Bradyarrhythmia after treatment with atenolol and mirtazapine in a cat with hypertrophic cardiomyopathy.

A nine-year-old spayed female domestic shorthair cat with a previous diagnosis of hypertrophic cardiomyopathy and treated for one month with atenolol (6.25 mg q 12 h) was referred for respiratory distress and anorexia. The cat was diagnosed with pulmonary oedema secondary to obstructive hypertrophic cardiomyopathy. After stabilisation, she was discharged with furosemide (1 mg/kg q 12 h), clopidogrel (18.75 mg q 24 h), atenolol (6.25 mg q 12 h), and mirtazapine (2 mg/cat q 24 h) to increase appetite. At recheck, the cat was lethargic and presented with severe bradycardia with a junctional escape rhythm and ventriculoatrial conduction. The mirtazapine was discontinued due to its possible side-effects on cardiac rhythm. After three days, the atenolol was halved because the bradyarrhythmia was still present. After 10 days, the rhythm returned to sinus; atenolol was reintroduced twice daily with no further side-effects. The absence of a sinus rhythm with a junctional escape rhythm and P' retroconduction is compatible with a third-degree sinus block or a sinus standstill; the differentiation of these rhythm disturbances is impossible, based on the surface electrocardiogram (ECG). The sinus rhythm was restored after mirtazapine was withdrawn. However, it is not possible to rule out the role of the atenolol or the combined effect of the two drugs. The cat was affected by hypertrophic cardiomyopathy, and the role of myocardial remodelling cannot be excluded. This is the first time that a bradyarrhythmia consequent to the treatment with atenolol and mirtazapine was described in a cat.

Aorto-septal angle, isolated basal septal hypertrophy, and systolic murmur in 122 cats.

INTRODUCTION/OBJECTIVES: Systolic murmurs in the absence of cardiac structural abnormalities are common in cats. Narrow aorto-septal angle (AoSA) and septal remodeling can be a cause of a systolic murmur in elderly human beings. The aim of this study was to measure the AoSA in cats and to investigate the association between the AoSA and the presence of a murmur and isolated basal septal hypertrophy (IBSH). ANIMALS: The study population comprised 122 cats. MATERIALS AND METHODS: A physical exam, blood pressure measurement, chest radiographs, and echocardiography were performed. RESULTS: A systolic murmur was audible in 39/122 cats. A difference between cats with and without a murmur was found for age (P=0.0001), interventricular basal septal thickness (BIVSd) (P=0.004), AoSA (P=0.003), aortic (P<0.0001), and pulmonic (P=0.021) flow velocity, the presence of IBSH (P<0.0001), and systolic anterior motion of the mitral valve (P=0.0002). More than 50% of cats with a murmur had an AoSA ≤122°. Less than 25% of the cats with an AoSA ≥137° had a murmur. The AoSA narrowed 0.55°/year of age (P<0.001), whereas the BIVSd increased 0.11 mm/year of age (P<0.0001); the BIVSd increased as the AoSA narrowed. In all cats with AoSA < 120°, IBSH was present. CONCLUSIONS: This study demonstrates that the probability of having a systolic murmur in cats is increased by the presence of a narrow AoSA. Aging was associated with a narrower AoSA and a thicker basal septum; these findings might represent an age-related heart remodeling.

Effect of sampling time on urinary electrolytes following oral furosemide administration in dogs with myxomatous mitral valve disease.

INTRODUCTION/OBJECTIVES: Urine chemistry has received growing attention to estimate the diuretic response in dogs with cardiac disease. The aim of the study was to evaluate the impact of time elapsed between the oral furosemide administration and sample collection on urine chemistry in dogs with myxomatous mitral valve disease (MMVD) receiving diuretic therapy in American College of Veterinary Internal Medicine (ACVIM) stage C. MATERIALS AND METHODS: Seventy-three dogs with MMVD ACVIM stage C and 106 healthy dogs were prospectively included. Dogs with MMVD were divided, based on the time of sampling, in morning group (MMVD-MG) of one to 6 h and an evening group (MMVD-EG) over 6 h from oral furosemide administration. Analogously, healthy dogs sampled between 9 a.m. and 1 p.m. and between 2 and 7 p.m. were divided in a morning group (H-MG) and an evening group (H-EG), respectively. Urine chemistry, including fractional excretion of electrolytes, was evaluated and compared among groups. RESULTS: Higher excretion of sodium and chloride and higher urine sodium to urine potassium ratio (uNa+:uK+) were detected in MMVD-MG than MMVD-EG (P = 0.021, P = 0.038, and P = 0.016, respectively). Natriuresis, chloriuresis, and uNa+:uK+ were higher in MMVD-MG than H-MG, while no differences were found in the comparison between H-MG and H-EG and between MMVD-EG and H-EG. CONCLUSIONS: Urinary electrolyte excretion is significantly increased within 6 h from furosemide administration in MMVD ACVIM stage C dogs. Time of sampling from furosemide administration significantly affects urine chemistry in MMVD dogs and should be considered in clinical practice and the research field.

The predictive value of clinical, radiographic, echocardiographic variables and cardiac biomarkers for assessing risk of the onset of heart failure or cardiac death in dogs with preclinical myxomatous mitral valve disease enrolled in the DELAY study.

OBJECTIVES: To identify the predictive value on time to onset of heart failure (HF) or cardiac death of clinical, radiographic, and echocardiographic variables, as well as cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I in dogs with preclinical myxomatous mitral valve disease (MMVD). ANIMALS: One hundred sixty-eight dogs with preclinical MMVD and left atrium to aortic root ratio ≥1.6 (LA:Ao) and normalized left ventricular end-diastolic diameter ≥1.7 were included. METHODS: Prospective, randomized, multicenter, single-blinded, placebo-controlled study. Clinical, radiographic, echocardiographic variables and plasma cardiac biomarkers concentrations were compared at different time points. Using receiving operating curves analysis, best cutoff for selected variables was identified and the risk to develop the study endpoint at six-month intervals was calculated. RESULTS: Left atrial to aortic root ratio >2.1 (hazard ratio [HR] 3.2, 95% confidence interval [95% CI] 1.9-5.6), normalized left ventricular end-diastolic diameter > 1.9 (HR: 6.3; 95% CI: 3.3-11.8), early transmitral peak velocity (E peak) > 1 m/sec (HR: 3.9; 95% CI: 2.3-6.7), and NT-proBNP > 1500 ρmol/L (HR: 5.7; 95% CI: 3.3-9.5) were associated with increased risk of HF or cardiac death. The best fit model to predict the risk to reach the endpoint was represented by the plasma NT-proBNP concentrations adjusted for LA:Ao and E peak. CONCLUSIONS: Logistic and survival models including echocardiographic variables and NT-proBNP can be used to identify dogs with preclinical MMVD at higher risk to develop HF or cardiac death.

DELay of Appearance of sYmptoms of Canine Degenerative Mitral Valve Disease Treated with Spironolactone and Benazepril: the DELAY Study.

INTRODUCTION: Efficacy of renin-angiotensin-aldosterone system (RAAS) blockade using angiotensin-converting enzyme inhibitors (ACEi) in dogs with preclinical myxomatous mitral valve disease (MMVD) is controversial. HYPOTHESIS: Administration of spironolactone (2-4 mg q 24 h) and benazepril (0.25-0.5 mg q 24 h) in dogs with preclinical MMVD, not receiving any other cardiac medications, delays the onset of heart failure (HF) and cardiac-related death. Moreover, it reduces the progression of the disease as indicated by echocardiographic parameters and level of cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI). ANIMALS: 184 dogs with pre-clinical MMVD and left atrium-to-aortic root ratio (LA:Ao) ≥1.6 and normalized left ventricular end-diastolic diameter (LVEDDn) ≥1.7. METHODS: This is a prospective, randomized, multicenter, single-blinded, placebo-controlled study. Primary outcome variable was time-to-onset of first occurrence of HF or cardiac death. Secondary end points included effect of treatment on progression of the disease based on echocardiographic and radiographic parameters, as well as variations of NT-proBNP and cTnI concentrations. RESULTS: The median time to primary end point was 902 days (95% confidence interval (CI) 682-not available) for the treatment group and 1139 days (95% CI 732-NA) for the control group (p = 0.45). Vertebral heart score (p = 0.05), LA:Ao (p < 0.001), LVEDDn (p < 0.001), trans-mitral E peak velocity (p = 0.011), and NT-proBNP (p = 0.037) were lower at the end of study in the treatment group. CONCLUSIONS: This study failed in demonstrating that combined administration of spironolactone and benazepril delays onset of HF in dogs with preclinical MMVD. However, such treatment induces beneficial effects on cardiac remodeling and these results could be of clinical relevance.

Wolbachia, doxycycline and macrocyclic lactones: New prospects in the treatment of canine heartworm disease.

Melarsomine dihydrochloride (Immiticide®, Merial) is the only approved adulticidal drug for the treatment of canine heartworm disease (HWD). However, in cases where arsenical therapy is not possible or is contraindicated, a monthly heartworm preventive along with doxycycline for a 4-week period, which targets the bacterial endosymbiont Wolbachia, might be considered. There are published reports on the efficacy of ivermectin and doxycycline in both experimentally and naturally infected dogs, but no data on the use of other macrocyclic lactones (MLs) with a similar treatment regime. Preliminary results of studies in dogs show that a topical formulation of moxidectin, the only ML currently registered as a microfilaricide, is also adulticidal when combined with doxycycline. It is not yet known if the efficacy of these combination therapies is due to pharmacokinetic synergism. A recent study showed that serum levels of doxycycline in dogs treated with the combination protocol were not statistically different compared to dogs treated with doxycycline alone. However, lungs from dogs treated with the combination therapy showed a marked reduction in T regulatory cells, indicating that treatment efficacy may be due to a heightened immune response against the parasite. Further studies are necessary to evaluate the long-term clinical outcome of combination protocols and to establish the most efficient treatment for HWD in dogs.

Preliminary Investigation of Cardiovascular-Renal Disorders in Dogs with Chronic Mitral Valve Disease.

BACKGROUND: Veterinary literature lacks data about cardiovascular-renal disorders (CvRD) and cardiorenal-anemia syndrome (CRAS) in dogs. HYPOTHESIS: A direct correlation exists between ACVIM class and IRIS stage; chronic kidney disease (CKD) complicates chronic mitral valve disease (CMVD) more often than does anemia in dogs. ANIMALS: One hundred and fifty-eight client-owned dogs with CMVD. METHODS: Signalment, physical examination findings, electrocardiography, thoracic radiographs, echocardiography, and blood analysis were retrospectively evaluated to assess the prevalence of CKD and anemia in dogs with CMVD and to investigate the relationships among ACVIM class, IRIS stage, and survival. RESULTS: The prevalence of CKD and anemia in dogs with CMVD was significantly higher than in the general population of dogs. Dogs being treated for heart failure had a significantly higher prevalence of CKD than did dogs that had not received treatment. A statistically significant direct correlation was found between ACVIM class and IRIS stage. Severe heart disease, severe renal disease or both, furosemide administration, and advanced age at diagnosis of heart disease were associated with shorter survival time. Survival time of dogs affected by CvRD was statistically shorter than survival time of dogs affected by CMVD alone. CONCLUSION AND CLINICAL RELEVANCE: Chronic mitral valve disease is associated with increased prevalence of CKD and anemia in dogs. Treatment for medical management of heart failure may play a role in inducing CKD. Class of heart disease and IRIS stage were directly correlated. Cardiovascular-renal disorders decrease survival time compared to the only presence of CMVD alone, whereas anemia does not play a central role in worsening heart function.

Cytokine expression in peripheral blood mononuclear cells of dogs with mitral valve disease.

Inflammation plays an important role in the pathogenesis of congestive heart failure (CHF). In humans with CHF, increased production and high plasma concentrations of tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1, IL-8 and transforming growth factor-ß (TGF-ß) have been associated with disease progression and a negative prognosis. The aim of this study was to investigate whether differences in cytokine blood mRNA expression exist between clinically healthy dogs and dogs with myxomatous mitral valve disease (MMVD); to determine if the expression was related to the severity of MMVD, and to detect any correlations with echocardiographic parameters of cardiac remodelling. Twenty-three dogs with MMVD of varying severity and six clinically healthy dogs were included in the study. Whole blood samples were obtained for measurement of mRNA expression of IL-1α, IL-1ß, IL-6, IL-8, TGF-ß1, TNF-α by reverse transcriptase-PCR (RT-PCR). There were statistically significant differences between clinically healthy dogs and dogs with MMVD for IL-8 and TGF-ß1 gene expression. IL-8 expression increased with increasing MMVD severity and TGF-ß1 expression was higher in asymptomatic dogs with echocardiographic signs of cardiac remodelling (American College Veterinary Internal Medicine class B2) than in all other groups. These results could suggest the involvement of these cytokines at different stages of the disease.

The influence of emotional stress on Doppler-derived aortic peak velocity in boxer dogs.

BACKGROUND: Subaortic stenosis (SAS) is a common congenital heart disease in Boxers. Doppler-derived aortic peak velocity (AoPV) is a diagnostic criterion for the disease. OBJECTIVES: To investigate the influence of emotional stress during echocardiographic examination on AoPV in normal and SAS-affected Boxers. To evaluate the effects of aortic root diameters on AoPV in normal Boxers. DOGS: Two hundred and fifteen normal and 19 SAS-affected Boxers. METHODS: The AoPV was recorded at the beginning of echocardiographic examination (T0), and when the emotional stress of the dog was assumed to decrease based on behavioral parameters and heart rate (T1). AoPV0-AoPV1 was calculated. In normal dogs, stroke volume index was calculated at T0 and T1. Aortic root diameters were measured and their relationship with AoPV and AoPV0-AoPV1 was evaluated. RESULTS: In normal dogs, AoPV was higher at T0 (median, 1.95 m/s; range, 1.60-2.50 m/s) than at T1 (median, 1.76 m/s; range, 1.40-2.20 m/s; P < .0001; reduction 9.2%). The stroke volume index at T0 also was greater than at T1 (P < .0001). Weak negative correlations were detected between aortic root size and aortic velocities. In SAS-affected dogs, AoPV0 was higher than AoPV1 (P < .0001; reduction 7.3%). CONCLUSION AND CLINICAL IMPORTANCE: Aortic peak velocity was affected by emotional stress during echocardiographic examination both in SAS-affected and normal Boxers. In normal Boxers, aortic root size weakly affected AoPVs, but did not affect AoPV0-AoPV1. Stroke volume seems to play a major role in stress-related AoPV increases in normal Boxers. Emotional stress should be taken into account when screening for SAS in the Boxer breed.

The relevance of echocardiography heart measures for breeding against the risk of subaortic and pulmonic stenosis in Boxer dogs.

The aims of this study were to investigate the role and relative importance of auscultation and echocardiography traits as risk factors for the diagnosis of subaortic (SubAS) and pulmonic (PS) stenosis and to estimate the heritability (h(2)) of cardiac measurements taken through echocardiography for a random sample of Italian Boxer dogs. The data were cardiovascular examination results of 1,283 Italian Boxer dogs (686 females and 597 males) enrolled in the national screening program for heart defects arranged by the Italian Boxer Club. Examinations were performed during a 6-yr period by a group of 7 veterinary cardiologists following a standard protocol. Occurrence and severity of SubAS and PS were diagnosed, taking into account clinical and echocardiography findings such as the grade of cardiac murmur, direct ultrasound imaging of the anatomic obstructive lesions, and values of aortic or pulmonary blood flow velocities. A Bayesian logistic regression analysis was performed to identify clinical and echocardiography variables related to SubAS and PS diagnosis. Estimation of variance components for clinical and echocardiography traits was performed using a mixed linear animal model, Bayesian procedures, and the Gibbs sampler. Prevalence of SubAS (PS) was 8.4% (2.2) and 10.7% (6.4) for female and male dogs, respectively. Cardiac murmur, peak velocities, and annulus areas behaved as risk factors for SubAS and PS. The risk of a positive diagnosis for SubAS was 3 times greater for dogs with aortic annulus area <2.1 cm(2) relative to dogs with areas >2.37 cm(2), 84 times greater for dogs showing aortic peak velocities >2.19 m/s relative to dogs with peak velocities <1.97 m/s, and 41 times greater for dogs with moderate to severe murmur grades relative to dogs with absent murmur. Similar results were obtained for PS. The estimated h(2) for the occurrence of cardiac defects was 23.3% for SubAS and 8.6% for PS. Echocardiography and cardiac murmur grades exhibited moderate h(2) estimates and exploitable additive genetic variation. The estimated h(2) was 36, 24, and 20% for aortic annulus area, aortic peak velocity, and cardiac murmur score, respectively. For the area of the pulmonary annulus and peak pulmonary velocity, the estimated h(2) were smaller, ranging from 9.5 to 12.8%. These measures are candidate indicator traits that might be effectively used in dog breeding to reduce the prevalence and severity of cardiac defects.

Disseminated histoplasmosis in a cat in Europe.

A cat was presented with a history of vomiting, decreased appetite and weight loss. Abnormal findings were poor body condition, pale mucous membranes, dehydration and a palpable abdominal mass. Abdominal ultrasound showed lymph node enlargement, a mass of uncertain origin, thickening of the muscularis layer of the small bowel, focal thickening of the ileum with loss of layering and free peritoneal fluid. Cytology revealed a piogranulomatous infiltrate and numerous macrophages containing oval or round yeast-like cells 2 to 5 microm diameter with a central, spherical, lightly basophilic body surrounded by a clear halo, compatible with Histoplasma capsulatum, within the cytoplasm. Post-mortem examination revealed cavity effusions, granulomatous nodules in lungs, intestine and omentum, thickened intestinal walls and intestinal perforation. Staining with Grocott and immunohistochemistry (IHC) revealed numerous organisms within the granulomatous reaction. H. capsulatum has a worldwide distribution in temperate and subtropical climates. To the author's knowledge, this is the first report of feline histoplasmosis in Europe.

A combination of doxycycline and ivermectin is adulticidal in dogs with naturally acquired heartworm disease (Dirofilaria immitis).

Canine heartworm disease is caused by infection with Dirofilaria immitis, a filarial nematode that resides in the pulmonary arteries and occasionally in the right heart chambers of infected dogs. Here the authors evaluated the effect of a combination of doxycycline (10 mg/kg/sid for 30 days) and ivermectin­pyrantel(6µg/kg [DOSAGE ERROR CORRECTED] of ivermectin+5mg/kg of pyrantel every 15 days for 180 days) on microfilariemia, antigenemia and parasite load at echocardiography in naturally infected dogs from an endemic region of Italy. Dogs were examined monthly for 6 months and followed-up 4 months later. One hundred percent of dogs became negative for circulating microfilariae by day 90, while 8/11 (72.7%) of dogs became antigen-negative by day 300. Of the 7 dogs that were positive for visualization of parasites at echocardiography, 6 (85.7%) became negative by day 300. Treatment was well-tolerated by all dogs. These results suggest that a combination of doxycycline and ivermectin is adulticide in dogs with D. immitis.

Aortic endocarditis associated with a perforated septal membranous aneurysm in a boxer dog.

Perimembranous ventricular septal defect is a common congenital heart disease in the dog. It can partially or completely close with age by development of a membranous ventricular septal aneurysm. Aortic endocarditis is a reported complication of ventricular septal defect and membranous ventricular septal aneurysm in human beings. This report describes a case of aortic endocarditis associated with a membranous ventricular septal aneurysm perforated by a small ventricular septal defect in a boxer dog.

Prevalence of congenital heart disease in boxers in Italy.

OBJECTIVE: To evaluate the prevalence of congenital heart disease in boxers in Italy by auscultation and echocardiography. METHODS: This randomized study involved 500 boxers. The inclusion criteria were that the animals should be asymptomatic, older than 1 year and with a pedigree. Dogs with a heart murmur underwent a complete echo-Doppler examination. The criteria for the diagnosis of aortic or pulmonic stenosis were: heart murmur on cardiac auscultation; direct imaging of the obstructive lesions; turbulent aortic or pulmonic flow with peak velocity of >2 m/sec and > 1.5 m/sec, respectively. RESULTS: 265 out of 500 dogs exhibited a heart murmur on cardiac auscultation. According to echo-Doppler examination, 89 (17.8%) dogs were affected with congenital heart disease. Subaortic stenosis and/or pulmonic stenosis accounted for all cases identified, although subaortic stenosis was more prevalent. Type I (63.75%) and Type II (21.25%) subaortic stenosis were the most common forms of the disease. Type A was the most prevalent type of pulmonic stenosis (74.2%). None of the dogs with a heart murmur of grade 1/6 or 2/6 complied with all the pre-selected criteria, and they were not considered to be affected with congenital heart disease. CONCLUSIONS: The prevalence of congenital heart disease in boxers in Italy appears to be very high (17.8%). In this study, subaortic stenosis and pulmonic stenosis accounted for all identified heart diseases. These findings support a the suspicion of these diseases when a heart murmur is found in a boxer, but only Doppler echocardiography can differentiate between subaortic stenosis and pulmonic stenosis.