K. Borgeat

Prognostic Indicators in Cats with Hypertrophic Cardiomyopathy

BACKGROUND Left atrial (LA) enlargement, congestive heart failure (CHF), and aortic thromboembolism (ATE) are associated with decreased survival in cats with hypertrophic cardiomyopathy (HCM), but the prognostic value of echocardiographic variables has not been well characterized. HYPOTHESIS/OBJECTIVES We hypothesized that LA echocardiographic variables and assessment of left ventricular (LV) diastolic and systolic function would have prognostic value in cats with HCM. ANIMALS Two hundred eighty-two cats diagnosed with HCM. METHODS Clinical and echocardiographic records of affected cats seen at the Royal Veterinary College from 2004 to 2009 were retrospectively analyzed. Only cats with echocardiographic confirmation of LV diastolic wall thickness ≥ 6 mm were included. Outcomes were obtained from clinical records or referring veterinarians and owners. RESULTS Deaths occurred in 164 cats, of which 107 were believed to have been cardiac deaths. Univariable predictors of an increased risk of cardiac death included older age, absence of a murmur, presence of a gallop sound or arrhythmia, presentation with either CHF or ATE, extreme LV hypertrophy (≥ 9.0 mm), LV fractional shortening (FS%) ≤ 30%, regional wall hypokinesis, increased left atrial size, decreased left atrial function, spontaneous echo-contrast/thrombus or both, absence of left ventricular outflow tract obstruction, and a restrictive diastolic filling pattern. Coxs proportional hazard analysis identified LA dysfunction, low LV systolic function, and extreme LV hypertrophy as independent predictors of decreased cardiac survival time. CONCLUSIONS AND CLINICAL IMPORTANCE Echocardiographic measurement of LA function, extreme LV hypertrophy, and LV systolic function provides important prognostic information in cats with HCM.

Plasma Cardiac Troponin I Concentration and Cardiac Death in Cats with Hypertrophic Cardiomyopathy

Background The use of cardiac biomarkers to assist in the diagnosis of occult and symptomatic hypertrophic cardiomyopathy (HCM) in cats has been established. There is limited data describing their prognostic utility in cats with HCM. Hypothesis Circulating concentrations of N‐terminal B‐type natriuretic peptide (NTproBNP) and cardiac troponin I (cTnI) predict cardiac death in cats with HCM. Animals Forty‐one cats diagnosed with HCM at a veterinary teaching hospital, between February 2010 and May 2011. Methods Prospective investigational study. Plasma samples were collected from cats diagnosed with HCM and concentrations of NTproBNP and cTnI were analyzed at a commercial laboratory. Echocardiographic measurements from the day of blood sampling were recorded. Long‐term outcome data were obtained. Associations with time to cardiac death were analyzed using Cox proportional hazards models. Results When controlling for the presence/absence of heart failure and echocardiographic measures of left atrial size and function, cTnI > 0.7 ng/mL was independently associated with time to cardiac death. In univariable analysis, NTproBNP > 250 pmol/L was associated with cardiac death (P = .023), but this did not remain significant (P = .951) when controlling for the effect of clinical signs or left atrial size/function. Conclusions and Clinical Importance Plasma concentration of cTnI (cutoff >0.7 ng/mL) is a predictor of cardiac death in cats with HCM that is independent of the presence of heart failure or left atrial dilatation.

Arterial Thromboembolism in 250 Cats in General Practice: 2004–2012

Background Population characteristics and outcome of cats with arterial thromboembolism (ATE) managed in general practice (GP) have been poorly described. Hypothesis Cats with ATE presenting to GP are usually euthanized at presentation, but survival times >1 year are possible. Animals Cats with ATE managed by 3 GP clinics in the United Kingdom. Methods Records of cases presenting to GP over a 98‐month period (2004–2012) were reviewed. Cats with an antemortem diagnosis of limb ATE were included. Outcome information was obtained. Results Over 98 months, 250 cats were identified with ATE. Prevalence was approximately 0.3%. At presentation, 153 cats (61.2%) were euthanized, with 68/97 (70.1%) of the remaining cats (27.2% of the total population) surviving >24 hours after presentation. Of these, 30/68 (44.1%) survived for at least 7 days. Hypothermia (HR, 1.44; 95% CI, 1.002–2.07; P = .049) and management by Clinic 2 (HR, 5.53; 95% CI, 1.23–24.8; P = .026) were independent predictors of 24‐hour euthanasia or death. For cats surviving >24 hours, hypothermia (HR, 2.25; 95% CI, 1.12–4.48; P = .021) and failure to receive aspirin, clopidogrel, or both (HR, 8.26; 95% CI, 1.39–50; P = .001) were independent predictors of euthanasia or death within 7 days. For cats that survived ≥7 days, median survival time was 94 (95% CI, 42–164) days, with 6 cats alive 1 year after presentation. Conclusions Although 153/250 cats were euthanized at presentation, 6 cats survived >12 months. No factors were identified that predicted euthanasia on presentation.

Association of Tricuspid Annular Plane Systolic Excursion with Survival Time in Boxer Dogs with Ventricular Arrhythmias

Background Tricuspid annular plane systolic excursion (TAPSE) is a useful estimate of right ventricular function in humans. Reference intervals for dogs have been generated, but the value of measuring TAPSE in other diseases, or investigating the association between TAPSE and outcome, is unknown. Hypothesis TAPSE is lower in Boxer dogs with ≥50 VPCs/24 h on Holter than in dogs with fewer ventricular ectopics, and lower TAPSE is associated with a shorter survival time. Animals Fifty Boxer dogs that presented for investigation of syncope or suspected arrhythmogenic right ventricular cardiomyopathy (ARVC) at a veterinary teaching hospital (2004–2011). Methods Retrospective study. Clinical records, Holter, and echocardiographic data were reviewed. TAPSE was measured in a blinded manner on stored echocardiographic cine‐loops using anatomic M‐mode. Outcome information was obtained and death was classified as cardiac or noncardiac. Survival analysis was performed using Kaplan‐Meier curves and Cox proportional hazards models. Results TAPSE was lower in Boxers with ≥50 VPCs/24 h (13.9 ± 4.04 mm) than Boxers with <50 VPCs/24 h (16.8 ± 3.21 mm; P < .001). TAPSE <15.1 mm was associated with shorter cardiac survival time in all dogs (P = .004) and also in dogs without left ventricular dysfunction (P = .035). When controlling for other variables, including ventricular tachycardia on Holter and left ventricular systolic dysfunction, multivariable analysis showed that TAPSE remained an independent predictor of time to cardiac death (HR >4.09, 95%CI 1.15–16.9, P < .029). Conclusions and Clinical Importance TAPSE offers prognostic value for Boxer dogs, including those with apparently normal systolic function and ≥50 VPCs/24 h on Holter analysis.

Risk factors associated with sudden death vs. congestive heart failure or arterial thromboembolism in cats with hypertrophic cardiomyopathy.

OBJECTIVES To evaluate risk factors associated with different types of cardiac death in cats with hypertrophic cardiomyopathy (HCM). ANIMALS Two hundred fifty-five cats with HCM referred to a veterinary teaching hospital. METHODS This is a retrospective study. Cats with HCM were identified that had either died within 2 years of diagnosis or were known to be alive 2 years after initial examination. Signalment, physical exam, electrocardiographic and echocardiographic data were analyzed separately for association with death due to congestive heart failure (CHF) vs. aortic thromboembolism (ATE) vs. sudden death. RESULTS Within 2 years of follow-up, 23/255 (9.0%) cats had died with ATE, 44/255 (17.3%) cats had died with CHF and 12/255 (4.7%) cats had experienced a sudden death, with 141/255 (55.3%) cats still alive at the end of 2 years. Presence of CHF at presentation and reduced left ventricular fractional shortening (FS%) were independently associated with a CHF death within 2 years of diagnosis. Presence of ATE and reduced left atrial fractional shortening (LA-FS%) were independently associated with dying with ATE within 2 years. No multivariable models were generated for risks of dying a sudden death owing to the low event rate, but syncope at presentation and arrhythmias on auscultation were associated with sudden death on univariable analysis. CONCLUSIONS Asymptomatic cats have a reduced risk of all three types of death. Reduced FS% and a history of CHF independently predict CHF death, and reduced LA-FS% and history of ATE independently predict ATE death. Sudden death is less commonly reported but is associated with syncope.

Retrospective evaluation of moderate-to-severe pulmonary hypertension in dogs naturally infected with Angiostrongylus vasorum

OBJECTIVES The outcome in dogs with pulmonary hypertension associated with natural Angiostrongylus vasorum infection is unclear. This study aimed to report long-term outcome of dogs with A. vasorum and pulmonary hypertension, and to evaluate factors associated with pulmonary hypertension development. It was hypothesised that dogs with pulmonary hypertension had a shorter survival time than dogs without pulmonary hypertension. METHODS Retrospective review of clinical records of dogs diagnosed with A. vasorum. Dogs were classified as having or not having pulmonary hypertension based on clinical signs and imaging findings. Signalment, signs and outcome were recorded. DNA obtained from banked samples was genotyped for the PDE5a:E90K polymorphism, a possible factor in development of pulmonary hypertension. RESULTS The proportion of dogs with moderate-to-severe pulmonary hypertension and A. vasorum infection in the study population was 14 · 6%. No difference in the population characteristics or PDE5a genotype was detected between dogs with and without pulmonary hypertension. Dogs with pulmonary hypertension had a significantly shorter survival time (P = 0 · 006) and a greater risk of death within 6 months of diagnosis (odds ratio 12 · 5, 95% confidence interval 2 · 1 to 74 · 9; P = 0 · 0053). CLINICAL SIGNIFICANCE A. vasorum-associated pulmonary hypertension is an important problem in naturally infected dogs and has a negative effect upon survival.

Mitral Annular Plane Systolic Excursion and Tricuspid Annular Plane Systolic Excursion in Cats with Hypertrophic Cardiomyopathy

Background Left ventricular (LV) systolic dysfunction is associated with increased risk of death in cats with hypertrophic cardiomyopathy (HCM). Mitral and tricuspid annular plane systolic excursion (MAPSE and TAPSE, respectively) are measures of longitudinal systolic function and are reduced in human patients with HCM. Hypotheses Cats with HCM have lower MAPSE and TAPSE compared to control cats; lower MAPSE and TAPSE are associated with the presence of congestive heart failure (CHF) and reduced survival time. Animals 64 cats with HCM and 27 healthy cats. Forty‐five cats with HCM were not showing clinical signs, and 19 had CHF. Methods Retrospective study. Anatomic M‐mode from the left apical 4‐chamber view was used to record MAPSE from the free wall (MAPSE FW) and septum (MAPSE IVS) and TAPSE. Results Compared to controls, cats with HCM had lower MAPSE IVS (controls 5.2 [4.6–5.6] mm, asymptomatic HCM 4.7 [4.1–5.2] mm, HCM with CHF 2.6 [2.5–3.2] mm, P < .001), MAPSE FW (controls 5.9 [5.3–6.2] mm, asymptomatic HCM 4.7 [4.1–5.1] mm, HCM with CHF 2.8 [2.4–3.2] mm) and TAPSE (controls 8.6 [7.4–10.2] mm, asymptomatic HCM 7.2 [6.3–8.2] mm, HCM with CHF 4.6 [4.1–5.4] mm), with the lowest in the CHF group. Univariate survival analysis showed a shorter survival in cats displaying lower MAPSE IVS, MAPSE FW, and TAPSE. Conclusions and Clinical Importance MAPSE and TAPSE were lower in cats with HCM than in control cats and were lowest in CHF, suggesting that systolic longitudinal dysfunction is present in cats with HCM. MAPSE and TAPSE have potential prognostic significance.

Cardiac biomarkers in cats.

Cardiac biomarkers have been used in cats as part of the clinical assessment of heart disease for over a decade. They are widely available to practitioners through commercial reference laboratories. The evidence base for the use of cardiac biomarkers (primarily N-terminal pro-B type natriuretic peptide and cardiac troponin I) in cats is comprehensively reviewed in this article, focusing on each of six specific areas: distinguishing cardiac from non-cardiac causes of respiratory distress; measurement of cardiac biomarkers in urine and pleural fluid; identification of occult cardiomyopathy; effects of systemic disease on circulating concentrations of cardiac biomarkers; point-of-care biomarker testing, and the possible prognostic utility of cardiac biomarker measurement.

Transient Myocardial Thickening in Cats Associated with Heart Failure

Background Cats with hypertrophic cardiomyopathy (HCM) and congestive heart failure (CHF) can have resolution of both left ventricular hypertrophy and CHF. Objectives To describe the clinical characteristics of cats with transient myocardial thickening (TMT) and CHF compared with a control population of cats without resolution of HCM. Animals A total of 21 cats with TMT, 21 cats with HCM. Methods Retrospective study. Clinical records at 4 veterinary centers were searched for TMT cases and a control group of cats with HCM and CHF. TMT was defined as initial maximal left ventricular wall thickness (LVWT) ≥6 mm with left‐sided CHF, with subsequent resolution of CHF, reduction in left atrium/aorta (LA/Ao), and LVWT<5.5 mm. HCM was defined as persistent LVWT ≥6 mm. Results Cats with TMT were younger (2 [0.4–11.4] years) than cats with HCM (8 [1.6–14] years) (P < 0.0001), and antecedent events were more common (15/21 versus 6/21, respectively) (P = 0.01). In cats with TMT, LVWT normalized from 6.8 [6.0–9.7] mm to 4.8 [2.8–5.3] mm and LA/Ao decreased from 1.8 [1.6–2.3] to 1.45 [1.2–1.7] after a mean interval of 3.3 (95% CI: 1.8–4.7) months. CHF recurred in 1 of 21 TMT and 15 of 21 cats with HCM. Cardiac treatment was discontinued in 20 of 21 cats with TMT and 0 of 21 HCM cats. All cats with TMT survived, whereas 8 of 19 cats with HCM died during the study period. Conclusions and Clinical Importance TMT occurs in younger cats, and antecedent events are common. The prognosis is better in cats with CHF associated with TMT than HCM.

The influence of clinical and genetic factors on left ventricular wall thickness in Ragdoll cats

OBJECTIVES To investigate the effect of various genetic and environmental modifiers on left ventricular (LV) wall thickness in a cohort of cats genotyped for the myosin binding protein C3 mutation (MYBPC3). ANIMALS Sixty-four Ragdoll cats. METHODS All cats were screened for HCM with echocardiography and genotyping for the HCM-associated MYBPC3:R820W mutation. Cats were also genotyped for previously identified variant polymorphisms of the angiotensin-converting enzyme (ACE) and cardiac beta-adrenergic receptor (ADRB1) genes. Plasma N-terminal pro-B-type natriuretic peptide and cardiac troponin I were also measured. Associations were evaluated between genotype (MYBPC3 negative/positive, and ACE and ADRB1 negative/heterozygous/homozygous), patient factors (body weight, age and sex) and echocardiographic measurements of LV wall thickness. RESULTS Male cats had greater maximum wall thickness (LVmax; 5.8 mm, IQR 5.1-6.4 mm) than females (4.7 mm, IQR 4.4-5.3 mm, p = 0.002). Body weight positively correlated with LVmax (ρ = 0.604, p < 0.001). The MYBPC3:R820W-positive cats had a greater LVmax (5.44 mm, IQR 4.83-6.28 mm) than the negative cats (4.76 mm, IQR 4.36-5.32 mm, p = 0.001). Also, the ACE polymorphism genotype was associated with LVmax: the homozygous cats (5.37 mm, IQR 5.14-6.4 mm) had greater LVmax than the heterozygous cats (4.73 mm, IQR 4.41-5.55 mm, p = 0.014). Only the MYBPC3 genotype and body weight were independently associated with wall thickness in multivariable analysis. CONCLUSIONS This study provides evidence that the MYBPC3:R820W mutation is independently associated with LV wall thickness in Ragdoll cats. Body weight is also independently associated with maximum LV wall thickness, but is not currently accounted for in HCM screening. In addition, other genetic modifiers may be associated with variation in LV wall thickness in Ragdolls.