Thanks for the US FDA reference. I perused much of it, but didn't see a warning. The "Conclusion" section states that VetMedin is effective in "the management of the signs of mild, moderate, or severe (modified NYHA Class II, III, or IV) congestive heart failure in dogs due to AVVI or DCM, when used in combination with other appropriate congestive heart failure therapy." Are you suggesting this being a warning for dogs not yet in CHF?
Yes. FDA approved pimo for dogs in CHF. FDA did not approve pimo for dogs not in CHF. FDA found that:
"VETMEDIN administered to healthy Beagles at three and five times the recommended dose caused severe left ventricular hypertrophy with multifocal subendocardial ischemic lesions, myxomatous thickening of the mitral valves, mitral valve insufficiency murmurs, left atrial jet lesions, endocardial thickening of the left ventricular outflow tract, a granulomatous lesion within the right atrial myocardium, decreased blood pressure, increased heart rate, and a subtle increase in ventricular premature contractions. These effects are typical of positive inotropic and vasodilator drug toxicity in normal dogs."
This means the healthy lab dogs -- those not in CHF -- suffered severe damage to their hearts as a result of taking pimo.
I have a call into the cardiologist. I anticipate she will say she believes Vetmedin is warranted for Freckles, given her Stage B2 condition, even with those references. (This is what the vet told me, based on her experience with Cavaliers, even after perusing, at my request, the "A Few Words About Pimobendan" section of
http://cavalierhealth.org/mitral_valve_disease.htm.) What then? Consult with another cardiologist (which will likely take some weeks to get an appointment with)?
It is up to you. If it was my dog, I would not give pimo prior to CHF. Been there; done that; won't ever do it again.
Update: I re-read the "A Few Words About Pinobendan" section. It states: "The FDA report states that pimobendan "is indicated for use with concurrent therapy for congestive heart failure (e.g., furosemide, etc.) as appropriate on a case-by-case basis." Furosemide is a diuretic." That sounds as though Furosemide is meant only for dogs in CHF, too, doesn't it? (As I've mentioned, Freckles is already taking Furosemide and Enalapril.)
Diuretics like furosemide are separate drugs from pimo, so different protocols apply to them. The ACVIM Consensus Statement --
http://www.cavalierhealth.org/images/acvim_guidelines_ccvhd_2009.pdf -- does not mention the use of furosemide for Stage B2 dogs. It does list it for Stage C dogs, meaning dogs in CHF. And this makes sense, because diuretics are given to reduce excess fluid, which is what "congested" means, in terms of fluid in the lungs due to heart failure.
Why is Freckles being given a diuretic if she is not in CHF? If she has fluid in the lungs, then she may be in Stage C, in which case this whole thread about no pimo before CHF may be moot.
As for the enalapril, which is an ACE-Inhibitor, the ACVIM Consensus Statement has not endorsed ACE-I therapy of MVD dogs at Stage B2 MVD. Further, ACE-inhibitors have not been approved for veterinary medicine for MVD dogs in Stage B2 by regulating authorities. Therefore, giving a non-CHF dog enalapril is called an "off label" prescription.
An additional reason for not prescribing ACE-inhibitors prior to congestive heart failure is a 2002 Scandinavian study (the "Scandinavian Veterinary Enalapril Prevention [SVEP] Trial") of
229 asymptomatic cavalier King Charles spaniels with mild MVD murmurs, which has shown that ACE-inhibitors had no significant affect upon the time from the initiation of ACE-I therapy to the point of heart failure. A 2007 study (the "VETPROOF Trial"), sponsored by a drug manufacturer and involving 124 dogs of several breeds (including only 10 cavaliers), showed that enalapril given to dogs with only mild MVD murmurs and some enlargement of the heart but which otherwise are symptomless, "modestly delayed" the onset of CHF. Further, in a 2013 study by Thai graduate students, of twenty dogs (none CKCS) in Stage B2, they found that ramipril did not affect cardiac chamber size, mitral regurgitation severity and systolic function assessed by echocardiography in 91-day period of treatment.
Based upon the SVEP study mentioned above, Dr. Mark Oyama, a board certified veterinary cardiologist at the University of Pennsylvania, told me that it is "a no-brainer" to hold off on giving cavaliers enalapril prior to CHF.
It also states: "the drug should not be prescribed for dogs whose hearts have remained strong despite the MVD". How can I know whether Freckles' heart has "remained strong" despite the MVD?
An ultrasound should enable the cardiologist to determine the strength of the heart muscle.
Lastly, it states: "Bottom line: pimobendan is hazardous to the health of cavaliers with MVD murmurs but no symptoms." Doesn't Freckles' enlarged heart and the presence of fluid indicate she has the symptoms they're referring to?
An enlarged heart is not a symptom. That would be a Stage B2 dog. The presence of fluid may be part of a symptom. Symptoms are such things as:
-- Class II: fatigue, shortness of breath, coughing, apparent when ordinary exercise is exceeded.
-- Class III: exercise capacity is minimal.
-- Class IV: no capacity for exercise and disabling clinical signs are present even at rest