Letter by Jones et al Regarding Article, "Optimized Treatment of ST-Elevation Myocardial Infarction".

To the Editor: We read with interest the article by Niccoli et al1 in the Journal, examining the hypothesis that microvascular obstruction (MVO) could be a primary target to improve outcomes after primary percutaneous coronary intervention (PCI) in patients with ST-segment–elevation myocardial infarction. We absolutely agree that MVO is now a well-established adverse prognostic marker in patients with ST-segment–elevation myocardial infarction undergoing successful primary PCI and a greater focus is needed regarding strategies aimed at its reduction. Consequently, we also agree with the hypothesis that simultaneously addressing infarct size and MVO may help to translate cardioprotective strategies into improved clinical outcomes in this patient group. The authors highlighted many pharmacological strategies while seemingly failing to inhibit infarct size in clinical trials may actually have procured benefit through reductions of MVO. We would like to add an additional intervention not mentioned in this context of sodium nitrite. We have shown in NITRITE-AMI (The Safety and Efficacy of Intra-Coronary Nitrite Infusion During Acute Myocardial Infarction),2,3 a randomized, placebo-controlled trial, that the intracoronary injection of sodium nitrite in patients with ST-segment–elevation myocardial infarction undergoing primary PCI was associated with a trend for reductions in cardiac magnetic resonance–determined infarct size, improved myocardial salvage index (P=0.05), and reduced major adverse cardiac events at 3 years, P=0.03). Interestingly, we also demonstrated a trend for reduction in MVO (P=0.13), over and above that for infarct size, supporting a targeted microcirculatory effect of NO. In a subgroup of patients with occluded vessels at the time of drug administration, we showed significant reductions in cardiac magnetic resonance–determined infarct size (20%, P=0.03), improved myocardial salvage index (30%, P=0.002), and MVO (48% reduction, P=0.015), a greater reduction relative to that seen in infarct size, highlighting MVO as a possible target for inorganic nitrite.3 In accord with this hypothesis, we identified substantial reductions in inflammatory markers (hs-CRP [high-sensitivity C-reaction protein]), neutrophil numbers (total circulating neutrophil counts) and activation state (reduced expression of neutrophil CD11b, plasma CXCL1 [CXC-chemokine-ligand 1], CXCL5 [CXC-chemokine-ligand 5], and CCL2 [C-Cchemokine ligand 2] levels [P<0.05]) postprimary PCI in patients who received nitrite treatment.2 These markers were associated with reductions in MVO intimating an inflammatory component to MVO in these patients that was sensitive to nitrite. We support the suggestion that MVO is an important target in improving outcomes in this patient group and think that the approach of NO replacement via nitrite to reduce myocardial reperfusion injury, specifically MVO is worthy of further study.