Saturday, April 05, 2014

STEM CELLS FOR LV REGENERATION POST MI. WHERE ARE WE?

This has been a very popular topic and I hear and seen some patients who told me that they have stem cells from some of my colleagues across the Klang Valley. Is there enough evidence to do this, and does it work?

Well, at the recently concluded Annual Scientific session of the American College of Cardiology, in Washington, one of the trials presented was the MSC-HF trial. The autologous mesenchymal cell in heart failure trial ran by our European colleagues. This trial was presented by lead investigator, Dr Anders Mathiasen of Rigshospitalet University of Copenhagen, Denmark. They enrolled 59 patients with NHYA class 2-3 heart failure, and randomise them in a 2:1 fashion, to receive either autologous mesenchymal stem cell injected into the LV myocardium guided by the NOGA XP ( Cordis ) machine for LV mapping. The control received LV  intramyocardial saline injection. These were all patients who were on maximal anti CCF medications and were not candidates for revascularisation.
After 6 months follow-up, they found that although there were significant improvements in some LV indices like LVEF, stroke volumes, LV end systolic mass, when compared to baseline and when compared to control, there were no improvements in LV end diastolic volume and mass and more importantly NYHA classification, the 6 min walk test and also the Kansas City Cardiomyopathy Questionaire. There were improvement in these indices when compared to baseline, but no significant difference when compared to placebo, because placebo also improved.

Changes in Cardiac Measures Six Months after Mesenchymal Stromal Cell (MSC) Therapy or Placebo in MSC-FH
End points at 6 moMSC group (p vs baseline)Placebop (MSC vs placebo)
LV end-systolic volume* (mL)-8.2 (0.001)+6.00.001
LVEF (percentage points)+5 (<0 .0001="" td="">-1.4<0 .0001="" td="">
Stroke volume (mL)+17.4 (<0 .002="" td="">-3.1<0 .0001="" td="">
End-systolic myocardial mass (g)+10.1 (<0 .0001="" td="">-2.1<0 .0001="" td="">
Scar-tissue mass (g)-4.4 (<0 .017="" td="">-0.5NS
*By MRI or CT, primary end point
Well, well well. What are we to make of this? Was the follow-up not long enough, or was the sample size too small, meaning that the improvement in this rather serious condition, minimal, therefore requiring a much larger sample size. It must also mean that maximal medical therapy in these people can still be further enhanced with counselling and close follow up, as must have happened, as they are on a clinical trial. Could it be that NOGA misled them? Or could it be all of the above.

The Danes have shown measurement improvements but no clinical improvements. That brings out two questions.
    1. How do we explain indices improved without symptoms improvement? Does that mean that the heart has enough reserves and that we are only improving the reserves?
Or 2. Does it mean that the indices are too crude and may not reflect improvement in clinical function.
So so much more to learn.

One thing for sure, if one the Danish way, it is safe. I wonder whether local interventionist harvesting bone marrow, centrifuging it and injecting into the infarct related artery, is it safe, and does it work. That is a mood point and we will never know unless submitted into a rigorous trial. I do not hear of any on the horizon.

I am aware of a small study by the dean of UTAR medical school who did a study in collaboration with some local private cardiologist. Again it did show some cardiac index improvement. There was no clinical assessment of symptoms improvement.

Well, one thing is for sure. Much more work needs to be done. We are not yet ready for primetime. We are NOT yet ready for guidelines and clinical use, for the moment until more works are done and results known.

By the way, it is not cheap and is potentially hazardous. 

2 comments:

Winston Yap said...

Dr Ng, please allow me to digress.
I knew of a test called CD24 which was developed by a Dr Arber a few years back.
It is a blood test to detect polyps in the colon and is about 80% accurate.
With the prevalence of colon cancer in this country, I think that it should be a very useful test.
Many people are put off by the colonoscopy procedure because, especially by the requirement to take a laxative to clear the colon before such procedure.
However, this procedure is not available locally or even in Singapore.
Perhaps someone should start the ball rolling to bring this test into this country.
In addition, Dr Arber is also researching a drug that will prevent polyps from forming in the colon!
That would no doubt be the icing on the cake!
Thank you.
Regards,

hmatter said...

Interesting.
I must do some reading on this. CD 24 as I understand it is a ligand on White Blood Cells.
But I am ignorant on this. Will have to check.
Thanks