Teresa DeFrancesco

Hypothesis: This proposed study involves two research hypotheses: (1) That point-of-care LUS will have a predictable pattern of resolution of B-lines in dogs hospitalized with and treated for cardiogenic pulmonary edema, with the cranial ventral lobes clearing last; and (2) That the number of LUS B-lines exhibit a strong correlation with resting respiratory rate; whereas, pulmonary auscultation and LUS B-lines will not exhibit good agreement. Aims of the study: The primary aim of this study is to describe the pattern and general time course in the resolution of B-lines in dogs treated for left-sided CHF. Current therapy for hospitalized patients with CHF includes some form of positive inotrope with or without a vasodilator, supplemental oxygen therapy, sedation as needed, and treatment with a parenteral diuretic. Selection of diuretic dose and titration of therapy is generally made through interpretation of subjective clinical data including respiratory rate and effort and lung auscultation. Because this data is subjective, its use may be limited by clinician experience, anxiety and fear in the hospitalized patient (which can induce tachypnea), concurrent respiratory or extra-pulmonary disease, or the need for mechanical ventilation, where respiratory rate is controlled. Objective data in response to therapy is more difficult to obtain, as it involves thoracic radiography as previously described. There is a strong need for an easy, accessible, safe and inexpensive monitoring tool for the resolution of cardiogenic pulmonary edema in hospitalized patients with CHF. If the pattern of resolution of B-lines in dogs treated for left-sided CHF is predictable, future studies can use this information to develop guidelines on the titration of treatment for cardiogenic pulmonary edema based on the results of the B-line burden and distribution identified by point-of-care LUS. The secondary aim of this study is to correlate the lung ultrasound findings in patients with left-sided CHF with traditional monitoring by auscultation and respiratory rate. There is a strong interest in the development of techniques for cardiopulmonary exam that are more sensitive and objective than traditional auscultation. With the surge in popularity and availability of point of care ultrasound, lung ultrasound might augment and complement traditional auscultation for assessment of the cardiopulmonary system

Sildenafil is the treatment of choice for clinically significant pulmonary hypertension due to a variety of causes in dogs. Despite its widespread use, its pharmacokinetics and pharmacodynamics in the target population remain ill-defined. The aims of this project are to describe the population pharmacokinetics of sildenafil and relevant covariates impacting this in dogs with naturally occurring pulmonary hypertension; and to identify echocardiographic variables which could be used for clinical monitoring of its effects.

The pharmacokinetic properties of pimobendan will be impacted by age, stage of disease, and the concurrent medications in dogs with heart disease Aims and significance: ��������������� To determine if the pharmacokinetics of oral pimobendan observed in clinical patients is comparable to what has been observed in healthy dogs without heart disease. ��������������� To determine if any patient characteristics, such as age, breed, gender, body condition score, presence of kidney or liver disease, length of treatment, mg/kg dose, stage of heart disease, manifestation of heart failure (right, left or biventricular failure) or concurrent medications impacts the pharmacokinetics of oral pimobendan. ��������������� The significance of this study is to provide a better understanding of the pharmacokinetics of oral pimobendan in clinical patients that will translate to enhanced medical management of their heart disease.

Mitral valve degeneration is the most common cause of heart disease in the dog. It is particularly common in small breed dogs including Cavalier King Charles Spaniels, Yorkshire Terriers, Miniature Poodles, Dachshunds and small mixed breed dogs. Although some dogs live comfortably with the disease, many affected dogs die of congestive heart failure and sometimes sudden death due to left atrial rupture. Mitral valve degeneration is known to be an inherited disease, at least in some breeds, although the causative mutation(s) have not been identified. Failure to understand the underlying cause of mitral valve degeneration has slowed the development of effective treatment and prevention plans. Here, we propose to identify genetic variants that lead to the development of mitral valve degeneration and to use this information to begin to develop treatment and prevention plans for dogs with high-risk DNA variants.

Mitral valve degeneration is the most common heart disease in the dog. It is particularly common in small breed dogs, and the Miniature Schnauzer is believed to be one of the most commonly affected breeds. Although some dogs live comfortably with the disease, many affected dogs die of congestive heart failure and sometimes sudden death due to a rupture of a weakened heart. Mitral valve degeneration is thought to be an inherited disease in the dog although the causative mutation(s) have not been identified. Failure to understand the underlying cause of mitral valve degeneration has slowed the development of effective treatment and prevention plans. Here, we propose to identify genetic variants that lead to the development of mitral valve degeneration in the Miniature Schnauzer and to use this information to begin to develop treatment and prevention plans for dogs with high-risk DNA variants.

Hypothesis: 1. Caudal vena cava distension, decreased vena caval collapsibility and increased RV:LV ratio will be present in cats with right sided or biventricular congestive heart failure. Aims of the study: 1. To determine the feasibility, and measure the intra- and inter-observer variability, and reference range parameters by echocardiography for the caudal vena at the level of the diaphragm and RV:LV ratio in unaffected cats. 2. To measure the caudal vena cava and RV:LV ratio in four populations of affected cats: a. Cats with predominant right sided congestive heart failure (large volume pleural effusion) or biventricular failure b. Cats with predominant left sided congestive heart failure (pulmonary edema) c. Cats with non-cardiac etiology of pleural effusion d. Cats with preclinical HCM with moderate to severe left atrial enlargement

The clinical syndrome of aortic thromboembolism (FATE) in cats is initiated by sudden migration of a left atrial thrombus (blood clot) into the systemic arterial system. This leads to an acute and emergent disorder characterized by pain, paralysis, and rhabdomyolysis (breakdown of muscle tissue) in the affected limb(s). Treatment options are limited with up to 90% of affected cats euthanatized due to the poor prognosis associated with standard therapies. Indeed, the survival rate for cats hospitalized and treated medically is only 30-40%. Although thrombolytic therapy is the standard of care for acute thrombotic disorders in humans, treatment of feline ATE (FATE) has focused on supportive care. Despite case reports of thrombolytic therapy in cats with FATE, no controlled clinical trials of therapy have been conducted. Administration of tissue plasminogen activator (TPA) is administered but not currently a standard of care. The study described herein prospectively evaluates the use of TPA in acute FATE. Results of this study will provide the data needed to more objectively assess the potential of TPA therapy for this syndrome.

Diagnosis of congestive heart failure can be challenging, particularly when a dog or cat presents with respiratory distress which limits the diagnostic evaluation. Thoracic radiographs are considered a relatively high-yield test for identifying cardiogenic pulmonary edema, but images are frequently equivocal and obtaining radiographs can exacerbate respiratory distress in a compromised patient. A recent advancement in the diagnostic imaging of dyspneic patients is the increased use of focused echocardiography and thoracic ultrasound.1,2 In humans, portable bed-side ultrasound of the lungs is now part of a routine evaluation of dyspneic patients, often prior to acquisition of thoracic radiographs. Lung ultrasound can function as a ?visual stethoscope? to supplement auscultation findings and improve diagnostic accuracy of the physical examination.3 Lung ultrasound can suggest the presence of pulmonary edema by identifying ultrasound artifacts (B-lines, or ?ultrasound lung rockets?) caused by increased lung water.4,5 B-lines are created when small fluid-filled alveoli, which are below the resolution threshold of the ultrasound beam, are surrounded by air, creating a high impedance gradient.4 These artifacts are identified ultrasonographically as discrete narrow-based vertical hyperechoic artifacts which extend from the pleural-pulmonary interface to the far aspect of the ultrasound screen without fading, and which move synchronously with respiration.4?10 Studies in human emergency patients suggest that lung ultrasound can differentiate cardiogenic versus non-cardiogenic causes of dyspnea with high sensitivity and specificity, and similar or greater positive predictive value than BNP8,9,11,12 or thoracic radiographs.4?6,13?15 Increased numbers of B-lines are also linearly correlated with amount of lung water and pulmonary capillary wedge pressure.16,17 Standard views for lung ultrasound in human medicine and definitions of various artifacts have been codified in the Bedside Lung Ultrasound in Emergency (BLUE) protocol.6 In veterinary patients, portable bed-side ultrasound is frequently used to evaluate the thorax and abdomen for the presence of free fluid and pneumothorax.18 Protocols have been published detailing a complete bedside thoracic ultrasound to evaluate for pleural effusion, pneumothorax, and pulmonary edema in small animals.10 A small pilot study19 suggested that B-line artifacts were more numerous and more widely distributed in dogs with previously diagnosed congestive heart failure compared to normal control dogs. However, there are no published studies prospectively evaluating the diagnostic accuracy of lung ultrasound in clinically dyspneic veterinary patients.

Currently there is no cardiac drug licensed for the treatment of preclinical myxomatous mitral valve disease. Pimobendan has been proven to be safe and to reduce mortality as well as morbidity associated with congestive heart failure (CHF) due to myxomatous mitral valve disease. The combination of preload and afterload reduction in combination with inotropic support may result in a reduction in cardiac size and filling pressures in dogs with significant remodelling secondary to myxomatous mitral valve disease. These effects are considered to be cardioprotective and therefore, in dogs with preclinical myxomatous mitral valve disease, would be anticipated to delay the onset of pulmonary oedema and clinical signs. The objective of the study is, to determine whether chronic oral administration of pimobendan (Vetmedin® chewable tablets) in dogs with evidence of increased heart size secondary to preclinical myxomatous mitral valve disease, can delay the onset of signs of congestive heart failure.

Clinical Trial