Yes....Cardiopet proBNP is useful.

Re: Yes....Cardiopet proBNP is useful.

Martin Atkinson — Tue, 21 Aug 2012 13:08:09 GMT

[quote user="David Mills"]

I assume, then, Mr Atikinson, you do this as well for both dogs and cats?

4. The client wants to spend money on something. Are you seriously suggesting you give them all the facts for and against each time? What about when they ask you, "What would you do?".

[/quote]

I don't automatically pre-emptively treat dogs because they can be treated as soon as they show symptoms and will respond in 99% of cases - you can't treat a dead cat!

I do very seriously discuss all the facts each time and I would give my own cats pre-emptive treatment with benazepril and aspirin if the NTproBNP was over 350. As every cat in my study had symptoms of cardiac failure and/or the owners reported a significant improvement in demeanour with treatment with levels above this figure I have enough faith in my findings to justify this. A cardiologist I discussed this with suggested that there was some evidence that beta blockers may help by decreasing dynamic LVOT gradients, putting less strain on the cardiac myocytes in non-symptomatic cats and thus increasing time before failure. Theoretically ACEi could worsen dynamic LVOT gradients but I think the potential to blunt the RAAS activation is more important.

I will report back in a few years time to see if I have been vindicated with increased longevity. In the meantime you can make your own judgements Mr Mills.

Re: Yes....Cardiopet proBNP is useful.

David Mills — Mon, 20 Aug 2012 16:40:33 GMT

[quote user="Martin Atkinson"]

[quote user="Simon Neuhoff"]

Pre emptively treat asymptomatic cats Martin? With what and on what basis?

[/quote] The basis is that from my little study there was a very strong correlation with cats over 357pmol/l developing cardiac failure. Given that often the first signs of cardiac failure in cats with HCM are FATE or sudden death it doesn't take a quantum leap to think that maybe it would be a good idea to pre-emptively treat. As Graham says echocardiography is still gold standard but how many cats will get echoed serially to determine when they need treatment? Therefore I think you are fully justified in putting every cat with a cardiac murmer and a NTproBNP over 350 at least onto low dose aspirin and probably also benazapril. AFAIA all human patients with a cardiac murmur are put on prophylactive ACEi and although admittedly there is little evidence to suggest that this is of benefit but equally little to show it is of harm and giving the client a choice between spending their money not knowing if the medication is beneficial but probably is, or waking up to a paralysed or dead cat I think its a no-brainer.

[/quote]

So, your clinical reasoning for ACEi goes something like this:

1. Not knowing if medication is beneficial but probably is. This is despite no studies at all in cats demonstrating any benefits. Especially devastating to this reasoning is:

http://www.ncbi.nlm.nih.gov/pubmed/17063701

There is a great phrase - 'client funded research' - which is what pre-treating effectively is. It may not do any harm - but neither does homeopathy.

2. Often ATE or sudden death - presumably you have figures to back this up? Most texts suggest around 10% develop ATE. Further to that, there are no studies demonstrating any efficacy of clopidogrel or aspirin - not even in those cats known to be hypercoagulable (i.e. those that have had ATEs in the past). Again, more client-funded research.

3. The argument that 'this is what they do in humans' is a terrible argument. Humans v rarely get primary HCM, and the use of ACEi is a whole different kettle of fish. It is not a one size fits all because the underlying mechanisms of the diseases are completely different. All humans are but on beta blockers as soon as they develop heart disease - I assume, then, Mr Atikinson, you do this as well for both dogs and cats?

4. The client wants to spend money on something. Are you seriously suggesting you give them all the facts for and against each time? What about when they ask you, "What would you do?".

Re: Yes....Cardiopet proBNP is useful.

Hannah Wynne Richards — Mon, 20 Aug 2012 15:16:07 GMT

I second that Martin

Wynne

Re: Yes....Cardiopet proBNP is useful.

Martin Atkinson — Mon, 20 Aug 2012 13:08:42 GMT

[quote user="Simon Neuhoff"]

Pre emptively treat asymptomatic cats Martin? With what and on what basis?

Re: Yes....Cardiopet proBNP is useful.

Hannah Wynne Richards — Mon, 20 Aug 2012 09:52:08 GMT

Well said Graham

Wynne

Re: Yes....Cardiopet proBNP is useful.

Graham Bilbrough — Sun, 19 Aug 2012 13:37:05 GMT

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_If_ the owner of an asymptomatic cat is able and willing for the patient to have a cardiac ultrasound, then that remains the ‘gold-standard’. There is no question of that. And, indeed, the experienced general practitioner with a high-quality US machine may well be confident and do a good job.

However, I have watched what general practice vets do as they are presented with a cat for vaccination when they find ‘a discovery’ on auscultation—and there are many such cats. In my experience, they type a note in to the pet’s record and make a nervous comment to the pet owner: “we will have a listen again next year”. Only a fraction of these cats get close to an ultrasound probe. As a generality, cat owners are slow to spend money when they do not perceive there to be a problem. General practice vets are slow to refer cats when they know the returned report will probably be "unexciting".

The situation does change with an Nt-proBNP concentration: “Tiddles seems to have increased stretch/stress on the heart and cardiac ultrasound is a good investment”. We don’t yet know whether the cat has pulmonary hypertension, cardiomyopathy or a false positive (yes, they happen) and a cardiac ultrasound is the appropriate next step.

Nt-proBNP results in more cats going for cardiac ultrasound, not fewer. If the Nt-proBNP is low, then you can provide reassurance to the pet owner.

Today, we do not recommend treatment for cats with cardiomyopathy and no symptoms. But, I still firmly believe that the owners will want to know. For comparison, we were looking for liver and renal dysfunction before we had special diets and supplements. We diagnose pancreatitis so we can discuss the likely sequelae. Furthermore, despite a lack of evidence base today, I am sure that anaesthetists would recommend different protocols. Depending on the individual cat, I might actually opt for more sedation, not less, and I would certainly avoid ketamine.

Rob rightly draws our attention to the work of Mark Kittleson’s group in the United States. This looked at a closed colony of Maine Coon cats and concluded that it only detects severe disease. We don’t know if this represents the population we see in general practice or Europe. Indeed, we could debate their definition of severe disease. That said, my experience of Maine Coon breeders is that they are very committed and demand the gold-standard. I would feel most comfortable passing these cases to a cardiologist. Obviously, Nt-proBNP is NOT a pre-breeding screen as it will tell you nothing about the likelihood of the cat passing the relevant alleles to their progeny.

By contrast, there are three independent studies (including one multicentre study) from peer-reviewed journals that suggest that Nt-proBNP can reliably discriminate normal cats from those with occult cardiomyopathy. Many of the diagnostic tests that we all use day-to-day do not have that evidence base! Their study populations vary somewhat, but this is clearly NOT a test to use in every cat that is carried through your consulting room door. However, if, after auscultation, you are suspicious, I think there is much to recommend the test for those cats—you will get confidence to invest in an ultrasound or reassurance.

Re: Yes....Cardiopet proBNP is useful.

bob lehner — Sun, 19 Aug 2012 12:15:41 GMT

[quote user="David Mills"]Further, if it does come back as showing OCM, what then? There's nothing you can give to slow the progression; you can't do anything for the cat's condition. In this instance the use if the test is simply client-funded research. [/quote]

Indeed - surely this is a very important point in the asymptomatic animal where a murmur might be picked up, say, at a vaccination check-over.

Not my area of expertise at all, but I was under the impression that in pre-symptomatic animals with MV disease or cardiomyopathy there is little or no value in treatment at that stage. Obviously quite different when symptoms are evident.

Is this still considered to be the case ??

Re: Yes....Cardiopet proBNP is useful.

David Mills — Sat, 18 Aug 2012 22:00:53 GMT

[quote user="Mark Hedberg"]

[quote user="Simon Neuhoff"]

This. So you have a routine vacc, pick up a murmur, get the Pro BNP test back - now what? How do you use this information for the benefit of that cat or the client? Stick it on aspirin? Refer it for echo - would this not have been the best bet in the first instance?

[/quote]

Not necessarily - some pets have murmurs for ages with no symptoms; and in terms of cost of examination; someone with limited funds might go for a cheaper blood test before a more expensive echo, especially if the only symptom is something the vet hears in the consult, as opposed to symptoms the owner may observe.

[/quote]

This is the whole point though - the blood test is not a good screening test and the money would be better spent - or not spent at all - on other things. There's a seduction with the blood test that its quick and easy but its incumbent on the vet to inform the owner exactly what info it will provide. In cats, there is no prognostic value (cf dogs) we're aware of. This is doubly an issue in cats with murmurs - they have heart disease - and the proBNP will not tell you a cent more. Therefore the blood test might be cheaper but that money buys you very little, if anything. The main use is in cats without murmurs - and in this population it is a poor test to pick up occult heart disease as its sens/spec is simply not high enough. It is very poor in some breed groups, as in MCs, above - the 44-55% is no better than tossing a coin!

Echo'ing a cat with no signs is not necessarily a referral job as in Big Referral - there are budding cardiologists/cert holders everywhere crying out for more cases.

Re: Yes....Cardiopet proBNP is useful.

Mark Hedberg — Sat, 18 Aug 2012 20:55:39 GMT

[quote user="Simon Neuhoff"]

[/quote]

Re: Yes....Cardiopet proBNP is useful.

Simon Neuhoff — Sat, 18 Aug 2012 16:44:00 GMT

[quote user="Martin Atkinson"]

[quote user="james herriot lied"]

In other words, if I haven't garbled that too much, is there any prognostic value in size of BNP value whilst still asymptomatic, for the disease which is presumably coming?

[/quote]

Before I comment on this I would like to say that although Graham would appear to have a vested interest in this when I did my humble little piece of investigation he was both supportive but very keen to point out the limitations of interpreting the test even though my findings have placed great faith in NTproBNP.

In answer to the question above I found that no cats showed signs of cardiac failure with a level of less than 357pmol/l (this is above Idexx's 270 cut off point) and although I would hasten to point out that this initially was in a series of 30 cats it has now risen to nearly 50 with similar results. There was a wide range of results between 357 and the maximum measurable 1047 and although the level of HTproBNP was not absolutely associated with the degree of heart disease there was a trend that those most severely affected had the highest levels. and all cats with a value over 564 showed evidence of cardiac failure or FATE either symptomatically from echocardiogaphy. There was also a correlation between rapidly rising levels of NTproBNP and the likelihood of the onset of heart disease. There is no statistical analysis of these figures I'm afraid but I am confident enough to say that I would pre-emptively treat cats with a level over 350pmol/l and serially test those over 270 to see if they are rising.

[/quote]

Pre emptively treat asymptomatic cats Martin? With what and on what basis?

Re: Yes....Cardiopet proBNP is useful.

David Mills — Sat, 18 Aug 2012 16:43:15 GMT

Understood. I wouldn't use it in this case because the diagnostic yield makes it in my view a waste of money. Echo would give you a more definite answer. Serial echo timings are subjects of opinion and their use is controversial especially given the lack of therapy available.

Re: Yes....Cardiopet proBNP is useful.

Simon Neuhoff — Sat, 18 Aug 2012 16:42:45 GMT

[quote user="David Mills"]

[quote user="robloxley"]

Was looking at proBNP for a worried Maine Coon owner and came across http://www.ncbi.nlm.nih.gov/pubmed/21036088 (NT-proBNP measurement fails to reliably identify subclinical hypertrophic cardiomyopathy in Maine Coon cats. Kittleson MD) so now not so sure where to go?

[/quote]

I don't think proBNP test is particularly useful as a 'screening' test in cats; its sensitivity/specificity is not high enough for it to perform well in the general population in this way, and arguably, it ain't designed for such. The studies above about picking out OCM cats are skewed in their population selection.

Further, if it does come back as showing OCM, what then? There's nothing you can give to slow the progression; you can't do anything for the cat's condition. In this instance the use if the test is simply client-funded research.

If the owner is worried enough then echo the cat, as it will give vastly more information that proBNP.

[/quote]

Re: Yes....Cardiopet proBNP is useful.

Rob Loxley — Sat, 18 Aug 2012 15:41:01 GMT

[quote user="David Mills"]I don't think proBNP test is particularly useful as a 'screening' test in cats; its sensitivity/specificity is not high enough for it to perform well in the general population in this way, and arguably, it ain't designed for such. [/quote]

Indeed, though it is marketed as such, depending on how much you read into "help": [quote user="Graham Bilbrough"]Nt-proBNP helps distinguishes normal cats from those with occult cardiomyopathy[/quote]

[quote user="David Mills"]If the owner is worried enough then echo the cat, as it will give vastly more information that proBNP.[/quote]

Yup, we have a Maine Coon breeder who regularly gets her stock scanned, but serial echo by a cardiologist doesn't come cheap, hence the interest in biomarkers.

Re: Yes....Cardiopet proBNP is useful.

David Mills — Sat, 18 Aug 2012 15:04:41 GMT

[quote user="robloxley"]

[/quote]

If the owner is worried enough then echo the cat, as it will give vastly more information that proBNP.

Re: Yes....Cardiopet proBNP is useful.

Rob Loxley — Sat, 18 Aug 2012 14:25:14 GMT

Re: Yes....Cardiopet proBNP is useful.

james herriot lied — Mon, 06 Feb 2012 19:51:42 GMT

Top stuff, Martin. I do remember you discussing this a while back, and it looks like you've made good use of the data. Unfortunately (!) I phoned up Idexx today to order some BNP tubes, to find that although the practice I'm at has an Idexx machine, it doesn't have a lab account. Need to sort this out.

Re: Yes....Cardiopet proBNP is useful.

Bob Russell — Mon, 06 Feb 2012 17:57:10 GMT

I think it is great that Industry members get involved with these discussions. As long as they have been open about the fact they have a vested interest then we can all make informed decisions!

We don't use this test and clearly I need to have a rethink!

Re: Yes....Cardiopet proBNP is useful.

Martin Atkinson — Mon, 06 Feb 2012 17:15:48 GMT

[quote user="james herriot lied"]

In other words, if I haven't garbled that too much, is there any prognostic value in size of BNP value whilst still asymptomatic, for the disease which is presumably coming?

[/quote]

Re: Yes....Cardiopet proBNP is useful.

Malcolm Ness — Sun, 05 Feb 2012 15:12:05 GMT

[quote user="james herriot lied"]But don't lurk hunched over the red star: it's demeaning to all of us and will just reduce the great variety of debate which we should be having on vetsurgeon[/quote]

Agree

Re: Yes....Cardiopet proBNP is useful.

james herriot lied — Sat, 04 Feb 2012 23:14:23 GMT

Can I ask, who's giving the red stars to Graham? Not sure I can see the reason for that: care to come out and comment?

Personally, I'm over the age of 13 and am not a unicorn-collecting gullible. I can see that Graham has a service to sell, and am interested in discussing it with him in theoretical terms before I use it, much in the same way as I would have a chat to a rep, but probably with more direct answers. If there's somebody out there who feels that his contribution is flawed, by all means come out and say so. But don't lurk hunched over the red star: it's demeaning to all of us and will just reduce the great variety of debate which we should be having on vetsurgeon.

Still keeping myself cheerful with thoughts of the Wales-Ireland game......

Re: Yes....Cardiopet proBNP is useful.

Laurence Webb — Sat, 04 Feb 2012 21:17:48 GMT

[quote user="james herriot lied"]We're quite a way from wetherby, so I can foresee a situation where we take 3 or 4 samples, freeze down all but one, and then keep sending them till one arrives on time[/quote] We're in the South West but IDEXX do a nightly courier from our practice so I guess they do the same for lots of the country, unless you're really remote. They also supply pre-paid special delivery envelopes so you can get guaranteed next day delivery - is this one of the reasons the 'add-on' price for BNP has gone up?

My main use of BNP has been to assess asymptomatic animals with murmurs where the owner's aren't keen to investigate. Mainly cats as they don't look ill until they're near death anyway. High BNP then I can persuade people to do some more investigation, low BNP then measure periodically and if it goes up then investigate. Is this a good use of the test?

Re: Yes....Cardiopet proBNP is useful.

Graham Bilbrough — Sat, 04 Feb 2012 20:55:29 GMT

Nt-proBNP helps distinguishes normal cats from those with occult cardiomyopathy. In the cat, we do not yet make any claim to using Nt-proBNP for prognostication. Meanwhile, in the dog, we have papers to support using Nt-proBNP for prognostication in asymptomatic small breed dogs with acquired MVD. For these "murmur dogs" that bounce around the consulting room, a yearly Cardiopet proBNP can help you know when to invest in further diagnostics.

If you are not on one of the IDEXX courier routes, we can supply you with free-of-charge guaranteed next day delivery envelops so that you can be confident that the sample will arrive within the 24 hours of stability provided by the (also free-of-charge) Cardiopet proBNP transport tubes.

If you send me an email (graham-bilbrough@idexx.com) I will send you the consumables and the scientific literature.

All the best

Graham

Re: Yes....Cardiopet proBNP is useful.

james herriot lied — Sat, 04 Feb 2012 19:58:09 GMT

[quote user="Graham Bilbrough"]

[Disclosure: I work for IDEXX Labs]

Results: NT-proBNP was higher (median, interquartile range [25th and 75th percentiles]) in

(1) OCM (186 pmol/L; 79, 478 pmol/L) versus normal (24 pmol/L; 24, 32 pmol/L) (P < .001); and

(2) hypertrophic obstructive cardiomyopathy (396 pmol/L; 205, 685 pmol/L) versus hypertrophic cardiomyopathy (112 pmol/L; 48, 318 pmol/L) (P < .001).

[/quote]

Interesting results there, Graham.

Normal hearts with a median BNP level of 24, which corresponds to the 25th percentile. Where would the mean be positioned in these cats?

Presumably the OCM patients were selected and included without recourse to further differentiation - so were all of the HCM cats symptomatic? Would that mean that a number of the OCMs were presumably hypertrophic also - and so if picked up when still asymptomatic, would there be any correlation between value of BNP and rate/severity of the ensuing clinical case? In other words, if I haven't garbled that too much, is there any prognostic value in size of BNP value whilst still asymptomatic, for the disease which is presumably coming?

We're quite a way from wetherby, so I can foresee a situation where we take 3 or 4 samples, freeze down all but one, and then keep sending them till one arrives on time I have a suitable candidate, I think, so may well try this one out this week.

Re: Yes....Cardiopet proBNP is useful.

Graham Bilbrough — Sat, 04 Feb 2012 15:07:05 GMT

The Cardiopet proBNP transport tubes hold the Nt-proBNP peptide stable for at least 24 hours at ambient temperature. This time period can be extended dramatically by freezing (multiple freeze-thaw cycles can be problematic).

The analysis for Cardiopet proBNP is done exclusively at IDEXX Wetherby. If you are submitting to one of our other labs (IDEXX Lea Green, IDEXX Wanstead, IDEXX Southwater), to ensure stability, the contents of the transport tubes are frozen within one hour of receipt and kept that way during transportation.

Thanks

Graham

Re: Yes....Cardiopet proBNP is useful.

Graham Bilbrough — Sat, 04 Feb 2012 14:59:12 GMT

[Disclosure: I work for IDEXX Labs]

With regard to cats without clinical symptoms, you may be interested to take a look at this new paper in detail (below). This follows on from other independent publications by Connolly et al (RVC, England) and Wess et al (Munich, Germany). The test does a great job!

However, it's important to know that these sort of studies look at the performance of the test in cats that have been sent to a referral centre to see a cardiologist--you can assume that the general practitioner involved has some suspicion of cardiac disease. Obviously, that is _not_ the same as using the test in each and every cat that walks (...is carried) into your practice. If you were to use Nt-proBNP in this manner, as with just about every test we use in practice, you could anticipate that the performance would not be as good.

Cardiac auscultation in the cat is not easy and it is not uncommon to be left with doubts--"was that a murmur I heard?". Sadly, the pet owner, looking at their apparently healthy cat, is often unwilling to consider the expense (and potential travel) for a cardiac ultrasound--especially true when you are making the recommendation without confidence in your voice. This is a great time to use Cardiopet proBNP (Nt-proBNP).

Thanks

Graham

Multicenter Evaluation of Plasma N-Terminal Probrain Natriuretic Peptide (NT-pro BNP) as a Biochemical Screening Test for
Asymptomatic (occult) Cardiomyopathy in Cats. There are other papers by Connolly et al (RVC) and Wess et al (Munich).

J Vet Intern Med 2011

P.R. Fox, J.E. Rush, C.A. Reynolds, T.C. DeFrancesco, B.W. Keene, C.E. Atkins, S.G. Gordon,
K.E. Schober, J.D. Bonagura, R.L. Stepien, H.B. Kellihan, K.A. MacDonald, L.B. Lehmkuhl,
T.P. Nguyenba, N. Sydney Moise, B.K. Lefbom, D.F. Hogan, and M.A. Oyama

Background: B-type natriuretic peptide concentrations reliably distinguish between cardiac and respiratory causes of dyspnea, but its utility to detect asymptomatic cats with occult cardiomyopathy (OCM) is unresolved. Hypothesis/Objectives: Determine whether plasma N terminal probrain natriuretic peptide (NT-proBNP) concentration can discriminate asymptomatic cats with OCM from normal cats, and whether NT-proBNP concentration correlates with clinical, biochemical, and echocardiographic parameters. Animals: One hundred and fourteen normal, healthy cats; 113 OCM cats.Methods: Prospective, multicenter, case‐controlled study. NT-proBNP was prospectively measured and cardiac status
was determined from history, physical examination, and M-mode/2D/Doppler echocardiography. Optimal cut-off values were derived using receiver operating characteristic (ROC) curve analysis.

Results: NT-proBNP was higher (median, interquartile range [25th and 75th percentiles]) in (1) OCM (186 pmol/L; 79,
478 pmol/L) versus normal (24 pmol/L; 24, 32 pmol/L) (P < .001); and (2) hypertrophic obstructive cardiomyopathy
(396 pmol/L; 205, 685 pmol/L) versus hypertrophic cardiomyopathy (112 pmol/L; 48, 318 pmol/L) (P < .001). In OCM,
NT-proBNP correlated (1) positively with LVPWd (ρ = 0.23; P = .01), LA/Ao ratio (ρ = 0.31; P < .001), LVs (ρ = 0.33;
P < .001), and troponin-I (ρ = 0.64; P < .001), and (2) negatively with %FS (ρ = 0.27; P = .004). Area under ROC
curve was 0.92; >46 pmol/L cut-off distinguished normal from OCM (91.2% specificity, 85.8% sensitivity); >99 pmol/L
cut-off was 100% specific, 70.8% sensitive.
Conclusions and Clinical Importance: Plasma NT-proBNP concentration reliably discriminated normal from OCM cats,
and was associated with several echocardiographic markers of disease severity. Further studies are needed to assess test
performance in unselected, general feline populations, and evaluate relationships between NT-proBNP concentrations and
disease progression.
Key words: Biomarker; Feline; Myocardial disease.