Kristin A. MacDonald

Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs

Mesenchymal stromal cells (MSCs) have the potential to treat many myocardial diseases. We investigated whether these multipotent stem cells derived from bone marrow could be administered safely into the coronary circulation of healthy dogs. We injected about 0.5 million cells per kg bodyweight of early passage autologous MSCs into the left circumflex coronary artery of anaesthetised dogs. During administration, we noted ST segment elevation and T wave changes characteristic of acute myocardial ischaemia. 7 days later, macroscopic and microscopic evidence of myocardial infarction was noted. Histological sections of myocardium showed several scattered regions of dense fibroplasia accompanied by macrophage infiltrates only in areas where the MSCs were observed. We also noted raised plasma concentrations of cardiac troponin I and collagen fibril deposition in the lesions. These findings show acute myocardial ischaemia and subacute myocardial microinfarction after intracoronary arterial injection of MSCs into dogs.

Utility of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) to distinguish between congestive heart failure and non-cardiac causes of acute dyspnea in cats.

BACKGROUND Circulating plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration facilitates emergency diagnosis of congestive heart failure (CHF) in people. Its utility to discriminate between dyspneic cats with CHF vs. primary respiratory disease requires further assessment. Our objectives were to determine if NT-proBNP (1) differentiates dyspneic cats with CHF vs. primary respiratory disease; (2) increases with renal insufficiency; (3) correlates with left atrial dimension, radiographic cardiomegaly, and estimated left ventricular filling pressure (E/E(a)). METHODS NT-proBNP was measured in 167 dyspneic cats (66 primary respiratory disease, 101 CHF) to evaluate (1) relationship with clinical parameters; (2) ability to distinguish CHF from primary respiratory disease; (3) optimal cut-off values using receiver operating characteristic (ROC) curve analysis. RESULTS NT-proBNP (1) was higher (median and inter-quartile [25th-75th] percentile) in CHF (754 pmol/L; 437, 1035 pmol/L) vs. primary respiratory disease (76.5 pmol/L; 24, 180 pmol/L) cohorts (P<0.001); (2) positively correlated in CHF cats with increased inter-ventricular septal end-diastolic thickness (rho=0.266; P=0.007) and LV free wall thickness (rho=0.218; P=0.027), but not with radiographic heart size, left atrial size, left ventricular dimensions, E/E(a) ratio, BUN, creatinine, or thyroxine; (3) distinguished dyspneic CHF cats from primary respiratory disease at 265 pmol/L cut-off value with 90.2% sensitivity, 87.9% specificity, 92% positive predictive value, and 85.3% negative predictive value (area under ROC curve, 0.94). CONCLUSIONS NT-proBNP accurately discriminated CHF from respiratory disease causes of dyspnea.

Multicenter Evaluation of Plasma N-Terminal Probrain Natriuretic Peptide (NT-pro BNP) as a Biochemical Screening Test for Asymptomatic (occult) Cardiomyopathy in Cats

BACKGROUND B-type natriuretic peptide concentrations reliably distinguish between cardiac and respiratory causes of dyspnea, but its utility to detect asymptomatic cats with occult cardiomyopathy (OCM) is unresolved. HYPOTHESIS/OBJECTIVES Determine whether plasma N terminal probrain natriuretic peptide (NT-proBNP) concentration can discriminate asymptomatic cats with OCM from normal cats, and whether NT-proBNP concentration correlates with clinical, biochemical, and echocardiographic parameters. ANIMALS One hundred and fourteen normal, healthy cats; 113 OCM cats. METHODS Prospective, multicenter, case-controlled study. NT-proBNP was prospectively measured and cardiac status was determined from history, physical examination, and M-mode/2D/Doppler echocardiography. Optimal cut-off values were derived using receiver operating characteristic (ROC) curve analysis. RESULTS NT-proBNP was higher (median, interquartile range [25th and 75th percentiles]) in (1) OCM (186 pmol/L; 79, 478 pmol/L) versus normal (24 pmol/L; 24, 32 pmol/L) (P < .001); and (2) hypertrophic obstructive cardiomyopathy (396 pmol/L; 205, 685 pmol/L) versus hypertrophic cardiomyopathy (112 pmol/L; 48, 318 pmol/L) (P < .001). In OCM, NT-proBNP correlated (1) positively with LVPWd (ρ = 0.23; P = .01), LA/Ao ratio (ρ = 0.31; P < .001), LVs (ρ = 0.33; P < .001), and troponin-I (ρ = 0.64; P < .001), and (2) negatively with %FS (ρ = -0.27; P = .004). Area under ROC curve was 0.92; >46 pmol/L cut-off distinguished normal from OCM (91.2% specificity, 85.8% sensitivity); >99 pmol/L cut-off was 100% specific, 70.8% sensitive. CONCLUSIONS AND CLINICAL IMPORTANCE Plasma NT-proBNP concentration reliably discriminated normal from OCM cats, and was associated with several echocardiographic markers of disease severity. Further studies are needed to assess test performance in unselected, general feline populations, and evaluate relationships between NT-proBNP concentrations and disease progression.

Echocardiographic and clinicopathologic characterization of pericardial effusion in dogs: 107 cases (1985-2006).

OBJECTIVE To evaluate sensitivity and specificity of echocardiography for diagnosis of cardiac masses in dogs with pericardial effusion. DESIGN Retrospective case series. ANIMALS 107 dogs with pericardial effusion. PROCEDURES Records of dogs with pericardial effusion examined at the University of California-Davis Veterinary Medical Teaching Hospital from 1985 to 2006 were reviewed. Dogs were included when echocardiography and pericardectomy or necropsy were performed. Sensitivity, specificity, and metastatic rates were calculated for various causes of pericardial effusion. RESULTS 107 dogs with pericardial effusion were evaluated by surgery (n = 48 dogs), necropsy (44), or both (15). Echocardiography revealed no mass (n = 41 dogs), a right atrial (RA) mass (38), a heart base (HB) mass (23), a pericardial mass (2), an HB and an RA mass (2), and a right ventricular mass (1). Sensitivity and specificity were 82% and 100%, respectively, for detection of a cardiac mass; 82% and 99%, respectively, for detection of an RA mass; and 74% and 98%, respectively, for detection of an HB mass. Most HB masses were neuroendocrine or ectopic thyroid gland tissue, but 3 were hemangiosarcomas and 4 were mesotheliomas. Most RA masses were hemangiosarcomas, but this group also included a neuroendocrine tumor, ectopic thyroid gland tissue, mesothelioma, lymphosarcoma, and sarcoma. Metastatic rates did not differ (50% to 66%) among neoplastic causes. CONCLUSIONS AND CLINICAL RELEVANCE Echocardiography had high sensitivity and specificity for diagnosis and differentiation of RA or HB masses in dogs with pericardial effusion. There was a high rate of metastasis for cardiac masses of all causes.

The effect of ramipril on left ventricular mass, myocardial fibrosis, diastolic function, and plasma neurohormones in Maine Coon cats with familial hypertrophic cardiomyopathy without heart failure.

BACKGROUND Hypertrophic cardiomyopathy (HCM) is the most common heart disease of cats, resulting in left ventricular (LV) hypertrophy, myocardial fibrosis, and diastolic dysfunction. HYPOTHESIS Ramipril will reduce LV mass, improve diastolic function, and reduce myocardial fibrosis in cats with HCM without congestive heart failure (CHF). ANIMALS This prospective, blinded, placebo-controlled study included 26 Maine Coon and Maine Coon cross-bred cats with familial HCM but without CHF. METHODS Cats were matched for LV mass index (LVMI) and were randomized to receive ramipril (0.5 mg/kg) or placebo q24h for 1 year, with investigators blinded. Plasma brain natriuretic peptide (BNP) concentration, plasma aldosterone concentration, Doppler tissue imaging (DTI), and systolic blood pressure were measured at baseline and every 3 months for 1 year. Cardiac magnetic resonance imaging (cMRI) was performed to quantify LV mass and myocardial fibrosis by delayed enhancement (DE) cMRI at baseline and 6 and 12 months. Plasma angiotensin-converting enzyme (ACE) activity was measured on 16 cats 1 hour after PO administration. RESULTS Plasma ACE activity was adequately suppressed (97%) in cats treated with ramipril. LV mass, LVMI, DTI, DE, blood pressure, plasma BNP, and plasma aldosterone were not different in cats treated with ramipril compared with placebo (P = .85, P = .94, P = .91, P = .89, P = .28, P = .18, and P = .25, respectively). CONCLUSION Treatment of Maine Coon cats with HCM without CHF with ramipril did not change LV mass, improve diastolic function, alter DE, or alter plasma BNP or aldosterone concentrations in a relevant manner.

Infective Endocarditis in a Dog and the Phylogenetic Relationship of the Associated “Bartonella rochalimae” Strain with Isolates from Dogs, Gray Foxes, and a Human

The first case of canine endocarditis caused by “Bartonella rochalimae” is reported. By PCR-restriction fragment length polymorphism, sequence, and phylogenetic analyses, Bartonella isolates from a dog with endocarditis, 22 gray foxes, and three dogs, described as B. clarridgeiae like, were confirmed to belong to the new species “B. rochalimae,” suggesting canids as the natural reservoir.

Effect of spironolactone on diastolic function and left ventricular mass in Maine coon cats with familial hypertrophic cardiomyopathy

BACKGROUND Myocardial fibrosis occurs in cats with hypertrophic cardiomyopathy (HCM), and is one factor that leads to diastolic dysfunction. Spironolactone (SPIR) reduces myocardial fibrosis in several models of HCM and in humans with cardiac disease. HYPOTHESIS SPIR will improve diastolic function and reduce left ventricular (LV) mass in Maine Coon cats with HCM. METHODS Maine Coon cats with familial HCM were included if there was concentric hypertrophy (> or =6 mm end diastolic wall thickness) and decreased early lateral mitral annular velocity (Em) or summated early and late mitral annular velocity (EAsum) measured by pulsed wave tissue Doppler imaging echocardiography. Cats were paired by Em-EAsum and randomized to receive 2 mg/kg SPIR (n = 13) or placebo (n = 13) PO q12 h for 4 months. Em-EAsum, systolic velocity, LV mass, and the ratio of left atrial to aortic diameter were measured at baseline, 2 months, and 4 months. Statistical analysis included 2-way repeated measures analysis of variance and the Students t-test. RESULTS Plasma aldosterone concentration increased in cats treated with SPIR (235 ng/mL, baseline; 935 ng/mL, 2 months; 1,077 ng/mL, 4 months; P < .001 at 2 and 4 months). No significant treatment effect was identified for early or early-late summated diastolic mitral annular velocity or any other variable except plasma aldosterone concentration. Severe facial ulcerative dermatitis developed in 4 of 13 cats treated with SPIR, requiring discontinuation of the drug. CONCLUSION SPIR did not improve Em or EAsum of the lateral mitral annulus or alter LV mass over 4 months. One third of cats treated with SPIR developed severe ulcerative facial dermatitis.

Tissue doppler imaging and gradient echo cardiac magnetic resonance imaging in normal cats and cats with hypertrophic cardiomyopathy

Cats with hypertrophic cardiomyopathy (HCM) often develop diastolic dysfunction, which can lead to development of left congestive heart failure. Tissue Doppler imaging (TDI) echocardiography has emerged as a useful, noninvasive method for assessing diastolic function in cats. Cardiac magnetic resonance imaging (cMRI) has been performed in cats and accurately quantifies left ventricular (LV) mass in normal cats. However, assessment of cardiac function in cats by cMRI has not been performed. Six normal Domestic Shorthair cats and 7 Maine Coon cats with moderate to severe HCM were sedated, and TDI of the lateral mitral annulus was performed. Peak early diastolic velocity (Em) was measured from 5 nonconsecutive beats. Cats were anesthetized with propofol and electrocardiogram-gated gradient echo cMRI was performed during apnea after hyperventilation. Short-axis images of the LV extending from the mitral annulus to the apex were obtained throughout the cardiac cycle. LV mass at end systole and LV volumes throughout the cardiac cycle were quantified according to Simpsons rule. To assess the possible influence of propofol on diastolic function, TDI was performed on the 7 cats with HCM while sedated and then while anesthetized with propofol. Em was significantly lower in cats with HCM than normal cats (6.7 +/- 1.3 cm/s versus 11.6 +/- 1.9 cm/s, P < .001, respectively). There was no difference in the cMRI indices of diastolic function in normal and HCM cats. Propofol did not reduce diastolic function (Em) in cats with HCM but mildly reduced systolic myocardial velocity (S) in Maine Coon cats with HCM that were anesthetized with propofol (P = .87 and P = .03, respectively).

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study—A Randomized Clinical Trial

Background Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. Hypothesis/Objectives Administration of pimobendan (0.4–0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac‐related death, or euthanasia. Animals 360 client‐owned dogs with MMVD with left atrial‐to‐aortic ratio ≥1.6, normalized left ventricular internal diameter in diastole ≥1.7, and vertebral heart sum >10.5. Methods Prospective, randomized, placebo‐controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac‐related death, or euthanasia. Results Median time to primary endpoint was 1228 days (95% CI: 856–NA) in the pimobendan group and 766 days (95% CI: 667–875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47–0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952–NA) in the pimobendan group and 902 days (95% CI: 747–1061) in the placebo group) (P = .012). Conclusions and Clinical Importance Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit.

Tissue Doppler Imaging in Maine Coon Cats with a Mutation of Myosin Binding Protein C with or without Hypertrophy

BACKGROUND The cardiac myosin binding protein C gene is mutated in Maine Coon (MC) cats with familial hypertrophic cardiomyopathy. HYPOTHESES Early diastolic mitral annular velocity is incrementally reduced from normal cats to MC cats with only an abnormal genotype to MC cats with abnormal genotype and hypertrophy. ANIMALS Group 1 consisted of 6 normal domestic shorthair cats, group 2 of 6 MC cats with abnormal genotype but no hypertrophy, and group 3 of 15 MC cats with hypertrophy and abnormal genotype. METHODS The genotype and echocardiographic phenotype of cats were determined, and the cats were divided into the 3 groups. Tissue Doppler imaging (TDI) of the lateral mitral annulus from the left apical 4-chamber view was performed. Five nonconsecutive measurements of early diastolic mitral annular velocity (EM) or summated early and late diastolic velocity (EAsum) and heart rate were averaged. RESULTS There was an ordered reduction in Em-EAsum as group number increased (group 1, range 9.7-14.7 cm/s; group 2, range 7.5-13.2 cm/s; group 3, range 4.5-14.1 cm/s; P = .001). Using the lower prediction limit for normal Em-EAsum, the proportion of cats with normal Em-EAsum decreased as the group number increased (P = .001). However, Em-EAsum was reduced in only 3 of 6 cats in group 2. CONCLUSION The incremental reduction of Em-EAsum as group severity increased indicates that diastolic dysfunction is an early abnormality that occurs before hypertrophy development. TDI measurement of Em or EAsum of the lateral mitral annulus is an insensitive screening test for identification of phenotypically normal, genotypically affected cats.