Door-to-Unload (DTU) in STEMI Trial Summary: Pilot Trial and Pivotal Trial Design

Navin K. Kapur, MD, FACC, FSCAI, FAHA, presents a summary of mechanical left ventricular unloading and delaying reperfusion in patients with anterior ST-segment elevation myocardial infarction (STEMI). Dr. Kapur is the executive director of the Cardiovascular Center for Research & Innovation and associate professor, Department of Medicine, Interventional Cardiology & Advanced Heart Failure Programs.

In chapter 1, Dr. Kapur discusses how scientists and laboratories around the world have spent the last 4 decades investigating whether using a circulatory support pump to reduce myocardial oxygen consumption limits damage by balancing myocardial oxygen supply and demand in AMI. At his lab at Tufts Medical Center, Dr. Kapur and colleagues have found that delayed reperfusion after unloading is a critically important component of enhancing the ability of unloading to reduce myocardial infarction. This delay, he explains, means initiating unloading and then intentionally waiting for a period of time before reperfusing the artery. This, he says, supports the idea of mechanically conditioning the myocardium so that its more receptive to reperfusion on the unloading platform.

In chapter 2, Dr. Kapur reviews 5 impacts of unloading:

• Reduced LV wall stress, when there’s a reduction in LV pressure and volume, reduces myocardial oxygen consumption
• When left atrial pressure is reduced, there’s improved atrial compliance and improved lung and right ventricular function
• LV unloading increases collateral coronary blood flow (functional reperfusion), correlating with reduction in infarct size
• Unloading promotes protective myocardial signaling
• Unloading preserves mitochondrial integrity in AMI

Dr. Kapur also describes how primary unloading reduces LV scarring and preserves cardiac output 30 days after AMI, highlighting the durable and lasting effect correlating with improved cardiac function downstream from the AMI.

In chapter 3, Dr. Kapur juxtaposes the traditional teaching that for every 30 minute delay in reperfusion there should be a 7.5% increase in infarct size, with the central hypothesis of the Door-to-Unload (DTU)-STEMI Pilot trial that compared to LV unloading and immediate reperfusion, LV unloading followed by a 30 minute delay to reperfusion is feasible and safe. He explains the DTU-STEMI Pilot trial design, safety and efficacy outcomes, patient and procedural characteristics, and results. With regard to the primary efficacy outcome of 30-day infarct size, he shows that unloading and delaying reperfusion for 30 minutes did not increase infarct size. He also discusses results from an exploratory subgroup analysis focusing on the size of the MI, noting that perhaps delaying reperfusion does condition the myocardium and allow for recovery after reduction of infarct size.

In chapter 4, Dr. Kapur reviews what was learned in the DTU-STEMI Pilot trial and discusses how that informed the design of the DTU-STEMI Pivotal trial. He presents a case illustrating the DTU experience at Tufts Medical center. He concludes by reiterating that heart attacks lead to heart failure; however, in this new era of the DTU-STEMI platform, he anticipates that we can stem the tide of those patients going on to develop heart failure.