Nitrate-induced paradoxical ischemia predicts adverse outcomes in elderly patients with healed myocardial infarcts.

BACKGROUND

It is well known that nitrates can induce paradoxical myocardial ischemia.

METHODS AND RESULTS

Fifty patients (median age 73 years; range 67 to 78 years; 80% male) with healed myocardial infarcts were selected. All patients underwent resting single-photon emission computed tomography (SPECT) and resting baseline gated-SPECT using sestamibi or thallium-201 after the sublingual administration of 5 mg isosorbide dinitrate (ISD). Forty-eight per cent (24 of 50) of the patients demonstrated ISD-induced peri-infarct ischemia as observed by SPECT. Compared with patients without ISD-induced ischemia, patients with ISD-induced ischemia presented larger infarcts as determined by the extent of perfusion defects (mean [± SD] 27±12 pixels versus 11±9 pixels; P<0.0001), lower ejection fractions (39±17% versus 50±15%; P<0.02) and a higher incidence of severe coronary artery disease (P<0.04). At five years, the survival probability on Kaplan-Meier analysis was 42% and 96% for patients with and without ISD-induced ischemia, respectively (HR 5.6 [95% CI 1.6 to 20]; P=0.009).

CONCLUSIONS

Nitrates may have low efficacy in improving blood flow through the coronary vessels that supply large myocardial infarcts with high-resistance microvascular damage. At the same time, nitrates induce dilation and blood pressure decrease in remotely patent or mildly stenotic vessels. The blood pressure gradient elicited between the high- and low-resistance coronary vessels may provide the force for a blood flow steal from the viable zones of the infarct toward the healthy myocardium. The resultant nitrate-induced paradoxical ischemia could be a silent marker of myocardial instability and adverse outcomes in elderly patients with healed myocardial infarcts.