cardiac disease in a rabbit

Re: cardiac disease in a rabbit

Rajat — Tue, 12 Jun 2012 00:19:33 GMT

Hi again!

[quote user="David Mills"]No, no negative studies but no positive either. The oft-quoted one as I'm sure you're aware is the abstract by Fox et al from the early 2000s which was nothing more than an interim analysis showing no benefit of ACEi/frus over frus alone for MST.[/quote]

Yes, and I think we all got tired of waiting for it to be published. How much one can rely on it in an abstract only form is doubtful to me. Nevertheless, I dug out 3 somewhat dodgy positive studies which were published : http://www.jaaha.org/content/34/1/38.short, and http://www.sciencedirect.com/science/article/pii/S1760273406700261 and http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1444904/).

[quote user="David Mills"] I'm not happy with the 'probably do live longer' argument largely because the the disease process in cats - assuming HCM - is fundamentally different to dogs, and in humans with HCM ACEi are contraindicated[/quote]

Of course it is, and no one is suggesting that we use them for the same reasons. To my knowledge, ACE-I are only contraindicated in the obstructive form of human HCM and not in the non obstructive form - an important distinction. Cats with DLVOTO (HOCM) don't seem to suffer the same s/e that ppl do i.e. risk of hypotension (Oyama presented this in 2003, but only at ACVIM-abstract form!) . AII blockers have shown some benefit in helping regression of LV hypertrophy in people with (non obstructive) HCM: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2607563/

Most veterinary cardiologists will use it to prevent progressive cardiac remodelling and LV fibrosis + ischaemia which as u know is mediated by aldosterone and angiotensin II. The Macdonald+Kittleson paper is a good rigorous study which shows no benefit in the pre clinical setting, and I was impressed by it not to use ACE inhibitors in these cases- the only time I would veer away from this is where there is severe progressive LV remodelling on echo with progressive worsening in echo doppler indices of diastolic dysfunction prior to congestive signs. But then, with warning to the owner, that it may just be wishful thinking that treatment will help. Some owners wish to try anything in this particular setting where the patients cardiac function is getting worse. Tough to make a cat do a treadmill test eh, would make life so much simpler!

Interestingly, the AII blocker Losartan has been shown to cause regression of hypertrophy in a rabbit model - finally we discuss the species the post was initially about!

As for the type of heart disease, diastolic dysfunction in people can be treated with ACE inhibitors. For e.g. losartan was shown to increase exercise tolerance in patients with diastolic dysfunction: http://content.onlinejacc.org/cgi/content/abstract/33/6/1567.

Also this from Circulation about treatment of diastolic dysfunction: http://circ.ahajournals.org/content/105/12/1503.full (I love the Circulation journal, most if not all older articles are free!)

[quote user="David Mills"]Are we expected to believe they suddenly at the onset of CHF do make a difference? It is becoming one of my crusades, the use of ACEi without any evidence (cats with mild CRF w/out proteinuria, for instance) - especially preclinical HCM (shocked its recommended by an author in BSAVA Manual) and, to a certain extent, HCM-CHF; because, in my view, it comes down to nothing more than opinion - certainly wouldn't stand up in court![/quote]

I think yes, because when CHF strikes, you have a massive upregulation of the RAAS, and ACE inhibitors help to counteract this and all the secondary bad effects (for lack of a better word!) they bring along with them. I certainly don't believe they are the cure to all evil, and certainly don't believe and use them in non proteinuric CRF for example.But I use them unreservedly in all CHF cats and dogs. I like crusades btw :). I have many !

Yes it is opinion, but in the lack of definitive evidence, a consensus of expert opinion holds a fair amount of weight in the EBM pyramid, and is possibly right at the top (I remember reading this somewhere, completely escapes me now where!). I wish we could have a study similar to the ones in dogs with a few hundred cats in CHF treated with ACEI and without ACEI to see if survival is prolonged. Obviously recruiting cats with just HCM (preferably with the same mutation, but that is just total wishful thinking ) at a similar stage of their disease will be tricky but hey it can be done, multi centre maybe?!

As for pimobendan, a classic case of a drug that is supposed to be contraindicated in a condition such as HCM, is now being used in HCM +CHF - and somewhat supportive of a drug classically used for a completely different indication (afterload reduction, systolic dysfunction) being used in cases of diastolic dysfunction due to HCM. Oft to very good effect too !I do love pimo, it works wonders in many many of our cases , tho not people, somehow we tend to die more when given it, odd isn't it?!

Nice having this debate with you David :)

Cheers

Raj

PS sorry for typos as ever, its late!!

Re: cardiac disease in a rabbit

David Mills — Mon, 11 Jun 2012 22:12:07 GMT

[quote user="Rajat"]

Cats do live and die by frusemide tho, so no debate there, but they probably live longer with ace inhibitors. I wish we had studies looking at this in cats, to my knowledge there are NO studies, are you aware of any or any negative studies re this?

[/quote]

No, no negative studies but no positive either. The oft-quoted one as I'm sure you're aware is the abstract by Fox et al from the early 2000s which was nothing more than an interim analysis showing no benefit of ACEi/frus over frus alone for MST. I'm not happy with the 'probably do live longer' argument largely because the the disease process in cats - assuming HCM - is fundamentally different to dogs, and in humans with HCM ACEi are contraindicated. So the dog extrapolation is fundamentally flawed, despite the theoretical benefits. Add to this the fact ACEi appear to make no difference whatsoever to preclinical disease:

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

Are we expected to believe they suddenly at the onset of CHF do make a difference? It is becoming one of my crusades, the use of ACEi without any evidence (cats with mild CRF w/out proteinuria, for instance) - especially preclinical HCM (shocked its recommended by an author in BSAVA Manual) and, to a certain extent, HCM-CHF; because, in my view, it comes down to nothing more than opinion - certainly wouldn't stand up in court!

Thanks for the graph, I hadn't seen that. And yes, I agree, they are useful in dogs with CHF but given the choice one/other I'd go for pimo - especially with its new licensing addition (I don't work for BI) the drug just gets better and better.

Re: cardiac disease in a rabbit

Rajat — Mon, 11 Jun 2012 19:02:11 GMT

sorry for typos- meant 'concur' not 'oncur' and that you 'may have already seen' not 'have already seen' - was furiously typing away between consults!

Cheers

Raj

Re: cardiac disease in a rabbit

Rajat — Mon, 11 Jun 2012 17:35:21 GMT

Hi David

I think while direct instillation into tissues will undoubtedly lead to greater local effects, I don't think one can say that no protective effects are conferred by oral dosing of ACE inhibitors. Several human studies show improved survival in cardiovascular disease as have canine studies so while one may not get very good tissue ace inhibition, I think most cardiologists oncur that their use is indicated in cases of RAAS activation despite this caveat including in cats with CHF. Cats do live and die by frusemide tho, so no debate there, but they probably live longer with ace inhibitors. I wish we had studies looking at this in cats, to my knowledge there are NO studies, are you aware of any or any negative studies re this?

I hope we get some newer ace inhibitors with greater tissue ace selectivity as this may have lead to better overall effects, found this interesting graph which you have already seen but have a look - figure 4 of document

http://eurheartjsupp.oxfordjournals.org/content/10/suppl_G/G13.full

Sorry for hijacking your thread Gillian

Best wishes

Raj

Re: cardiac disease in a rabbit

David Mills — Sat, 09 Jun 2012 13:02:12 GMT

[quote user="Rajat"]

Ramipril vs Enalapril.

http://www.ncbi.nlm.nih.gov/pubmed/1661764

[/quote]

I came across this study a while back - I thought since its publication in 1991 the efficacy of tissue inhibition from oral meds had been actually shown to be rather negligible, and the only way of achieving tissue benefits was through direct instillation into tissue:

http://www.ncbi.nlm.nih.gov/pubmed/9577944

[quote user="Rajat"]

So are you treating some of your patients in CHF with frusemide alone?

[/quote]

Yes and no. In dogs, we tend to use (charity) pimo + frus - pimo/ACE/frus is prohibitively expensive, and where there exists a choice between pimo and ACE, pimo consistently shown to offer longer MST.

In cats, however, we have used frusemide alone with reasonable success. This is largely due to the fact there is no evidence for efficacy oaf ACEi in increasing MSTs in cats with CHF from any cardiomyopathy. Some will still use ACEi/frus; other pimo/frus. The evidence is so poor that its very difficult to decide, really.

Re: cardiac disease in a rabbit

Rajat — Sat, 09 Jun 2012 11:19:15 GMT

[quote user="David Mills"]I am increasingly sceptical about the RAAS inhibition story (in any species). I agree that ACEi are very useful, but there's pretty convincing evidence that escape (chymase/tissue pathways) pathways return RAAS products back to pre-treatment levels very quickly.[/quote]

Hi David

I totally agree Ace escape via pathways you mentioned does occur and is a bit worrying but it doesn't mean we won't get some RAAS inhibition with ace inhibitors, and there is an increase in survival demonstrated with 'plasma' ace inhibitors in this situation (CHF) in several different studies and species. I think it would be premature to jump to a conclusion of not using ace inhibitors when obvious RAAS induction is occuring such as with CHF and subsequent treatment with Frusemide. While there is a theoretical reduction of action of ACE, there is a demonstrable survival benefit. It has been shown a total lack of ACE in healthy rats also leads to problems, so I think what we probably need is a reduction of total ACE back towards normal levels rather than a complete inhibition of ACE. But I still wonder why we don't use more 'tissue' ace inhibitors such as Ramipril vs Enalapril.

http://www.ncbi.nlm.nih.gov/pubmed/1661764

So are you treating some of your patients in CHF with frusemide alone?

Best wishes

Raj

Re: cardiac disease in a rabbit

David Mills — Fri, 08 Jun 2012 22:55:43 GMT

[quote user="Rajat"]

I think you are doing absolutely the right thing by using ace inhibitors too, inhibiting the RAAS is neccessary in CHF (if we can agree to extrapolate from other species before someone jumps in with lack of evidence in bunnies etc!)

[/quote]

I am increasingly sceptical about the RAAS inhibition story (in any species). I agree that ACEi are very useful, but there's pretty convincing evidence that escape (chymase/tissue pathways) pathways return RAAS products back to pre-treatment levels very quickly. I certainly don't regard some experts' policy of always using ACEi when using frusemide as necessary.

Re: cardiac disease in a rabbit

Gillian Mostyn — Fri, 08 Jun 2012 21:58:24 GMT

I am starting on 0.25mg/kg and we'll see how we get on....

Re: cardiac disease in a rabbit

Rajat — Fri, 08 Jun 2012 21:55:15 GMT

Hi Gillian and David

I agree DCM is likely though I have seen valvular dzs in bunnies too with similar frequency ( n=not many at all!).

I agree pimo would help both if in CHF tho sounds like your bunny is also syncopal, whether this is a 'block' or tachyarrhythmia causing hypotension -->reduced cerebral perfusion is tough to say. I would have thought pimo wont improve an arrhythmia - once the myocardium has a substrate for arrhythmia ie ischaemic diseased muscle I reckon it aint gonna recover. But am only guessing

Either way no harm trying pimobendan. I think you are doing absolutely the right thing by using ace inhibitors too, inhibiting the RAAS is neccessary in CHF (if we can agree to extrapolate from other species before someone jumps in with lack of evidence in bunnies etc!)

Azotemia and cardiac dzs always a bad combo as we all know - good on the lady- she is helping so many bunnies. I think echo gives u a diagnosis and idea of severity but most importantly if resp rate came down with frusemide then we can make a reasonable assumption there has been (cardiogenic) pulmonary oedema which has resolved. Would be good to know how bunny gets on. What dose of pimobendan are you using btw?

Best wishes

Raj

Re: cardiac disease in a rabbit

David Mills — Fri, 08 Jun 2012 21:12:02 GMT

Most rabbits 'tend' to get DCM and so pimobendan would be a superior choice to ACEi, extrapolating from dogs. I don't think you necessarily need echo/rads in this case if the signs/clinical exam fit. DCM patients will classically develop arrhythmias of many guises, including blocks - some of these can improve with treatment of the underlying DCM.

Re: cardiac disease in a rabbit

Gillian Mostyn — Fri, 08 Jun 2012 18:51:46 GMT

I'm afraid not. The rabbit has various issues and we did discuss further diagnostics, including radiography and echo, but we decided against it. Money is not an issue - this lady has 50+ rescued rabbits and lots of them are on chronic illness meds-but I certainly don't want to spend her hard earned money without good indication it will then change things. This rabbit has various issues and as it was rescued we know it is old but not sure of exact age. I would need to refer for cardiac echo on a rabbit so it would be costly. It was decided that diagnostics were unlikely to change things ... if I am missing something obvious I am happy to be told though!

As far as meds, rabbit is currently on frusemide and fortekor and she did improve a little but is still not 'well'. Her lungs are pretty clear now but she has episodes where she 'collapses' onto her side, pants for a while, but then gets up and trots off again. Her heart rate is also slower than I would expect so some form of block is possible. I know this isn't typical CHF but am just trying all the options....!!!

Re: cardiac disease in a rabbit

Rajat — Fri, 08 Jun 2012 18:33:49 GMT

Hi Gillian

Curious to know if the bunny had an echo/the cause of the murmur determined?

Is it in heart failure? If its not on frusemide and not in severe forward failure tough to see how its azotemia would resolve with pimobendan..just thinking aloud I hope yr bunny does well!

Cheers

Raj

Re: cardiac disease in a rabbit

Gillian Mostyn — Fri, 08 Jun 2012 18:27:21 GMT

Thanks. I've used ACEi and diuretics and always found them sufficient for control (I've got an 11yr old bunny who has been on fortekor for the last 5 years!!!!) but I currently have an elderly bunny with a very loud murmer who just isn't doing so well - the azotaemia and lethargy just aren't improving. Lets hope the vetmedin helps....

Thanks!

Re: cardiac disease in a rabbit

Mark Rowland — Fri, 08 Jun 2012 17:10:52 GMT

I've got several on the drug at the dog dose. They all seem to be doing well. I put a deslorelin implant in one last week. It has a grade 6 murmur and I didn't expect it to reach spey age but it has and is now quite aggressive. I think you can understand why I didn't want to GA it.

No complaints re pimobendan thus far.