Nitric oxide for inhalation in ST-elevation myocardial infarction (NOMI): a multicentre, double-blind, randomized controlled trial

Abstract

Inhalation of NO at 80 ppm for 4 h in STEMI was safe but did not reduce infarct size relative to absolute LVmass at 48-72h. The observed functional recovery and clinical event rates at follow-up and possible interaction with nitroglycerine warrant further studies of iNO in STEMI.

Pharmacological preconditioning with inhaled nitric oxide (NO): Organ-specific differences in the lifetime of blood and tissue NO metabolites

“…The lack of nitrite increases in blood and tissues is noteworthy and would seem to exclude this NO metabolite as a major contributor to tissue protection when iNO is used as a preconditioning agent. While this observation is consistent with our own earlier results [ 20 ] and most human studies in which circulating nitrite increases with 80 ppm NO are typically on the order of 10–20% [ 42 , 58 ] there are two notable exceptions: one relates to a randomized controlled trial of iNO in human liver transplantation [ 59 ], the other to the use of an even lower concentration (20 ppm) of iNO in newborn babies [ 60 ] in which circulating nitrite levels rose 3 and 4-fold, respectively. The reasons for this discrepancy are not immediately obvious, may involve multiple factors (including species differences, study design, NO delivery specifics as well as duration and timing of iNO application) and are likely to be complex as the origin of nitrite in the circulation and details of its sensing and regulation remain largely unknown.…”

“…Since similar increases in NO metabolite concentrations were observed in other tissues NO inhalation may also protect organs other than the heart in the peri-operative setting. Our study is timely inasmuch as results from NOMI, the largest double-blind randomized controlled trial on NO inhalation in patients with ST-elevation myocardial infarction to date, have just been published [ 42 ]. While iNO (80 ppm, given before PCI and up to 4 h after reperfusion) was found to be safe, it did not reduce infarct size.…”

“…While iNO (80 ppm, given before PCI and up to 4 h after reperfusion) was found to be safe, it did not reduce infarct size. At 4 months, an improved recovery of left ventricular function was apparent with iNO, but for the primary end point the combination of nitroglycerin (a peri-procedural medication that is part of routine clinical practice in many countries) and iNO showed a trend towards harm [ 42 ]. The reason for this unfavorable effect is unknown, but similar interactions may have contributed to the disappointing results with nitrite as peri-conditioning agent in two other recent clinical trials [ 43 , 44 ].…”

Co‐morbidities and co‐medications as confounders of cardioprotection—Does it matter in the clinical setting?

“…A retrospective subgroup analysis of a study on cardioprotection by inhaled nitric oxide in STEMI patients identified an interaction of inhaled NO and intra‐arterial nitroglycerin. Nitroglycerin‐naïve patients had reduced infarct size by inhaled NO, those with nitroglycerin not (Janssens, Bogaert et al, 2018). In a registry, chronic nitrate treatment of STEMI patients was associated with less cardiac biomarker release, indicating cardioprotection by chronic nitrate treatment per se (Ambrosio et al, 2010).…”

Peripheral Blood RNA Levels of QSOX1 and PLBD1 Are New Independent Predictors of Left Ventricular Dysfunction After Acute Myocardial Infarction

“… 1 Up to 15% of patients with ST-segment–elevation MI have a left ventricular (LV) ejection fraction <40% at follow-up. 2 Heart failure post-MI encompasses high morbidity and a high cost for rehospitalizations, drugs, and device therapies. Therefore, position papers have recently emphasized the need to identify new predictors and identify new targets for intervention.…”