Karsten E. Schober

Noninvasive assessment of myocardial cell injury in dogs with suspected cardiac contusion

OBJECTIVES To determine the suitability of serologic biochemical tests to diagnose myocardial cell injury in dogs with suspected cardiac contusion. BACKGROUND Myocardial contusion after blunt thoracic trauma will frequently be overlooked or missed unless hemo-dynamic instability or dramatic electrocardiographic findings are observed. There are no available non-invasive tests to definitely detect blunt myocardial lesions in dogs. METHODS Circulating biochemical markers of skeletal muscle and myocardial cell integrity (aspartate aminotransferase, lactate dehydrogenase, a-hydroxybutyrate dehydrogenase, creatine kinase [CK], CK isoenzyme MB, and cardiac troponins I [cTnT] and T [cTnT]) were analyzed in 33 dogs with blunt chest injury and in 40 control dogs. Results were compared with ECG abnormalities diagnosed from serial short-time surface ECGs. RESULTS Cardiac TnI and CK-MB in serum were not detectable in 36 and 26 healthy dogs (median and range were 0 and 0 to 1.37 ng/ml and 0 and 0 to 3.17 ng/ml, respectively). Serum cTnT was not found in normal dogs. In dogs with thoracic trauma, circulating cTnI was elevated in 18 dogs (range 0 to 160.1 ng/ml), CK-MB in 14 dogs (range 0 to 24.9 ng/ml) and cTnT in 9 dogs (range 0 to 2.35 ng/ml), suggesting myocardial cell injury in 58% of dogs. Relevant electrocardiographic abnormalities were observed in 10/33 (30%) dogs. No differences in serum concentrations of markers of myocardial injury were found between dogs with or without relevant ECG abnormalities. CONCLUSION Myocardial cell injury is a frequent event in dogs with blunt thoracic trauma. Analysis of serum cTnI is more sensitive in detecting myocardial abnormalities than determination of circulating cTnT and CK-MB or electrocardiography.

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

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

Detection of congestive heart failure in dogs by Doppler echocardiography.

BACKGROUND Echocardiographic prediction of congestive heart failure (CHF) in dogs has not been prospectively evaluated. HYPOTHESIS CHF can be predicted by Doppler echocardiographic (DE) variables of left ventricular (LV) filling in dogs with degenerative mitral valve disease (MVD) and dilated cardiomyopathy (DCM). ANIMALS Sixty-three client-owned dogs. METHODS Prospective clinical cohort study. Physical examination, thoracic radiography, analysis of natriuretic peptides, and transthoracic echocardiography were performed. Diagnosis of CHF was based upon clinical and radiographic findings. Presence or absence of CHF was predicted using receiver-operating characteristic (ROC) curve, multivariate logistic and stepwise regression, and best subsets analyses. RESULTS Presence of CHF secondary to MVD or DCM could best be predicted by E:isovolumic relaxation time (IVRT) (area under the ROC curve [AUC]=0.97, P<.001), respiration rate (AUC=0.94, P<.001), Diastolic Functional Class (AUC=0.93, P<.001), and a combination of Diastolic Functional Class, IVRT, and respiration rate (R2=0.80, P<.001) or Diastolic Functional Class (AUC=1.00, P<.001), respiration rate (AUC=1.00, P<.001), and E:IVRT (AUC=0.99, P<.001), and a combination of Diastolic Functional Class and E:IVRT (R2=0.94, P<.001), respectively, whereas other variables including N-terminal pro-brain natriuretic peptide, E:Ea, and E:Vp were less useful. CONCLUSION AND CLINICAL IMPORTANCE Various DE variables can be used to predict CHF in dogs with MVD and DCM. Determination of the clinical benefit of such variables in initiating, modulating, and assessing success of treatments for CHF needs further study.

Assessment of Left Atrial Appendage Flow Velocity and its Relation to Spontaneous Echocardiographic Contrast in 89 Cats with Myocardial Disease

The hypotheses of this prospective study were that (1) left atrial appendage (LAA) blood flow velocities can be recorded in cats with myocardial disease by transthoracic Doppler echocardiography, (2) LA enlargement, LA mechanical dysfunction, and left ventricular (LV) diastolic abnormalities are associated with decreased LAA flow velocities, and (3) low LAA flow velocities predict the appearance of spontaneous echocardiographic contrast in cats with cardiomyopathy. Transthoracic 2-dimensional, M-mode, and Doppler echocardiographic studies were performed in 89 cats with hypertrophic, restrictive, dilated, or unclassified cardiomyopathy or with hyperthyroid heart disease. Maximal LAA flow velocity (LAAmax) was decreased (P < .001) in cats with cardiomyopathy (median, 0.28 m/s; range, 0.08-1.35) compared to normal cats. Associated with decreased LAA flow velocities were increased LA size, decreased LA function, increased severity of LV diastolic dysfunction, and the presence of congestive heart failure. Multivariate logistic regression analysis detected an LAAmax <0.20 m/s as the only independent variable to predict LA spontaneous echocardiographic contrast (odds ratio, 30.1; 95% confidence interval [CI], 4.1 222.3; P < .001). Receiver operating characteristic analysis performed to predict spontaneous echocardiographic contrast indicated an area under the curve of 0.88 (95% CI, 0.80-0.95; P < .001) with sensitivities of 100 and 74% and specificities of 69 and 83% for LAAmax <0.25 and <0.20 m/s, respectively. Thus, low LAA flow velocities identified a subgroup of patients at increased risk of spontaneous echocardiographic contrast and possible thromboembolism. These findings may have important clinical implications for anticoagulation therapy and prognostication in cats with cardiomyopathy.

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

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

Diagnostic Accuracy of Electrocardiography and Thoracic Radiography in the Assessment of Left Atrial Size in Cats: Comparison with Transthoracic 2‐Dimensional Echocardiography

BACKGROUND Left atrial (LA) enlargement (LAE) is a morphologic expression of the severity and chronicity of left ventricular (LV) diastolic dysfunction, volume overload, and increased atrial pressure and has diagnostic, therapeutic, and prognostic importance in cats. The noninvasive gold standard for assessing LA size is 2-dimensional echocardiography (2DE). HYPOTHESIS ECG and thoracic radiography may be used to predict LAE in cats. ANIMALS Twenty-one healthy control cats and 31 cats with cardiomyopathy were prospectively studied. METHODS 2DE studies, including determination of the maximum LA dimension (LAD) and area (LAA), were performed prospectively in all cats and compared to the assessment of LA size based on thoracic radiography and indices obtained from a 6-lead ECG. Results obtained from healthy cats were used to generate discrimination limits suggestive of LAE as defined by LAD > 1.57 cm and LAA > 2.75 cm2. RESULTS In cats with LAE, P wave duration and PR interval were prolonged and radiographic LA vertebral heart size (LA-VHS) was increased (P < .05). P wave-related indices had low sensitivity (Se; range, 0.12 to 0.60) but high specificity (Sp; range, 0.81 to 1.00) for the prediction of LAE. Radiographic indices had low Se (range, 0.28 to 0.72) and high Sp (range, 0.74 to 0.95) for the prediction of LAE. Correlation analyses identified correlations between LAA and P wave duration (r = 0.47, P = .003) and LAD and LA-VHS (r = 0.70, P < .001). CONCLUSION AND CLINICAL IMPORTANCE ECG and thoracic radiography are reasonably specific but less sensitive predictors of LAE in cats.

Correlation of Serum Cardiac Troponin I and Myocardial Damage in Cattle with Monensin Toxicosis

BACKGROUND Cardiac troponin I (cTnI) is used as a biomarker of myocardial injury in people and small animals. Little is known about the diagnostic use of cTnI in cattle. HYPOTHESIS Serum cTnI correlates to myocardial function and histopathologic lesions in cattle with monensin-induced myocardial injury. ANIMALS Ten healthy cows. METHODS Experimental study. Animals received 1 dose of monensin PO; 30 mg/kg (n = 1) or 40 mg/kg (n = 1) (Group A) or 50 mg/kg monensin (n = 8) (Group B) of body weight. Repeated measurements were performed of serum cTnI, biochemistry, and ECG and echocardiography until study termination at 80 (Group A) and 144 hours (Group B) after dosing. Semiquantitative histopathologic examinations of the heart were performed in each cow. A scoring system with regard to the magnitude of myocardial injury was established and a total heart score was compared with maximum cTnI concentration measured after monensin administration. Five hearts from healthy cows served as controls. RESULTS Increased cTnI (>0.07 ng/mL) was found in 9/10 cows. cTnI was significantly associated with left ventricular shortening fraction (r(2)= 0.51; P= .02) and myocardial histopathologic lesion score (r(2)= 0.49; P= .021). All cows (n = 7) with evidence of myocardial necrosis had a cTnI concentration > or = 1.04 ng/mL. CONCLUSION AND CLINICAL IMPORTANCE cTnI is related to myocardial necrosis and severity of myocardial damage in cattle with monensin toxicosis. cTnI could become a useful diagnostic tool in the noninvasive assessment of myocardial injury in cattle with naturally occurring cardiac disease.

Left Ventricular Radial and Circumferential Wall Motion Analysis in Horses Using Strain, Strain Rate, and Displacement by 2D Speckle Tracking

BACKGROUND Noninvasive assessment of left-ventricular (LV) function is clinically relevant, but is incompletely studied in horses. OBJECTIVES To document the feasibility, describe the techniques, and determine the reliability of 2D speckle tracking (2DST) for characterization of LV radial and circumferential wall motion in horses. ANIMALS Three Standardbreds, 3 Thoroughbreds; age 8-14 years; body weight 517-606 kg. METHODS Observational study. Repeated 2-dimensional echocardiographic examinations were performed in unsedated horses by 2 observers and subsequently analyzed by 2DST. Test reliability was determined for segmental and for averaged 2DST indices (including strain, strain rate, displacement, and rotation) by estimating measurement variability, within-day interobserver variability, between-day interobserver variability, and between-day intraobserver variability. Variability was expressed as coefficient of variation (percent) and the absolute value below which the difference between 2 measurements will lie with 95% probability. RESULTS 2DST analyses were feasible in 16 of 18 echocardiographic studies. The automated tracking was accurate during systole but inaccurate during diastole. Reliability was higher for radial compared to circumferential measurements. For radial strain, radial systolic strain rate, and radial systolic displacement, the test-retest variabilities ranged between 2.4 and 33.1% for segmental and between 4.1 and 16.1% for averaged measurements. CONCLUSIONS AND CLINICAL IMPORTANCE Systolic radial motion of the LV at the chordal level could be reliably characterized in horses by 2DST. Circumferential measurements were less reliable. Diastolic measurements were invalid because of inaccurate tracking. The clinical value of LV wall motion analysis by 2DST in horses requires further investigation.

Methods and Reliability of Tissue Doppler Imaging for Assessment of Left Ventricular Radial Wall Motion in Horses

BACKGROUND Noninvasive assessment of left ventricular (LV) function is incompletely studied in horses. OBJECTIVES The goals of this study were to investigate the feasibility, techniques, and reliability of tissue Doppler imaging (TDI) for characterization of LV radial wall motion in healthy horses. ANIMALS Three Standardbreds, 3 Thoroughbreds; age 8-14 years; body weight 517-606 kg. METHODS Repeated echocardiographic examinations were performed by 2 observers in unsedated horses using TDI. Test reliability was determined by estimating measurement variability, within-day interobserver variability, and between-day interobserver and intraobserver variability of all echocardiographic variables. Variability was expressed as coefficient of variation (CV) and the absolute value below which the difference between 2 measurements will lie with 95% probability. RESULTS Assessment of LV radial wall motion by TDI was feasible in all horses. Measurement variabilities were very low (CV < 5%) to low (CV 5-15%) for most variables. Within-day interobserver variability as well as between-day interobserver and intraobserver variabilities were low to moderate (CV 16-25%) for most variables. All pulsed-wave TDI variables of systolic LV function showed very low to low variability, whereas some of the variables of LV diastolic and LA function showed moderate to high (CV > 25%) variability. Pulsed-wave TDI variables appeared more reliable than color TDI variables. CONCLUSIONS AND CLINICAL IMPORTANCE Measurement of TDI indices of LV function is feasible and reliable in adult Standardbred and Thoroughbred horses. The clinical relevance of LV function assessment by TDI remains to be determined.

Estimation of Left Ventricular Filling Pressure by Doppler Echocardiography in Dogs with Pacing-Induced Heart Failure

BACKGROUND Congestive heart failure (CHF) is a common clinical syndrome characterized by elevated filling pressure. HYPOTHESIS Doppler echocardiographic (DE) variables of left ventricular (LV) filling can predict a decline of LV end-diastolic pressure (LVEDP) induced by acute preload reduction in dogs with compensated CHF. ANIMALS Five male hound dogs. METHODS Dogs previously instrumented with a transvenous cardiac pacemaker and a LV pressure gauge were paced at 160-180 bpm to induce mild CHF characterized by LVEDP > 20 mmHg. LVEDP and 9 DE variables of LV filling derived from diastolic time intervals, transmitral and pulmonary venous flow, and tissue Doppler imaging were measured simultaneously at baseline and 30, 60, 120, and 240 minutes after furosemide (4 mg/kg, IV) or placebo (0.9% saline, IV). Repeated measures analysis of variance and correlation analysis were used to determine the association between the decline of LVEDP after furosemide and DE measures of LV filling pressure (LVFP). RESULTS Furosemide but not placebo decreased LVEDP (P < .001). The ratio of early transmitral flow velocity to LV isovolumic relaxation time (E : IVRT) predicted LVEDP best (R(2)= .50; P < .001). Correlations were also found between LVEDP and IVRT, E, ratio between E and late diastolic transmitral flow velocity (E : A), and early diastolic velocity of the mitral annulus (Ea). The ratio of E to Ea (E : Ea) was not useful in the prediction of LVEDP in this model. CONCLUSION AND CLINICAL IMPORTANCE E : IVRT can be used to predict LVFP in dogs with mild left-sided CHF induced by rapid pacing.