Our study demonstrates that ATP is a safe and potent vasodilator that can be used in stress CMR. ATP infusion was associated with fewer adverse events and demonstrated unique SSO to clearly indicate myocardial stress. Furthermore, stress CMR shows significant clinical value in accurately diagnosing patients with reversible myocardial ischemia by comparing the perfusion images captured during stress and at rest conditions.
Intravenously infused ATP is sequentially metabolized into adenosine diphosphate,adenosine monophosphate, and adenosine. Therefore, the vasodilatory effects of ATP are similar to adenosine, which activates A1 and A2 receptors . Moreover, in our study, the hemodynamic response was observed within 2 minutes after injecting ATP. This was significantly shorter than previously reported for ATP .Thus, our research shows that ATP is a valuable stress agent because of its excellent vasodilatory properties and shorter hemodynamic response times after injection.
ATP is readily accessible and economical in China and other countries in the Asia-Pacific region compared withother stress agents. The cost of adenosine is 40 times higher than the cost of ATP. Furthermore, it is difficult to procure adenosine and other stress agents such as regadenoson because of licensing and manufacturing issues. Thus, ATP can be readily used for CMR in China and other countries in the Asia-Pacific region, provided its efficacy and safety are well established. However, compared with other commonly used agents, such as adenosine or dobutamine, the role of ATP as a stress agent in CMR is not well established. The Society for Cardiovascular Magnetic Resonance(SCMR) updated the standardized cardiovascular magnetic resonance imaging (CMR) protocols in 2020 and included ATP as a stress agent along with details regarding the injection dose and contraindications. Our study provides further evidence for using ATP in stress CMR experiments because it is cost-effective, efficient, and safe .
Nearly 71% of our study subjects that received ATP infusions at 0.16 mg/kg/min remained asymptomatic during the examination. Shortness of breath, chest pain, and headaches were the most common adverse effects of ATP infusion in our study and were consistent with previously reported data[11, 25]. However, these adverse effects were mild and were resolved within 5 mins after stopping ATP infusion. Previous studies [9, 26] demonstrated the feasibility and safety of increasing ATP infusion rate by 50% in patients that did not respond adequately. However, our study shows that 99% of patients were stressed with an ATP infusion rate of 0.16 mg/kg/min. Thus, our study demonstrates that ATP is a safe and clinically feasible stress agent for CMR.
The “splenic switch-off” phenomenon is used to determine stress adequacy in myocardial adenosine perfusion MR imaging . SSO is a quick marker of stress adequacy and does not require the acquisition of additional measures. In our study, SSO was visually observed in 91% of ATP perfusion examinations. Therefore, SSO can also assess stress adequacy during stress CMR. Splenic blood flow attenuation and SSO have not been observed when using other commonly used stress drugs, such as dobutamine and regadenoson. This provides another advantage of using ATP as a stress agent because visualization of SSO provides a clear analysis of stress adequacy.
Our study has a few limitations. First, this was a retrospective study conducted at a single center. Thus, future multi-center studies with larger cohorts are necessary to confirm our findings.Secondly,we did not follow-up with the patients after conducting stress CMR.Therefore,we did not know if major adverse cardiovascular events (MACE) had occurred in these patients.Thus,we currently lack information regarding the use of ATP as a prognostic marker of stressed patients.Thirdly,we did not compare the efficacy of other widely used vasodilator agents like adenosine or dipyridamole with ATP for stress CMR.Lastly,a few patients did not undergo FFR or IMR to confirm the presence of reversible myocardial ischemia.
In conclusion, our study shows that ATP is a potent coronary vasodilator that is safe for stress CMR. The hyperemic response to ATP is quick and comparable to adenosine. In patients undergoing stress CMR, stress adequacy can be evaluated by SSO. Further research is required to clearly establish the prognostic value of ATP in stress CMR examinations.