Pimobendan improves clinical signs in short term compared to digoxin or placebo in dogs with heart failure due to chronic degenerative mitral valve disease

Background: Chronic degenerative mitral valve disease (CDMVD) continues to be the most common cause of heart failure (HF) in small breed dogs. Pimobendan (PIMO) is a mixed action drug with inotropic and vasodilator properties and is widely used to treat heart disease in dogs. Therefore, PIMO increases cardiac output, reduces both preload and afterload and increases myocardial contractility without increasing energy consumption and myocardial oxygen. Digoxin (DIG) is a cardiac glycoside acting through inhibition of the sarcolemmal Na+/K+ ATPase pump, hence increasing intracellular calcium. It exerts benefi cial effects on left ventricular function, symptoms and exercise tolerance. The purpose of this prospective, randomized, double blind clinical trial was to evaluate the clinical response and QoLQ in heart failure (HF) dogs treated with digoxin or pimobendan in addition to conventional therapy (furosemide and benazepril). Materials, Methods & Results: Inclusion criteria: dogs in class III or stabilized class IV (NYHA). Exclusion criteria: use of positive inotrope and antiarrhythmic, presence of atrial fi brillation, renal or hepatic disease or neoplasia. Thirty three dogs were included and randomly assigned to DIG (n = 11), PIMO (n = 14) and placebo (PL) (n = 8) and followed up weekly. Data was evaluated for days zero, 7, 14 and 28. Increasing score was assigned to each variable depending on worsening of clinical evaluation (history and physical exam, QoLQ and echocardiogram (echo).Three dogs died during treatment due to worsening of HF, one of PL group and two of DIG group; furthermore, one of PIMO group was censored due to worsening of heart failure. There was no signifi cant difference between and within groups for echo and radiography. PL and DIG groups did not show any signifi cant difference throughout the 28 days of treatment. PIMO group showed lower physical exam score and increased early mitral infl ow velocity on day 28. Serum creatinine increased on days 14 and 28 compared to baseline, but within normal limits. The groups were similar within each evaluation day. Discussion: This is the fi rst short term prospective randomized double blind study comparing PIMO to DIG or PL additionally to conventional therapy (ACEi and furosemide) for dogs with HF due to CDMVD. It was observed an early signifi cant clinical improvement in dogs receiving PIMO compared to those receiving DIG or PL. The increase in early mitral infl ow velocity (E-wave) on day 28 for PIMO group is suggestive of diastolic dysfunction improvement, but this is only one variable related to diastolic function. Creatinine concentration increased in PIMO group, although it remained within normal range. In the present study, although all the three groups received furosemide, only PIMO group showed increase in blood creatinine between baseline and days 7 and 28. This result must be explored in later studies. Regarding the exercise intolerance assessment in a QoLQ, it must be aware that the owner evaluation is strongly infl uenced by the level of exercise that the dog is regularly submitted. Considering that most of the times, small breed dogs in a more advanced age is probably more sedentary and this fact surely precludes the owner to assess the exercise capacity. A more objective evaluation of the exercise tolerance should be considered in further clinical trials. Probably because of the small number of animals included in this study, differences in other studied variables were not found. The short-term follow-up of these patients may also have infl uenced the lack of differences among groups. Considering that stronger clinical evidence is needed to guide clinical decisions, longer prospective studies are also needed to compare the effects of DIG and PIMO, as well as to consider the benefi ts of the use or not of DIG associated with PIMO for dogs in HF due to CDMVD.Funding. This project was fi nancially supported by FAPESP - São Paulo Research Foundation, process number 08/57620-2

Ultrasound Evaluation of Lung Fields in Healthy Dogs: Scanning Technic and Aspects of Normality.

Background: The ultrasound exam has always played a secondary role in pulmonary imaging, with its applicability restricted in emergency care to screen for pleural and/or pericardial effusion, pneumothorax and pulmonary contusion. The recognition of different reverberating artifacts arising from the normal aerated lungs (A lines) and in the presence of lungs with interstitial and/or alveolar infiltrates (B lines) led to wider application of the technique in patients with respiratory syndrome. The objective of this study was to describe the ultrasound imaging methodology and the aspects of the pleura, pleural space and lung fields in healthy dogs.Materials, Methods & Results: Twenty healthy dogs of different breeds and ages, males and females were evaluated in this study; good health status was confirmed by physical examination, electro and echocardiographic assessment, thoracic radiography and systemic arterial blood pressure measurements. Dogs were scanned by a single examiner experienced in diagnostic imaging and previously trained for 6 months in thoracic ultrasound image interpretation. A MyLab 40 with a microconvex multifrequency probe (5-8 MHz) was used in this study.  Evaluation was performed in an orthopneic position (standing or sternal recumbecy) under manual containment. Ultrasound examinations were based on the VetBLUE (Veterinary Bedside Lung Ultrasound Exam) protocol. Lung fields were regionally scanned at the 2nd-3rd, 4-5th, 6-7th and 8-9th intercostal spaces in the right and left hemithorax. A subxiphoid window was added to screen for free fluid in the pleural space and/or pericardial sac. Pleural sliding and A lines, that are hyperechoic parallel equidistant lines arising from the visceral pleura-lung interface could be easily seen at all intercostal spaces in all dogs in this sample, with more difficult visualization at the 2nd-3rd intercostal space. B lines were observed in seven out of twenty dogs (35%). However, this artifact was limited to one intercostal space and a maximum of two lines were detected per field. B line artifacts were more commonly seen in the right hemithorax, at the level of the 8-9th intercostal space however without significant differences. In the subxiphoid window evaluation A lines were not detected.Discussion: The observation of B lines in healthy dogs was previously described and as in our study there were no significant differences relative to B line observation relatively to the intercostal space neither between the right and the left hemithorax. B lines are generally associated with decreased pulmonary aeration in response to interstitial/alveolar infiltration, which generates reflections and comet tail artifacts. The low number of B lines observed in this study may be associated with larger veins or lymphatics vessels, focal interstitial thickening or microatelectasia. The high respiratory frequency does not interfere in the sonographic evaluation. The dyspnea presented for animals with acute respiratory syndromes can be aggravated in stress situations, such as the displacement to the radiology service and manipulation necessary to the radiographic projections. Regional scanning by some acoustic windows allows rapid assessment of the thorax, with significant contributions to decision making in emergency situations. However, ultrasonography does not eliminate the need for other imaging modalities such as radiography and computed tomography and should be seen as a screening tool for patients presenting with acute respiratory syndromes

Comparative Evaluation of the Echocardiographic Parameters of Dogs with Chronic Mitral Valve Regurgitation Treated with Amlodipine or Pimobendan

Background: Chronic mitral valve regurgitation is the most common heart disease in dogs. It is caused by myxomatous mitral valve degeneration, an acquired degenerative disease that can lead to congestive heart failure. Pimobendan is a mixed action drug, with inotropic and vasodilator proprieties, widely used to treat such dogs. Amlodipine is a pure vasodilator drug used as an anti-hypertensive agent, with no inotropic effects. This study aimed to compare  echocardiographic, electrocardiographic and blood pressure parameters between dogs with congestive heart failure treated with pimobendan and those treated with amlodipine in addition to conventional therapy.Materials, Methods & Results: A prospective, randomized, double-blind study was conducted in dogs with stage C chronic mitral valve regurgitation according to the 2009 American College of Veterinary Internal Medicine (ACVIM) guidelines, who weighed up to 15 kg. Randomization was performed using appropriate software and the sealed envelope technique. Blinding of the owner, the main researcher, and the person who performed the clinical analysis was guaranteed by the use of identical capsules and bottles for both pimobendan and amlodipine. Statistical analysis was performed using specialized software. Eligibility was determined by predefined inclusion and exclusion criteria. Dogs with cardiac disease other than mitral and/or tricuspid degeneration, patients already undergoing pharmacological treatment with drugs other than enalapril and furosemide, patients with systolic blood pressure below 100 mmHg, patients with chronic kidney disease in stages III or IV according to International Renal Interest Society staging system for chronic kidney disease (2009), and patients with other systemic debilitating diseases were excluded from the study. The animals were randomized into two groups based on the drug they received. Group A received pimobendan (n = 10) and group B received amlodipine (n = 11). All animals were also treated with furosemide and enalapril maleate and evaluated three times over a period of sixty days (T0, T30, T60). Changes in echodopplercardiographic and electrocardiographic parameters and systolic blood pressure were investigated. There were no significant differences in electrocardiographic parameters or systolic blood pressure between the groups at any time. Among the echocardiographic parameters, only early diastolic myocardial peak velocity (Em) and late diastolic myocardial peak velocity (Am) showed a significant difference between groups.Discussion: This was the first prospective randomized double-blind study comparing pimobendan and amlodipine in the treatment of dogs with stage C chronic mitral valve regurgitation according to the ACVIM consensus statement. The use of pimobendan in these patients has been debated because myocardial inotropism is generally preserved in them. Some authors argue that early use of the drug can even lead to deleterious effects on the heart. In the present study, the groups showed no statistically significant differences in systolic blood pressure or electrocardiographic parameters. Among the echocardiographic parameters, statistically significant differences were only observed in the speed of Em waves between groups at T0, in the speed of Em waves in the amlodipine group between T0 and T60 times, and in the speed of Am waves in the amlodipine group between T30 and T60 times. Both parameters are indices of diastolic function and may indicate a change in early myocardial relaxation. From the findings of this study, we could not conclude whether one drug was superior to the other

Comparative Evaluation of the Echocardiographic Parameters of Dogs with Chronic Mitral Valve Regurgitation Treated with Amlodipine or Pimobendan

Background: Chronic mitral valve regurgitation is the most common heart disease in dogs. It is caused by myxomatous mitral valve degeneration, an acquired degenerative disease that can lead to congestive heart failure. Pimobendan is a mixed action drug, with inotropic and vasodilator proprieties, widely used to treat such dogs. Amlodipine is a pure vasodilator drug used as an anti-hypertensive agent, with no inotropic effects. This study aimed to compare  echocardiographic, electrocardiographic and blood pressure parameters between dogs with congestive heart failure treated with pimobendan and those treated with amlodipine in addition to conventional therapy.Materials, Methods & Results: A prospective, randomized, double-blind study was conducted in dogs with stage C chronic mitral valve regurgitation according to the 2009 American College of Veterinary Internal Medicine (ACVIM) guidelines, who weighed up to 15 kg. Randomization was performed using appropriate software and the sealed envelope technique. Blinding of the owner, the main researcher, and the person who performed the clinical analysis was guaranteed by the use of identical capsules and bottles for both pimobendan and amlodipine. Statistical analysis was performed using specialized software. Eligibility was determined by predefined inclusion and exclusion criteria. Dogs with cardiac disease other than mitral and/or tricuspid degeneration, patients already undergoing pharmacological treatment with drugs other than enalapril and furosemide, patients with systolic blood pressure below 100 mmHg, patients with chronic kidney disease in stages III or IV according to International Renal Interest Society staging system for chronic kidney disease (2009), and patients with other systemic debilitating diseases were excluded from the study. The animals were randomized into two groups based on the drug they received. Group A received pimobendan (n = 10) and group B received amlodipine (n = 11). All animals were also treated with furosemide and enalapril maleate and evaluated three times over a period of sixty days (T0, T30, T60). Changes in echodopplercardiographic and electrocardiographic parameters and systolic blood pressure were investigated. There were no significant differences in electrocardiographic parameters or systolic blood pressure between the groups at any time. Among the echocardiographic parameters, only early diastolic myocardial peak velocity (Em) and late diastolic myocardial peak velocity (Am) showed a significant difference between groups.Discussion: This was the first prospective randomized double-blind study comparing pimobendan and amlodipine in the treatment of dogs with stage C chronic mitral valve regurgitation according to the ACVIM consensus statement. The use of pimobendan in these patients has been debated because myocardial inotropism is generally preserved in them. Some authors argue that early use of the drug can even lead to deleterious effects on the heart. In the present study, the groups showed no statistically significant differences in systolic blood pressure or electrocardiographic parameters. Among the echocardiographic parameters, statistically significant differences were only observed in the speed of Em waves between groups at T0, in the speed of Em waves in the amlodipine group between T0 and T60 times, and in the speed of Am waves in the amlodipine group between T30 and T60 times. Both parameters are indices of diastolic function and may indicate a change in early myocardial relaxation. From the findings of this study, we could not conclude whether one drug was superior to the other

Comparative study of 4 echocardiographic methods of left ventricular measurement in German Shepherd dogs

Objectives: To compare dimensions and shortening fraction (SF) of the left ventricle (LV) obtained from two-dimensional (2D) and M-mode imaging of short and long-axis views. Animals: 40 healthy, adult German Shepherd dogs. Methods: Left ventricular measurements were obtained using 4 echocardiographic methods: M-mode in short and long-axis and 2D imaging in short and long-axis. The methods were compared by studying the effects of imaging mode and axis on LV parameters, taking into account the influence of weight and gender. Results: Mean LV end-diastolic diameter was greater in short-axis views. However, this difference was not considered clinically relevant. Mean SF was higher when derived from 2D measurements with poor agreement among methods. A combined influence of axis, gender, and weight was observed on interventricular septal thickness in end diastole with poor agreement among methods. Conclusions: Some LV parameters were significantly affected by mode and axis, either in isolation or in combination with weight and gender, although the differences observed were not always clinically relevant. These findings show that using the different echocardiographic methods interchangeably to assess LV dimensions should be done with caution

Displasia valvar tricúspide em um felino doméstico: relato de caso

Tricuspid valve dysplasia (TVD) is a congenital heart defect described in dogs and cats; however, in Brazil there are no reports of this condition in cats. Therefore, our goal was to report a case of TVD in a domestic cat. A four-year-old, female, domestic short hair cat that was seen at the Cardiology Service of the Veterinary Teaching Hospital, University of São Paulo, for apathy, appetite loss and dyspnea for five days. During physical examination, dyspnea with a restrictive respiratory pattern due to pleural effusion was observed. Thoracocentesis was performed and 450 mL of serosanguineous fluid was drained. Two-dimensional echocardiography in the right parasternal short-axis plane at the level of the papillary muscles showed right ventricular dilatation and paradoxical septal motion. On the left parasternal apical four-chamber view, significant dilatation of the right chambers, loss of mobility of the septal leaflet of the tricuspid valve and a thickened mural leaflet chordae with anomalous insertion were observed. Based on clinical and echocardiographic aspects, a diagnosis of TVD was given. Treatment was initiated with enalapril 0.5 mg/kg, furosemide 0.5 mg/kg and pimobendan 0.3 mg/kg every 12 hours, all per os. The patient experienced remission of clinical manifestations and survived for 50 days after diagnosis.Displasia valvar tricúspide (DVT) é um defeito cardíaco congênito descrito em cães e gatos. Entretanto no Brasil ainda não há relato desta cardiopatia em felinos. Desta forma, objetivou-se relatar um caso de DVT em um felino doméstico. Uma gata de pelo curto, com quatro anos de idade foi atendida no Serviço de Cardiologia do Hospital Veterinário da Universidade de São Paulo, apresentando apatia, perda de apetite e dispneia há cinco dias. Durante o exame físico observou-se dispneia com padrão respiratório restritivo devido a presença de efusão pleural. Foram drenados 450 mL de líquido serosanguinolento por meio de toracocentese. O ecocardiograma no modo bidimensional, pela janela paraesternal direita, ao eixo curto transversal ao nível dos músculos papilares, revelou hipertrofia excêntrica do ventrículo direito e movimento septal paradoxal. Pela vista apical quatro câmaras, na janela paraesternal esquerda, observou-se importante remodelamento de câmaras cardíacas direitas. A valva tricúspide apresentou-se com perda de mobilidade de sua cúspide septal e espessamento de cordoalha tendínea da cúspide mural, com inserção anômala. Com base nos aspectos clínicos e ecocardiográficos, instituiu-se o dianóstico de DVT. Iniciou-se o tratamento com enalapril (0,5 mg/kg), furosemida (0,5 mg/kg) e pimobendan (0,3 mg/kg), pela via oral a cada 12 horas. O paciente apresentou remissão das manifestações clínicas, sobrevivendo por 50 dias após o diagnóstico