Echocardiographic measurements of right heart size and function in healthy horses.

REASONS FOR PERFORMING STUDY: Right ventricular (RV) function is scarcely described in horses. OBJECTIVES: To establish reliable echocardiographic measurements of right heart size and function in horses. STUDY DESIGN: Descriptive study in healthy horses. METHODS: Ten healthy untrained adult trotter horses underwent repeated echocardiography performed by 2 sonographers from right and left parasternal standard and nonstandard views. Nonstandard views included a right parasternal view focused on the right atrium, left parasternal long-axis pulmonary artery view, left parasternal long-axis view focused on the right ventricle including anatomical M-mode of tricuspid annular motion and left parasternal pulsed wave Doppler recording of pulmonary flow. During off-line analysis, 2 observers performed two-dimensional, M-mode, pulsed wave Doppler, tissue Doppler imaging (TDI) and two-dimensional speckle tracking (2DST) measurements of RV size and function. Acquisition and measurement variability were assessed by calculating coefficients of variation (CV) from one-way repeated measures analyses of variance. The degree of variability was classified as low (CV<15%), moderate (CV 15-25%) or high (CV>25%). RESULTS: Most two-dimensional and M-mode measurements of RV, right atrial and pulmonary artery size showed low variability. The two-dimensional, M-mode and pulsed wave Doppler measurements of RV function showed a low to moderate variability. Right ventricular functional measurements by 2DST showed low variability, except for segmental strain rate. Right ventricular functional measurements by TDI showed a low to high variability, with a lower variability for timing than for peak measurements and a lower variability for velocity compared with deformation measurements. CONCLUSIONS: Right heart size and function can be assessed with low variability in horses.

Atrial Premature Depolarization-Induced Changes in QRS and T Wave Morphology on Resting Electrocardiograms in Horses.

BACKGROUND: The electrocardiographic differentiation between atrial (APDs) and ventricular (VPDs) premature depolarizations is important. P wave prematurity and normal QRS and T wave morphology generally are used as discriminating criteria for APDs. HYPOTHESIS/OBJECTIVES: The aim of this study was to determine whether P, Q, R, S, and T wave amplitude, PQ interval, QRS and P wave duration and P and T wave morphology differ between APDs and sinus beats. To determine the relationship between the RR coupling interval and the change in S wave amplitude between sinus beats and APDs. METHODS: Case-control study. From a modified base-apex configuration of 30 horses with APDs at rest, sinus beat and APD associated preceding RR interval, P, PQ and QRS duration and P, R, S, and T wave amplitudes were measured. Linear mixed models and logistic regression were used to determine the effect of APDs on the ECG variables studied. RESULTS: In comparison to sinus beats, APDs were associated with a significant (P < .001) change in P amplitude (-0.03 ± 0.01 mV) and increase in S (0.20 ± 0.02 mV) and T (0.08 ± 0.03 mV) amplitude. PQ (-20.3 ± 5.2 ms) and RR (-519 ± 14 ms) interval and P duration (-21.1 ± 3.0 ms) decreased (P < .001). APDs were significantly associated with a singular positive P wave (OR: 11.0, P < .001) and were more likely to have a monophasic positive T wave (OR: 9.2, P < .001). A smaller RR coupling interval was associated with an increased relative difference in S amplitude (P < .01). CONCLUSIONS: Atrial premature depolarizations may lead to changes in QRS and T wave morphology. Knowledge of these changes is important to avoid interpreting certain APDs as VPDs.

Assessing aortic regurgitation severity from 2D, M-mode and pulsed wave Doppler echocardiographic measurements in horses.

Aortic regurgitation (AR) in horses can lead to left ventricular (LV) eccentric hypertrophy, ventricular arrhythmia and heart failure. Objective quantification of the severity of regurgitation is difficult. The aim of this study was to evaluate dimensional measurements, systolic time intervals and blood flow velocities, acquired by standard 2D, M-mode and pulsed wave Doppler echocardiography, for quantification of AR. Echocardiography was performed in 32 healthy horses and 35 horses with AR that were subdivided in three groups (mild, moderate or severe AR). From the recorded images LV, left atrial and aortic dimensions, systolic time intervals and aortic blood flow velocities were measured. Diastolic run-off in the aorta (AoDiastDecr) was calculated as the difference in aortic diameter between early diastole and late diastole. Stroke volume (SV) was calculated from pulsed wave Doppler measurements, by the bullet method (SVbullet) and by the area-length method. Pre-ejection period (PEP) and ejection time (LVET) were determined from the M-mode images. Horses with AR showed enlargement of the LV, left atrium and aorta compared to the control group. The SV, the AoDiastDecr and the rate of AoDiastDecr were significantly larger than controls. PEP decreased significantly in horses with AR, whereas LVET did not change. PEP and the newly defined variable AoDiastDecr proved to be easy to measure parameters that provided a good indication of AR severity. There was increased SV in horses with AR using all three methods, but SVbullet was superior for the detection of increased AR severity.

Pharmacokinetics of intravenously and orally administered sotalol hydrochloride in horses and effects on surface electrocardiogram and left ventricular systolic function.

Arrhythmias are common in horses. Some, such as frequent atrial or ventricular premature beats, may require long-term anti-arrhythmic therapy. In humans and small animals, sotalol hydrochloride (STL) is often used for chronic oral anti-arrhythmic therapy. STL prolongs repolarization and the effective refractory period in all cardiac tissues. No information on STL pharmacokinetics or pharmacodynamics in horses is available and the aim of this study was to evaluate the pharmacokinetics of intravenously (IV) and orally (PO) administered STL and the effects on surface electrocardiogram and left ventricular systolic function. Six healthy horses were given 1 mg STL/kg bodyweight either IV or PO. Blood samples to determine plasma STL concentrations were taken before and at several time points after STL administration. Electrocardiography and echocardiography were performed at different time points before and after IV STL administration. Mean peak plasma concentrations after IV and PO administration of STL were 1624 ng/mL and 317 ng/mL, respectively. The oral bioavailability was intermediate (48%) with maximal absorption after 0.94 h, a moderate distribution and a mean elimination half-life of 15.24 h. After IV administration, there was a significant increase in QT interval, but no significant changes in other electrocardiographic and echocardiographic parameters. Transient transpiration was observed after IV administration, but no adverse effects were noted after a single oral dose of 1 mg/kg STL in any of the horses. It was concluded that STL has an intermediate oral bioavailability in the horse and might be useful in the treatment of equine arrhythmias.

Influence of detomidine on atrial fibrillation cycle length measured by intracardiac electrogram recording and by colour tissue Doppler imaging in horses.

REASONS FOR PERFORMING STUDY: Shortening of atrial fibrillation cycle length (AFCL) is a marker of atrial electrical remodelling due to atrial fibrillation (AF). OBJECTIVES: To investigate the effect of administration of detomidine on AFCL measured invasively from an intra-atrial electrogram (AFCLEGM) and noninvasively by tissue Doppler imaging (AFCLTDI). We hypothesised that detomidine would have no effect on AFCL but would improve the ease of TDI measurements and facilitate noninvasive AFCL determination. STUDY DESIGN: Prospective clinical study. METHODS: Measurements were performed before and after i.v. administration of 7.5 µg/kg bwt detomidine in 33 episodes of AF in 32 horses (582 ± 64 kg bwt, 10 ± 3 years old) referred for electrical cardioversion. The AFCLEGM was measured from a right atrial intracardiac electrogram. The AFCLTDI was measured from atrial colour tissue velocity curves in 5 atrial wall regions. Mean AFCLEGM and AFCLTDI without and with sedation were compared using a repeated-measures linear mixed model with Bonferroni correction for multiple comparisons and calculation of the Bland-Altman mean bias and limits of agreement between AFCLEGM and AFCLTDI. RESULTS: The mean AFCL was significantly increased after sedation, but this increase was very small (mean difference +4 ms). For AFCLTDI measurements, sedation significantly improved the quality of the atrial myocardial velocity curves and the number of AF cycles that could be measured per cardiac cycle. The Bland-Altman bias between AFCLEGM without sedation and AFCLTDI with sedation ranged from -18 to +15 ms depending on wall region. Bland-Altman limits of agreement were similar between AFCLEGM without sedation and AFCLTDI without and with sedation. Therefore, noninvasive AFCLTDI measurements with sedation can be used to estimate the atrial fibrillatory rate. CONCLUSIONS: Sedation facilitates noninvasive AFCL measurements but causes a slight increase in AFCL. Noninvasive AFCL measurements can be used as an indicator of atrial electrical remodelling, to study AF pathophysiology and to investigate the effect of anti-arrhythmic drugs.

Right atrial and right ventricular ultrasound-guided biopsy technique in standing horses.

REASONS FOR PERFORMING STUDY: Endomyocardial biopsies could be a valuable tool in equine cardiology for diagnosing myocardial disease, which is probably underdiagnosed in horses because of lack of specific diagnostic measures and limitations of currently available diagnostic methods. OBJECTIVES: To describe a technique for serial right atrial and right ventricular endomyocardial biopsy in standing horses using a percutaneous approach through the jugular vein. STUDY DESIGN: Prospective study. METHODS: Biopsy was performed in 10 healthy standing horses sedated with detomidine, under continuous electrocardiography monitoring. A 10 cm (n = 6), 45 cm (n = 1) or 98 cm (n = 3) introducer sheath was inserted into the right jugular vein. Under echocardiographic guidance, a biopsy forceps was introduced through the sheath into the right ventricle and right atrium and endomyocardial biopsies were acquired. RESULTS: In all horses, 3 right ventricular biopsies were obtained from the right ventricular apex and 3 right atrial biopsies were obtained from the dorsal right atrial wall near the tuberculum intervenosum. The presence of myocardial tissue was confirmed by histology. All horses showed atrial and ventricular premature depolarisations associated with acquisition of the biopsies. In 9 horses, the arrhythmia disappeared after retraction of the forceps and introducer sheath. In one horse, ventricular premature depolarisations disappeared only after 8 h. No other complications were observed. CONCLUSIONS: Endomyocardial biopsy of the right atrium and right ventricle could be performed in standing horses using a percutaneous approach through the jugular vein and was not associated with complications other than temporary arrhythmias. This technique may be useful for research purposes or as a diagnostic tool, although further research is needed to establish the safety of the technique in clinical patients with myocardial disease.

Atrial natriuretic peptide vs. N-terminal-pro-atrial natriuretic peptide for the detection of left atrial dilatation in horses.

REASONS FOR PERFORMING STUDY: Studies on the use of atrial natriuretic peptide (ANP) as a biomarker for left atrial dilatation in horses have produced variable results. Few have been performed, and the results may have been influenced by ANP instability, differences in sampling protocol and changes in the assay over time. N-Terminal proANP (NT-proANP) is a more stable molecule and might be a good alternative for clinical use. OBJECTIVES: To compare ANP and NT-proANP in terms of the detection of left atrial dilatation and to determine the influence of sample storage at temperatures of -80 and -20°C. STUDY DESIGN: Prospective clinical study. METHODS: Atrial natriuretic peptide and NT-proANP concentrations were compared between healthy horses (Group 1, n = 20), horses with mitral valve regurgitation and a normal atrial size (Group 2, n = 11) and horses with mitral valve regurgitation associated with left atrial dilatation (Group 3, n = 16). The ANP concentration was measured with an equine enzyme-linked immunosorbent assay and the NT-proANP concentration with an enzyme-linked immunosorbent assay developed for use in human patients. Samples were stored at -20 and -80°C and analysed within 7 months. RESULTS: The NT-proANP concentrations were not significantly different between the groups. Horses in Group 3 had a significantly higher ANP concentration (median 366 pg/ml; interquartile range [IQR] 74-2000 pg/ml) compared with horses in Group 1 (median 31 pg/ml; IQR 31-333 pg/ml) or Group 2 (median 31 pg/ml; IQR 31-1152 pg/ml; P = 0.02). The ANP cut-off value for detection of left atrial dilatation was 52 pg/ml (sensitivity 81%; specificity 84%) for sample storage at -80°C, and 44 pg/ml (sensitivity 69%; specificity 84%) for storage at -20°C. A larger decrease in ANP (45 ± 126 pg/ml) than in NT-proANP (10 ± 31 pg/ml) was found associated with sample storage at -20 instead of -80°C. CONCLUSIONS: Atrial natriuretic peptide, but not NT-proANP, can be used to detect left atrial dilatation in horses. Atrial natriuretic peptide is less stable than NT-proANP when samples are stored at -20°C. Atrial natriuretic peptide is a more suitable biomarker of left atrial dilatation in horses than NT-proANP.

Total plasma proANP increases with atrial dilatation in horses.

Equine atrial natriuretic peptide (ANP) plasma concentrations are correlated with left atrial size. However, species-specific assays are lacking and the results from human assays are poorly reproducible. A new methodology called processing independent analysis (PIA) that measures the total proANP product in plasma has proven to be successful in human medicine, but has never been used in horses. The aims were to establish an equine proANP reference interval by measurement of the total proANP product using PIA and to examine the proANP concentrations in horses with atrial dilatation. Sample stability was studied by comparison of storage at -80°C and -20°C. Plasma samples were obtained from 23 healthy horses, 12 horses with moderate or severe valvular regurgitation without atrial dilatation and 42 horses with valvular regurgitation and atrial dilatation. The proANP concentration was significantly (P<0.001) higher in horses with atrial dilatation (761.4 (442.1-1859.1) pmol/l) than in healthy horses (491.6 (429.5-765.9) pmol/l; P<0.001) or horses with cardiac disease but without atrial dilatation (544.4 (457.0-677.6) pmol/l). A cut-off value (573.8 pmol/l) for detection of atrial dilatation was calculated. Sample storage at -80°C did not differ from sample storage at -20°C. The measurement of total proANP in plasma detects atrial dilatation in horses and may be useful for clinical evaluation in equine medicine.

Risk factors for recurrence of atrial fibrillation in horses after cardioversion to sinus rhythm.

BACKGROUND: Although atrial fibrillation (AF) can be successfully treated in horses, recurrence occurs frequently. In humans, atrial function after cardioversion can predict recurrence. OBJECTIVES: To examine the prognostic value of atrial mechanical function at 24 hours after cardioversion and other potential predictor variables for AF recurrence in horses. ANIMALS: 117 horses treated for AF at 4 referral centers. METHODS: Retrospective study. Inclusion criteria were successful cardioversion, echocardiography at 24 hours after cardioversion and ≥4 months follow-up. To determine factors associated with AF recurrence, a multivariable survival model was built. RESULTS: 133 AF episodes in 117 horses were included. AF recurred in 36/100 horses with a first AF episode and in 57/133 AF episodes overall. Factors associated with recurrence in horses with a first episode were previous unsuccessful treatment attempt (hazard ratio HR 2.36, 95% confidence interval CI 1.11-4.99, P = .025) and mild or moderate mitral regurgitation (HR 2.70, 95% CI 1.23-5.91, P = .013). When the last AF episode of all horses was included, previous AF (HR 2.53, 1.33-4.82, P = .005) and active left atrial fractional area change ≤9.6% (HR 3.43, 1.22-9.67, P = .020) were significant predictors. CONCLUSIONS AND CLINICAL IMPORTANCE: The only echocardiographic variable of left atrial function with significant prognostic value for recurrence was low active left atrial fractional area change. Further research is necessary to evaluate whether echocardiography at a later timepoint could provide more prognostic information.

Cardiac troponin I as compared to troponin T for the detection of myocardial damage in horses.

BACKGROUND: Different cardiac troponin I (cTnI) assays give different results. Only 1 manufacturer has marketed troponin T (cTnT) assays. Therefore, cTnT often is preferred for detection of myocardial infarction in human patients. Studies of cTnT in horses are limited. OBJECTIVES: To compare a cTnI and a high-sensitive cTnT assay (hs-cTnT) in horses. ANIMALS: Cardiac troponin I and cTnT were determined in 35 healthy horses (group 1), 23 horses suspected to have primary myocardial damage (group 2a), and 41 horses with secondary myocardial damage caused by structural heart disease (group 2b). METHODS: All cTnI samples were analyzed at laboratory A (limit of detection [LOD]: 0.03 ng/mL), whereas cTnT samples were analyzed at 2 laboratories with the same hs-cTnT assay (laboratory B, LOD: 10.0 pg/mL; laboratory C, LOD: 4.0 pg/mL). RESULTS: The median cTnI concentration in group 2a (0.90 ng/mL; range, 0.03-58.27 ng/mL) was significantly higher (P < .001) than in group 1 (0.03 ng/mL; range, 0.03-0.09 ng/mL) or group 2b (0.05 ng/mL; range, 0.03-30.92 ng/mL), and the optimal cut-off for detection of primary myocardial damage was 0.095 ng/mL (sensitivity: 90.5%, specificity: 100%). Using an LOD of 10.0 pg/mL for all cTnT samples, a cut-off value of 10.5 pg/mL was found, but sensitivity was low (42.9%). When only samples analyzed at laboratory C (n = 58) were included, a cut-off of 6.6 pg/mL was found (sensitivity: 81%, specificity: 100%). CONCLUSIONS AND CLINICAL IMPORTANCE: Despite large quantitative differences, cTnI and cTnT are both useful for detection of myocardial damage in horses.

Evaluation of assays for troponin I in healthy horses and horses with cardiac disease.

Cardiac troponin I (cTnI) is a marker for detection of myocardial damage in horses. Many cTnI assays exist and medical studies have shown that the clinical performance of assays differs. The aim of this study was to compare two different cTnI assays in horses. Serum samples were taken from 23 healthy horses (group 1) and 72 horses with cardiac disease (group 2). Cardiac troponin I was determined using assay 1 in laboratory A (limit of detection, LOD, 0.03 ng/mL) and assay 2 in laboratories B and C (LOD 0.01 ng/mL). In group 1, a median cTnI concentration of <0.03 (<0.03-0.04) ng/mL and <0.01 (<0.01-0.15) ng/mL was found with assays 1 and 2, respectively. A higher median value was demonstrated in group 2 for both assays (assay 1: 0.11 ng/mL, range 0.03-58.27 ng/mL, P < 0.001; assay 2: 0.02 ng/mL, range 0.01-22.87 ng/mL, P = 0.044). Although a significant correlation between assays existed, large mean differences that could be important for clinical interpretation of test results were found. A small mean difference was found between laboratories B and C. A significant optimal (P < 0.001) cut-off value for detection of cardiac disease could only be determined for assay 1 (0.035 ng/mL, sensitivity 70%, specificity 91%). Assay 1 performed better for detection of cardiac disease in horses in this study.

Atrial fibrillation cycle length and atrial size in horses with and without recurrence of atrial fibrillation after electrical cardioversion.

BACKGROUND: Atrial fibrillation (AF) cycle length (CL) and atrial size have been used in humans to characterize electrical and structural remodeling to predict outcome of cardioversion of AF and risk for AF recurrence (rAF). HYPOTHESIS: Atrial fibrillation cycle length can be determined in horses with AF, and AFCL and atrial size are related to risk for rAF. ANIMALS: Eighteen horses with naturally occurring AF that were successfully converted to sinus rhythm (SR) by transvenous electrical cardioversion (TVEC). METHODS: Prospective study. Horses with severe valvular regurgitation, left atrial enlargement, or that required sedation for catheter placement were excluded. In all horses intra-atrial electrograms were recorded and estimated AF duration and echocardiographic parameters were determined before TVEC. The follow-up time was 1 year after TVEC. RESULTS: Atrial fibrillation cycle length could be determined in all horses. The AFCL and the shortest 5th percentile (p5) AFCL in horses with rAF (n = 6 or 33%) were (mean ± SD) 157 ± 28 and 134 ± 24 milliseconds, respectively, and in those maintaining SR (n = 12 or 67%) 166 ± 13 and 141 ± 13 milliseconds, respectively. Significant parameters to predict rAF were (1) the ratios of the p5AFCL to the left atrium (LA) sizes corrected to the size of aorta (AO) and (2) LA sizes corrected to the size of AO. CONCLUSIONS AND CLINICAL IMPORTANCE: Before TVEC, assessment of LA size and atrial electrophysiologic characteristics might help to identify horses at increased risk for AF recurrence.

Noninvasive determination of atrial fibrillation cycle length by atrial colour tissue Doppler imaging in horses.

REASONS FOR PERFORMING STUDY: Atrial fibrillation cycle length (AFCL) is an indicator of atrial electrical remodelling during atrial fibrillation (AF). OBJECTIVES: To compare AFCL measured invasively from an intra-atrial electrogram (AFCLEGM ) with AFCL measured noninvasively by atrial colour tissue Doppler imaging (AFCLTDI ). STUDY DESIGN: Prospective descriptive clinical study. METHODS: Measurements were performed in 31 episodes of AF or flutter in 29 horses (588 ± 61 kg bwt, 9 ± 3 years old) admitted for transvenous electrical cardioversion. The AFCLEGM was measured from an intracardiac electrogram using a bipolar sensing/pacing electrode inserted into the right atrium. The AFCLTDI was measured from atrial colour tissue velocity curves in the following 5 regions: 1) left atrial free wall from a right parasternal 4-chamber view, 2) left atrial free wall from a short-axis view, 3) left atrial free wall from a left parasternal long-axis view, 4) interatrial septum, and 5) right atrial dorsal wall near the tuberculum intervenosum. The AFCLEGM and AFCLTDI from the 5 regions were compared using a one-way repeated-measures ANOVA with Bonferroni correction for multiple comparisons and calculation of the Bland-Altman mean bias and limits of agreement of AFCLEGM and AFCLTDI . RESULTS: The AFCLEGM was 161 ± 18 ms in 29 AF episodes. Two horses showed atrial flutter and had an AFCLEGM of 244 and 324 ms. The mean bias between AFCLTDI and AFCLEGM ranged from -18 to +9 ms depending on the atrial wall region. The AFCLTDI was significantly shorter in the left atrial free wall from the right parasternal 4-chamber view and short-axis view than in the other regions (P<0.001). CONCLUSIONS: Tissue Doppler imaging allows noninvasive measurement of AFCL in horses with AF and is able to identify spatial differences within the equine atria. Atrial fibrillation cycle length is an indicator of atrial electrical remodelling and is an important parameter to study AF pathophysiology or the effect of antiarrhythmic drugs.

Ventricular response during lungeing exercise in horses with lone atrial fibrillation.

REASONS FOR PERFORMING THE STUDY: Atrial fibrillation (AF) is the most important dysrhythmia affecting performance in horses and has been associated with incoordination, collapse and sudden death. Limited information is available on ventricular response during exercise in horses with lone AF. OBJECTIVES: To investigate ventricular response in horses with lone AF during a standardised lungeing exercise test. METHODS: A modified base-apex electrocardiogram was recorded at rest and during a standardised lungeing exercise test from 43 horses diagnosed with lone AF. During the test horses walked for 7 min, trotted for 10 min, cantered for 4 min, galloped for 1 min and recovered for 7 min. RESULTS: Individual average heart rate during walk ranged from 42 to 175 beats/min, during trot from 89 to 207 beats/min, during canter from 141 to 269 beats/min, and during gallop from 191 to 311 beats/min. Individual beat-to-beat maximal heart rate ranged from 248 to 492 beats/min. Ventricular premature depolarisations were present in 81% of the horses: at rest (16%), during exercise (69%), and during recovery (2%). In 33% of the horses, broad QRS complexes with R-on-T morphology were found. CONCLUSIONS: Exercising horses with lone AF frequently develop disproportionate tachycardia. In addition, QRS broadening and even R-on-T morphology is frequently found. QRS broadening may originate from ventricular ectopic foci or from aberrant intraventricular conduction, for example due to bundle branch block. This might explain the high number of complexes currently classified as ventricular premature depolarisations. POTENTIAL RELEVANCE: Prevalence of QRS broadening and especially R-on-T was very high in horses with AF and was found at low levels of exercise. These dysrhythmias are considered risk factors for the development of ventricular tachycardia and fibrillation and they might explain signs of weakness, collapse or sudden death that have been reported in horses with AF.