Investigation into the use of plasma NT-proBNP concentration to screen for feline hypertrophic cardiomyopathy

ObjectiveTo evaluate the utility of feline NT-proBNP plasma concentration [NT-proBNP] as a screening tool for cats with subclinical hypertrophic cardiomyopathy (HCM).Animals, materials and methodsForty adult Maine Coon or Maine Coon crossbred cats from the feline HCM research colony at the University of California, Davis were studied. All cats had previously been genotyped as heterozygous or negative for the A31P myosin binding protein C (MYBPC) mutation. Echocardiograms were performed to assess the severity of HCM in each cat. Blood samples were collected for evaluation of [NT-proBNP].ResultsIn these cats with severe HCM, [NT-proBNP] was significantly elevated (P < 0.0001) when compared to all other groups of cats and an [NT-proBNP] > 44pmol/L accurately predicted the presence of severe HCM. However, [NT-proBNP] was not increased in cats with moderate or equivocal HCM when compared to normal cats. Cats heterozygous for the MYBPC mutation had a significantly elevated [NT-proBNP] when compared to cats without the A31P mutation (P = 0.028).ConclusionsMeasurement of [NT-proBNP] has a high sensitivity and specificity as a means of detecting severe HCM in cats, but it is not sensitive for the identification of moderate HCM as judged by the evaluation of Maine Coon and Maine Coon cross cats in our colony. Consequently, we conclude that this test cannot be used to screen cats for the presence of mild to moderate HCM.     

Analysis of 8 Sarcomeric Candidate Genes for Feline Hypertrophic Cardiomyopathy Mutations in Cats with Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats. Causative mutations have been identified in the Maine Coon (MC) and Ragdoll breed in the cardiac myosin binding protein C gene (MYBPC3). HCM is thought to be inherited in other breeds.
Hypothesis: That a causative mutation for HCM in the British Shorthair (BSH), Norwegian Forest (NWF), Siberian, Sphynx, or MC cats would be identified in the exonic and splice site regions of 1 of 8 genes associated with human familial HCM.
Animals: Three affected BSH, NWF, Siberians, Sphynx, 2 MC (without the known MC mutation), and 2 Domestic Shorthair cats (controls) were studied.
Methods: Prospective, observational study. Exonic and splice site regions of the genes encoding the proteins cardiac troponin I, troponin T, MYBPC3, cardiac essential myosin light chain, cardiac regulatory myosin light chain, α tropomyosin, actin, and β–myosin heavy chain were sequenced. Sequences were compared for nucleotide changes between affected cats, the published DNA sequences, and control cats. Changes were considered to be causative for HCM if they involved a conserved amino acid and changed the amino acid to a different polarity, acid-base status, or structure.
Results: A causative mutation for HCM was not identified, although several single nucleotide polymorphisms were detected.
Conclusions and Clinical Importance: Mutations within these cardiac genes do not appear to be the only cause of HCM in these breeds. Evaluation of additional cardiac genes is warranted to identify additional molecular causes of this feline cardiac disease.     

Hypertrophic cardiomyopathy in young Maine Coon cats caused by the p.A31P cMyBP-C mutation - the clinical significance of having the mutation

Background

In Maine Coon (MC) cats the c.91G > C mutation in the gene MYBPC3, coding for cardiac myosin binding protein C (cMyBP-C), is associated with feline hypertrophic cardiomyopathy (fHCM). The mutation causes a substitution of an alanine for a proline at residue 31 (p.A31P) of cMyBP-C. The pattern of inheritance has been considered autosomal dominant based on a single pedigree. However, larger studies are needed to establish the significance of cats being heterozygous or homozygous for the mutation with respect to echocardiographic indices and the probability of developing fHCM. The objective of the present study was to establish the clinical significance of being homozygous or heterozygous for the p.A31P cMyBP-C mutation in young to middle-aged cats.

Methods

The cohort consisted of 332 MC cats, 282 cats < 4 years (85%). All cats were examined by 2-D and M-mode echocardiography. DNA was extracted from blood samples or buccal swabs and screened for the p.A31P cMyBP-C mutation in exon 3 of the gene, using polymerase chain reaction followed by DNA sequencing.

Results

The fHCM prevalence was 6.3% in the cohort. Eighteen cats were homozygous and 89 cats were heterozygous for the mutation. The odds ratio for having fHCM for homozygous cats was 21.6 (95% confidence interval 7.01-66.2) - when the group of equivocal cats was categorized as non-affected. Overall, 50% of the cats that were homozygous for the mutation had fHCM. p.A31P heterozygosity was not associated with a significant odds ratio for fHCM. In cats in the 4 to 6 years of age range a similar, non significant, odds ratio was seen in heterozygous cats. Only two cats over four years were homozygous and both were diagnosed with fHCM.

Conclusion

As there is no significant odds ratio associated with being heterozygous for the pA31P cMyBP-C mutation at this age, the mutation must have a very low penetrance in this group. From our data it would appear that most MC cats that develop fHCM due to the p.A31P mutation prior to the age of approximately 6 years do so because they are homozygous for this mutation.     

Effect of treatment with atenolol on 5-year survival in cats with preclinical (asymptomatic) hypertrophic cardiomyopathy

ObjectivesTo investigate the effect of treatment with atenolol on 5-year survival in cats with preclinical hypertrophic cardiomyopathy (HCM).Animals63 Client-owned cats with preclinical HCM and 31 healthy control cats.MethodsProspective, observational, open-label, clinical cohort study. Cats with HCM were diagnosed by echocardiography, treated with atenolol (6.25–12.5 mg q12h, PO; n = 42) or untreated (n = 21), and were observed for 5 years after enrollment. The study end point was death from any cause. Cats of similar body weight, age, gender, and breed without evidence of heart disease were studied concurrently and served as controls.ResultsDuring the observational period, 27 cats with HCM died; 14 (22%) due to cardiac disease and 13 (21%) due to non-cardiac disease. Ten control cats (32%) died of non-cardiac disease. There was no significant difference (P = 0.307) in all-cause mortality between control and HCM. Cardiac mortality was higher in cats with HCM compared to control cats (P = 0.005). There was no significant difference in all-cause mortality (P = 0.729) and cardiac mortality (P = 0.897) between cats with HCM treated or untreated with atenolol. Age and left atrial size at diagnosis were the only predictors of 5-year outcome.ConclusionsOur study failed to demonstrate an effect of atenolol on 5-year survival in cats with preclinical HCM.     

Heart rate and arrhythmia frequency of normal cats compared to cats with asymptomatic hypertrophic cardiomyopathy

ObjectivesTo compare heart rate and arrhythmia frequency and complexity in a normal population of cats to a population of cats with hypertrophic cardiomyopathy (HCM).Animals17 cats with HCM and 15 cats with normal echocardiograms.MethodsResults for echocardiography, electrocardiography, Doppler blood pressure, and 24-h Holter monitoring were compared between groups.ResultsThere was no difference in heart rate between HCM cats and normal cats regardless of modality used. All (17/17) HCM cats had ventricular arrhythmias (geometric mean 124 complexes/24 h) with 82% (14/17) exhibiting complex arrhythmias (couplets, triplets, or ventricular tachycardia). Most (14/15) normal cats had ventricular arrhythmias (geometric mean 4 complexes/24 h), but only 20% (3/15) exhibited complexity. HCM cats had significantly more total ventricular complexes, ventricular premature complexes and accelerated idioventricular rhythm than normal cats (P < 0.0001, P < 0.0001, and P = 0.01, respectively). Eighty eight percent (15/17) of HCM cats had supraventricular arrhythmias (geometric mean 9 complexes/24 h) with 23% (4/17) exhibiting complexity. Sixty percent (9/15) of normal cats had supraventricular arrhythmias (geometric mean 1 complex/24 h) with 13% (2/15) exhibiting complexity. Cats with hypertrophic cardiomyopathy had significantly more supraventricular complexes than normal cats (P = 0.0148).ConclusionCats with asymptomatic HCM have more frequent and complex ventricular and supraventricular arrhythmias than normal cats but do not have different overall heart rates compared to normal cats. Further studies are needed to determine if these arrhythmias are associated with an increased risk of sudden cardiac death or influence long-term survival.     

Prevalence of the myosin-binding protein C mutation in Maine Coon cats

BACKGROUND: An autosomal dominant mutation has been identified in the myosin-binding protein C (MYBPC3) gene of Maine Coon cats. This mutation changes a conserved amino acid and computationally alters the protein conformation of this gene in Maine Coon cats with hypertrophic cardiomyopathy. The prevalence of this mutation is unknown. OBJECTIVE: To determine the genetic prevalence of the MYBPC3 mutation in a large cohort of predominantly Maine Coon cats. ANIMALS: Three thousand three hundred and ten DNA samples (blood or buccal swab) from cats. METHODS: This retrospective study reviewed the Veterinary Cardiac Genetics Laboratory database at Washington State University for samples submitted for evaluation of the Maine Coon MYBPC3 mutation. The data were analyzed with respect to the breed of cat, mutation status (negative, heterozygous, homozygous), and geographic origin of the submission. RESULTS: In the population of cats studied, Maine Coon cats accounted for 100% of all cats positive for the mutation, and the worldwide percentage of Maine Coon cats carrying the MYBPC3 mutation was 34%. CONCLUSIONS AND CLINICAL IMPORTANCE: The prevalence of the mutation (heterozygous or homozygous) was very similar among countries of submission, suggesting that the 34% mutation rate of the tested samples is a reasonable estimate of the true prevalence of the mutation within the breed. Because of the high prevalence of this mutation, a breeding recommendation to eliminate all cats with the mutation could have a substantial impact on the gene pool. Additional studies are indicated to explore the relationship between genotype and clinical outcome in affected cats.     

Prospective echocardiographic and tissue Doppler screening of a large Sphynx cat population: Reference ranges,heart disease prevalence and genetic aspects

Objectives(1) To investigate heart morphology and function using echocardiography and tissue Doppler imaging (TDI), (2) to determine heart disease prevalence and characteristics, and (3) to assess potential genetic features in a population of Sphynx cats presented for cardiovascular screening.AnimalsA total of 147 echocardiographic examinations, including 33 follow-ups, were performed by trained observers on 114 Sphynx cats of different ages (2.62 ± 1.93 years [0.5–10.0]) from 2004 to 2011.MethodsSphynx cats underwent a physical examination, conventional echocardiography, and, if possible, two-dimensional color TDI.ResultsConventional echocardiographic findings included 75/114 normal (65.8%) and 39/114 (34.2%) abnormal examinations with a diagnosis of either congenital heart diseases (n = 16) or hypertrophic cardiomyopathy (HCM, n = 23). In adult healthy cats, a significant body weight effect was observed for several echocardiographic variables, including end-diastolic left ventricular (LV) free wall (P < 0.01), interventricular septum (P < 0.001), and LV diameter (P < 0.001). Mitral valve dysplasia (MVD) was observed as a single or associated defect in 15/16 cats with congenital heart diseases. A significant increase in HCM prevalence (P < 0.001) was observed according to age. The pedigree analysis of a large family (n = 81) suggested an autosomal dominant mode of inheritance with incomplete penetrance for HCM.ConclusionsBody weight should be taken into account when interpreting values of diastolic myocardial wall thicknesses in Sphynx cats. Additionally, HCM and MVD are two relatively common heart diseases in this feline breed. More pedigree data are required to confirm the inheritance pattern of HCM at the breed level.     

Congenital supravalvular mitral stenosis in 14 cats

ObjectivesTo describe the clinical features of congenital supravalvular mitral stenosis (SVMS) in cats.BackgroundSupravalvular mitral stenosis is an uncommon congenital cardiac defect that has not been previously reported in a series of cats.Animals14 cats with SVMS.MethodsMedical records, relevant diagnostic studies and preserved pathology specimens were reviewed.ResultsCats were presented over a wide age range (5 months–10 years; median 3 years); males (n = 9) and the Siamese breed were over-represented. Presenting complaints included respiratory distress (n = 6), hindlimb paralysis due to aortic thromboembolism (n = 5) and asymptomatic heart murmur (n = 3). Echocardiographic examination often identified pulmonary hypertension (PHT) (n = 7) and concurrent cardiac abnormalities (n = 7), especially partial atrioventricular septal defect (PAVSD) (n = 4). Status 12 months following diagnosis was known for 9 cats; 8 of these had died or were euthanized.ConclusionsCats with SVMS are usually presented as young adults for respiratory signs attributable to congestive heart failure, aortic thromboembolism or incidental murmur identification. Congestive heart failure, PHT and concurrent congenital cardiac abnormalities (specifically PAVSD) are common. Long-term prognosis for symptomatic cats is poor.     

Prevalence,geographic distribution,and impact on lifespan of a dilated cardiomyopathy-associated RNA-binding motif protein 20 variant in genotyped dogs

IntroductionThe study objectives were to determine the prevalence and geographic distribution of a dilated cardiomyopathy (DCM)-associated RNA-binding motif protein 20 (RBM20) variant in canine DNA samples submitted for testing and to evaluate the influence of the genotype on cardiac phenotype and lifespan.AnimalsSamples from 2136 dogs including 1834 Standard Schnauzers (SSNZ), 266 Giant Schnauzers (GSNZ), and 36 dogs of other breeds.MethodsThe University of Missouri Canine Genetics Laboratory's sample-accession spreadsheet and Orthopedic Foundation for Animals' database were retrospectively reviewed for samples submitted for RBM20 genotyping from November, 2013, through May, 2018. Data analyzed included breed, date of birth, RBM20 genotype (homozygous wild-type, heterozygous variant [HET], or homozygous variant [HOM]), geographic origin of submission, pedigree, cardiac phenotype, and date of death or current age if alive.Results and DiscussionThe RBM20 variant was only detected in SSNZ and GSNZ. A total of 389 SSNZ were variant-positive (prevalence = 21.2%), with 361 HET (19.7%) and 28 HOM (1.5%). Of the HOM SSNZ, DCM was confirmed in 26 of 28 (92.9%), with the remainder lost to follow-up. The median lifespan of HOM SSNZ (3.06 years) was significantly shorter than that for HET (15.11 years) and wild-type (15.18 years) SSNZ. Twenty-six GSNZ were variant-positive (prevalence = 9.8%), with 23 HET (8.6%) and three HOM (1.1%). Nine GSNZ belonged to one family, including the three HOM GSNZ that all had DCM.ConclusionsThe HOM genotype is associated with DCM and premature death in SSNZ and GSNZ.     

Identification of a nonsense mutation in feline ABCB1

The aim of this study was to sequence all exons of the ABCB1 (MDR1) gene in cats that had experienced adverse reactions to P‐glycoprotein substrate drugs (phenotyped cats). Eight phenotyped cats were included in the study consisting of eight cats that experienced central nervous system toxicosis after receiving ivermectin (n = 2), a combination product containing moxidectin and imidacloprid (n = 3), a combination product containing praziquantel and emodepside (n = 1) or selamectin (n = 2), and 1 cat that received the product containing praziquantel and emodepside but did not experience toxicity (n = 1). Fifteen exons contained polymorphisms and twelve exons showed no variation from the reference sequence. The most significant finding was a nonsense mutation (ABCB11930_1931del TC) in one of the ivermectin‐treated cats. This cat was homozygous for the deletion mutation. All of the other phenotyped cats were homozygous for the wild‐type allele. However, 14 missense mutations were identified in one or more phenotyped cats. ABCB11930_1931del TC was also identified in four nonphenotyped cats (one homozygous and three heterozygous for the mutant allele). Cats affected by ABCB11930_1931del TC would be expected to have a similar phenotype as dogs with the previously characterized ABCB1‐1Δ mutation.     

Reproduction traits of heterozygous myostatin knockout sows crossbred with homozygous myostatin knockout boars

Few studies exist on homozygous myostatin gene mutant (MSTN^−/−) pigs, especially on their reproductive ability. We have previously shown that semen quality of homozygous MSTN^−/− boars is comparable to that of wild type (WT). However, no data exist on the reproductive ability of heterozygous MSTN gene mutant (MSTN^+/−) sows. The present study highlights showed that the heterozygous MSTN^+/− sows have delayed pubertal age than WT sows (255.80 ± 6.79 versus 191.10 ± 3.42, respectively). The number of services per pregnancy of heterozygous MSTN^+/− sows is significantly higher than that of WT sows (3.33 ± 0.43 versus 1.60 ± 0.25, respectively). Moreover, although heterozygous MSTN^+/− sows have natural reproduction ability, their litter size was significantly lower than that of WT sows (7.75 ± 0.44 versus 14.25 ± 0.60, respectively). Offsprings generated from heterozygous MSTN^+/− sow and homozygous MSTN^−/− boar were genotyped with the PCR and sequencing method to detect myostatin mutation and to identify whether the piglets are homozygous MSTN^−/− or heterozygous MSTN^+/−. The proportion of homozygous MSTN^−/− piglets was significantly lower than that of heterozygous MSTN^+/− piglets (2.50 ± 0.35 versus 5.25 ± 0.60, respectively). Furthermore, none of the sows presented dystocia, and the phenotype of heterozygous MSTN^+/− piglets was normal. However, 10% homozygous MSTN^−/− piglets died of dyspnoea within 2 hr after birth, 60% of homozygous MSTN^−/− piglets showed large tongues, and 50% had umbilical hernias. In summary, this study for the first time reports the reproduction traits of heterozygous MSTN^+/− sows crossbred with homozygous MSTN^−/− boars. This study will pave the way in a new direction for the breeding and development of super lean meat varieties in the future.     

The influence of demeanor on scores from two validated feline pain assessment scales during the perioperative period

ObjectiveTo evaluate the effects of demeanor on validated pain assessment scales.Study designProspective, blind, clinical trial.Animal populationThirty three adult domestic cats scheduled for orchiectomy.MethodsCats were assessed for pain pre (baseline) and 1, 2, 4 hours postoperatively using two validated pain scales [Composite Measures Pain Scale-Feline (rCMPS-F) and UNESP-Botucatu multidimensional composite pain scale (psychomotor and pain expression subscales; U-B MCPS-psych and -painex)], and a demeanor scale. Return of sternal recumbency and postoperative feeding were recorded. Anesthesia consisted of a single intramuscular injection of dexmedetomidine-ketamine-hydromorphone with intratesticular lidocaine and atipamezole and meloxicam postoperatively. Following data collection, cats were assigned to two groups based on baseline demeanor scores (LO ≤ 5/21, 18 cats; HI ≥ 6/21, 15 cats) and data from each group compared.ResultsBaseline demeanor predicted pain scores with the U-B MCPS-psych scale: baseline [LO 0 (0–0), HI 2 (0–6), p = 0.0005], 1 hour [LO 1 (0–5), HI 3 (1–5), p = 0.02], and 4 hours [LO 0 (0–2), HI 1 (0–6), p = 0.01]. A similar pattern was observed with the rCMPS-F. This resulted in more crossings of the analgesic intervention threshold in the HI group: U-B UNESP-psych (9 versus 1, p = 0.005) and rCMPS-F (23 versus 3, p < 0.0001). In contrast, U-B MCPS-painex scores did not differ between LO/HI groups: baseline (p > 0.99), 1 hour (p = 0.34), 2 hours (p > 0.99) and 4 hours (p = 0.31). LO cats ate sooner (61% versus 33% by 1 hour, p < 0.0001) despite similar times to sternal recumbency (p = 0.48).Conclusions and clinical relevanceDemeanor affected pain assessment with U-B UNESP-psych and rCMPS-F scales, but not U-B UNESP-painex scale. Demeanor had a significant effect on postoperative feeding. These data highlight the potential for demeanor to confound pain assessment.     

Effect of sample volume size and sampling method on feline longitudinal myocardial velocity profiles from color tissue Doppler imaging

ObjectivesThe aims of this study were to compare the effect of sample volume (SV) size settings and sampling method on measurement variability and peak systolic (s′), and early (e′) and late (a′) diastolic longitudinal myocardial velocities using color tissue Doppler imaging (cTDI) in cats.AnimalsTwenty cats with normal echocardiograms and 20 cats with hypertrophic cardiomyopathy.MethodsWe quantified and compared empirical variance and average absolute values of s′, e′ and a′ for three cardiac cycles using eight different SV settings (length 1,2,3 and 5 mm; width 1 and 2 mm) and three methods of sampling (end-diastolic sampling with manual tracking of the SV, end-systolic sampling without tracking, and random-frame sampling without tracking).ResultsNo significant difference in empirical variance could be demonstrated between most of the tested SVs. However, the two settings with a length of 1 mm resulted in a significantly higher variance compared with all settings where the SV length exceeded 2 mm (p < 0.001). There was an overall significant effect of sampling method on the variability of measurements (p = 0.003) and manual tracking obtained the lowest variance. No difference in average values of s′, e′ or a′ could be found between any of the SV settings or sampling methods.ConclusionWithin the tested range of SV settings, an SV length of 1 mm resulted in higher measurement variability compared with an SV length of 3 and 5 mm, and should therefore be avoided. Manual tracking of the sample volume is recommended.     

Prospective Echocardiographic and Tissue Doppler Imaging Screening of a Population of Maine Coon Cats Tested for the A31P Mutation in the Myosin-Binding Protein C Gene: A Specific Analysis of the Heterozygous Status

Background: A mutation in the sarcomeric gene coding for the myosin-binding protein C gene has been identified in a colony of Maine Coon cats with hypertrophic cardiomyopathy (MyBPC3-A31P mutation). However, the close correlation between genotype and phenotype (left ventricular hypertrophy [LVH] and dysfunction) has never been assessed in a large population, particularly in heterozygous (Hetero) cats.
Objectives: To investigate LV morphology and function with echocardiography and tissue Doppler imaging (TDI) in a population of Maine Coon cats tested for the MyBPC3-A31P mutation with focus on Hetero animals.
Animals: Ninety-six Maine Coon cats.
Methods: Prospective observational study. Cats were screened for the MyBPC3-A31P mutation and examined with both echocardiography and 2-dimensional color TDI.
Results: Fifty-two out of 96 cats did not have the mutation (wild-type genotype, Homo WT), 38/96 and 6/96 were Hetero- and homozygous-mutated (Homo M) cats, respectively. Only 11% of Hetero cats (4/38) had LVH and 29% (10/34) of Hetero cats without LVH were >4 years old (4.1–11.5 years). LVH was also detected in 2 Homo WT cats (4%). A significantly decreased ( P < .05) longitudinal E/A (ratio between early and late diastolic myocardial velocities) in the basal segment of the interventricular septum was observed in Hetero cats without LVH (n = 34) compared with Homo WT cats without LVH (n = 50), thus confirming that the Hetero status is associated with regional diastolic dysfunction ( P < .05).
Conclusions: The heterozygous status is not consistently associated with LVH and major myocardial dysfunction. Moreover, Homo WT cats can also develop LVH, suggesting that other genetic causes might be implicated.     

Effect of cilobradine in cats with a first episode of congestive heart failure due to primary cardiomyopathy

IntroductionHeart rate (HR) is often elevated in cats with cardiomyopathies (CMPs). Pharmacologic modulation of HR may reduce cardiac morbidity and mortality.ObjectivesTo investigate the effects of cilobradine vs. placebo, regarding time to cardiac mortality or morbidity in cats with first episode of congestive heart failure (CHF) due to primary CMP.AnimalsThree hundred and sixty-seven client-owned cats with primary CMP that had presented with a first episode of CHF at 50 centers in Europe. Per-protocol population comprised 193 cats (n = 89 cilobradine, n = 104 placebo). An interim analysis for futility was planned.MethodsProspective, randomized, placebo-controlled, double-blinded, multicenter clinical trial. Primary outcome variable was the time to a composite of cardiac mortality or cardiac morbidity.ResultsMedian time to primary outcome was 84 days (95% confidence interval [CI]: 63–219 days) in the cilobradine group (CG) and 203 days in the placebo group (95% CI: 145–377 days) with observed hazard ratio of 1.44, indicating a higher hazard for the CG (P = 0.057). Mean HR was 28 beats per minute (bpm) lower at Day 7 (P < 0.0001) and remained 29 bpm lower at Day 360 (P = 0.026) in the CG than that in the placebo group. Although the number of adverse events did not differ, there were more serious adverse events in the CG.ConclusionsHeart rate reduction by cilobradine in cats with a first episode of CHF due to primary CMP did not reduce cardiac mortality and morbidity.     

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

BackgroundCirculating 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).MethodsNT-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.ResultsNT-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 (ρ = 0.266; P = 0.007) and LV free wall thickness (ρ = 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).ConclusionsNT-proBNP accurately discriminated CHF from respiratory disease causes of dyspnea.     

Azotemia in cats with feline hypertrophic cardiomyopathy: Prevalence and relationships with echocardiographic variables

ObjectivesThe prevalence of renal azotemia in cats with acquired heart disease is not well documented. The aims of this study were therefore (1) to determine the prevalence of azotemia within a hospital population of cats with hypertrophic cardiomyopathy (HCM), and (2) to evaluate the relationship between echocardiographic variables and plasma urea and creatinine.Animals, materials and methods134 client-owned cats were retrospectively studied including 102 cats with HCM and 32 control cats. A complete physical examination, electrocardiography, systolic arterial blood pressure measurement, thoracic radiographs, and echocardiography were performed. Plasma creatinine and urea were determined in all cats. The animal was considered azotemic if plasma creatinine was >1.8 mg/dL and/or urea >65 mg/dL (i.e. BUN> 30 mg/dL).ResultsThe prevalence of azotemia was lower in control cats (25.0%) than in cats with HCM (58.8%) (P = 0.003). No significant differences in plasma urea and creatinine were observed between the HCM and control cats. There was no effect of plasma creatinine and urea on conventional echocardiographic variables in cats with HCM.ConclusionsAzotemia is a frequent finding in cats with HCM but is not dependent on echocardiographic variables.     

Comparison of alfaxalone and propofol on haematological and serum biochemical variables in cats undergoing radiotherapy with sevoflurane maintenance

ObjectiveTo evaluate effects of repeated alfaxalone or propofol administration on haematological and serum biochemical variables in cats undergoing radiotherapy.Study designProspective, block-randomized, clinical trial.AnimalsA group of 39 client-owned cats.MethodsAfter butorphanol (0.2 mg kg^–1) and midazolam (0.1 mg kg^–1) sedation, cats were randomly assigned to receive either alfaxalone or propofol for induction of anaesthesia and sevoflurane maintenance. Cats were anaesthetized daily with the same induction agent for 10–12 days. Complete blood counts, reticulocytes, Heinz body score and serum biochemistry were performed before the first treatment (T1), at T6, T10 and 3 weeks after the final treatment (T21). Cumulative induction agent dose for each cat at each time point was evaluated for an effect on Heinz body score. Data are shown as mean ± standard deviation; p < 0.05.ResultsAt baseline there were no significant differences in signalment or blood variables between groups. A significant decrease in haematocrit of 2.3% ± 0.77 (p = 0.02) between T1-T6 and T1-T10 [mean 4.1% (± 0.78, p < 0.0001)] was detected, with a significant increase in haematocrit of 2.1% ± 0.80 (p = 0.046) between T6-T21 and 4.0% ± 0.8 (p < 0.001) between T10-T21. Heinz body score significantly increased by 1.86 ± 0.616 (p = 0.013) between T1-T10. In the propofol group, reticulocytes increased significantly between T1-T6 [mean 23,090 μL^–1 ± 7670 (p = 0.02)] and T1-T10 [mean 27,440 μL^–1 ± 7990 (p = 0.007)]. Mean cumulative dose at T10 was 19.65 mg kg^–1 ± 5.3 and 43.4 mg kg^–1 ± 14.4 for alfaxalone and propofol, respectively, with no significant effect on Heinz body formation at any time point.Conclusions and Clinical relevanceHaematocrit decreased in both groups with recovery after 3 weeks. Repeated alfaxalone and propofol administration was not associated with marked haematological or serum biochemistry changes.     

Assessment of the diagnostic accuracy of circulating natriuretic peptide concentrations to distinguish between cats with cardiac and non-cardiac causes of respiratory distress

ObjectivesTo determine if serum natriuretic peptide (NP) concentrations could distinguish cardiac from non-cardiac causes of respiratory distress (RD) in cats.AnimalsSeventy-four cats from 1 university hospital were used.MethodsSerum NP concentrations were measured in 41 cats with non-cardiac respiratory distress (RD-NC) and compared to 33 cats with RD due to congestive heart failure (RD + CHF) using sandwich enzyme immunoassays (ELISA).ResultsRD-NC cats had lower (P = 0.0001) median NT-proANP and NT-proBNP concentrations (614 and 45 fmol/mL, respectively) than RD + CHF cats (1690 and 523 fmol/mL, respectively). The area under the curve was 0.88 and 0.96 for the receiver operating curve analysis of the diagnostic accuracy of NT-proANP and NT-proBNP concentrations to discriminate RD + CHF from RD-NC cats (P = 0.036). An optimum cut-off concentration of 986 fmol/mL for NT-proANP and 220 fmol/mL for NT-proBNP accurately discriminated RD-NC from RC + CHF cats with a sensitivity of 93.8% and 93.9% and a specificity of 80.3% and 87.8%, respectively.ConclusionsSerum NP concentrations were different in RD + CHF cats compared to RD-NC cats. Evaluation of circulating NP concentrations may be helpful in the initial approach to cats presenting with respiratory distress, particularly if advances in ELISA technology result in a rapid cage-side test.     

Non-invasive assessment of left ventricular relaxation property using color M-mode-derived intraventricular pressure gradients in cats

IntroductionDiastolic dysfunction is an early clinical feature of feline hypertrophic cardiomyopathy (HCM). The left ventricular filling in early diastole is facilitated by the diastolic intraventricular pressure gradient (IVPG). The study objectives were to evaluate color Doppler M-mode-derived IVPG calculation in cats as a non-invasive assessment of the left ventricular relaxation property to determine the normal ranges of peak IVPG in cats and investigate the influence of left ventricular function and heart rate (HR).AnimalsOne hundred and six client-owned apparently healthy cats.MethodsProspective cross-sectional study. Quantitative analysis of color Doppler M-mode images was used to estimate total and segmental IVPGs non-invasively.ResultsThe total IVPG was 0.76 mmHg (95% reference interval (RI): 0.28–1.29 mmHg), the basal IVPG 0.34 mmHg (95% RI: 0.07–0.63 mmHg), and the mid-apical IVPG 0.42 mmHg (95% RI: 0.15–0.71 mmHg). Total and segmental IVPG increased with HR (P < 0.003), while segmental percent IVPG was HR independent. A short isovolumic relaxation time (IVRT) and a high mitral annular velocity in early diastole were associated with an increase in total IVPG (P = 0.008 and P = 0.009, respectively) adjusted for HR. An increase in IVPG was associated with an increase in mitral inflow velocity (P < 0.001).ConclusionsFeline IVPGs increase with HR and a short IVRT, which was believed to be a normal physiologic adrenergic response associated with an increased sympathetic tone. Future studies of segmental IVPG changes in feline HCM are needed to evaluate the clinical applicability of color Doppler M-mode estimated IVPGs in feline cardiology.