J Vet Intern Med 2013;27:1427–1436
Prognostic Indicators in Cats with Hypertrophic Cardiomyopathy J.R. Payne, K. Borgeat, D.J. Connolly, A. Boswood, S. Dennis, T. Wagner, P. Menaut, I. Maerz, D. Evans, V.E. Simons, D.C. Brodbelt, and V. Luis Fuentes 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. Cox’s 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. Key words: Echocardiography; Feline; Hypertrophic cardiomyopathy; Survival.
ypertrophic cardiomyopathy (HCM) is defined as a hypertrophied, nondilated left ventricle (LV) in the absence of other systemic or cardiac disease capable of producing a similar degree of hypertrophy.1 It is the most common familial heart disease in humans2 and the most commonly diagnosed myocardial disease in cats.3 Hypertrophic cardiomyopathy is a heterogeneous disease, both in terms of presentation and outcome. Some affected cats are presented with signs of congestive heart failure (CHF) or thromboembolism, and some cats die suddenly. Other affected cats can have long survival times and die of noncardiac causes.4–8 Prognostic factors have been reported in a number of retrospective studies of HCM in cats.5,7–11 Factors
H
From the Clinical Sciences and Services, Royal Veterinary College, Hatfield, Hertfordshire UK (Payne, Borgeat, Connolly, Boswood, Simons, Brodbelt, Luis Fuentes); the School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA (Dennis); the Southern Counties Veterinary Specialists LLP, Ringwood, Hampshire UK (Wagner); the Clinique V et erinaire, Aquivet, Eysines, France (Menaut); the Klinik fur Kleintiere (Innere Medizin), Justus-Liebig-University Giessen, Giessen, Germany (Maerz); and the Ash Tree Veterinary Practice, Market Harborough, Leicestershire UK (Evans). Meeting, if any, at which the paper was presented: ECVIM-CA, Toulouse, September 2010 (diastolic function in part of this cohort); 2012 ACVIM Forum, New Orleans, LA (overall survival in this cohort). Corresponding author: V. Luis Fuentes, Clinical Sciences and Services, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire, AL9 7TA, UK; e-mail: [email protected].
Submitted October 10, 2012; Revised July 31, 2013; Accepted September 3, 2013. Copyright © 2013 by the American College of Veterinary Internal Medicine 10.1111/jvim.12215
Abbreviations: Adur:ARdur
ATE CHF CVs E:A E:E′ E′:A′ FS% HCM IVRT LA:Ao LAA LAD
LA-EF% LA-FS% LA LV LVWd MR QMHA S:D SAM SEC
ratio of the duration of the late filling transmitral wave (Adur) to the duration of the pulmonary venous atrial reversal wave (ARdur) arterial thromboembolism congestive heart failure coefficients of variation ratio of mitral inflow peak early filling (E) to late filling (A) velocities ratio of mitral inflow peak early filling to early diastolic tissue Doppler mitral annular velocity ratio of early diastolic tissue Doppler mitral annular velocity to the late diastolic mitral annular velocity left ventricular fractional shortening hypertrophic cardiomyopathy isovolumic relaxation time ratio of diastolic left atrial diameter to aortic root diameter measured from a short axis image left auricular appendage velocity the diameter of the left atrium measured parallel with the mitral annulus in the last frame before mitral valve opening total left atrial ejection fraction total left atrial fractional shortening left atrial left ventricle end-diastolic left ventricular septal or free wall thickness mitral regurgitation Queen Mother Hospital for Animals ratio of the pulmonary venous peak systolic (S) to peak diastolic (D) velocity systolic anterior motion of the mitral valve spontaneous echo-contrast
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suggested to be associated with a worse outcome have included the presence of clinical signs at diagnosis,5,8,10,11 left atrial (LA) enlargement,7–10,12 and increased age at diagnosis.8,10,12 Certain breeds may have shorter survival times, including the Ragdoll10 and Maine Coon.11 An early study found that a heart rate ≥200 bpm at initial diagnosis was negatively associated with survival,5 but this has not been demonstrated in subsequent studies.8,10 Systolic anterior motion (SAM) is a negative prognostic indicator in people,13–15 but the prognostic effect in cats remains unclear,7,8,10 because there are no prospective longitudinal studies of SAM in cats, and the long-term relationship between outcome and the presence or absence of dynamic LV outflow tract obstruction has not been established. Maximal LV wall thickness was found to be greater in cats that later died because of their cardiac disease compared with survivors in another study.7 Prognosis has not been found to be linked to sex5,10 or body weight.5 In asymptomatic cats, the administration of atenolol has not been found to influence survival to 5 years post diagnosis.12 In HCM of humans, and other cardiac conditions, echocardiographic measures are used routinely as prognostic indicators. These include measures of LA function,16 LV systolic function,17–19 and diastolic function.20–28 Although LA enlargement is considered a very important prognostic indicator in cats with HCM,7–10 little has been done to investigate other echocardiographic markers of prognosis. We hypothesized that although LA echocardiographic variables would provide prognostic information in cats with HCM, assessment of left ventricular diastolic and systolic function would provide
additional prognostic value. The aim of this study was, therefore, to investigate the prognostic value of echocardiographic variables in cats with HCM.
Materials and Methods Cases of HCM were identified by searching the electronic patient records of cats seen at the Royal Veterinary College, Queen Mother Hospital for Animals (QMHA) between June 2004 and August 2009. Cats were included if a diagnosis of HCM had been made by a board-certified cardiologist or a cardiology resident supervised by a board-certified cardiologist based on 2D or M-mode echocardiography or botha and if follow-up information was available. Cats were excluded from the study if they had a known diagnosis of hyperthyroidism or hypertension, defined as either systolic blood pressure ≥180 mmHg; systolic blood pressure ≥160 mmHg with retinal changes suggestive of hypertension; medically controlled hypertension; or where renal disease was present and blood pressure had not been determined. The first visit date was defined as the date of the first echocardiographic examination. Cats with a prior diagnosis of HCM were not excluded, but data were taken from the first visit with an echocardiographic examination within the study period rather than the original diagnosis date. The medical records for each cat were reviewed for date of birth, sex, breed, and date of first visit to the QMHA, with age calculated at that visit. Physical examination findings were recorded, as well as systolic arterial pressureb and serum total thyroxine concentrations, where available. Clinical status at presentation was recorded (Table 1) and grouped into “asymptomatic” (cats presenting asymptomatically, with concurrent disease, with concurrent respiratory disease, or with noncardiac chylothorax), “syncope,” “CHF” (cats presenting with CHF or chylothorax of a cardiac cause), and “ATE” (cats presenting with ATE with or without CHF). Cats with exertional open-mouth breathing were not analyzed because of small numbers. Cats with HCM with “non-cardiac chylothorax” were defined as having persistently normal LA size and function despite progressive or
Table 1. Definitions of categorization of clinical signs at presentation. Clinical Status at Presentation Asymptomatic Concurrent disease Concurrent respiratory disease
Syncope Exertional open-mouth breathing Congestive heart failure
Chylothorax Noncardiac chylothorax Arterial thromboembolism
Definition Referred for investigation of a murmur, gallop, or arrhythmia, but without clinical signs Referred for investigation of noncardiac disease, but cardiac disease suspected during hospitalization. No clinical signs referable to cardiac disease Referred for investigation of respiratory disease, but cardiac disease suspected during hospitalization. Primary respiratory disease subsequently confirmed on further investigations Episodes described as syncopal or seizure-like activity. No noncardiac cause for syncope identified Open-mouth breathing only during periods of excitement, stress, or exercise Any of the following: present or previous radiographic evidence of pulmonary edema; present or previous radiographic/ultrasonographic evidence of pleural or pericardial effusion; or severe tachypnea that showed a clear response to furosemide administration Milky white-colored pleural effusion, with triglyceride concentrations exceeding serum concentrations and the absence of infectious organisms identified on fluid analysis Chylothorax with normal atrial chamber dimensions and normal left atrial function Limb: Sudden onset of lower motor neuron deficits in one or more limbs diagnosed as arterial thromboembolism by attending clinician Brain: Magnetic resonance imaging findings of a well-demarcated lesion, hyperintense on T2-weighted image Mesenteric: History of acute onset abdominal pain, high creatine kinase levels, and echocardiographic evidence of spontaneous echo-contrast in the left atrium
Prognostic Indicators in Cats with HCM persistent chylothorax. Presence of arrhythmias was determined from available ECG recordings (6-lead, Holter, or both) and by reviewing the concurrent ECG recorded during echocardiography. Arrhythmias were classified as “bradyarrhythmias,” “supraventricular arrhythmias,” “ventricular arrhythmias,” or both “supraventricular and ventricular arrhythmias.” All echocardiographic examinations were reviewed and remeasured by 1 board-certified cardiologist (VLF) or a resident (KB). Measurements were obtained only from images with optimal image quality with average values reported from at least 3 cardiac cycles except for maximal 2D LV end-diastolic wall thickness, for which the maximum measurement of at least 3 cardiac cycles was reported. Left ventricular hypertrophy was defined as LV septal or free wall end-diastolic thickness ≥6 mm,7 whether measured from 2D or M-mode images.29 Otherwise, M-mode images were used only to obtain LV fractional shortening (FS%) values, and 2D images were used for measuring maximal LV end-diastolic wall thickness from either the septum or free wall. The presence of any left ventricular regional wall hypokinesis was noted, based subjectively on 2D images and defined as a region of LV wall that was thinner than the rest of the LV, with minimal excursion or moving asynchronously with the rest of the ventricle. Left atrial size was assessed by 2 separate methods, LA:Ao and LAD. LA:Ao was obtained from a 2D right parasternal short-axis view to calculate the ratio of LA diameter to aortic root diameter measured at the onset of the QRS.28 LAD was measured from a right parasternal long-axis view in which the diameter of the left atrium in the last frame before mitral valve opening was measured parallel with the mitral annulus, bisecting the left atrium.30 The presence of either spontaneous echocontrast (SEC) or a thrombus in the left atrium was recorded. Maximal LA appendage velocities (LAA) were recorded where available.31 LA systolic function was assessed by both 2D and M-mode methods. In the 2D method (LA-EF%), “total” LA ejection fraction was calculated from maximum and minimum LA volumes measured by a single plane modified Simpson’s method from right parasternal long-axis images.16,32,33 Anatomic M-mode was used to calculate LA-FS% based on minimum and maximum LA diameter in a short-axis image at the level of the aortic valve and left atrium.34 If systolic anterior motion of the mitral valve (SAM) or mitral regurgitation (MR) was present on a 2D image or color flow Doppler, respectively, this was recorded. SAM was identified on 2D echo by identifying any abnormal motion of the anterior mitral leaflet from cine-loops played at slow speed, and confirmed by demonstrating variance in the LV outflow tract on color flow Doppler. Transmitral flow patterns, pulmonary venous flow patterns, and septal tissue Doppler imaging variables all were recorded where available. Calculated variables included E:A, the ratio of mitral inflow peak early filling (E) to late filling (A) velocities in cats with E wave velocities ≤0.2 m/s at E and A wave separation35; E:IVRT, the ratio of the mitral E wave (in m/s) to the isovolumic relaxation time (in ms); E′:A′, the ratio of the early diastolic tissue Doppler septal mitral annular velocity to the late diastolic septal mitral annular velocity; E:E′, the ratio of the mitral E wave to the early diastolic tissue Doppler septal annular velocity (E′); S:D, the ratio of the pulmonary venous peak systolic (S) to peak diastolic (D) velocity; and Adur : ARdur, the ratio of duration of the late filling transmitral wave (Adur) to duration of the pulmonary venous atrial reversal wave (ARdur).31,36 For E:IVRT, E′:A′ and E:E′ values only were calculated if the E or E′ components were adequately separated from the A or A′ components, respectively. The diastolic filling pattern was classified according to transmitral flow patterns. An E:A ratio of 2 was a restrictive filling pattern.36 Normal and pseudonormal filling patterns were differentiated by a sequence of factors. If LA enlargement was present (LA:Ao >1.537 or LAD >16 mm36) or the cat had presented with CHF, the pattern was considered pseudonormal. For cats with normal LA size and without CHF, differentiation of normal from pseudonormal filling was based on assessment of E:E′, Adur : ARdur, and E′:A′, depending on availability. Diastolic filling pattern in these cats was considered pseudonormal in the presence of any of the following: E:E′ >10, Adur : ARdur
Prognostic Indicators in Cats with Hypertrophic Cardiomyopathy J.R. Payne, K. Borgeat, D.J. Connolly, A. Boswood, S. Dennis, T. Wagner, P. Menaut, I. Maerz, D. Evans, V.E. Simons, D.C. Brodbelt, and V. Luis Fuentes 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. Cox’s 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. Key words: Echocardiography; Feline; Hypertrophic cardiomyopathy; Survival.
ypertrophic cardiomyopathy (HCM) is defined as a hypertrophied, nondilated left ventricle (LV) in the absence of other systemic or cardiac disease capable of producing a similar degree of hypertrophy.1 It is the most common familial heart disease in humans2 and the most commonly diagnosed myocardial disease in cats.3 Hypertrophic cardiomyopathy is a heterogeneous disease, both in terms of presentation and outcome. Some affected cats are presented with signs of congestive heart failure (CHF) or thromboembolism, and some cats die suddenly. Other affected cats can have long survival times and die of noncardiac causes.4–8 Prognostic factors have been reported in a number of retrospective studies of HCM in cats.5,7–11 Factors
H
From the Clinical Sciences and Services, Royal Veterinary College, Hatfield, Hertfordshire UK (Payne, Borgeat, Connolly, Boswood, Simons, Brodbelt, Luis Fuentes); the School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA (Dennis); the Southern Counties Veterinary Specialists LLP, Ringwood, Hampshire UK (Wagner); the Clinique V et erinaire, Aquivet, Eysines, France (Menaut); the Klinik fur Kleintiere (Innere Medizin), Justus-Liebig-University Giessen, Giessen, Germany (Maerz); and the Ash Tree Veterinary Practice, Market Harborough, Leicestershire UK (Evans). Meeting, if any, at which the paper was presented: ECVIM-CA, Toulouse, September 2010 (diastolic function in part of this cohort); 2012 ACVIM Forum, New Orleans, LA (overall survival in this cohort). Corresponding author: V. Luis Fuentes, Clinical Sciences and Services, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire, AL9 7TA, UK; e-mail: [email protected].
Submitted October 10, 2012; Revised July 31, 2013; Accepted September 3, 2013. Copyright © 2013 by the American College of Veterinary Internal Medicine 10.1111/jvim.12215
Abbreviations: Adur:ARdur
ATE CHF CVs E:A E:E′ E′:A′ FS% HCM IVRT LA:Ao LAA LAD
LA-EF% LA-FS% LA LV LVWd MR QMHA S:D SAM SEC
ratio of the duration of the late filling transmitral wave (Adur) to the duration of the pulmonary venous atrial reversal wave (ARdur) arterial thromboembolism congestive heart failure coefficients of variation ratio of mitral inflow peak early filling (E) to late filling (A) velocities ratio of mitral inflow peak early filling to early diastolic tissue Doppler mitral annular velocity ratio of early diastolic tissue Doppler mitral annular velocity to the late diastolic mitral annular velocity left ventricular fractional shortening hypertrophic cardiomyopathy isovolumic relaxation time ratio of diastolic left atrial diameter to aortic root diameter measured from a short axis image left auricular appendage velocity the diameter of the left atrium measured parallel with the mitral annulus in the last frame before mitral valve opening total left atrial ejection fraction total left atrial fractional shortening left atrial left ventricle end-diastolic left ventricular septal or free wall thickness mitral regurgitation Queen Mother Hospital for Animals ratio of the pulmonary venous peak systolic (S) to peak diastolic (D) velocity systolic anterior motion of the mitral valve spontaneous echo-contrast
1428
Payne et al
suggested to be associated with a worse outcome have included the presence of clinical signs at diagnosis,5,8,10,11 left atrial (LA) enlargement,7–10,12 and increased age at diagnosis.8,10,12 Certain breeds may have shorter survival times, including the Ragdoll10 and Maine Coon.11 An early study found that a heart rate ≥200 bpm at initial diagnosis was negatively associated with survival,5 but this has not been demonstrated in subsequent studies.8,10 Systolic anterior motion (SAM) is a negative prognostic indicator in people,13–15 but the prognostic effect in cats remains unclear,7,8,10 because there are no prospective longitudinal studies of SAM in cats, and the long-term relationship between outcome and the presence or absence of dynamic LV outflow tract obstruction has not been established. Maximal LV wall thickness was found to be greater in cats that later died because of their cardiac disease compared with survivors in another study.7 Prognosis has not been found to be linked to sex5,10 or body weight.5 In asymptomatic cats, the administration of atenolol has not been found to influence survival to 5 years post diagnosis.12 In HCM of humans, and other cardiac conditions, echocardiographic measures are used routinely as prognostic indicators. These include measures of LA function,16 LV systolic function,17–19 and diastolic function.20–28 Although LA enlargement is considered a very important prognostic indicator in cats with HCM,7–10 little has been done to investigate other echocardiographic markers of prognosis. We hypothesized that although LA echocardiographic variables would provide prognostic information in cats with HCM, assessment of left ventricular diastolic and systolic function would provide
additional prognostic value. The aim of this study was, therefore, to investigate the prognostic value of echocardiographic variables in cats with HCM.
Materials and Methods Cases of HCM were identified by searching the electronic patient records of cats seen at the Royal Veterinary College, Queen Mother Hospital for Animals (QMHA) between June 2004 and August 2009. Cats were included if a diagnosis of HCM had been made by a board-certified cardiologist or a cardiology resident supervised by a board-certified cardiologist based on 2D or M-mode echocardiography or botha and if follow-up information was available. Cats were excluded from the study if they had a known diagnosis of hyperthyroidism or hypertension, defined as either systolic blood pressure ≥180 mmHg; systolic blood pressure ≥160 mmHg with retinal changes suggestive of hypertension; medically controlled hypertension; or where renal disease was present and blood pressure had not been determined. The first visit date was defined as the date of the first echocardiographic examination. Cats with a prior diagnosis of HCM were not excluded, but data were taken from the first visit with an echocardiographic examination within the study period rather than the original diagnosis date. The medical records for each cat were reviewed for date of birth, sex, breed, and date of first visit to the QMHA, with age calculated at that visit. Physical examination findings were recorded, as well as systolic arterial pressureb and serum total thyroxine concentrations, where available. Clinical status at presentation was recorded (Table 1) and grouped into “asymptomatic” (cats presenting asymptomatically, with concurrent disease, with concurrent respiratory disease, or with noncardiac chylothorax), “syncope,” “CHF” (cats presenting with CHF or chylothorax of a cardiac cause), and “ATE” (cats presenting with ATE with or without CHF). Cats with exertional open-mouth breathing were not analyzed because of small numbers. Cats with HCM with “non-cardiac chylothorax” were defined as having persistently normal LA size and function despite progressive or
Table 1. Definitions of categorization of clinical signs at presentation. Clinical Status at Presentation Asymptomatic Concurrent disease Concurrent respiratory disease
Syncope Exertional open-mouth breathing Congestive heart failure
Chylothorax Noncardiac chylothorax Arterial thromboembolism
Definition Referred for investigation of a murmur, gallop, or arrhythmia, but without clinical signs Referred for investigation of noncardiac disease, but cardiac disease suspected during hospitalization. No clinical signs referable to cardiac disease Referred for investigation of respiratory disease, but cardiac disease suspected during hospitalization. Primary respiratory disease subsequently confirmed on further investigations Episodes described as syncopal or seizure-like activity. No noncardiac cause for syncope identified Open-mouth breathing only during periods of excitement, stress, or exercise Any of the following: present or previous radiographic evidence of pulmonary edema; present or previous radiographic/ultrasonographic evidence of pleural or pericardial effusion; or severe tachypnea that showed a clear response to furosemide administration Milky white-colored pleural effusion, with triglyceride concentrations exceeding serum concentrations and the absence of infectious organisms identified on fluid analysis Chylothorax with normal atrial chamber dimensions and normal left atrial function Limb: Sudden onset of lower motor neuron deficits in one or more limbs diagnosed as arterial thromboembolism by attending clinician Brain: Magnetic resonance imaging findings of a well-demarcated lesion, hyperintense on T2-weighted image Mesenteric: History of acute onset abdominal pain, high creatine kinase levels, and echocardiographic evidence of spontaneous echo-contrast in the left atrium
Prognostic Indicators in Cats with HCM persistent chylothorax. Presence of arrhythmias was determined from available ECG recordings (6-lead, Holter, or both) and by reviewing the concurrent ECG recorded during echocardiography. Arrhythmias were classified as “bradyarrhythmias,” “supraventricular arrhythmias,” “ventricular arrhythmias,” or both “supraventricular and ventricular arrhythmias.” All echocardiographic examinations were reviewed and remeasured by 1 board-certified cardiologist (VLF) or a resident (KB). Measurements were obtained only from images with optimal image quality with average values reported from at least 3 cardiac cycles except for maximal 2D LV end-diastolic wall thickness, for which the maximum measurement of at least 3 cardiac cycles was reported. Left ventricular hypertrophy was defined as LV septal or free wall end-diastolic thickness ≥6 mm,7 whether measured from 2D or M-mode images.29 Otherwise, M-mode images were used only to obtain LV fractional shortening (FS%) values, and 2D images were used for measuring maximal LV end-diastolic wall thickness from either the septum or free wall. The presence of any left ventricular regional wall hypokinesis was noted, based subjectively on 2D images and defined as a region of LV wall that was thinner than the rest of the LV, with minimal excursion or moving asynchronously with the rest of the ventricle. Left atrial size was assessed by 2 separate methods, LA:Ao and LAD. LA:Ao was obtained from a 2D right parasternal short-axis view to calculate the ratio of LA diameter to aortic root diameter measured at the onset of the QRS.28 LAD was measured from a right parasternal long-axis view in which the diameter of the left atrium in the last frame before mitral valve opening was measured parallel with the mitral annulus, bisecting the left atrium.30 The presence of either spontaneous echocontrast (SEC) or a thrombus in the left atrium was recorded. Maximal LA appendage velocities (LAA) were recorded where available.31 LA systolic function was assessed by both 2D and M-mode methods. In the 2D method (LA-EF%), “total” LA ejection fraction was calculated from maximum and minimum LA volumes measured by a single plane modified Simpson’s method from right parasternal long-axis images.16,32,33 Anatomic M-mode was used to calculate LA-FS% based on minimum and maximum LA diameter in a short-axis image at the level of the aortic valve and left atrium.34 If systolic anterior motion of the mitral valve (SAM) or mitral regurgitation (MR) was present on a 2D image or color flow Doppler, respectively, this was recorded. SAM was identified on 2D echo by identifying any abnormal motion of the anterior mitral leaflet from cine-loops played at slow speed, and confirmed by demonstrating variance in the LV outflow tract on color flow Doppler. Transmitral flow patterns, pulmonary venous flow patterns, and septal tissue Doppler imaging variables all were recorded where available. Calculated variables included E:A, the ratio of mitral inflow peak early filling (E) to late filling (A) velocities in cats with E wave velocities ≤0.2 m/s at E and A wave separation35; E:IVRT, the ratio of the mitral E wave (in m/s) to the isovolumic relaxation time (in ms); E′:A′, the ratio of the early diastolic tissue Doppler septal mitral annular velocity to the late diastolic septal mitral annular velocity; E:E′, the ratio of the mitral E wave to the early diastolic tissue Doppler septal annular velocity (E′); S:D, the ratio of the pulmonary venous peak systolic (S) to peak diastolic (D) velocity; and Adur : ARdur, the ratio of duration of the late filling transmitral wave (Adur) to duration of the pulmonary venous atrial reversal wave (ARdur).31,36 For E:IVRT, E′:A′ and E:E′ values only were calculated if the E or E′ components were adequately separated from the A or A′ components, respectively. The diastolic filling pattern was classified according to transmitral flow patterns. An E:A ratio of 2 was a restrictive filling pattern.36 Normal and pseudonormal filling patterns were differentiated by a sequence of factors. If LA enlargement was present (LA:Ao >1.537 or LAD >16 mm36) or the cat had presented with CHF, the pattern was considered pseudonormal. For cats with normal LA size and without CHF, differentiation of normal from pseudonormal filling was based on assessment of E:E′, Adur : ARdur, and E′:A′, depending on availability. Diastolic filling pattern in these cats was considered pseudonormal in the presence of any of the following: E:E′ >10, Adur : ARdur
