RESULTS OF THE MULTICENTER SPANIEL TRIAL (MUST) - TAURINE-RESPONSIVE AND CARNITINE-RESPONSIVE DILATED CARDIOMYOPATHY IN AMERICAN COCKER-SPANIELS WITH DECREASED PLASMA TAURINE CONCENTRATION

Fourteen American Cocker Spaniels (ACS) with dilated cardiomyopathy (D CM) were studied to determine if individuals of this breed with DCM ar e systemically taurine-or carnitine-deficient and to determine if they are responsive to taurine and carnitine supplementation. American Coc ker Spaniels with DCM were identified using echocardiography, and plas ma was analyzed for taurine and carnitine concentrations. Each dog was randomly assigned to receive either taurine and carnitine supplementa tion or placebos. Echocardiograms and clinical examinations were repea ted monthly for 4 months. During this period, the investigators and ow ners were blinded with respect to the treatment being administered. Ea ch dog was weaned off Its cardiovascular drugs (furosemide, digoxin, a nd an angiotensin converting enzyme inhibitor) if an echocardiographic response was identified. At the 4-month time period, each investigato r was asked to decide whether he or she thought his or her patient was receiving placebo or taurine/ carnitine, based on presence or absence of clinical and echocardiographic improvement. Unblinding then occurr ed, and dogs receiving placebos were switched to taurine and carnitine supplementation and followed monthly for 4 additional months. All dog s were reexamined 6 months after starting supplementation; survival ti me and cause of death were recorded for each dog. Data from 3 dogs wer e not included because of multiple protocol violations. Each dog had a plasma taurine concentration <50 nmol/ml. (mean +/-SD for the group 1 5 +/- 17 nmol/ mL) at baseline; normal range, 50-180 nmol/mL. The plas ma taurine concentration did not exceed 50 nmol/mL at any time in the dogs receiving placebos (n = 5), but increased to 357 +/- 157 nmol/mL (range 140-621 nmol/mL) during taurine and carnitine supplementation ( n = 11). Plasma carnitine concentration was within, only slightly belo w, or slightly above reported limits of normality at baseline (29 +/- 15 mu mol/L); did not change during placebo administration; and increa sed significantly during supplementation (349 +/- 119 mu mol/L; n = 11 ). Echocardiographic variables did not change during placebo administr ation. During supplementation, left ventricular end-diastolic and end- systolic diameters, and mitral valve E point-to-septal separation decr eased significantly in both groups. Shortening fraction increased sign ificantly but not into the normal range. Echocardiographic variables r emained improved at 6 months. All dogs were successfully weaned off fu rosemide, an angiotensin converting enzyme inhibitor, and digoxin once an echocardiographic response was identified. Nine of the dogs have d ied since the onset of the study in 1992. One dog died of recurrence o f DCM and heart failure 31 months after starting supplementation; six dogs died of noncardiac causes. Two dogs developed degenerative mitral valve disease and died of complications of this disease. Dogs less th an 10 years of age lived for 46 +/- 11 months, whereas dogs older than 10 years of age lived for 14 +/- 7 months. Two of the 11 dogs were al ive at the time of publication, having survived for 3.5 and 4.5 years, respectively. We conclude that ACS with DCM are taurine-deficient and are responsive to taurine and carnitine supplementation. Whereas myoc ardial function did not return to normal in most dogs, it did improve enough to allow discontinuation of cardiovascular drug therapy and to maintain a normal quality of life for months to years. Copyright (C) 1 997 by the American College of Veterinary Internal Medicine.