Take a Deep (Nitric Oxide) Breath and Follow the Reverse Translational Research Pathway

Manuel Lobo; Borja Ibanez


Eur Heart J. 2018;39(29):2726-2729. 

In This Article

Primary Outcome Selection

The extent of LGE CMR, the authors' choice of primary outcome measure, is the most accurate and reliable surrogate for MI size, and revealed 18% LV mass in the iNO group vs. 19% LV mass in controls (P = 0.4). Interestingly, the authors did find a trend toward smaller MI size in the iNO group when normalized to the oedematous region on T2W CMR (used as a surrogate for area at risk; AAR): 53% vs. 60% (P = 0.09). Recent evidence from experimental models and human patients shows that oedema development after STEMI is a bimodal phenomenon: an initial reperfusion-related wave of oedema is significantly attenuated after 24 h and is followed by a deferred healing-related wave of oedema peaking between day 4 and 7.[12,13] In addition, oedema formation has been shown to be greatly affected by the duration of ischaemia and by cardioprotective interventions such as conditioning manoeuvres.[14–16] Janssens et al. found that NO inhalation was associated with a significantly smaller extent of oedema on CMR in the patient subgroup not receiving nitroglycerin.[11] The recently gained knowledge about the bimodal nature of post-MI oedema and its unpredictable response to therapies challenges the use of oedema-based methodologies as surrogates for AAR. Given that the primary outcome measure of the NOMI trial was CMR-measured MI size (% of LV),[11] and not MI size relative to oedema, primary outcome selection will have had no influence on the observed results.