyopathy (ARVC) at a veterinary teaching hospital (2004–2011).

Methods

Retrospective study. Clinical records, Holter, and echocardiographic data were reviewed. TAPSE was measured in a blinded manner on stored echocardiographic cine‐loops using anatomic M‐mode. Outcome information was obtained and death was classified as cardiac or noncardiac. Survival analysis was performed using Kaplan‐Meier curves and Cox proportional hazards models.

Results

TAPSE was lower in Boxers with ≥50 VPCs/24 h (13.9 ± 4.04 mm) than Boxers with <50 VPCs/24 h (16.8 ± 3.21 mm; P < .001). TAPSE <15.1 mm was associated with shorter cardiac survival time in all dogs (P = .004) and also in dogs without left ventricular dysfunction (P = .035). When controlling for other variables, including ventricular tachycardia on Holter and left ventricular systolic dysfunction, multivariable analysis showed that TAPSE remained an independent predictor of time to cardiac death (HR >4.09, 95%CI 1.15–16.9, P < .029).

Conclusions and Clinical Importance

TAPSE offers prognostic value for Boxer dogs, including those with apparently normal systolic function and ≥50 VPCs/24 h on Holter analysis.     

Daily Rhythms of Left Atrial Pressure in Beagle Dogs with Mitral Valve Regurgitation

Background: Mitral valve regurgitation (MR) causes increased left atrial pressure (LAP) and is associated with occurrence of clinical signs. It will be useful to understand diurnal variations of LAP for the management of MR.
Hypothesis: Circulatory parameters and diurnal rhythm are linked to clinical signs in cardiac diseases. LAP also exhibits a diurnal rhythm in dogs with MR.
Animals: Five healthy Beagle dogs weighing 9.8–12.8 kg (3 males and 2 females; aged 2 years) were used.
Methods: A radiotelemetry system for continuous measurement of LAP was used in this study. Rupture of the chordae tendineae was experimentally induced via left atriotomy, and a transmitter catheter was inserted into the left atrium. The body of the transmitter was implanted SC. After clinical condition was stabilized, the severity of MR was evaluated by echocardiography, and LAP was recorded for 72 consecutive hours for the analysis of diurnal variation.
Results: Abrupt increases in LAP, which averaged 16.7 mmHg, were observed at feeding periods. In contrast, strong diurnal LAP variations were found, with a significant but slight increase in daytime LAP compared with nighttime LAP.
Conclusions and Clinical Importance: Diurnal LAP is characterized by a slight but significant nocturnal decrease and abrupt increases in response to excitation. The latter seemed to be more important considering the relationship with clinical manifestations. The clinical relevance of exercise restriction in the management of MR was acknowledged.     

Echocardiographic Estimates of Right Ventricular Systolic Function in Dogs with Myxomatous Mitral Valve Disease

Background

Right ventricular (RV) dysfunction independently predicts outcomes in human myxomatous mitral valve disease (MMVD). There is limited information regarding RV systolic function in dogs with MMVD.

Hypothesis

Right ventricular systolic function differs among stages of disease, decreasing in decompensated MMVD.

Animals

Thirty‐sixclient‐owned dogs with MMVD not receiving oral cardiovascular medications.

Methods

Prospective clinical study. Dogs were categorized according to disease severity as ACVIM Stage B1, B2, or C. Seven echocardiographic indices of RV systolic function were measured. Groups were compared by 1‐way ANOVA and Tukey's HSD test. Frequencies of cases with cardiac remodeling falling outside previously established reference intervals were compared using Fisher's exact test. Intra‐ and interobserver measurement variability was calculated for each RV function index.

Results

The indices TAPSE (P = 0.029), RV St_L (P = 0.012), and RV StR_L (P = 0.041) were significantly different between groups. A greater proportion of B2 dogs (7 of 12) had TAPSE values above reference intervals compared with B1 (2 of 12) or C (2 of 12) dogs (P = 0.027). Measurement variability of TAPSE, RV S', and RV St_G was clinically acceptable.

Conclusions and Clinical Importance

Right ventricular systolic function differs between stages of MMVD, increasing in stage B2, and declining in stage C. The prognostic importance of RV function indices, particularly TAPSE, might be worth evaluating in dogs with MMVD.     

Arrhythmogenic right ventricular cardiomyopathy coincided with the cardiac fibrosis in the inner muscle layer of the left ventricular wall in a boxer dog

A 7-year-old female boxer dog died suddenly without any clinical signs. It was suspected that the dog had arrhythmogenic right ventricular cardiomyopathy (ARVC) due to ventricular premature complexes and ventricular tachycardia at 3 years of age. The final diagnosis of ARVC was confirmed by histological characteristics, such as loss of cardiocytes and fibrofatty replacement, occurring in the right and left ventricular walls. In the cardiocytes, non-lipid vacuoles were observed. Cardiac fibrosis and intimal thickening of the small arteries occurred without fatty replacement in the inner muscle layer including the papillary muscles of the left ventricular wall. This paper describes the pathomorphological details of an ARVC case with coincidental cardiac fibrosis in the inner muscle layer of the left ventricular wall.     

A review of the underlying genetics and emerging therapies for canine cardiomyopathies

Cardiomyopathies such as dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are common in large breed dogs and carry an overall poor prognosis. Research shows that these diseases have strong breed predilections, and selective breeding has historically been recommended to reduce the disease prevalence in affected breeds. Treatment of these diseases is typically palliative and aimed at slowing disease progression and managing clinical signs of heart failure as they develop. The discovery of specific genetic mutations underlying cardiomyopathies, such as the striatin mutation in Boxer arrhythmogenic right ventricular cardiomyopathy and the pyruvate dehydrogenase kinase 4 and titin mutations in Doberman Pinschers, has strengthened our ability to screen and selectively breed individuals in an attempt to produce unaffected offspring. The discovery of these disease-linked mutations has also opened avenues for the development of gene therapies, including gene transfer and genome-editing approaches. This review article discusses the known genetics of cardiomyopathies in dogs, reviews existing gene therapy strategies and the status of their development in canines, and discusses ongoing challenges in the clinical translation of these technologies for treating heart disease. While challenges remain in using these emerging technologies, the exponential growth of the gene therapy field holds great promise for future clinical applications.     

Radiofrequency Catheter Ablation of Atrioventricular Accessory Pathways in 3 Dogs with Subsequent Resolution of Tachycardia-Induced Cardiomyopathy

Incessant supraventricular tachyarrhythmias are known to result in myocardial dysfunction indistinguishable from idiopathic dilated cardiomyopathy by current testing methods. This tachycardia-induced cardiomyopathy (TICM), however, is uniquely reversible with adequate rhythm control. Two dogs were presented to The Ohio State University for incessant supraventricular tachycardia (SVT) and echocardiographic signs of dilated cardiomyopathy, later proven to be TICM. A 3rd dog presented for frequent paroxysms of SVT and syncope had echocardiographic signs of mild myocardial systolic dysfunction. All 3 dogs had inadequate rhythm control with multiple antiarrhythmic agents, and 1 dog suffered from recurrent left-sided congestive heart failure. Generalized cardiomegaly was found in 1 dog and left-sided dilatation without concurrent right-sided enlargement in 1 dog. Mild-to-severe left ventricular systolic dysfunction was confirmed echocardiographically in all dogs. A total of 4 atrioventricular accessory pathways (APs) were found during invasive electrophysiologic studies in these 3 dogs. All APs were successfully ablated with radiofrequency energy delivered through a thermistor-tipped catheter. Elimination of AP conduction, and thus orthodromic atrioventricular reciprocating tachycardia, resulted in resolution of all clinical and echocardiographic evidence of TICM in these dogs. This result confirms that the cardiomyopathy was, in fact, reversible TICM. All cardiovascular medications were discontinued, and no complications occurred during a 15-25-month follow-up period.     

Ability of a 5‐Minute Electrocardiography (ECG) for Predicting Arrhythmias in Doberman Pinschers with Cardiomyopathy in Comparison with a 24‐Hour Ambulatory ECG

Background: Ventricular premature contractions (VPCs) are common in the occult stage of cardiomyopathy in Doberman Pinschers. Although the gold standard for detecting arrhythmia is the 24‐hour ambulatory electrocardiography (ECG) (Holter), this method is more expensive, time‐consuming and often not as readily available as common ECG. Objectives: Comparison of 5‐minute ECGs with Holter examinations. Animals: Eight hundred and seventy‐five 5‐minute ECGs and Holter examinations of 431 Doberman Pinschers. Methods: Each examination included a 5‐minute ECG and Holter examination. A cut‐off value of >100 VPCs/24 hours using Holter was considered diagnostic for the presence of cardiomyopathy. Statistical evaluation included calculation of sensitivity, specificity, positive predictive value, and negative predictive value. Results: Holter examinations revealed >100 VPCs/24 hours in 204/875 examinations. At least 1 VPC during a 5‐minute ECG was detected in 131 (64.2%) of these 204 examinations. No VPCs were found in the 5‐minute ECG in 73 (35.8%) examinations of affected Doberman Pinschers. A 5‐minute ECG with at least 1 VPC as cut‐off had a sensitivity of 64.2%, a specificity of 96.7%, a positive predictive value of 85.6% and a negative predictive value of 89.9% for the presence of >100 VPCs/24 hours. Conclusions and Clinical Importance: A 5‐minute ECG is a rather insensitive method for detecting arrhythmias in Doberman Pinschers. However, the occurrence of at least 1 VPC in 5 minutes strongly warrants further examination of the dog, because specificity (96.7%) and positive predictive value (85.6%) are high and could suggest occult cardiomyopathy.     

两种组胺受体拮抗剂对肺动脉高压肉鸡右心功能的影响

探讨组胺H,受体拮抗剂扑尔敏和H。受体拮抗剂西咪替丁对低温诱发肺动脉高压肉鸡右心功能的影响,由此反证内源性组胺在低温诱发肉鸡肺动脉高压形成过程中的作用。采用160只17日龄AA肉鸡随机分为4组,每组40只。（1）常温组：在常温条件下饲养（22～23℃）,每天注射生理盐水2次;（2）低温组：低温环境中饲养（9～11℃）,每天注射生理盐水2次;（3）扑尔敏组：与低温组相同饲养,每天注射扑尔敏2次;（4）西眯替丁组：与低温组相同饲养,每天注射西眯替丁2次。分别于低温处理后1周（24日龄）、2周（31日龄）、3周（38日龄）、4周（45日龄）从每组中各随机抽取7只,利用右心导管法测定右心室内压和右心室压最大变化速率,计算腹水心脏指数（AHI）和右心衰竭率。剖杀后用常规阿尔新蓝法对心脏中肥大细胞（MC）染色,免疫组化方法显示组胺。结果：（1）低温处理后使肉鸡肥大细胞和组胺阳性细胞数量显著降低,但2种组胺受体拮抗剂对肥大细胞数量及组胺阳性细胞数无明显影响;（2）扑尔敏组肉鸡右心内压相对稳定,45日龄时右心室舒张压显著低于低温组（P〈0．05）。西咪替丁组肉鸡右心收缩压和舒张压处于较低水平,且在31和38日龄时显著低于低温组（P〈0．05）;（3）扑尔敏组右心内压最大变化速率相对稳定,31日龄时显著低于低温组（P〈0．05）,而45日龄时显著高于低温组（P〈0．05）。西咪替丁组右心内压最大变化速率处于较低水平;（4）45日龄时,扑尔敏组AHI显著低于低温组（P〈0．05）;（5）扑尔敏组显著（P〈0．05）降低了右心肥大指数和右心衰竭发生率,西咪替丁组仅显著（P〈0．05）降低了右心衰竭率。以上结果表明,内源性组胺可能通过H3受体介导肉鸡右心肥大和衰竭,从而促进肺动脉高压综合征的发生发展。