Inducing upper-limb ischemia in the ambulance during transfer to primary PCI reduces myocardial perfusion injury and infarct size in patients with ST-segment elevation myocardial infarction (STEMI).
Presenting the results of the study during a clinical-trials session of the i2 Summit here at the American College of Cardiology 2009 Scientific Sessions, lead investigator Dr Hans Erik Bøtker (Aarhus University Hospital Skejby, Denmark) said that occluding the brachial artery to induce ischemic conditioning is a simple and safe intervention that has the potential to reduce mortality and morbidity in STEMI patients.
"It is impossible to precondition a patient prior to a heart attack, because you don't know when it's going to come," said Bøtker. "But if you change the timing so that you do the conditioning procedure during an ongoing myocardial ischemia, which means that you're doing it when the patient is having the heart attack, the damage that is caused by the reperfusion when you open the artery is what we're aiming to modify. It seems, from some of our experimental studies, that the reperfusion injury takes place in the first minute after you open the vessel, but we are able to modify it."
Modifying the reperfusion injury
In an interview with heartwire, Bøtker explained that the size of the infarct is caused by ischemic damage and reduced by perfusion and the restoration of blood flow. Recent studies, however, have suggested that part of the infarct damage might also be caused by the abrupt reperfusion, and with that in mind, modifying it could limit injury and harness the full benefits reperfusion therapy.
Occluding the brachial artery to induce ischemic preconditioning in coronary stenting was recently shown to reduce myocardial necrosis as a result of the procedure and was also shown to reduce ischemic chest pain and ECG abnormalities during PCI. In this study, however, Bøtker and colleagues sought to induce ischemia prior to the catheterization laboratory.
In total, 108 patients with STEMI underwent conventional PCI while 105 patients underwent ischemic conditioning in the ambulance. In these patients, the paramedic obtained the electrocardiogram, transmitted the data to the hospital, and, when the attending physician confirmed STEMI, had a blood-pressure cuff placed around the patient's upper arm and inflated to 200 mm Hg for five minutes. The conditioning process was repeated four times.
The primary end point, the myocardial salvage index at 30 days, an assessment of the myocardial area at risk, and final infarct size, was available in 70 patients in both treatment arms. Patients treated with ischemic conditioning while en route to the hospital had a significantly higher salvage ratio than those who underwent PCI without remote conditioning. Final infarct size assessed by nuclear scintigraphy was significantly less among those who underwent conditioning. Interestingly, the benefit appeared driven by infarcts caused by left anterior descending (LAD) lesions.
During the clinical-trials session, Dr Roxana Mehran (Columbia University, New York) asked investigators about the primary end point, questioning their choice of myocardial salvage over infarct size, which has been validated in other clinical trials. Bøtker said that investigators chose myocardial salvage as the primary end point because it allowed them, once they had assessed the area at risk, to calculate the index based on the final infarct size. Choosing infarct size as the primary end point would have required a much larger study, somewhere around 500 patients, he said.
Regarding the mechanism of benefit, Bøtker said they do not exactly know how conditioning works, but it's likely that a compound or a series of compounds, as part of a generalized endogenous protective system, is released during ischemia to reduce infarct size.
Postconditioning after PCI
Not to be outdone with conditioning during ambulance transfer, Dr Thomas Engstrøm (Copenhagen University Hospital, Denmark) and colleagues showed that conditioning after PCI, through a series of interruptions of coronary blood flow, reduced infarct size and improved functional heart-failure class.
In this study, STEMI patients undergoing primary PCI were randomized to conventional treatment or mechanical postconditioning with a series of four 30-second balloon inflations to occlude the coronary artery. The balloon inflations were followed by 30-second reperfusions, and, like the study by Bøtker, were designed to limit the amount of injury following PCI. The thought, according to investigators, is that reopening the artery by degrees might save more myocardium with a gradual reperfusion.
With positive results in both conditioning trials, Bøtker told heartwire that his group is planning a future study that will combine remote ischemic conditioning in the ambulance with conditioning in the cath lab to see whether the benefits are additive.
