Preconditioning May Counteract Platelet Increase Associated with RF Ablation in A-fib

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In patients with paroxysmal atrial fibrillation (A-fib) undergoing high frequency radiofrequency (RF) ablation, remote ischemic preconditioning appears to counteract platelet activation elicited by the ablation procedure, according to a small study published online November 25, 2013, ahead of print in Circulation.

For the study, Gaetano A. Lanza, MD, of Catholic University of the Sacred Heart (Rome, Italy), and colleagues enrolled 19 consecutive paroxysmal A-fib patients from November 2011 to April 2013. All were referred to undergo RF ablation and randomized to receive remote ischemic preconditioning (IPC; n = 10) or sham intermittent ischemia (n = 9) immediately before the procedure. All patients were in stable sinus rhythm at the time of RF ablation, and platelet activation and reactivity were assessed by flow cytometry.

Preconditioning Works

Testing for both platelet activation and reactivity showed an increase in biomarkers in both groups immediately after RF ablation (P < 0.01 for all variables in both groups), which persisted until 24 hours after the procedure.

However, compared with controls, the ischemic preconditioning group had a less substantial increase in all platelet variables, including:

• Monocyte-platelet aggregates (MPA; P < 0.0001)
• Glycoprotein IIb/IIIa (P = 0.002) in the MPA gate
• Glycoprotein (GP) IIb/IIIa (P < 0.0001) and P-selectin (P = 0.002) in the platelet gate

Additionally, remote ischemic preconditioning also was associated with a lower ADP-induced increase of all platelet markers.

According to the study authors, increased platelet activation can occur as a result of RF-induced injury of the subendocardial left atrium wall, in turn causing activation of the coagulation cascade and inflammatory reaction. While antiplatelet agents can be given, the study demonstrates that ischemic preconditioning offers another option for heading off potential thromboembolic events.

“This potential clinical effect, however, needs to be assessed in appropriately designed large clinical trials, even considering that the IPC-induced reduction of platelet activation in our study appeared relatively modest,” Dr. Lanza and colleagues write.

They acknowledge that the small size of the cohort and the lack of patients with comorbidities or those at high risk for platelet activation limit the generalizability of their findings.

Needs Repeating in Different Populations

In an accompanying editorial, Francesco Violi, MD, and Pasquale Pignatelli, MD, both of Sapienza University of Rome (Rome, Italy), concur that the study was “underpowered to analyze the relationship between changes of platelet activation and asymptomatic cerebral emboli, an issue which should be investigated in the future.”

Furthermore, Drs. Violi and Pignatelli say that due to the “well selected population with no previous history of cardiovascular or cerebrovascular disease,” it is likely that patients had relatively low CHA2DS2-VASc scores. Therefore, the findings might have more relevance if the study were repeated in patients with higher scores to see if preexisting vascular risk has a different impact on platelet activation. They also note that approximately 30% of patients in the study were already on aspirin therapy, so the negative impact of ablation on platelet activation could be even more relevant.

Drs. Violi and Pignatelli explain that the mechanism through which remote ischemic preconditioning attenuates platelet response “is still unclear and, at the moment, only a matter of speculation. [Therefore, while the findings] are of interest and could provide more insight in the mechanism accounting for thrombosis in AF patients undergoing RF ablation, they should be considered preliminary at the moment.” They add, however, that it is “crucial” to establish if the RF-induced platelet activation is relevant in terms of cerebral embolism risk in this patient population. Until then, “inhibition of platelet activation by remote IPC or antiplatelet drugs before, during, or after RF ablation seems to be premature,” they conclude.

Study Details

Remote ischemic preconditioning involved the application of 3 short episodes (5 minutes each) of forearm ischemia by cuff inflation, separated by 5 minutes of reperfusion. The cuff was placed in the standard position on the right arm and inflated to a pressure value 50 mm Hg higher than the systolic blood pressure of the patient. In the sham group, the cuff was inflated for 3 times at 10 mm Hg for 5 minutes, with 5-minute intervals.

1. Stazi A, Scalone G, Laurito M, et al. Effect of remote ischemic preconditioning on platelet activation and reactivity induced by ablation for atrial fibrillation. Circulation. 2013;Epub ahead of print.

2. Violi F, Pignatelli P. Platelet activation after radiofrequency ablation in atrial fibrillation: Is there any clinical implication? Circulation. 2013;Epub ahead of print.

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