Mechanical postconditioning after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) reduces infarct size at 3-month follow-up. Moreover, patients receiving the adjunctive treatment are also less likely to develop heart failure, according to research published online January 26, 2010, ahead of print in Circulation: Cardiovascular Interventions.

The study, led by Jacob Lønborg, MD, of Rigshospitalet (Copenhagen, Denmark), included 118 STEMI patients treated within 12 hours of symptom onset. Patients were randomized to receive primary PCI with (n = 59) or without postconditioning (n = 59), which was performed immediately after reperfusion. Postconditioning involved a cycle of 4 balloon occlusions, each interrupting blood flow for 30 seconds and followed by 30-second deflation periods that allowed reperfusion. The postconditioning took place at the site of the lesion in the index artery.

Baseline clinical, angiographic, and procedural characteristics were similar between the 2 groups, with the majority of patients being implanted with DES. Overall, 16% of patients did not receive a stent.

To evaluate infarct size, the researchers performed delayed enhancement cardiac MRI in 86 patients (the remaining 32 did not undergo MRI, mostly because of patient refusal). Infarct size at 3 months as judged by MRI was significantly lower in the postconditioning group, amounting to a 19% relative reduction. This corresponded to a 31% increase in salvage ratio. LVEF values, however, were exactly the same between the 2 groups (table 1).

Table 1. Outcomes Evaluated by Cardiac MRI

^a Percentage of LV mass.

Despite the equivalent LVEF values, fewer patients in the postconditioning group had New York Heart Association (NYHA) class 2 to 4, indicating that the treatment appears to curb the development of heart failure at 3-month follow-up (P = 0.05; table 2). Other clinical endpoints, including death, repeat PCI in the target vessel, MI, death, stent thrombosis, and angina, were similar between the control and postconditioning patients.

Table 2. Functional Class at 3-Month Follow-up

In an e-mail communication with TCTMD, Dr. Lønborg said that while the paper is not the first to evaluate ischemic postconditioning, it still adds to the literature. “Previous studies have demonstrated ischemic postconditioning to be an efficient, safe, and simple adjuvant therapy to primary percutaneous intervention, but the previous studies are few and relatively small,” he noted, adding that the prior research efforts also had relatively strict inclusion and exclusion criteria.

Another positive aspect of the study is cardiac MRI, which is “the most accurate method to measure infarct size. This study is the first to use this means to evaluate the effect of ischemic postconditioning,” he explained, adding that the researchers also used inclusion criteria intended to capture real-world clinical practice. “Furthermore, this study is the first study, to our knowledge, to demonstrate a positive effect on functional status using New York Heart Association class.”

One surprising finding was that although infarct size and functional class were significantly better with postconditioning, there was no improvement in LVEF or LV dimensions, Dr. Lønborg commented.

In an e-mail communication with TCTMD, Spyridon Deftereos, MD, of Athens General Hospital (Athens, Greece), called the study “well-planned,” adding that it provides new evidence about the benefit conferred by postconditioning in the context of primary PCI.

While not the first study to investigate this issue, Dr. Deftereos said, its findings are valuable for 2 main reasons: MRI is a “very reliable method” to assess infarct size and previous studies have involved small numbers of patients. “This is understandable since [postconditioning] doesn’t involve new devices or pharmacological agents and thus cannot easily attract corporate support,” he added.

Direct vs. Remote Postconditioning

Dr. Deftereos recently published research in the January 2010 issue of JACC: Cardiovascular Interventions showing that remote postconditioning—involving inflating and deflating a blood pressure cuff on the upper arm—improved ST-segment resolution within 30 minutes of primary PCI. In that scenario, conditioning was applied at around the same time as PCI, not after. “To make a long story short, the 2 studies investigated 2 different forms of ischemic conditioning,” he explained, adding that while both methods were effective, the studies “largely differed in terms of endpoints and [length of] follow-up.”

“The use of ‘direct’ ischemic postconditioning (repetitive occlusion and opening of the coronary artery by means of the PTCA balloon) is feasible and applicable,” said Dr. Deftereos, referring to the method examined by Dr. Lønborg and colleagues. “It may prolong the procedure time of primary PCI and increase the complexity of the procedure, but these are not really big problems for the experienced interventionalist.”

Remote ischemic postconditioning is “even simpler,” he continued, due to the fact that the method is performed on the arm. Thus, the “PCI procedure itself is not affected or altered in any way.” Both direct and remote preconditioning are thought to protect cardiomyocytes from reperfusion injury.

Larger clinical studies powered to assess hard clinical outcomes such as cardiovascular events and death are needed, said Dr. Deftereos. “Moreover, the pathophysiology underlying ischemic postconditioning is not clear,” he noted. “Suggestions have been made, but elucidating the mechanisms of ischemic conditioning could result in optimization of the procedure used to induce it and potentially facilitate the search for pharmacological agents mimicking its effects.”

Dr. Lønborg agreed that a large randomized multicenter trial must be performed to settle the question of whether the treatment’s cardioprotective effect will translate into clinically relevant improvements. While current evidence is insufficient to support the use of postconditioning in everyday practice, he sees few downsides to the technique.

As of yet, no adverse effects have been reported, noted Dr. Lønborg. But direct postconditioning, as an invasive treatment, can be given only to patients undergoing primary PCI, not those treated with thrombolysis. In addition, it “takes up to 8 minutes, which can be quite a long time for critically ill patients with ischemia-induced arrhythmias or cardiogenic shock who need intensive treatment and/or hemodynamic support” with an LVAD or aortic balloon pump, he said.

Disclosures:

• Drs. Lønborg and Deftereos report no conflicts of interest.
  

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