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Abstract Background Reliability of echocardiographic calculations for stroke volume and mitral regurgitant fraction (RFMR) are affected by observer variability and lack of a gold standard. Variability is used to calculate critical change values (CCVs) that are thresholds representing real change in a measure not associated with observer variability. Hypothesis Observed intra‐ and interobserver accuracy and variability in healthy dogs help model CCV for RFMR. Animals Reliability cohort of 34 healthy dogs; allometric scaling cohort of 99 dogs with heart disease and 25 healthy dogs. Methods Accuracy, variability, and CCV of 2 observers using geometric and flow‐based echocardiography were prospectively compared against a standard of RFMR = 0% and extrapolated across a range of expected RFMR values in the reliability cohort partly derived from cardiac dimensions predicted by the allometric cohort. Results Accuracy of methods to determine RFMR in descending order was 4‐chamber bullet (Bullet4CH), mitral inflow, cube formula, and Simpson's method of disks. Intraobserver variability was relatively high. The CCV for RFMR ranged from 28% to 88% and was inversely related to RFMR when extrapolated for use in affected dogs. For both observers, the Bullet4CH method had the lowest intraobserver CCV (Operator 1:28%, Operator 2:41%). Interobserver strength of agreement was low with intraclass correlation coefficients ranging from 0.210 to 0.413. Conclusions and Clinical Importance Echocardiographic volumetric methods used to calculate stroke volume and RFMR have low accuracy and high variability in healthy dogs. Extrapolation of observed CCV to a range of expected RFMR suggests observers and methods are not interchangeable and variability might hinder routine clinical usage. Individual observers should be aware of their own variability and CCV.

Abstract Background Differentiation of the subclinical phases of myxomatous mitral valve disease (MMVD) in dogs relies heavily on echocardiography. Focused cardiac ultrasonography (FCU) is a point‐of‐care technique that can assess heart size. Hypothesis/Objectives Veterinary students trained in FCU can differentiate dogs with subclinical MMVD based on left ventricular (LV) and left atrial (LA) dimensions. Animals Forty‐eight dogs with subclinical MMVD. Methods Veterinary students were trained to measure LV dimension and LA‐to‐aortic root dimension ratio (LA : Ao) using FCU. Dogs were categorized into 2 cohorts based on whether or not the LV normalized internal diastolic dimension was ≥1.7 and LA : Ao was ≥1.6. Agreement between FCU and echocardiographic studies performed by cardiologists was evaluated. Results One‐hundred and forty‐six FCU examinations were performed by 58 veterinary students on 48 dogs. Overall agreement between students and cardiologists was moderate (Fleiss' kappa, 0.54; 95% confidence interval [CI], 0.39‐0.69; P

Abstract Background Poor natriuresis is a potential marker of diuretic resistance in dogs with acute congestive heart failure (CHF) but little is known about the relationship between urine sodium concentration (uNa) and frequency of successful decongestion. Supplemental O2 is a common treatment in dogs with severe CHF. The time from start to discontinuation of supplemental O2 therapy (DCSO2) typically reflects the time course and ease of decongestion. Hypothesis/Objectives Urine Na concentration after IV administration of furosemide will be correlated with duration of treatment with supplemental O2 (timeO2) and the cumulative frequency of successful DCSO2 during hospitalization. Animals Fifty‐one dogs with acute CHF. Methods Retrospective observational single center study. Results Dogs with low uNa had significantly longer mean timeO2 than dogs with high uNa (uNa

Abstract Background Little is known about the effect of renin angiotensin aldosterone system‐inhibiting (RAASi) drugs on alternative angiotensin peptides (APs) such as angiotensin 1‐7 (Ang1‐7), which are mediated by angiotensin‐converting enzyme 2 (ACE2). Hypothesis/Objectives Angiotensin receptor blockers (ARBs) would alter balance of APs and differences would be magnified in vitro by incubation of plasma samples with recombinant human ACE2 (rhACE2). Animals Six cats with cardiomyopathy (CM), 8 healthy cats. Methods Prospective open label trial. Plasma equilibrium concentrations of APs were measured in healthy cats as well as in CM cats that first received no RAASi drugs (CMnoRAASi) and then after 14 days of PO telmisartan (CMARB). Plasma APs also were measured after in vitro incubation with rhACE2. Results No significant differences were found between healthy and CMnoRAASi groups. Concentrations of several APs, including angiotensin I (AT1) and angiotensin II (AT2) were significantly different between CMnoRAASi and CMARB groups. Incubation with rhACE2 decreased AT1 and AT2 in both groups. The geometric mean concentration of Ang1‐7 was significantly higher in CMARB (4.9 pg/mL; 95% confidence interval [CI], 3.7‐6.4 pg/mL) vs CMnoRAASi (3.2 pg/mL; 95% CI, 2.2‐4.7 pg/mL; P = .01) and in CMARB + ACE2 (5.0 pg/mL; 95% CI, 3.9‐6.4 pg/mL) vs CMnoRAASi + ACE2 (3.0 pg/mL; 95% CI, 1.7‐5.5 pg/mL; P = .01). The most favorable theoretical AP profile that maximized Ang1‐7 and other alternative APs was CMARB + ACE2. Conclusions and Clinical Importance Balance between traditional and alternative APs can be favorably shifted using ARBs and in vitro incubation with rhACE2. These data shed light on new AP‐targeting strategies in cats with CM.

Abstract Background The pathophysiology of heart failure involves maladaptive angiotensin peptides (APs) and enzymes, including angiotensin 2 (AT2) and angiotensin converting enzyme (ACE), as well as recently described alternative components, such as angiotensin 1‐7 (Ang1‐7) and angiotensin converting enzyme 2 (ACE2). The relative effects of different neurohormonal‐targeting drugs on balance of APs in dogs with heart disease are unknown. Hypothesis/Objectives Plasma AP concentrations differ in dogs receiving angiotensin converting enzyme inhibitors (ACEIs) vs angiotensin receptor blockers (ARBs) and recombinant human ACE2 (rhACE2) will further increase these differences. Animals Eight dogs with degenerative mitral valve disease (DMVD). Methods Prospective open‐label trial. Equilibrium concentrations of APs from plasma during PO ACEI treatment and then after 14 days of PO ARB treatment using telmisartan were measured using liquid chromatography‐tandem mass spectroscopy before and after in vitro incubation with rhACE2. Results Concentration of Ang1‐7 was increased during ARB treatment (Ang1‐7: 443 pg/mL; 95% confidence interval [CI] = 247‐794 pg/mL) vs ACEI (Ang1‐7: 182 pg/mL; 95% CI = 66.2‐503 pg/mL; P = .01). Incubation with rhACE2 decreased traditional APs while increasing beneficial alternative APs, and Ang1‐7 was significantly higher in the ARB + rhACE2 (880 pg/mL; 95% CI = 560‐1383 pg/mL) vs ACEI + rhACE2 (455 pg/mL; 95% CI = 188‐1104 pg/mL; P = .03) group. The most favorable theoretical AP profile was achieved in the ARB + rhACE2 group. Conclusions and Clinical Importance The AP profile during telmisartan treatment is associated with higher plasma Ang1‐7 as compared with during ACEI. This favorable shift is potentiated in vitro by combination of ARB + rhACE2. These data support potential AP‐targeting strategies and drugs in dogs with DMVD.