I-PRESERVE trial: I-PROTEST!! DOE and large ankles : A "normal EF" in wolves' clothing?

    Ibersartan didn't work in patients with normal EF with "symptoms" of "CHF". REALLY?

  I can't help it that I found the design of this trial slightly annoying.  All that was required was that the patient had "heart failure symptoms", and LVEF of at least 45% and "COULD" include an abnormal CXR, LVH or LAE on echo OR LVH OR LBBB on ECG.  If my residents gave a permanent diagnosis of  "CHF"  to a patient based only on the above criteria of  shortness of breathe and LVH by ECG , I would NOT  give them a very good review at the end of their rotation.  The  design of this trial took me back to one of the most rudimentary pieces of advice that I ever give to any medical student:  "Just because someone tells you it's  CHF, don't ever EVER believe it until you have proof ", or at least until you have exluded ALL OTHER possiblities." 

 The reason?  Simple.  It's because we already know in clinical practice that nothing much works for these patients.  You know them because you see them every week:  They have hypertension, an EF of 50%, large ankles, fatigue and they keep coming into the ER for more and more doses of diuretic that works for about 3 days, then they are back with the same symptoms.  I feel very badly for these patients because they are patients who are desparately seeking a diagnosis.  I feel even worse when we give them one just to try and make them feel better.

Basically, I teach my students that  in the patient with normal EF and dyspnea we start with assessing valvular regurgitation, then if that's not the issue,  we look first and foremost at their (a) medication regimen, assessing for those that make them take on fluid like the great Titanic:  ACTOS, NIFEDIPINE, STEROIDS.  40% of these study  patients were on calcium channel blockers, and the removal of such should be the first order of business whenever possible in someone with fluid management issues. I tell them about my patient who once had a 40 pound weight gain with nifedipine.  Removing that along with a gastric lap band procedure "CURED" her "normal EF heart failure". Perhaps just being on a calcium channel blocker should be in the exlucsion criteria for entry into one of these normal EF studies. 

 (B) we look at the U/A:  ?proteinuric?   and if yes, we do a 24 hour urine both for Cr.clearance and protein.  Occasionally we are suprised to find nephrotic syndrome,  BUT OFTEN we find the GFr is lower than we estimated which spells trouble with salt eaters who are drinking a lot of water because they are desperate  to replace what we're stealing with our diuretics. 

(c) we look for sleep apnea which can turn the delicate small ankles of any school girl into large uncomfortable pitting tree trunks in a 70 something year old.  It might be worth it just to asked if anyone ever complained that  she snores. 

(d) we look at albumin, assess for  issues with cirrhosis (something I spent years trying to figure out in a patient who actually responded beautifully to natrecor....yes natrecor worked for a normal EF patient who was drowning in fluid , and we asess for hypoxemia from pulmonary fibrosis/COPD, even adult onset asthma can have strange presentations. Perhaps consider doing  a six minute walk and a PFT and see where you land.

(e) on the first minute of our evaluation, we must always keep in mind the chronic thromboembolic patient with near normal PA pressures, a hint of resting tachycardia, but subtle RV dysfunction that might not have been immediately obvious.  This patient gets a CTA and sometimes  a diagnosis of chronic recurrent PE. 

 (F) finally, we address the weight issue. In this study the average BMI was 30 +/- 5, so I'm not certain what percentage were actually overweight, but if they are overweight, they have a substantial reason to retain fluid from that issue alone, not to mention lack of conditioning as an etiology of shortness of breath.

But the BNP was a median of 320 -360 you say?  It's not like the BNP was a 1000 in all of these patients as if it's often not, because guess what, that is BECAUSE it's NOT  always congestive HEART failure when the BNP is midly elevated.  Some Humans make BNP for unexplained reasons, but a fairly  common reason for elevated BNP  and big ankles is renal insufficiency inherent to being 75.

   So, after it 's all said and done, if my patient just keeps coming in for "CHF" with very little to make their case, it's worth it just to do a "left heart cath" to check for recurrent ischemia, measure their LVEDP and get another look at their MR jet.  So many of my "heart failure" patients just get better with addressing at least one or more of the above issues.  I get more information there than from just slipping in a swan.  At least I come out with an EDP and their coronary anatomy. 

Which brings me to why I made the annoying point today that perhaps before we  continue to be "bewildered" by the normal EF patient with "CHF" and their lack of response to a heart failure treatment, we should perhaps establish the diagnosis FIRST, and  as definitively as possible, THEN study entities like Irbesartan to see how they will respond.  Blaming a normal EF  heart whose being taxed  by fluid overload combined with renal insufficiency in someone eating salt and drinking 2 liters per day with severe sleep apnea on nifedipine seems hardly fair.  I'd like to declare the  diagnosis of CHF as  both  prejudicial and unjust in many  cases.   

If every single one of these patients had undergone a quick LVEDP measurement (we certainly do more horrific things than that to study cohorts in clincal trials so it wasn't that far -fetched) we may have found the magic subset that actually would respond to therapy.  For the rest of those patients, it's a matter of a great amount of detective work, weight loss, fluid restriction and removing any offending agent from their regimen.   

As Dr. Milton Packer put it "We don't really know what we are studying here.  In many instances the heart is an innocent by-stander and the problem is in the periphery".

Yeah,............what he said.

Melissa     

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