The study cohort comprised 82 client-owned dogs, all free of clinical signs of pancreatitis and gastrointestinal disease. Sixty-seven dogs had myxomatous mitral valve disease, classified according to the American College of Veterinary Internal Medicine consensus statement: 24 in stage B1, 22 in stage B2, 9 in stage C without cardiac medication, and 12 in stage C with cardiac medication. Fifteen healthy dogs served as controls. The breed distribution reflected the typical small-breed predisposition of the disease, with Maltese, Pomeranians, Toy Poodles, and Spitz dominating the MMVD group. Serum pancreatic lipase activity was measured using a validated colorimetric assay based on the DGGR substrate, a point-of-care test widely used in veterinary practice.

The central finding emerged from a comparison that previous studies had never made. Among dogs not receiving cardiac medications, pancreatic lipase activity did not differ significantly across disease stages (Kruskal–Wallis H = 0.488; df = 3; P = .921). This was a striking result, because it meant that disease severity—whether the dog had early-stage valve changes or full-blown congestive heart failure—had no measurable effect on the pancreatic enzyme marker. The result directly contradicts earlier reports that had linked pancreatic lipase immunoreactivity to congestive heart failure and to echocardiographic indices of cardiac remodeling, including left atrial-to-aortic root ratio and normalized left ventricular internal diameter in diastole.

When medicated stage C dogs entered the analysis, the picture changed dramatically. These dogs had significantly higher pancreatic lipase activity than every other group. The Hodges–Lehmann median differences were substantial: 67.5 U/L above healthy controls (95% CI, 19.0–184.0), 57.0 U/L above stage B1 (95% CI, 12.0–145.0), 65.8 U/L above stage B2 (95% CI, 18.0–156.0), and 58.0 U/L above non-medicated stage C dogs (95% CI, 9.0–268.0). Effect sizes, measured with Cliff’s δ, ranged from 0.56 to 0.67—large by conventional standards. More clinically alarming, 25% of medicated stage C dogs (3 of 12) exceeded 400 U/L, a diagnostic threshold suggestive of pancreatitis, whereas no non-medicated stage C dog reached this level. Notably, these three dogs showed no signs of gastrointestinal disease during long-term therapy, and prior abdominal imaging in two cases confirmed no ultrasonographic abnormalities of the pancreas.

The correlation analyses added a temporal dimension to the finding. Among the 12 medicated stage C dogs, pancreatic lipase activity was positively correlated with the duration of furosemide administration (Spearman ρ = 0.67; 95% CI, 0.10–0.91; P = .028) and with the duration of angiotensin-converting enzyme inhibitor administration (ρ = 0.62; 95% CI, 0.01–0.89; P = .048). Pimobendan, the positive inotrope that is standard therapy for advanced MMVD, showed no significant correlation (ρ = 0.50; P = .104). The longer the dogs had been on the diuretic and the ACE inhibitor, the higher their pancreatic enzyme activity climbed—a dose–duration relationship that points toward a pharmacological mechanism rather than a hemodynamic one.

The multivariable linear regression analysis sealed the argument. After adjusting for age, ACVIM stage, and symmetric dimethylarginine concentration—a renal marker that could theoretically confound lipase levels through reduced clearance—medication status was the only independent predictor of pancreatic lipase activity (P = .004). On the log10-transformed scale, the regression coefficient for medication was 0.414, corresponding to an approximately 2.59-fold higher pancreatic lipase activity in medicated dogs compared with non-medicated dogs. The overall model was statistically significant (adjusted R² = 0.14; P = .01), and neither age nor SDMA reached independent significance. Renal dysfunction, historically invoked as an explanation for hyperlipasemia in dogs with cardiac disease, was excluded by design: dogs with serum creatinine above 1.4 mg/dL or SDMA above 18 μg/dL were excluded according to International Renal Interest Society guidelines.

The pharmacological mechanisms behind the furosemide association are plausible and well documented. High-ceiling diuretics reduce pancreatic blood flow by causing extracellular volume loss, an effect demonstrated in experimental pharmacology studies. Long-term furosemide treatment in rats has been shown to alter the electrolyte composition of pancreatic acinar cells and to cause accumulation of secretory material within the pancreatic ductules, leading to direct cellular toxicity and obstruction of the pancreatic tissue. Furosemide has previously been identified as a potential risk factor for pancreatitis in dogs in a case-control analysis of 101 cases. Angiotensin-converting enzyme inhibitors, meanwhile, have been linked to pancreatitis in humans, possibly through local angioedema or direct pancreatic toxicity, and a population-based case-control study found an increased risk of acute pancreatitis among ACE inhibitor users.

Pimobendan’s apparent neutrality is equally informative. An experimental study using a canine tachycardia-induced heart failure model showed that pimobendan preserved pancreatic blood flow and prevented acinar cell injury by maintaining cardiac output. This finding is highly relevant clinically, because pimobendan is the standard treatment for most dogs with advanced MMVD. The drug may, in effect, offset the hypoperfusion that heart failure would otherwise impose on the pancreas—suggesting that the standard cardiac regimen is not uniformly harmful, but that specific components of it carry pancreatic risk.

The implications for clinical interpretation are immediate. Elevated pancreatic lipase activity in a dog with MMVD has traditionally been read as evidence of pancreatic injury driven by the failing heart. The new data suggest that this interpretation should be reevaluated. The elevations reported in earlier studies might have been confounded by concurrent cardiac medication use—particularly furosemide and ACE inhibitors—which are the standard treatment regimens for dogs with congestive heart failure. The correlation between serum lipase activity and echocardiographic indices of remodeling reported in previous work might represent confounding by long-term medication administration rather than a direct effect of cardiac remodeling. Veterinarians interpreting pancreatic lipase results in dogs with MMVD should now consider medication history alongside disease stage.

The study has limitations that warrant cautious interpretation. As a retrospective cross-sectional analysis, it can describe associations but cannot establish causal relationships. The sample size in certain subgroups was limited, and the correlation analyses evaluating medication duration should be considered exploratory, potentially subject to type I errors due to the lack of adjustment for multiple comparisons. The statistical significance in the medicated stage C group was largely driven by three dogs with markedly elevated values, and non-medicated stage C dogs generally presented with their first episode of congestive heart failure, whereas medicated dogs were under long-term management—so disease chronicity could have contributed to the difference. Dose–response relationships could not be evaluated retrospectively, and concurrent abdominal ultrasonography was not performed for the entire cohort. Stored serum samples were used, but DGGR lipase activity is known to remain stable at −80°C for up to 12 months, making storage effects unlikely. Prospective studies with larger populations, longitudinal follow-up, and standardized pancreatic imaging are needed to confirm the relationship. Withholding essential cardiac medications from dogs with heart failure would be ethically inappropriate, so the retrospective design, for all its constraints, offers insights that a randomized trial never could.

Subject of Research: veterinary cardiology

Article Title: Evaluation of serum pancreatic lipase activity in dogs with myxomatous mitral valve disease

Article References: Kim, C., Chae, Y., Yun, T., Kang, B.-T., & Kim, H. (2026). Evaluation of serum pancreatic lipase activity in dogs with myxomatous mitral valve disease. Journal of Veterinary Internal Medicine, 40(5), Article aalag218. https://doi.org/10.1093/jvimsj/aalag218

Image Credits: AI Generated

DOI: 10.1093/jvimsj/aalag218

Keywords: myxomatous mitral valve disease, pancreatic lipase, furosemide, ACE inhibitors, pimobendan, canine pancreatitis, veterinary medicine, cardiac medications, Evaluation, serum, pancreatic, lipase

Myxomatous mitral valve disease is a degenerative condition in which the mitral valve, the one-way gate between the left atrium and left ventricle of the heart, gradually thickens and deforms. The disease involves profound changes in the cellular makeup and extracellular matrix of the valve tissue, particularly in collagen content and alignment. The spongy middle layer of the valve leaflets expands as proteoglycans accumulate, while activated myofibroblasts break down collagen and elastin through increased release of proteolytic enzymes. The result is a malformed valve apparatus that no longer seals properly, allowing blood to leak backward from the left ventricle into the left atrium with every heartbeat. This leakage, known as mitral regurgitation, drives progressive enlargement of the left-sided heart chambers and eventually culminates in congestive heart failure.

A key anatomical feature in this disease is the coaptation gap, the space between the anterior and posterior leaflets of the mitral valve when they should be meeting to form a seal. The larger this gap, the greater the volume of blood that escapes backward with each contraction. In most patients, once heart failure sets in, the only options are medications to manage the symptoms and, in some specialized centers, surgical valve repair. Without surgery, the valve condition deteriorates in nearly all cases, and as diuretic resistance develops and the ceiling effect of these drugs is reached, patients progress to Stage D of the American College of Veterinary Internal Medicine classification, a refractory state defined in dogs by a total daily furosemide dose of 8 milligrams per kilogram or an equivalent torsemide dosage. At that point, the prognosis is grim.

The three dogs in the report, all Maltese, arrived at the hospital with classic signs of left heart failure: coughing, breathing difficulties, and elevated sleeping respiratory rates. All three underwent echocardiography performed by a single experienced operator using the same ultrasound system, with standardized imaging views and measurement protocols applied consistently. Each dog showed severe mitral regurgitation, partial rupture of the chordae tendineae, the tendon-like strands that anchor the valve leaflets, and significant enlargement of the left atrium and left ventricle. Standard heart failure treatment was initiated, including furosemide, an angiotensin-converting enzyme inhibitor, pimobendan, and spironolactone, and in all cases the clinical symptoms improved. What happened next was anything but standard.

The first case, a 14-year-old spayed female Maltese, presented with a sleeping respiratory rate exceeding 35 breaths per minute for more than three consecutive days. Her initial echocardiogram revealed an anterior mitral valve leaflet thickened to 4.63 millimeters, a coaptation gap of 4.18 millimeters, and a regurgitant volume of 98.8 milliliters with a regurgitant fraction of 95.4 percent, figures consistent with catastrophic valve leakage. Her furosemide dose was eventually escalated to 8 milligrams per kilogram per day along with torsemide at 0.4 milligrams per kilogram per day. Yet 26 months after her initial visit, radiographs showed her heart had shrunk, with the vertebral heart size falling from 12.8 to 11.6 and the vertebral left atrial size dropping from 3.2 to 2.4. The valve had actually thickened further to 9.55 millimeters, but the coaptation gap had vanished, becoming too small to measure. Her regurgitant volume plummeted to 5.67 milliliters and the regurgitant fraction to 34.5 percent. She has now been managed with pimobendan alone for six months, free of diuretics.

The second case, a 9-year-old castrated male Maltese, arrived with dyspnoea and coughing and required intravenous furosemide and oxygen supplementation to stabilize. His initial echocardiogram showed a coaptation gap of 3.61 millimeters, a regurgitant fraction of 96 percent, and a regurgitant jet occupying 88.5 percent of the left atrial area. Twenty-eight months later, his vertebral heart size had decreased from 11.3 to 10.0, the coaptation gap was no longer measurable, and the jet area ratio had collapsed to 11.1 percent, indicating mild regurgitation. His regurgitant volume fell from 28.33 to 3.46 milliliters. He has been maintained on pimobendan alone for 22 months. The third case, a 12-year-old castrated male Maltese, followed a similar arc over 12 months: his regurgitant fraction dropped from 96.36 to 62.61 percent, his left atrial-to-aortic ratio improved from 2.53 to 1.55, and he has been diuretic-free for nine months.

The quantitative echocardiographic methods used to track these changes were rigorous. Regurgitant volume and regurgitant fraction were calculated from four key measurements: the diameter of the aortic valve during systole, the velocity-time integral of aortic outflow, the diameter at the tips of the mitral leaflets during early diastole, and the velocity-time integrals of the E and A waves of mitral inflow. A semi-quantitative measure, the ratio of the regurgitant jet area to the left atrial area, provided an additional cross-check. In all three dogs, every parameter moved in the direction of improvement, even as the valves themselves continued to degenerate and thicken, a paradoxical combination that has never before been documented at this stage of the disease.

The authors propose that the phenomenon may parallel rare human cases in which severe regurgitation caused by a flail mitral valve improves spontaneously. In human medicine, such improvement has been attributed to mitral valve adaptation, in which the anterior leaflet enlarges to close the coaptation gap, promoting reverse ventricular remodelling without surgery. This process has been suggested to involve the reactivation of embryonic developmental pathways, including endothelial-to-mesenchymal transformation, leading to increased leaflet area and thickness that restore coaptation and reduce leakage. Whether a similar mechanism operated in these dogs remains unknown, and the authors caution that the exact structural changes underlying their observations are unclear. The report also acknowledges an important limitation: the contribution of pimobendan, a drug known to improve haemodynamics, cannot be fully excluded, although there is currently limited evidence that it can induce marked and sustained reductions in regurgitation severity and cardiac remodelling in advanced disease.

The prognostic implications are striking. Using the Mitral INsufficiency Echocardiographic score, a tool for predicting severity and survival in dogs with severe mitral regurgitation, the expected median survival duration for these three dogs was approximately 623 days. Instead, all three survived well beyond that window, remaining alive without dyspnoea, coughing, or syncope months to years after discontinuing diuretics. The authors suggest the cases point to three remarkable possibilities: spontaneous healing of valve function despite ongoing degeneration, reversal of cardiac remodelling without surgery, and long-term survival that current prognostic models fail to predict. Recent evidence from surgical studies has shown that restoring coaptation length can reverse remodelling even in late-stage disease, but these dogs achieved similar outcomes naturally, as if they had undergone repair without ever seeing an operating theatre.

For now, the authors emphasize caution. The prognosis for myxomatous mitral valve disease accompanied by chordae tendineae rupture remains poor, and such spontaneous improvements are exceedingly rare. But the report opens a genuinely new avenue of inquiry: if the valve apparatus can, in some patients, remodel itself to close the leak, identifying the biological signals that drive this adaptation could transform how veterinarians and perhaps even human cardiologists approach degenerative valve disease. Further research is needed to uncover the mechanisms behind this phenomenon and to find markers that might predict which patients will experience such favourable outcomes. In the meantime, three elderly Maltese dogs are breathing easily on a single daily medication, living proof that even the most predictable of diseases can occasionally surprise the experts who study it.

Subject of Research: Spontaneous reduction of mitral regurgitation in dogs with severe myxomatous mitral valve disease

Article Title: Spontaneous Reduction in Mitral Valve Regurgitation in Three Dogs With Severe Myxomatous Mitral Valve Disease: An Unusual Case Report

Article References: Nam, H.-S., & Oh, Y. (2026). Spontaneous Reduction in Mitral Valve Regurgitation in Three Dogs With Severe Myxomatous Mitral Valve Disease: An Unusual Case Report. Veterinary Medicine and Science, 12(6), Article e71155. https://doi.org/10.1002/vms3.71155

Image Credits: AI Generated

DOI: 10.1002/vms3.71155

Keywords: myxomatous mitral valve disease, mitral regurgitation, dogs, veterinary cardiology, echocardiography, coaptation gap, chordae tendineae rupture, heart failure, pimobendan, diuretics, reverse remodelling, case report