Naturally occurring torsades de pointes and QT interval prolongation in a domestic cat.

A 10-year-old male American Shorthair cat was presented after a witnessed syncopal event. A Holter monitor demonstrated a long QT interval and revealed a rhythm characteristic of torsades de pointes (TdP) coincident with a bout of syncope. On subsequent Holter monitor recordings, sotalol did not prolong the QT interval further and did not reduce the severity of the underlying ventricular tachyarrhythmias, but no TdP was identified. When another syncopal event occurred, sotalol was discontinued, and oral amiodarone and magnesium were started. This resulted in improvement in the ventricular tachyarrhythmia. No syncopal events occurred in the ensuing 3 months, but the cat died of an unrelated disease shortly after. This is the first report of naturally occurring torsades de pointes in a domestic cat.

Congenital cardiac defects in neonatal foals: 18 cases (1992-2007).

BACKGROUND: Literature available regarding congenital cardiac defects in foals is limited to reports of individual cases or small case series. OBJECTIVE: To describe the clinical, echocardiographic, and necropsy findings and breed predilection of congenital cardiac defects in neonatal foals. ANIMALS: Eighteen foals < 15 days of age with 1 or more congenital cardiac defects. METHODS: Medical records of foals diagnosed with congenital cardiac defects at the William R. Pritchard Veterinary Medical Teaching Hospital were reviewed. Data collected included history, signalment, clinical signs, laboratory data, diagnostic and necropsy results, and outcome. RESULTS: Arabian foals represented 39% of cases with congenital cardiac defects and were significantly (P = .004) overrepresented (OR = 4.7 [CI: 1.8-12.4]) compared with the general hospital population. Ventricular septal defect (VSD) (14/18), tetralogy of Fallot (5/18), and tricuspid valve atresia (4/18) were the most common defects identified. A > or = 3/6 heart murmur (14/ 14) accompanied by tachycardia (14/17), tachypnea (17/17), and cyanosis of mucous membranes (7/16) were the most common clinical signs. Concurrent congenital defects were common (9/18). Two foals, both with VSD, survived for > or = 8 years after diagnosis and 1 was a successful performance horse. CONCLUSIONS AND CLINICAL RELEVANCE: Arabian horses appear to have a predisposition for cardiac defects. The presence of a loud murmur (> or = 3/6), cyanotic membranes, and tachycardia or tachypnea in a neonatal foal should warrant thorough evaluation of the heart for congenital defects. Foals with cardiac defects should be closely evaluated for concurrent congenital defects in other body systems.

Assisted reproduction mediated resurrection of a feline model for Chediak-Higashi syndrome caused by a large duplication in LYST.

Chediak-Higashi Syndrome (CHS) is a well-characterized, autosomal recessively inherited lysosomal disease caused by mutations in lysosomal trafficking regulator (LYST). The feline model for CHS was originally maintained for ~20 years. However, the colonies were disbanded and the CHS cat model was lost to the research community before the causative mutation was identified. To resurrect the cat model, semen was collected and cryopreserved from a lone, fertile,  CHS carrier male. Using cryopreserved semen, laparoscopic oviductal artificial insemination was performed on three queens, two queens produced 11 viable kittens. To identify the causative mutation, a fibroblast cell line, derived from an affected cat from the original colony, was whole genome sequenced. Visual inspection of the sequence data identified a candidate causal variant as a ~20 kb tandem duplication within LYST, spanning exons 30 through to 38 (NM_001290242.1:c.8347-2422_9548 + 1749dup). PCR genotyping of the produced offspring demonstrated three individuals inherited the mutant allele from the CHS carrier male. This study demonstrated the successful use of cryopreservation and assisted reproduction to maintain and resurrect biomedical models and has defined the variant causing Chediak-Higashi syndrome in the domestic cat.

Myocardial failure in cats associated with low plasma taurine: a reversible cardiomyopathy.

Thousands of pet cats die each year with dilated cardiomyopathy, the cause of which is unknown. Although taurine is present in millimolar concentrations in the myocardium of all mammals, taurine depletion has not previously been associated with a decrease in myocardial function in any species. In this study, low plasma taurine concentrations associated with echocardiographic evidence of myocardial failure were observed in 21 cats fed commercial cat foods and in 2 of 11 cats fed a purified diet containing marginally low concentrations of taurine for 4 years. Oral supplementation of taurine resulted in increased plasma taurine concentrations and was associated with normalization of left ventricular function in both groups of cats. Since myocardial concentrations of taurine are directly related to plasma concentrations and low plasma concentrations were found to be associated with myocardial failure in cats, a direct link between decreased taurine concentration in the myocardium and decreased myocardial mechanical function is proposed.

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, alpha tropomyosin, actin, and beta-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.

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 Student's 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.

The effect of hydration status on the echocardiographic measurements of normal cats.

BACKGROUND: Diagnosis of cardiomyopathy of cats is based on 2-dimensional (2D) echocardiography. However, circulating fluid volume largely determines diastolic cardiac chamber dimensions, and reduced diastolic volume in other species results in what has been called "pseudohypertrophy of the ventricular myocardium." HYPOTHESIS: Altered hydration produces changes on 2D echocardiography that may confound the diagnosis or severity assessment of cardiomyopathy of cats. ANIMALS: Ten normal colony-sourced mixed breed cats were included. METHODS: Cats were examined by echocardiography at baseline and at completion of 3 protocols (volume depletion and maintenance-rate and anesthetic-rate IV fluid administration) applied in randomized crossover design with a 6-7 day washout period. RESULTS: Volume depletion increased diastolic left ventricular interventricular septal (IVSd) and free wall diameter (4.5 +/- 0.4 to 5.8 +/- 0.6 mm; P < .001) with wall thickness exceeding 6 mm in 4 cats. Diastolic left ventricular internal diameter (LVIDd) decreased, and reduction in systolic left ventricular internal diameter (LVIDs) produced end-systolic cavity obliteration in 7 cats. Left-atrial-to-aortic-root ratio (LA: Ao, 1.4 +/- 0.2 to 1.2 +/- 0.1, P < .05) and left atrial area in diastole (LAAd) decreased with volume depletion. Maintenance-rate IV fluid administration increased LAAd and fractional shortening (FS%). Anesthetic-rate IV fluid administration increased LVIDd, FS%, LAAd, and LA:Ao ratios (to 1.7 +/- 0.1, P < .01), producing an LA: Ao ratio above normal limits in 6 cats. A systolic heart murmur developed with administration of fluid at maintenance (n = 1) and anesthetic rates (n = 6). CONCLUSIONS: Altered hydration status produces changes in the echocardiographic examination of normal cats that may lead to an erroneous diagnosis of cardiomyopathy or mask its presence. Hydration status should be considered during echocardiographic examination in cats.

Echocardiographic Features of Giant Right Atrial Diverticulum in a Dog.

A 12-year-old spayed female miniature Poodle presented for coughing, respiratory distress, and anorexia. After thoracentesis for pleural effusion, radiography revealed an enlarged cardiac silhouette with a bulge in the area of the body of the right atrium. Echocardiography revealed an anechoic chamber-like cavity lateral to the right atrium that communicated with the right atrium through a 13 mm defect in the right atrial free wall. Contrast echocardiography and color flow Doppler were used to prove that the cavity communicated with the right atrium. The cavity was diagnosed as a giant right atrial diverticulum.

Balloon Valvuloplasty of Tricuspid Stenosis: A Retrospective Study of 5 Labrador Retriever Dogs.

BACKGROUND: There are limited reports of severe tricuspid valve stenosis in dogs and limited data regarding treatment and outcome. OBJECTIVE: To evaluate clinical signs, echocardiographic features, and outcome of balloon valvuloplasty (BV) in dogs with severe tricuspid valve stenosis (TVS) in which BV was attempted. ANIMALS: Five client-owned dogs with severe TVS. METHODS: Records were retrospectively reviewed and data collected regarding signalment, clinical signs, diagnostic findings, procedures, and outcome. RESULTS: All dogs were Labrador Retrievers. Presenting complaints included episodic weakness/syncope (4/5), abdominal distension (4/5), lethargy (2/5), and exercise intolerance (2/5). The median and range of measurements before BV were as follows: TV mean velocity 1.5 m/s (range 1.4-1.7 m/s); velocity-time integral (VTI) 79.8 cm (42.4-99.1 cm); and TV maximum velocity 2.9 m/s (2.3-3.2 m/s). Measurements (available for 3 of 5 dogs) after BV were as follows: TV mean velocity 1.15 m/s (0.9-1.4 m/s); VTI 44.95 cm (41.4-54.8 cm); and TV maximum velocity 1.15 m/s (1.9-2.3 m/s). The procedure was attempted in all dogs and completed in 4/5 dogs. The largest balloon diameter ranged from 15 mm to 25 mm, and length ranged from 4 cm to 5 cm. Right atrial pressure decreased in 4/5 dogs. All but 1 dog had clinical improvement after BV, but recurrence of clinical signs occurred (2/5). Tricuspid regurgitation worsened in 1 dog culminating in right heart failure and euthanasia. CONCLUSIONS AND CLINICAL IMPORTANCE: BV can be an effective treatment; however, clinical signs can recur. Right heart failure due to worsened TR is a potential complication in dogs with pre-existing moderate-to-severe TR.

Naturally Occurring Biventricular Noncompaction in an Adult Domestic Cat.

A definitively diagnosed case of left ventricular noncompaction (LVNC) has not been previously reported in a non-human species. We describe a Maine Coon cross cat with echocardiographically and pathologically documented LVNC. The cat was from a research colony and was heterozygous for the cardiac myosin binding protein C mutation associated with hypertrophic cardiomyopathy (HCM) in Maine Coon cats (A31P). The cat had had echocardiographic examinations performed every 6 months until 6 years of age at which time the cat died of an unrelated cause. Echocardiographic findings consistent with LVNC (moth-eaten appearance to the inner wall of the mid- to apical region of the left ventricle (LV) in cross section and trabeculations of the inner LV wall that communicated with the LV chamber) first were identified at 2 years of age. At necropsy, pathologic findings of LVNC were verified and included the presence of noncompacted myocardium that consisted of endothelial-lined trabeculations and sinusoids that constituted more than half of the inner part of the LV wall. The right ventricular (RV) wall also was affected. Histopathology identified myofiber disarray, which is characteristic of HCM, although heart weight was normal and LV wall thickness was not increased.

Use of Anti-Thymocyte Globulin for Induction Therapy in Cardiac Transplantation: A Review.

The most common causes of death after heart transplantation (HTx) include acute rejection and multi-organ failure in the early period and malignancy and cardiac allograft vasculopathy (CAV) in the late period. Polyclonal antibody preparations such as rabbit anti-thymocyte globulin (ATG) may reduce early acute rejection and the later occurrence of CAV after HTx. ATG therapy depletes T cells, modulates adhesion and cell-signaling molecules, interferes with dendritic cell function, and induces B-cell apoptosis and regulatory and natural killer T-cell expansion. Evidence from animal studies and from retrospective clinical studies in humans indicates that ATG can be used to delay calcineurin inhibitor (CNI) exposure after HTx, thus benefiting renal function, and to reduce the incidence of CAV and ischemia-reperfusion injury in the transplanted heart. ATG may reduce de novo antibody production after HTx. ATG does not appear to increase cytomegalovirus infection rates with longer prophylaxis (6-12 months). In addition, ATG may reduce the risk of lymphoproliferative disease and does not appear to confer an additive effect on acquiring lymphoma after HTx. Randomized, controlled trials may provide stronger evidence of ATG association with patient survival, graft rejection, renal protection through delayed CNI initiation, as well as other benefits. It can also help establish optimal dosing and patient criteria to maximize treatment benefits.

Combined Heart and Kidney Transplantation: A 23-Year Experience.

BACKGROUND: We report clinical experience with combined heart and kidney transplantation (HKTx) over a 23-year time period. METHODS: From June 1992 to August 2015, we performed 83 combined HKTx procedures at our institution. We compared the more recent cohort of 53 HKTx recipients (group 2, March 2009 to August 2015) with the initial 30 previously reported HKTx recipients (group 1, June 1992 to February 2009). Pre-operative patient characteristics, peri-operative factors, and post-operative outcomes including survival were examined. RESULTS: The baseline characteristics of the two groups were similar, except for a lower incidence of ethanol use and higher pre-operative left-ventricular ejection fraction, cardiac output, and cardiac index in group 2 when compared with group 1 (P = .007, .046, .037, respectively). The pump time was longer in group 2 compared with group 1 (153.30 ± 38.68 vs 129.60 ± 37.60 minutes; P = .007), whereas the graft ischemic time was not significantly different between the groups, with a trend to a longer graft ischemic time in group 2 versus group 1 (195.17 ± 45.06 vs 178.07 ± 52.77 minutes; P = .056, respectively). The lengths of intensive care unit (ICU) and hospital stay were similar between the groups (P = .083 and .39, respectively). In addition, pre-operative and post-operative creatinine levels at peak, discharge, 1 year, and 5 years and the number of people on post-operative dialysis were similar between the groups (P = .37, .75, .54, .87, .56, and P = .139, respectively). Overall survival was not significantly different between groups 2 and 1 for the first 5 years after transplant, with a trend toward higher survival in group 2 (P = .054). CONCLUSIONS: The most recent cohort of combined heart and kidney transplant recipients had similar ICU and hospital lengths of stay and post-operative creatinine levels at peak, discharge, and 1 and 5 years and a similar number of patients on post-operative dialysis when compared with the initial cohort. Overall survival was not significantly different between the later and earlier groups, with a trend toward higher overall survival at 5 years in the more recent cohort of patients. In selected patients with co-existing heart and kidney failure, combined heart and kidney transplantation is safe to perform and has excellent outcomes.

Immediate and late outcomes of transarterial coil occlusion of patent ductus arteriosus in dogs.

Records from dogs (n = 125) that underwent attempted transarterial coil occlusion of patent ductus arteriosus (PDA) at the University of California, Davis, between 1998 and 2003, were reviewed, and a subset of these dogs (n = 31) in which the procedure was performed at least 12 months earlier were reexamined to determine long-term outcome. Coil implantation was achieved in 108 dogs (86%). Despite immediate complete ductal closure in only 34% of dogs, the procedure was hemodynamically successful as evidenced by a reduction in indexed left ventricular internal diameter in diastole (LVIDd; P < .0001), fractional shortening (P < .0001), and left atrial to aortic ratio (LA: Ao; P = .022) within 24 hours. Complete ductal closure was documented in 61% of dogs examined 12 to 63 months after coil occlusion. Long-standing residual ductal flow in the other 39% of dogs was not associated with increased indexed LVIDd or LA: Ao and was not hemodynamically relevant. Repeat intervention was deemed advisable in only 4 dogs with persistent (n = 1) or recurrent (n = 3) ductal flow. Complications included aberrant embolization (n = 27), death (n = 3), ductal reopening (n = 3), transient hemoglobinuria (n = 2), hemorrhage (n = 1), aberrant coil placement (n = 1), pulmonary hypertension (n = 1), and skin abscessation (n = 1). Serious infectious complications did not occur despite antibiotic administration to only 40% of these dogs. Transarterial coil occlusion was not possible in 14 dogs (11%) because of coil instability in the PDA and was associated with increased indexed minimum ductal diameter (P = .03), LVIDd (P = .0002), LVIDs (P = 0.001), and congestive left heart failure (P = .03) reflecting a relatively large shunt volume.

Atrial Fibrillation as a Prognostic Indicator in Medium to Large-Sized Dogs with Myxomatous Mitral Valvular Degeneration and Congestive Heart Failure.

BACKGROUND: The prevalence and prognostic importance of atrial fibrillation (AF) on survival in nonsmall breed dogs with myxomatous mitral valvular disease (MMVD) and congestive heart failure (CHF) remain unknown. AIM: To identify the prevalence of AF in nonsmall breed dogs with CHF because of MMVD and to characterize the impact of AF on survival outcome. ANIMAL: Sixty-four client-owned dogs (>15 kg) with MMVD and CHF. METHODS: Retrospective review of medical records for dogs weighing >15 kg with MMVD treated for CHF. RESULTS: Thirty-three dogs presented with AF or developed AF during follow-up examinations, and 31 dogs were free of AF until cardiac-related death. For dogs with AF, median survival time (MST) was 142 days (range: 9-478) while dogs without AF lived 234 days (range: 13-879 days). AF increased risk of cardiac-related death (HR = 2.544; 95% CI = 1.41-4.59; P = .0019) when compared to dogs without AF. MST was significantly prolonged for dogs with AF whose rates were adequately controlled (<160 bpm; 171 days; n = 13) when compared to dogs that failed to respond to negative chronotropic agents (61 days; n = 20; P = .032). The administration of combination treatment (diltiazem and digoxin) significantly decreased median HR to 144 bpm (range: 84-218 bpm) in dogs with AF and significantly prolonged MST (diltiazem+digoxin: 130 days versus diltiazem: 35 days, P = .0241) when compared to diltiazem alone. CONCLUSIONS AND CLINICAL IMPORTANCE: Inadequately controlled AF is associated with a higher rate of mortality. Optimization of therapeutic strategies for the rate control of AF remains determined.

Familial hypertrophic cardiomyopathy in maine coon cats: an animal model of human disease.

BACKGROUND: A naturally occurring animal model of familial hypertrophic cardiomyopathy (FHCM) is lacking. We identified a family of Maine coon cats with HCM and developed a colony to determine mode of inheritance, phenotypic expression, and natural history of the disease. METHODS AND RESULTS: A proband was identified, and related cats were bred to produce a colony. Affected and unaffected cats were bred to determine the mode of inheritance. Echocardiography was used to identify affected offspring and determine phenotypic expression. Echocardiograms were repeated serially to determine the natural history of the disease. Of 22 offspring from breeding affected to unaffected cats, 12 (55%) were affected. When affected cats were bred to affected cats, 4 (45%) of the 9 were affected, 2 (22%) unaffected, and 3 (33%) stillborn. Findings were consistent with an autosomal dominant mode of inheritance with 100% penetrance, with the stillborns representing lethal homozygotes that died in utero. Affected cats usually did not have phenotypic evidence of HCM before 6 months of age, developed HCM during adolescence, and developed severe HCM during young adulthood. Papillary muscle hypertrophy that produced midcavitary obstruction and systolic anterior motion of the mitral valve was the most consistent manifestation of HCM. Cats died suddenly (n=5) or of heart failure (n=3). Histopathology of the myocardium revealed myocardial fiber disarray, intramural coronary arteriosclerosis, and interstitial fibrosis. CONCLUSIONS: HCM in this family of Maine coon cats closely resembles the human form of FHCM and should prove a valuable tool for studying the gross, cellular, and molecular pathophysiology of the disease.

Intramyocardial pressure and distribution of coronary blood flow during systole and diastole in the horse.

Transmural myocardial blood flow was measured with microspheres in systole and in diastole, along with intramyocardial pressure, in seven anaesthetised horses. Intramyocardial pressures were measured with a miniature manometer implanted in the tip of a 16-gauge needle. Peak systolic intramyocardial pressure decreased from subendocardium to subepicardium and never exceeded intraventricular pressure. Systolic blood flow decreased from epicardium to endocardium where it did not differ from zero. Diastolic blood flow increased from epicardium to subendocardium, but then decreased in the most endocardial layer to a level not different from the immediate subepicardial layer. The horse was a useful model for studying these parameters because the ventricular walls are so thick and the heart rate is so slow that injections may be made during various phases of the cardiac cycle. These results of transmural myocardial blood flow and intramyocardial pressure measured in the same animal are identical with those of others, except for the reduction in subendocardial blood flow compared with the layers just epicardial to that.