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Troponin and cardiac events in stable ischemic heart disease and diabetes

Selected in The New England Journal of Medicine by G. Harris

References

Authors

Everett BM, Brooks MM, Vlachos HE, Chaitman BR, Frye RL, Bhatt DL; BARI 2D Study Group

Reference

N Engl J Med. 2015 Aug 13;373(7):610-20

Published

August 2015

Link

Access the Abstract

My Comment

Background

The BARI 2D study enrolled 2386 patients with both type 2 DM and stable ischemic heart disease (≥ 50% stenosis of a major epicardial coronary artery associated with a positive stress test or ≥70% stenosis and classic angina) with mild or no symptoms of angina [18% of these patients had no documented angina (Gersh, BJ, 2012)].

In the acute coronary syndrome setting, cardiac troponin T is used to identify those patients who would benefit from urgent revascularization.

This trial sought to answer two questions. Can an abnormally elevated plasma, high sensitivity cardiac troponin T level be clinically useful (an independent predictor) in patients who are known to have stable ischemic heart disease as well as type 2 diabetes mellitus to identify those, who are at increased risk of dying from cardiovascular causes, increased risk of myocardial infarction or stroke (primary endpoint of this study).

The second was to establish whether an abnormally high, high sensitivity cardiac troponin T level, could be used as an independent predictor to determine benefit from revascularization.  2285 patients were included in this ancillary study.

Major findings

  1. 99.6% of patients had a detectable (≥3ng per litre) trop T.
  2. 39.3% of patients had an abnormally high (≥14ng per litre) trop T at baseline.
  3. The primary endpoint was reached in 27.1% of patients with an abnormal trop T level at baseline vs. 12.9% in those with a normal baseline trop T.
  4. The hazard ratio was 1.85 (95% CI,1.48-2.32; P<0.001) in those with an abnormal trop T at baseline (after adjusting for CVS risk factors, severity of DM, glomerular filtration rate, myocardial jeopardy index of the myocardium supplied by the diseased coronary arteries, electrocardiographic abnormalities, nr of coronary lesions and abnormal ejection fraction).
  5. An abnormal Trop T was NOT useful in discerning which patients would benefit from revascularization (HR. 0.96;    95% CI, 0.74 to 1.25). 

My comment

In the BARI 2D trial, the coronary artery bypass graft group of patients were at higher risk (based on angiographic and clinical variables) and derived the most benefit from revascularization.

It would have been interesting to delineate the difference in predictive potential of high sensitive trop T in the CABG group of patients alone.

In a post hoc, nonrandomized analysis of the completeness of revascularization (Schwartz,L et al. Circ Cardiovasc Interv. 2012), the adjusted increased event free survival of patients with more complete revascularization was demonstrated (HR 1,14; P=0.0018). Only 37.9% of the patients in BARI 2D trial were completely revascularized.

The patients in this trial were all type 2 diabetics. They probably all had micro vascular disease (to some degree or the other), not just elsewhere (kidneys, brain etc.), but also in the heart.

The specific pathophysiologic origin of the “predictive trop T value” is probably debatable. When trying to link this to revascularization, which mechanism are you targeting (measuring)?

If based on revascularization of ischemic producing lesions, FFR would have been helpful to identify this subgroup. Protection against future rupture of non-flow low obstructing macro vascular lesions (ie future NSTEMI) could also be a possibility, but then baseline trop T should play less of a role, unless you postulate that the trop T is associated with increased inflammation. 

Revascularization could improve or delay regression of microvascular endothelial function, not only due to improved blood supply past flow obstructing (ischemia) lesions, but also by decreasing the increased shear stress associated complications of these lesions.

Coronary flow reserve (CFR) would be a usefull measuring tool, post revascularization.

Another thought would be to repeat CFR not only in those patients, with a decreased CFR, without FFR positive macrovascular disease, who were revascularized, but also in those who were on medical treatment alone. And then to measure the associated change in CFR and abnormal trop T.

But for now, this study tells us that yes, an abnormally high baseline high sensitive troponin T value predicts increased risk independently in this patient population. But how that translates to altering clinical management, except for possibly even more aggressive risk factor reduction, I am not sure.

It does not tell us, based on an abnormally high baseline high sensitive troponin T, who would benefit from revascularization, above and beyond current tools at our disposal. Whilst remembering that not even 40% of the patients in this trial who underwent either CABG or PCI, had complete revascularization.

 

1 comment

  • Hugo chinchilla 09 Oct 2015

    Dr Hugo Chinchilla Calix interesting comment but there are many questions to answer on the stable chronic patients?