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Background: Predicting progression of myxomatous mitral valve disease (MMVD) in dogs can be challenging. Hypothesis/Objectives: The mitral regurgitation severity index (MRSI) will predict time to congestive heart failure (CHF) and all‐cause death in dogs with MMVD. Animals: Eight hundred sixty‐nine client‐owned dogs. Methods: Retrospective study pooling data from 4 previous samples including dogs with MMVD stage B2 or C. MRSI was calculated as: (heart rate [HR]/120) × left atrium‐to‐aorta ratio (LA:Ao) × (age in years/10) × 100. Alternative MRSI formulas substituting radiographic measures of left atrial size were also calculated. Cox proportional hazard modeling and time‐dependent receiver‐operator characteristic curves quantified prognostic performance. Results: For Stage B2 pooled samples, MRSI > 156 was predictive of time to CHF (median 407 vs 1404 days; area under the curve [AUC] 0.68; hazard ratio 3.02 [95% CI 1.9‐4.9]; P <.001). MRSI > 173 was predictive of all‐cause death (median survival 868 vs 1843 days; AUC 0.64; hazard ratio 4.26 [95% CI 2.4‐7.5]; P <.001). MRSI showed superior predictive value compared to the individual variables of HR, LA:Ao, and age. Variations of the MRSI equation substituting radiographic vertebral left atrial size for LA:Ao were also significantly predictive of outcome in stage B2. MRSI was not consistently predictive of outcome in Stage C. Conclusions and Clinical Importance: MRSI was predictive of outcome (onset of CHF and all‐cause death) in MMVD Stage B2, demonstrating utility as a useful prognostic tool. Echocardiographic LA:Ao can be effectively replaced by radiographically determined LA size in the MRSI formula. [ABSTRACT FROM AUTHOR]

Diuretics, such as furosemide, are routinely administered to dogs with congestive heart failure (CHF). Traditionally, dose and determination of efficacy primarily are based on clinical signs rather than quantitative measures of drug action. Treatment of human CHF patients increasingly is guided by quantification of urine sodium concentration (uNa) and urine volume after diuretic administration. Use of these and other measures of diuretic responsiveness is associated with decreased duration of hospitalization, complication rates, future rehospitalization, and mortality. At their core, loop diuretics act through natriuresis, and attention to body sodium (Na) stores and handling offers insight into the pathophysiology of CHF and pharmacology of diuretics beyond what is achievable from clinical signs alone. Human patients with low diuretic responsiveness or diuretic resistance are at risk for difficult or incomplete decongestion that requires diuretic intensification or other remedial strategies. Identification of the specific etiology of resistance in a patient can help tailor personalized interventions. In this review, we advance the concept of loop diuretic responsiveness by highlighting Na and natriuresis. Specifically, we review body water homeostasis and congestion in light of the increasingly recognized role of interstitial Na, propose definitions for diuretic responsiveness and resistance in veterinary subjects, review relevant findings of recent studies, explain how the particular cause of resistance can guide treatment, and identify current knowledge gaps. We believe that a quantitative approach to loop diuretic usage primarily involving natriuresis will advance our understanding and care of dogs with CHF. [ABSTRACT FROM AUTHOR]

Background: Estrogen modulates the renin‐angiotensin‐aldosterone system (RAAS) in women, but sex differences have not been fully explored in dogs. Objective: We hypothesized that the RAAS profile of intact female (IF) Doberman Pinschers (DP) would differ from spayed female (SF) and intact male (IM) DP. Animals: Eighteen healthy DP (6 IF, 6 SF, 6 IM). Methods: Absolute and indexed RAAS metabolites, angiotensin‐converting enzyme (ACE) and ACE2 activities, and genotypes (pyruvate kinase dehydrogenase 4, titin, and ACE variants) were compared among sex groups using Kruskal‐Wallis or chi‐square tests, and linear regression controlling for age. Data are expressed as median (minimum, maximum) and P <.05 was considered significant. Results: The ACE activity was higher in IF DP (656 pmol/L; 436, 784) compared to SF DP (411 pmol/L; 287, 451; P =.01) and IM DP (365 pmol/L; 276, 1200; P =.04) after controlling for age. Angiotensin II, angiotensin I, and plasma renin activity marker (PRA‐S) were higher in IF DP compared to SF DP, but not significantly (P ≤.25). After controlling for age, angiotensin 1‐7/angiotensin I was lower in IF DP compared to SF DP (P =.01). Genotypes did not differ among groups. Most DP (94%) were ACE variant positive. Conclusions and Clinical Significance: Sex and reproductive status influenced the RAAS of DP, with IF DP showing genotype‐independent higher ACE activity. These findings hold implications for sterilization practices in female dogs, and support sex and reproductive status as a source of variability in RAAS studies. Additionally, the frequency of the ACE gene variant was very high in this group of DP. [ABSTRACT FROM AUTHOR]

Background: Hypochloremia associated with congestive heart failure (CHF) in dogs is likely multifactorial. Loop diuretics cause 1:2 sodium [Na+]:chloride [Cl−] loss, whereas water retention causes a 1:1 [Na+]:[Cl−] dilution. Mathematical [Cl−] correction separates these effects on [Cl−]. Hypothesis: We hypothesized that corrected [Cl−] (c[Cl−]) would not differ from measured [Cl−] (m[Cl−]) in dogs with controlled CHF because of loop diuretics, and dogs with refractory CHF would have higher c[Cl−] than m[Cl−], indicating relative water excess. Animals Seventy‐one client‐owned dogs with acquired heart disease, without CHF (NO‐CHF), 76 with Stage C CHF and 24 with Stage D CHF. Methods: Clinicopathological data from a previous study were retrospectively analyzed. Corrected [Cl−], m[Cl−], and differences were compared among NO‐CHF, Stage C CHF, and Stage D CHF, using the formula: c[Cl−] = (mid‐reference range [Na+]/measured [Na+]) × m[Cl−]. Results: Corrected [Cl−] and m[Cl−] were lower in Stage D vs Stage C and NO‐CHF (all P <.0001). The c[Cl−] was higher than m[Cl−] in Stage D (P <.0001) but not Stage C or NO‐CHF. Median difference between c[Cl−] and m[Cl−] was higher for Stage D vs Stage C (P =.0003). No hypochloremic Stage D dogs had normal c[Cl−], but 11/24 had [Cl−] that was increased by >2 mmol/L. Conclusions and Clinical Importance: Serum [Cl−] increased after mathematical correction in Stage D CHF dogs but not in Stage C and NO‐CHF dogs. Although c[Cl−] was higher than m[Cl−] in Stage D dogs supportive of relative water excess, hypochloremia persisted, consistent with concurrent loop diuretic effects on electrolytes. Future study correlating c[Cl−] to antidiuretic hormone concentrations is warranted. [ABSTRACT FROM AUTHOR]

Background: Refractory congestive heart failure (CHF) and associated diuretic resistance are not well defined. Objectives: To characterize renal function, electrolyte concentrations, indices of diuretic efficacy, and renin‐angiotensin‐aldosterone system (RAAS) activation in dogs with naturally occurring heart disease (HD) in American College of Veterinary Internal Medicine stages B1, B2, C, and D and to determine their usefulness in defining HD stages. Animals: Group 1:149 dogs with HD stages B1, B2, C, and D. Group 2:22 dogs with HD stages C and D. Methods: Group 1: Renal parameters, serum and urine electrolyte and diuretic concentrations, and urine aldosterone concentrations were measured. Medication dosages and measured variables were compared among stages. Correlation of furosemide dosages to serum concentrations was explored. Group 2: Angiotensin‐converting enzyme activity and RAAS components were measured and compared among CHF stages. Results: Serum chloride concentration was the best differentiator of HD stage. Furosemide PO dosages (≤6 mg/kg/day) were weakly correlated with serum furosemide concentrations, whereas higher dosages were not significantly correlated. Angiotensin‐converting enzyme inhibitor dosage and RAAS inhibition were greater in stage D, compared to stage C dogs. Conclusions and Clinical Importance: Hypochloremia is a useful marker for stage D HD in dogs. Poor furosemide dosage correlation to serum concentration may indicate variable and poor absorption, especially at higher dosages, advanced disease, or both. A small number of stage D dogs met proposed criteria for diuretic resistance. Greater RAAS inhibition in stage D versus stage C indicates effectiveness of RAAS‐suppressive treatments in this group of dogs with refractory CHF. [ABSTRACT FROM AUTHOR]