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SAN FRANCISCO -- Pressure-controlled intermittent coronary sinus occlusion (PiCSO) for acute myocardial infarction (AMI) appeared safe but ineffective in reducing infarct size, the PiCSO-AMI-I trial showed.

Use of the device during primary percutaneous coronary intervention (PCI) didn't result in any difference in infarct size on cardiac MR imaging at 5 days (27.2% vs 28.3% of the left ventricle, P=0.59), Giovanni Luigi De Maria, MD, PhD, of Oxford University Hospitals in England, reported "with a pinch of disappointment."

Nor were there differences in infarct size or left ventricular function measures at 6 months in the findings presented at the Transcatheter Cardiovascular Therapeutics (TCT) meeting hosted by the Cardiovascular Research Foundation.

"At the moment we are back at the drawing board to probably be a bit more refined and fine tuning the selection of those patients that actually should be included in a STEMI [ST-segment elevation myocardial infarction] trial like this one," he said. "This is a long series of clinical trials trying to do something more in STEMI patients, and it's always getting disappointed."

But the procedure appeared safe and feasible, though it prolonged procedural time and increased contrast dye volume and radiation exposure. There were no higher rates of adverse events, whether device or non-device related, at 6 months follow-up.

The procedure involves inserting a balloon-tipped catheter into the coronary sinus and intermittently inflating it to block coronary venous outflow from the left anterior descending artery (LAD). This increases mean coronary sinus pressure and coronary sinus pulse pressure with the hope of by opening collaterals to ischemic myocardium.

Primary PCI to open up the major blockage dramatically changed prognosis in patients with ST-segment elevation MI, De Maria noted. "But the reality is, over the last decade, our ability to improve further clinical outcome in these patients has kind of plateaued."

Suboptimal myocardial reperfusion is common in STEMI and can lead to heart failure.

"I think the reason we're all disappointed is not because of this device in particular, but if you look at what happens with these patients with anterior MIs, this is how heart failure happens," said TCT press conference moderator Ajay Kirtane, MD, of NewYork-Presbyterian/Columbia University Irving Medical Center in New York City. "So we really, as clinicians, feel that we need something that can hopefully prevent that from happening. It's just a series of negative trials."

The trial randomized 145 adults with anterior STEMI to primary PCI either conventional or assisted with the PiCSO Impulse Catheter via femoral venous access after antegrade flow restoration of the culprit vessel prior to inserting a stent. Median PiCSO treatment time was 20-30 minutes. Inclusion criteria also required a culprit lesion in the proximal or mid left anterior descending artery, pre-PCI TIMI flow 0 or 1, and treatment within 12 hours of MI symptoms onset.

Secondary outcomes included myocardial salvage, microvascular obstruction, and intramyocardial hemorrhage at 5 days, left ventricular ejection fraction at 5 days and 6 months, and infarct size at 6 months -- none of which showed any significant difference between the standard and PiCSO-assisted PCI groups.

However, PiCSO also didn't impair ST segment resolution at 60 to 90 minutes after restoring flow, nor was there an increase in myocardial hemorrhage occurrence or extent. No cases of coronary sinus injury occurred with PiCSO.

While PiCSO success, defined as delivery for at least 20 minutes, reached most patients (86.1%), the proportion who hit the target of at least 45 minutes of PiCSO was only 63.9%, which Kirtane noted might have hampered the potential to find an effect in a small trial population.

"One of the most important things about the study is you showed it was safe to be used, so now we can continue to look for what groups might benefit most from this device," said TCT press conference panelist B. Hadley Wilson, MD, president of the American College of Cardiology.

One potential direction, he suggested, would be to target a narrower timeframe after symptom onset, either early (within 6 hours) or even late-presenting STEMIs up to 48 hours.

While not significant, patients who got PiCSO applied after stent implantation tended to do worse, so very early phase treatment might be better, even before reopening the vessel, although likely to be challenging to implement, De Maria suggested.

There was no difference in single versus multivessel disease or between patients who had longer versus shorter PiCSO times or re-occlusion versus maintenance of patency, De Maria noted. But he agreed that there's room for further trials with better patient selection.

For example, infarct size varied from 5% to 50% and selection was just based on STEMI timing, location, and poor flow at baseline, he noted. "There is an argument that if you include in a study patient with a small infarct size, it's going to be very difficult to prove an additional value of an extra therapy like this one."

TCT late-breaking clinical trial session discussant Adnan Kastrati, MD, of Deutsches Herzzentrum Munchen in Munich, Germany, noted that preliminary PiCSO studies had used an index of microcirculatory resistance (IMR) for patient selection and were positive.

That tool wasn't as validated as it is now, De Maria noted. "If there is to be a second trial, it should probably be similar in structure as this one but including some extra selection criteria, quite possibly physiology based, IMR, for example to restrict a bit more the patients selected for extra treatment."

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