Paradoxical improvement of mitral regurgitation associated with hyperadrenocorticism-related cardiac hypertrophy in a dog with myxomatous mitral valve disease
Authors: Hyo-Seung Nam, Yein Oh
Published: 2026

ABSTRACT
In this case report, we describe an atypical clinical course in a dog with preexisting myxomatous mitral valve disease (MMVD) subsequently complicated by the development of hyperadrenocorticism. Typically, hyperadrenocorticism can exacerbate cardiac conditions; however, this dog demonstrated paradoxical improvement. A retrospective analysis of the clinical, radiographic, echocardiographic, and hormonal data was conducted to investigate the marked reduction in cardiac size in a Maltese dog with MMVD following the diagnosis of hyperadrenocorticism. A 10-year-old spayed female Maltese dog presented with dyspnea. The initial clinical presentation, diagnosis of MMVD, subsequent identification of hyperadrenocorticism, and observed changes in cardiac size were comprehensively documented. At initial presentation, the dog exhibited severe cardiomegaly and left-sided heart failure due to mitral valve prolapse associated with MMVD and resulting severe mitral regurgitation. Nineteen months later, hyperadrenocorticism was diagnosed. Subsequent echocardiography revealed ventricular hypertrophy and diastolic dysfunction, which may have contributed to changes in mitral valve geometry and reduced mitral regurgitation. Echocardiography revealed a significant reduction in cardiomegaly and an improvement in hemodynamic parameters. Diuretic therapy was gradually discontinued, and the dog was successfully managed with pimobendan and trilostane. This case report highlights the complex interplay between hyperadrenocorticism and MMVD and demonstrates an atypical clinical outcome characterized by cardiac improvement.

Background

Myxomatous mitral valve disease (MMVD) is the most common degenerative acquired cardiac condition in aging dogs, characterized by progressive mitral valve degeneration leading to mitral regurgitation (MR). As MR worsens, left atrial and ventricular enlargement occur, and the resulting elevation in left atrial pressure ultimately leads to left-sided congestive heart failure, typically presenting as dyspnea. Diuretics are essential for symptomatic management during American College of Veterinary Internal Medicine (ACVIM) stage C of MMVD. In the absence of surgical mitral repair, the disease typically progresses to stage D and may result in cardiac death (Keene et al. 2019). The accurate assessment of MR severity is critical for monitoring disease progression and guiding treatment strategies. Quantitative echocardiographic indices, such as regurgitant volume and regurgitant fraction, provide an objective evaluation of MR burden. Additionally, semi-quantitative measures, including the mitral regurgitant jet area-to-left atrial area ratio, provide practical clinical insight. The combined use of these variables facilitates a comprehensive and dynamic assessment of disease status and cardiac remodeling (Muzzi et al. 2003).

Canine hyperadrenocorticism (HAC) is an endocrine disorder characterized by chronic glucocorticoid excess. Cardiovascular complications, including systemic hypertension and increased risk of thromboembolic events, may occur in affected dogs (Behrend et al. 2013). Elevated glucocorticoid levels reportedly induce left ventricular hypertrophy through the activation of the renin-angiotensin system and direct stimulation of cardiac myocyte receptors (Chen et al. 2014).

Although MMVD and HAC are common in aging dogs, limited information is available regarding their coexistence and the potential effects of endocrine dysfunction on MR severity and cardiac structure. In this report, we describe the case of a dog with ACVIM stage C MMVD that remained clinically stable with medical management but was subsequently diagnosed with HAC 19 months after initial presentation. Notably, the onset of HAC was associated with myocardial hypertrophy, resulting in a paradoxical reduction in MR and marked improvement in the echocardiographic indices of left heart size. This case report provides a novel perspective on the dynamic interplay between the endocrine and cardiovascular systems, underscoring the significance of hormonal influences in the diagnosis, management, and prognosis of chronic valvular heart disease.

Case presentation

A 10-year-old spayed female Maltese dog presented to our hospital with labored breathing. On physical examination, the body weight (BW) had decreased from a previously stable 4.2 kg to 3.7 kg. Auscultation revealed a grade 4/6 left apical systolic murmur at the cardiac apex and crackles in the right caudal lung field. The respiratory rate was 42 breaths per minute, and the systemic systolic blood pressure was measured using an indirect Doppler method, with the cuff placed around the proximal portion of the limb. A size 3 cuff was used. Measurements were obtained while the patient was as calm as possible, and the final value was calculated as the average of five readings, excluding the highest and lowest values. The resulting value was 108 mmHg. Hematological and biochemical analyses (Table 1) revealed no significant abnormalities aside from mild hypokalemia, mild thrombocytosis, and slight elevations in the aspartate aminotransferase (AST), alanine aminotransferase (ALT), and blood urea nitrogen (BUN) levels. Radiographic examination revealed a vertebral heart size (VHS) of 14.2 (> 10.5) and vertebral left atrial size (VLAS) of 3.4 (> 3.0), indicating severe cardiomegaly (Table 2; Fig. 1) (Keene et al. 2019). Mild perihilar infiltration was also observed on the right lateral view. In the ventrodorsal view, mild infiltration was observed in the right caudal lung lobe. Serial echocardiographic examinations were performed using commercially available ultrasound systems (Vivid E90, GE Healthcare; ARIETTA 850, Hitachi Aloka Medical) with phased-array transducers. The initial echocardiographic examination at the time of pulmonary edema was performed by a different operator, whereas all subsequent examinations were performed by the same operator. To minimize inter-operator variability, consistent imaging planes and measurement techniques were applied across all examinations. All studies were conducted under similar conditions without sedation. Heart rate, cardiac rhythm, and blood pressure were recorded at the time of examination. Standard right parasternal and left apical views were obtained, and measurements were performed were performed using consistent imaging planes and techniques across serial examinations. Color Doppler and spectral Doppler settings were kept as consistent as possible across examinations. Echocardiographic examination (Table 2; Fig. 1) identified marked mitral valve prolapse associated with severe mitral regurgitation. Key measurements included a left ventricular internal diameter in diastole normalized to BW (LVIDDN) of 2.31 (> 2.3), a left atrial to aortic root ratio (LA:Ao) of 2.34 (1.91–2.5), a fractional shortening (FS) of 58.8% (> 50%), and an early diastolic transmitral flow velocity (E peak) of 2.2 m/s (> 1.5) (Vezzosi et al. 2021). The semi-quantitative assessment of MR, expressed as the ratio of the MR jet area to LA area, was 82.8%. Quantitative assessment of MR was performed using Doppler-derived volumetric methods by calculating the regurgitant volume and fraction from four echocardiographic parameters. Aortic valve diameter measured during systole from the right parasternal five-chamber view was used to estimate the forward stroke volume through the aorta. Mitral valve diameter at the leaflet tips was measured during early diastole from the left apical four-chamber view to calculate mitral forward stroke volume. The time–velocity integrals of the E and A waves were obtained from pulsed-wave Doppler in the left apical four-chamber view, and the time–velocity integral of aortic outflow was measured from the left apical five-chamber view. Quantitative assessment of MR was performed using Doppler-derived regurgitant volume and regurgitant fraction. For each Doppler-derived variable, measurements were repeated and averaged over three consecutive cardiac cycles. No clinically relevant arrhythmias were observed during the echocardiographic examinations. Aortic and mitral annular dimensions were measured at consistent anatomic levels across examinations, using the same measurement approach whenever possible. Quantitative evaluation revealed a regurgitant volume and fraction of 14.39 mL and 73.79%, respectively (Muzzi et al. 2003). Based on the presence of respiratory distress and pulmonary infiltration confirmed on radiographic examination, the dog was classified as having ACVIM stage C (Keene et al. 2019). Clinical signs improved following two intravenous injections of furosemide at a dose of 2 mg/kg administered 2 h apart, in combination with supplemental oxygen therapy. The patient was subsequently stabilized and managed without respiratory distress using oral furosemide (2 mg/kg BID), enalapril (0.5 mg/kg BID), pimobendan (0.3 mg/kg BID), and spironolactone (1 mg/kg BID).

Fig. 1Thoracic radiographs and echocardiographic images at initial presentation. (a) Right lateral chest radiographs showing a vertebral heart size (VHS) of 14.2 and a vertebral left atrial size (VLAS) of 3.4, indicating cardiomegaly. Mild perihilar infiltration is also noted. (b) Ventrodorsal chest radiograph demonstrating mild infiltration in the right caudal lung lobe. (c) Bidimensional right parasternal four-chamber long-axis echocardiographic view revealing marked mitral valve prolapse. (d) Color Doppler left apical echocardiographic view showing a mitral regurgitation jet to LA area ratio of 82.8%. (e) M-mode right parasternal short-axis echocardiographic view indicating a normalized left ventricular internal diameter during diastole (LVIDDN) of 2.31. (f) Bidimensional right parasternal short-axis echocardiographic view showing a two-dimensional left atrial-to-aortic root ratio (LA:Ao) of 2.34. (g) Pulsed wave Doppler left apical four-chamber echocardiographic view showing a transmitral E wave velocity of 2.2 m/s

Thoracic radiographs and echocardiographic images at initial presentation. (a) Right lateral chest radiographs showing a vertebral heart size (VHS) of 14.2 and a vertebral left atrial size (VLAS) of 3.4, indicating cardiomegaly. Mild perihilar infiltration is also noted. (b) Ventrodorsal chest radiograph demonstrating mild infiltration in the right caudal lung lobe. (c) Bidimensional right parasternal four-chamber long-axis echocardiographic view revealing marked mitral valve prolapse. (d) Color Doppler left apical echocardiographic view showing a mitral regurgitation jet to LA area ratio of 82.8%. (e) M-mode right parasternal short-axis echocardiographic view indicating a normalized left ventricular internal diameter during diastole (LVIDDN) of 2.31. (f) Bidimensional right parasternal short-axis echocardiographic view showing a two-dimensional left atrial-to-aortic root ratio (LA:Ao) of 2.34. (g) Pulsed wave Doppler left apical four-chamber echocardiographic view showing a transmitral E wave velocity of 2.2 m/s

Table 1Blood test results between initial presentation and 19 months laterVariablesReference intervalBeforeAfterHCT (%)37.3–61.752.946.0WBC (K/µL)5.05–16.768.679.69NEU (K/µL)2.95–11.645.737.07LYM (K/µL)1.05–5.12.332.05PLT (K/µL)148–484499629GLU (mg/dL)70–143112107TP (g/dL)5.2–8.27.77.5ALB (g/dL)2.2–3.93.93.3GLOB (g/dL)2.5–4.53.84.2AST (U/L)0–50109104ALT (U/L)10–100186155ALP (U/L)23–21249104GGT (U/L)0–1101CHOL (mg/dL)110–320316334T.BIL (mg/dL)0–0.90.30.3BUN (mg/dL)7–272829CREA (mg/dL)0.5–1.41.00.9P (mg/dL)2.5–6.83.94.2Ca (mg/dL)7.9–1210.79.9SDMA (µg/dL)0–14712CRP (mg/dL)0–0.9< 0.9< 0.9CPL (ng/mL)0–200< 50152.8D-DIMER (µg/mL)0–0.3< 0.10.1Na+ (mmol/L)145–151146148K+ (mmol/L)3.9–5.13.24.19Cl− (mmol/L)110–119113116HCT, Hematocrit; WBC, White blood cell; NEU, Neutrophil; LYM, Lymphocyte; PLT, Platelet; GLU, Glucose; TP, Total protein; ALB, Albumin; GLOB, Globulin; AST, Aspartate aminotransferase; ALT, Alanine aminotransferase; ALP, Alkaline Phosphatase; GGT, Gamma-Glutamyl Transferase; CHOL, Cholesterol; T.BIL, Total bilirubin; BUN, Blood urea nitrogen; CREA, Creatinine; P, Phosphorus; Ca, Calcium; SDMA, Symmetric Dimethylarginine; CRP, C-reactive protein; CPL, canine pancreatic lipase

Table 1Blood test results between initial presentation and 19 months laterVariablesReference intervalBeforeAfterHCT (%)37.3–61.752.946.0WBC (K/µL)5.05–16.768.679.69NEU (K/µL)2.95–11.645.737.07LYM (K/µL)1.05–5.12.332.05PLT (K/µL)148–484499629GLU (mg/dL)70–143112107TP (g/dL)5.2–8.27.77.5ALB (g/dL)2.2–3.93.93.3GLOB (g/dL)2.5–4.53.84.2AST (U/L)0–50109104ALT (U/L)10–100186155ALP (U/L)23–21249104GGT (U/L)0–1101CHOL (mg/dL)110–320316334T.BIL (mg/dL)0–0.90.30.3BUN (mg/dL)7–272829CREA (mg/dL)0.5–1.41.00.9P (mg/dL)2.5–6.83.94.2Ca (mg/dL)7.9–1210.79.9SDMA (µg/dL)0–14712CRP (mg/dL)0–0.9< 0.9< 0.9CPL (ng/mL)0–200< 50152.8D-DIMER (µg/mL)0–0.3< 0.10.1Na+ (mmol/L)145–151146148K+ (mmol/L)3.9–5.13.24.19Cl− (mmol/L)110–119113116HCT, Hematocrit; WBC, White blood cell; NEU, Neutrophil; LYM, Lymphocyte; PLT, Platelet; GLU, Glucose; TP, Total protein; ALB, Albumin; GLOB, Globulin; AST, Aspartate aminotransferase; ALT, Alanine aminotransferase; ALP, Alkaline Phosphatase; GGT, Gamma-Glutamyl Transferase; CHOL, Cholesterol; T.BIL, Total bilirubin; BUN, Blood urea nitrogen; CREA, Creatinine; P, Phosphorus; Ca, Calcium; SDMA, Symmetric Dimethylarginine; CRP, C-reactive protein; CPL, canine pancreatic lipase

Blood test results between initial presentation and 19 months later

HCT, Hematocrit; WBC, White blood cell; NEU, Neutrophil; LYM, Lymphocyte; PLT, Platelet; GLU, Glucose; TP, Total protein; ALB, Albumin; GLOB, Globulin; AST, Aspartate aminotransferase; ALT, Alanine aminotransferase; ALP, Alkaline Phosphatase; GGT, Gamma-Glutamyl Transferase; CHOL, Cholesterol; T.BIL, Total bilirubin; BUN, Blood urea nitrogen; CREA, Creatinine; P, Phosphorus; Ca, Calcium; SDMA, Symmetric Dimethylarginine; CRP, C-reactive protein; CPL, canine pancreatic lipase

Table 2Echocardiographic and radiographic variables at initial presentation, 19 months later, and 13 months after diuretic withdrawalCardiac indexInitial presentation19 months later13 months after diuretic withdrawalLA:Ao(< 1.70 = score 1 ; 1.70–1.90 = score 2 ; 1.91–2.5 = score 3 ; > 2.50 = score 4)2.341.641.67LVIDDN(< 1.70 = score 1; 1.70-2.00 = score 2; 2.10–2.30 = score 3; > 2.30 = score 4)2.311.141.31LVIDd (mm)34.418.4120.43LVIDs (mm)14.211.8611.23IVSd (mm)6.010.2212.11LVPWd (mm)4.08.957.69FS (%)58.835.6245.06E peak (m/s)(< 1.20 = score 1; 1.20–1.50 = score 2; >1.5 = score 3)2.20.450.43Regurgitant volume (mL)(mild MR = 5.39 ± 3.24, moderate MR = 15.21 ± 10.05, severe MR = 32.92 ± 20.28)14.395.982.42Regurgitant fraction (%)(mild MR = 33 ± 11.74, moderate MR = 57 ± 14.32, severe MR = 75 ± 8.08)73.7936.5018.14Ratio of the MR jet area to the LA area (%)(< 30% =mild MR 30%-70%=moderate MR, > 70% =severe MR)82.836.6418.15VHS(No heart enlargement < 10.5)14.21211.8VLAS(Left atrial enlargement > 3)3.42.52.3LA:Ao ratio, left atrial-to-aortic root ratio; LVIDDN, left ventricular internal diameter in diastole normalized to body weight; LVIDd, left ventricular internal diameter in diastole; LVIDs, left ventricular internal diameter in systole; IVSd, interventricular septal thickness in diastole; LVPWd, left ventricular posterior wall thickness in diastole; FS, fractional shortening; E peak, early diastolic transmitral flow velocity; MR, mitral regurgitation; LA, left atrium; VHS, vertebral heart size; VLAS, vertebral left atrial size. Score categories for LA:Ao, LVIDDN, and E peak are based on the Mitral INsufficiency Echocardiographic (MINE) score classification described by Vezzosi et al. (2021). Quantitative assessment of regurgitant volume, regurgitant fraction, and MR jet area ratio follows the method of Muzzi et al. (2003). Vertebral heart size (VHS) and vertebral left atrial size (VLAS) classifications follow ACVIM consensus guidelines (Keene et al. 2019)

Table 2Echocardiographic and radiographic variables at initial presentation, 19 months later, and 13 months after diuretic withdrawalCardiac indexInitial presentation19 months later13 months after diuretic withdrawalLA:Ao(< 1.70 = score 1 ; 1.70–1.90 = score 2 ; 1.91–2.5 = score 3 ; > 2.50 = score 4)2.341.641.67LVIDDN(< 1.70 = score 1; 1.70-2.00 = score 2; 2.10–2.30 = score 3; > 2.30 = score 4)2.311.141.31LVIDd (mm)34.418.4120.43LVIDs (mm)14.211.8611.23IVSd (mm)6.010.2212.11LVPWd (mm)4.08.957.69FS (%)58.835.6245.06E peak (m/s)(< 1.20 = score 1; 1.20–1.50 = score 2; >1.5 = score 3)2.20.450.43Regurgitant volume (mL)(mild MR = 5.39 ± 3.24, moderate MR = 15.21 ± 10.05, severe MR = 32.92 ± 20.28)14.395.982.42Regurgitant fraction (%)(mild MR = 33 ± 11.74, moderate MR = 57 ± 14.32, severe MR = 75 ± 8.08)73.7936.5018.14Ratio of the MR jet area to the LA area (%)(< 30% =mild MR 30%-70%=moderate MR, > 70% =severe MR)82.836.6418.15VHS(No heart enlargement < 10.5)14.21211.8VLAS(Left atrial enlargement > 3)3.42.52.3LA:Ao ratio, left atrial-to-aortic root ratio; LVIDDN, left ventricular internal diameter in diastole normalized to body weight; LVIDd, left ventricular internal diameter in diastole; LVIDs, left ventricular internal diameter in systole; IVSd, interventricular septal thickness in diastole; LVPWd, left ventricular posterior wall thickness in diastole; FS, fractional shortening; E peak, early diastolic transmitral flow velocity; MR, mitral regurgitation; LA, left atrium; VHS, vertebral heart size; VLAS, vertebral left atrial size. Score categories for LA:Ao, LVIDDN, and E peak are based on the Mitral INsufficiency Echocardiographic (MINE) score classification described by Vezzosi et al. (2021). Quantitative assessment of regurgitant volume, regurgitant fraction, and MR jet area ratio follows the method of Muzzi et al. (2003). Vertebral heart size (VHS) and vertebral left atrial size (VLAS) classifications follow ACVIM consensus guidelines (Keene et al. 2019)

Echocardiographic and radiographic variables at initial presentation, 19 months later, and 13 months after diuretic withdrawal

LA:Ao

(< 1.70 = score 1 ; 1.70–1.90 = score 2 ; 1.91–2.5 = score 3 ; > 2.50 = score 4)

LVIDDN

(< 1.70 = score 1; 1.70-2.00 = score 2; 2.10–2.30 = score 3; > 2.30 = score 4)

E peak (m/s)

(< 1.20 = score 1; 1.20–1.50 = score 2; >1.5 = score 3)

Regurgitant volume (mL)

(mild MR = 5.39 ± 3.24, moderate MR = 15.21 ± 10.05, severe MR = 32.92 ± 20.28)

Regurgitant fraction (%)

(mild MR = 33 ± 11.74, moderate MR = 57 ± 14.32, severe MR = 75 ± 8.08)

Ratio of the MR jet area to the LA area (%)

(< 30% =mild MR 30%-70%=moderate MR, > 70% =severe MR)

VHS

(No heart enlargement < 10.5)

VLAS

(Left atrial enlargement > 3)

LA:Ao ratio, left atrial-to-aortic root ratio; LVIDDN, left ventricular internal diameter in diastole normalized to body weight; LVIDd, left ventricular internal diameter in diastole; LVIDs, left ventricular internal diameter in systole; IVSd, interventricular septal thickness in diastole; LVPWd, left ventricular posterior wall thickness in diastole; FS, fractional shortening; E peak, early diastolic transmitral flow velocity; MR, mitral regurgitation; LA, left atrium; VHS, vertebral heart size; VLAS, vertebral left atrial size. Score categories for LA:Ao, LVIDDN, and E peak are based on the Mitral INsufficiency Echocardiographic (MINE) score classification described by Vezzosi et al. (2021). Quantitative assessment of regurgitant volume, regurgitant fraction, and MR jet area ratio follows the method of Muzzi et al. (2003). Vertebral heart size (VHS) and vertebral left atrial size (VLAS) classifications follow ACVIM consensus guidelines (Keene et al. 2019)

Nineteen months after the initial diagnosis, the patient developed clinical signs suggestive of HAC, including polydipsia, polyuria, polyphagia, weight gain, and a pronounced pot-bellied appearance. The BW had increased to 4.98 kg, and auscultation revealed a diminished left systolic apical murmur (graded at 2/6). Systemic systolic blood pressure, measured using a Doppler device, was elevated at 140 mmHg compared with the previous assessment. Blood test results revealed no significant abnormalities aside from mild thrombocytosis and mild elevations in the AST, ALT, cholesterol, and BUN levels. Although ALP was not markedly increased, which is not uncommon in dogs with HAC, the diagnosis was established based on the combination of clinical signs, imaging findings, urinary testing, and hormonal evaluation. A comparison of the blood test results at initial presentation and 19 months is presented in Table 1. Radiographic examination (Fig. 2) revealed a decreased VHS of 12 and reduced VLAS of 2.5 (versus 14.2 and 3.4 at initial presentation, respectively). Hepatomegaly was also observed. Abdominal ultrasound (Fig. 2) showed bilateral adrenal gland enlargement, with the left adrenal gland measuring 1.47 cm (cranial pole) and 0.83 cm (caudal pole) and right adrenal gland measuring 0.5 cm (cranial pole) and 0.76 cm (caudal pole). A urinary cortisol-to-creatinine ratio test was performed using morning urine samples collected at home over 3 days in a stress-free environment, yielding values of 39, 37, and 36, all exceeding the reference threshold of 34. The urinary cortisol-to-creatinine ratio was measured using a commercial assay (IDEXX Laboratories, Westbrook, ME, USA) and interpreted according to manufacturer guidelines. In the adrenocorticotropic hormone (ACTH) stimulation test, serum cortisol concentrations were measured using an in-house commercial immunoassay analyzer. The reference intervals and diagnostic interpretation for the ACTH stimulation test were as follows: post-ACTH cortisol concentrations < 2 µg/dL were considered consistent with hypoadrenocorticism in the presence of clinical signs; 2–6 µg/dL were considered equivocal; 6–18 µg/dL were considered within the normal range; 18–22 µg/dL were considered suggestive of hyperadrenocorticism; and > 22 µg/dL were considered consistent with hyperadrenocorticism in the presence of compatible clinical signs (IDEXX Laboratories Inc., Westbrook, ME, USA). The ACTH stimulation test was performed using Synacthen® (tetracosactide), administered intravenously at a dose of 0.005 mg/kg. Post-ACTH cortisol levels were measured 1 h after administration. No exogenous glucocorticoids had been administered within the previous 3 months. The pre-ACTH cortisol level was 2.5 µg/dL, whereas the post-ACTH cortisol level exceeded 30 µg/dL. Based on symptoms, imaging findings, urinalysis, and hormonal testing, a definitive diagnosis of HAC was established. Echocardiographic examination (Fig. 2) revealed left ventricular hypertrophy, with an interventricular septal thickness in diastole normalized to BW (IVSdN) of 0.7 (reference value < 0.44) and a left ventricular posterior wall thickness in diastole normalized to BW (LVPWdN) of 0.58 (reference value < 0.47) (Matos et al. 2024). The E/A ratio was 0.58 (reference range: 1–2) (Matos et al. 2024), confirming left ventricular diastolic dysfunction. Mild systolic narrowing of the left ventricular outflow tract was observed; however, no systolic anterior motion of the mitral valve was identified, and LVOT velocity remained within normal limits, indicating no hemodynamically significant obstruction (Schober et al. 2022). These findings were consistent with HAC-associated myocardial hypertrophy. Notably, significant hypertrophy of the interventricular septum and left ventricular wall may have altered left ventricular and mitral valve geometry, which was associated with a marked reduction in MR. The ratio of the MR jet area to LA area decreased to 36.64% (versus 82.8% at initial presentation). The regurgitant volume reduced to 5.98 mL, and the regurgitant fraction decreased to 36.5% compared with previous measurements (versus 14.39 mL and 73.79% at initial presentation, respectively). Consequently, the previously noted severe left atrial enlargement, left ventricular enlargement, and elevated E peak showed marked improvement. Notable echocardiographic improvements included a LVIDDN of 1.14 (versus 2.31), a LA:Ao of 1.64 (versus 2.34), an FS of 35.62% (versus 58.8), and an E peak of 0.45 m/s (versus 2.2). The MINE score improved from 13 at initial presentation to 4 at the 19-month follow-up (Vezzosi et al. 2021). A comparison of the radiographic and echocardiographic results at initial presentation and 19 months is presented in Table 2. Furosemide was gradually tapered over 5 months with close monitoring of cardiac size to ensure the absence of recurrent cardiomegaly. The dog remained clinically stable and free of heart failure symptoms for 13 months following the discontinuation of furosemide, enalapril, and spironolactone, while being managed solely with pimobendan. Pimobendan was administered at 0.3 mg/kg BID. Pimobendan was continued based on the patient’s history of ACVIM stage C MMVD and persistent mitral regurgitation, considering its overall hemodynamic benefits, although the optimal management strategy in such complex cases remains uncertain. Trilostane was initiated for the management of HAC. Trilostane was initiated at 1 mg/kg BID and subsequently titrated to 2.2 mg/kg BID based on monitoring for drug efficacy and potential adverse effects related to hypoadrenocorticism. At the current dosage, the post-ACTH cortisol concentration was 10 µg/dL. Clinical signs reported by the owner, including polyuria, polydipsia, and polyphagia, showed partial improvement. At 13 months following discontinuation of diuretics, interventricular septal and left ventricular wall thickness remained increased, while left ventricular internal dimension in diastole showed a mild increase compared to previous measurements but remained within normal limits, suggesting that these findings were not solely attributable to reduced preload. The echocardiographic and radiographic findings obtained 13 months after diuretic discontinuation are presented in Table 2; Fig. 3. A clinical timeline summarizing the disease course, treatment modifications, and associated cardiac changes is presented in Fig. 4.

Fig. 2Thoracic radiographs, abdominal ultrasound, and echocardiographic images obtained 19 months after the initial diagnosis. (a) Right lateral chest radiograph showing a vertebral heart size (VHS) of 12 and a vertebral left atrial size (VLAS) of 2.5, indicating a decrease in cardiac size. (b) Abdominal ultrasound showing enlargement of the left adrenal gland, measuring 1.47 cm at the cranial pole and 0.83 cm at the caudal pole. (c) Abdominal ultrasound showing enlargement of the right adrenal gland, measuring 0.5 cm at the cranial pole and 0.76 cm at the caudal pole. (d) Left apical echocardiographic view demonstrating a reduction in the mitral regurgitant (MR) jet area-to-left atrial (LA) area ratio to 36.6%. (e) Right parasternal long-axis echocardiographic view showing mild systolic narrowing of the left ventricular outflow tract with apparent thickening of the interventricular septum. (f) M-mode image from the right parasternal short-axis view showing interventricular septal thickness in diastole normalized for body weight (IVSdN) at 0.7 and LVPWdN at 0.58, indicating myocardial thickening. The normalized left ventricular internal diameter in diastole (LVIDDN) is reduced 1.14. (g) Two-dimensional LA:Ao ratio measured at 1.64 from the right parasternal short axis view, showing a decrease from baseline. (h) Left apical echocardiographic view showing a transmitral E wave velocity of 0.45 m/s and an E/A ratio of 0.58, consistent with diastolic dysfunction

Thoracic radiographs, abdominal ultrasound, and echocardiographic images obtained 19 months after the initial diagnosis. (a) Right lateral chest radiograph showing a vertebral heart size (VHS) of 12 and a vertebral left atrial size (VLAS) of 2.5, indicating a decrease in cardiac size. (b) Abdominal ultrasound showing enlargement of the left adrenal gland, measuring 1.47 cm at the cranial pole and 0.83 cm at the caudal pole. (c) Abdominal ultrasound showing enlargement of the right adrenal gland, measuring 0.5 cm at the cranial pole and 0.76 cm at the caudal pole. (d) Left apical echocardiographic view demonstrating a reduction in the mitral regurgitant (MR) jet area-to-left atrial (LA) area ratio to 36.6%. (e) Right parasternal long-axis echocardiographic view showing mild systolic narrowing of the left ventricular outflow tract with apparent thickening of the interventricular septum. (f) M-mode image from the right parasternal short-axis view showing interventricular septal thickness in diastole normalized for body weight (IVSdN) at 0.7 and LVPWdN at 0.58, indicating myocardial thickening. The normalized left ventricular internal diameter in diastole (LVIDDN) is reduced 1.14. (g) Two-dimensional LA:Ao ratio measured at 1.64 from the right parasternal short axis view, showing a decrease from baseline. (h) Left apical echocardiographic view showing a transmitral E wave velocity of 0.45 m/s and an E/A ratio of 0.58, consistent with diastolic dysfunction

Fig. 3Thoracic radiographs and echocardiographic images obtained 13 months after diuretic withdrawal. (a) Right lateral chest radiographs showing a vertebral heart size (VHS) of 11.8 and a vertebral left atrial size (VLAS) of 2.3, indicating no progression of cardiac enlargement and a stable cardiac silhouette following diuretic withdrawal. (b) Ventrodorsal chest radiograph demonstrating clear lung fields without pulmonary infiltration after diuretic withdrawal. (c) Bidimensional right parasternal short-axis echocardiographic view showing a two-dimensional left atrial-aortic root ratio (LA:Ao) of 1.67. (d) Two-dimensional echocardiographic image obtained in diastole from the right parasternal short-axis view, demonstrating persistent myocardial thickening consistent with structural changes associated with hyperadrenocorticism despite diuretic withdrawal. (e) M-mode right parasternal short-axis echocardiographic view demonstrating persistent concentric myocardial hypertrophy, with increased normalized interventricular septal thickness (IVSdN 0.86) and left ventricular posterior wall thickness (LVPWdN 0.52), while the normalized left ventricular internal diameter in diastole (LVIDDN 1.31) remained essentially unchanged despite diuretic withdrawal. (f) Color Doppler left apical echocardiographic view showing a MR jet to LA area ratio of 18.15%. (g) Pulsed wave Doppler left apical four-chamber echocardiographic view showing a transmitral E wave velocity of 0.43 m/s and an E/A ratio of 0.55, indicating ongoing diastolic dysfunction

Thoracic radiographs and echocardiographic images obtained 13 months after diuretic withdrawal. (a) Right lateral chest radiographs showing a vertebral heart size (VHS) of 11.8 and a vertebral left atrial size (VLAS) of 2.3, indicating no progression of cardiac enlargement and a stable cardiac silhouette following diuretic withdrawal. (b) Ventrodorsal chest radiograph demonstrating clear lung fields without pulmonary infiltration after diuretic withdrawal. (c) Bidimensional right parasternal short-axis echocardiographic view showing a two-dimensional left atrial-aortic root ratio (LA:Ao) of 1.67. (d) Two-dimensional echocardiographic image obtained in diastole from the right parasternal short-axis view, demonstrating persistent myocardial thickening consistent with structural changes associated with hyperadrenocorticism despite diuretic withdrawal. (e) M-mode right parasternal short-axis echocardiographic view demonstrating persistent concentric myocardial hypertrophy, with increased normalized interventricular septal thickness (IVSdN 0.86) and left ventricular posterior wall thickness (LVPWdN 0.52), while the normalized left ventricular internal diameter in diastole (LVIDDN 1.31) remained essentially unchanged despite diuretic withdrawal. (f) Color Doppler left apical echocardiographic view showing a MR jet to LA area ratio of 18.15%. (g) Pulsed wave Doppler left apical four-chamber echocardiographic view showing a transmitral E wave velocity of 0.43 m/s and an E/A ratio of 0.55, indicating ongoing diastolic dysfunction

Fig. 4Patient timeline. Clinical timeline illustrating the progression of myxomatous mitral valve disease (MMVD), the development of hyperadrenocorticism (HAC), associated cardiac remodeling, and changes in medical management. *ACVIM, American College of Veterinary Internal Medicine; HAC, hyperadrenocorticism; MMVD, myxomatous mitral valve disease

Patient timeline. Clinical timeline illustrating the progression of myxomatous mitral valve disease (MMVD), the development of hyperadrenocorticism (HAC), associated cardiac remodeling, and changes in medical management. *ACVIM, American College of Veterinary Internal Medicine; HAC, hyperadrenocorticism; MMVD, myxomatous mitral valve disease

Discussion and conclusion

This case report presents an atypical clinical course, in which a dog with ACVIM stage C MMVD exhibited significant structural cardiac improvement following the onset of HAC. Typically, MMVD is a progressive condition, characterized by worsening MR, left atrial and ventricular enlargement, and an eventual transition to congestive heart failure, requiring escalating doses of diuretics (Keene et al. 2019). By contrast, the present case demonstrated a paradoxical reduction in MR and cardiac chamber dimensions, ultimately allowing for the discontinuation of furosemide, enalapril, and spironolactone, while pimobendan was maintained. Spontaneous improvement of MR is exceedingly rare in MMVD. However, HAC-associated myocardial hypertrophy in this dog may have altered left ventricular and mitral valve geometry, which was associated with a reduction in regurgitation. The observed decline in regurgitant volume (from 14.39 mL to 5.98 mL), regurgitant fraction (from 73.79% to 36.5%), and MR jet area-to-LA area ratio (from 82.8% to 36.64%) indicates a meaningful physiological change rather than mere measurement variation. However, the MR jet area-to-LA area ratio is a semi-quantitative parameter and should be interpreted with caution, as it can be influenced by loading conditions, jet eccentricity, and technical factors such as color Doppler gain and Nyquist limit. In the present case, Doppler settings, including gain and Nyquist limit, were kept as consistent as possible across examinations to minimize technical variability. Furthermore, MR severity was assessed using multiple complementary parameters, including Doppler-derived regurgitant volume and regurgitant fraction, as well as LA:Ao, LVIDDN, and transmitral E wave velocity. Radiographic findings were also considered in the overall assessment. Therefore, the reduction in MR severity was interpreted in the context of these combined findings rather than relying on a single parameter. These improvements were accompanied by echocardiographic evidence of reverse remodeling, including normalization of the LA:Ao, LVIDDN, and E wave velocity. Clinical severity, measured by the MINE score, also improved dramatically, from an initial score of 13, indicative of a late-stage condition with a median survival time of 157 days (95% confidence interval: 53–257 days), to a score of 4, indicating a mild clinical state at 19 months post-diagnosis (Vezzosi et al. 2021). In this study, the original MINE score was used for severity assessment. While a simplified version (MINE score 2) has been recently proposed, it was specifically developed and validated in dogs with preclinical MMVD and therefore does not include advanced stages such as congestive heart failure. In contrast, the present case involved ACVIM stage C disease with dynamic changes in cardiac structure over time. The original MINE score, which includes a late-stage category, allows a more comprehensive assessment across the full spectrum of disease severity. Although fractional shortening (FS) has known limitations due to its load dependency, it may still reflect clinically relevant changes in ventricular dynamics in conditions associated with significant alterations in preload and afterload, as observed in this case. Furthermore, at the time of manuscript preparation, the original MINE score represented the standard echocardiographic severity classification available.

The cardiovascular effects of chronic glucocorticoid excess are multifactorial. Prolonged exposure may induce systemic hypertension and activate the renin–angiotensin–aldosterone system, contributing to increased afterload and myocardial remodeling (Behrend et al. 2013). Additionally, direct stimulation of mineralocorticoid and glucocorticoid receptors in cardiomyocytes promotes concentric hypertrophy, particularly in the interventricular septum and left ventricular posterior wall (Chen et al. 2014). In this dog, hypertrophy of both regions was evident, along with diastolic dysfunction (E/A ratio: 0.58), consistent with the echocardiographic phenotype of hypertrophic cardiomyopathy (HCM). Although primary HCM in dogs is rare and requires the exclusion of systemic causes such as HAC, renal disease, and systemic hypertension (Schober et al. 2022), the pattern of ventricular thickening observed in this case is more consistent with that in secondary HAC-associated myocardial hypertrophy. Notably, the myocardial hypertrophy appeared to exert a compensatory effect on mitral valve function, as evidenced by reduced MR severity and improved hemodynamic parameters. Although spontaneous reduction in MR is extremely rare in dogs, a few human case reports have documented similar improvements attributed to mitral valve leaflet remodeling, particularly anterior leaflet elongation (Asmer et al. 2010). However, such mechanisms have not been reported in veterinary patients and differ fundamentally from the endocrine-driven cardiac remodeling observed in this dog. Although pseudohypertrophy due to reduced preload should be considered, particularly in patients receiving diuretics, similar echocardiographic findings were observed even after discontinuation of diuretics and during long-term follow-up. In addition, no laboratory evidence suggestive of dehydration or hypovolemia was identified at the time of initial hypertrophic changes. These findings make hypovolemia-related pseudohypertrophy less likely as the sole explanation, although a definitive distinction cannot be made. Although pimobendan may theoretically influence ventricular loading conditions and myocardial structure, the observed concentric hypertrophy in this case is more likely associated with HAC-related myocardial remodeling, although a contributory role of pimobendan cannot be entirely excluded. This case report underscores the potential impact of systemic endocrine disorders on the progression and clinical trajectory of chronic cardiac diseases. Underlying hormonal conditions, such as HAC, should be considered in dogs with MMVD that exhibit atypical clinical responses or unexpected echocardiographic changes. Although this case report suggests a transient beneficial effect of HAC-associated myocardial hypertrophy on MR severity, HAC remains a pathological condition. If left untreated, it may lead to systemic hypertension, thromboembolic complications, and progressive cardiovascular dysfunction. In this dog, trilostane therapy was initiated to regulate cortisol levels and mitigate these risks.

Further research is warranted to explore the complex interplay between the endocrine and cardiovascular systems in dogs. Future studies involving serial echocardiography, myocardial histopathology, and molecular analyses are essential to elucidate the mechanisms by which HAC-associated myocardial alterations influence the progression of MMVD. This case report provides novel insights into an underrecognized aspect of canine cardiology and highlights the importance of a multidisciplinary approach in managing patients with concurrent endocrine and cardiac disorders.

This case report illustrates an atypical clinical course in which secondary myocardial remodeling associated with HAC coincided with a marked reduction in MR in a dog with ACVIM stage C MMVD. Contrary to the expected progression of cardiac enlargement and increasing reliance on diuretics, the patient demonstrated structural cardiac improvement, ultimately enabling the discontinuation of furosemide, enalapril, and spironolactone, with continued administration of pimobendan. The reduction in regurgitant burden may have been associated with alterations in left ventricular and mitral valve geometry in the setting of interventricular septal and left ventricular hypertrophy. Importantly, HAC remains a pathological condition, and the observed reduction in MR should not be interpreted as a beneficial effect of untreated HAC. Rather, this case highlights that endocrine-associated myocardial remodeling may alter the clinical and echocardiographic expression of MMVD. Although this outcome may represent an incidental effect rather than a consistent pathophysiological benefit, it highlights the complexity of endocrine–cardiac interactions. Further investigation is needed to clarify how systemic endocrine disorders may alter the course of chronic valvular heart disease.