Author + information
- C. Richard Conti, MD⁎ ()
- ↵⁎Division of Cardiovascular Medicine, Department of Medicine, University of Florida, P.O. Box 100277, Gainesville, Florida 32610-0277
I read with interest the paper by Stone et al. (1), in which the authors investigated the relationship between ST-segment depression and the rate-pressure product during exercise. Based on their findings, they suggested that ranolazine's beneficial action is most likely primarily due to improvement of regional coronary blood flow in areas of myocardial ischemia. I do not refute that statement, but I would like to remind the readers that the current hypothesis of the mechanism of action of ranolazine is that it works only after myocardial ischemia has been present. When that happens, the late sodium channel remains open, leading to intracellular sodium overload, and the sodium–calcium exchanger then leads to intracellular calcium overload, which results in increased calcium ions intracellularly and impaired diastolic relaxation and increased tension. Ranolazine inhibits the myocardial late inward sodium current associated with ischemia and thus breaks up the cycle (2).
The authors emphasize in their article that under low stress conditions of exercise where there was mild ischemia, the ranolazine did not seem to be effective; however, as the ischemia became more pronounced, the anti-ischemic effects of ranolazine became more marked.
My question to the investigators is this: Since it has been shown many times that patients with chronic stable angina have multiple episodes of asymptomatic cardiac ischemia, is it possible or probable that these multiple episodes of silent cardiac ischemia are prevented from becoming manifest symptoms of myocardial ischemia (i.e., angina) by the drug ranolazine?
I suspect that the only way one could find the answer is to have chronic ambulatory electrocardiogram (ECG) monitoring of these patients. I know that patients who were in the MERLIN–TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST-Segment Elevation Acute Coronary Syndromes–Thrombolysis In Myocardial Infarction 36) trial (3) had 7 days of ambulatory ECG monitoring, but the published study revealed that only arrhythmias were assessed. Would it be possible to go back and investigate those ambulatory ECGs to see whether or not silent ST-segment depression was present on several occasions without any manifestations of angina?
- American College of Cardiology Foundation