Korean Registry Casts Fresh Light on Late STEMI Care, Outcomes

Patients presenting late to the hospital with STEMI fare “remarkably” worse than people who get to the hospital within the first 12 hours after symptom onset, but late presentation in and of itself does not independently predict worse outcomes, a large, retrospective analysis from Korea confirms.

However, the nationwide data also point to a steep decline in the use of invasive procedures as time to presentation lengthened, with investigators recording a strong, inverse relationship between use of invasive procedures and mortality.

“Inverse steep differences in the use of invasive interventional procedures and mortality rates were found between the first (< 12 hours) and the second (12 to 24 hours) symptom-to-door time 12-hour interval in STEMI patients presenting at < 48 hours, indicating that the practice pattern of interventional procedures might affect the clinical outcomes of STEMI late presenters,” Kyung Hoon Cho, MD, PHD (Chonnam National University Hospital, Gwangju, Republic of Korea), and colleagues write.

International guidelines are mixed on the management of STEMI patients after the first 12 hours have passed, but as Cho et al point out in the paper, that 12-hour cut point was established during the fibrinolysis era, when STEMI patients presenting after 12 hours derived no benefits from lytics. And as an editorial points out, though the analysis was conducted pre-COVID-19, the findings are particularly relevant as the pandemic drags on, since hospitals around the globe have reported an increase in late ACS presentations as well as the attendant complications of delayed care.

PCI as the Default Strategy in Late Presenters

The study, in the April 20, 2021, issue of the Journal of the American College of Cardiology, examined 180-day and 3-year mortality among 624 patients presenting 12 to 48 hours after symptoms (“late”), as compared with 5,202 patients who presented within 12 hours (“early”). All 13,707 patients were being tracked in the Korea Acute Myocardial Infarction Registry-National Institutes of Health database.

While both 180-day and 3-year mortality were significantly worse for the late versus early presenters, late presentation itself was not independently associated with increased mortality after STEMI (HR 1.14; 95% CI 0.87-1.48).

Mortality by Symptom-to-Door Times

Instead, key independent predictors were patient-related factors including Killip class, blood pressure, glomerular filtration rate, heart rate, anemia, and LV function, as well as patient management. In particular, a “no primary PCI strategy” was associated with a significantly increased risk of 180-day death (adjusted HR: 1.82; 95% CI 1.37 to 2.43).

In an accompanying editorial, Harold L. Dauerman, MD (University of Vermont, Burlington), and Borja Ibanez, MD, PhD (Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain), point to existing guidelines.

They note that the 2013 American College of Cardiology/American Heart Association guidelines recommend that patients who present 12 to 24 hours after symptom onset while having ongoing symptoms or signs of ischemia should undergo primary PCI (class IIa, level of evidence B). In contrast, the 2017 European Society of Cardiology (ESC) guidelines recommend that patients presenting after 12 hours who have ongoing symptoms, hemodynamic instability, or arrhythmias undergo primary PCI (class I, level of evidence B), and also—echoing the US stance—that all patients presenting late (up to 48 hours) can be considered for PCI (class IIa, level of evidence B).

To TCTMD, Dauerman pointed out that the only randomized clinical trial to inform the recommendations about optimal STEMI management in the late window studied here is BRAVE-2, back in 2005. Well-developed STEMI systems, he said, “have made a lot of progress,” such that in the US and most of Europe over the last two decades, late presentations have fallen from around 22% to closer to 10% or 12%. In the current study, late presenters made up just 10.7% of the STEMI cohort.

In China, however, both prior to and during COVID-19, late STEMI presenters continue to make up about one-fifth of the caseload, said Dauerman. While a randomized trial in this STEMI window is unlikely, “if we were going to see a randomized clinical trial of conservative therapy versus primary PCI through late presenters, the best place to recruit patients would be in places like China.”

For now, he said, “I think that the totality of evidence makes [PCI] the default strategy: that everybody within 48 hours of symptom onset should get primary PCI. . . . I do not think we should wait for more evidence, because we have registries and we have other mechanistic studies with cardiac MRI showing the potential for late salvage despite long coronary occlusion times. I think this should be the default for every patient in every emergency room.”

What about Guideline-Directed Medical Therapy?

Also commenting on the paper for TCTMD, Kameswari Maganti, MD (Northwestern University, Chicago, IL), agreed that the question of what to do with late presenters has long been controversial. “A lot of us do presume that [for] people who present really late after having symptoms—which is a lot of women and a lot of the elderly, especially elderly women, that we know do really poorly with an increased risk of death and an increased risk of heart failure—that just making sure they are actually seen in a very prospective, clear-cut manner actually makes a lot of sense.”

A missing piece of puzzle in the current study, she noted, was any information on concomitant, potentially lifesaving medications and how those impacted mortality over time

“The takeaway for me, looking at this, is that I may use more cardiac MRI . . . to look for viability and if there is viable myocardium or myocardium at risk that we can actually salvage, I would be sending those patients for intervention, even if they present late,” Maganti said. “I think this also tells us that we may have to figure out what medications they're on, [because] these medications may have an impact on mortality.”

Another important aspect, particularly in the later presenters, would be to be on the look out for mechanical complications, which would necessitate more of a heart team discussion, she added. An MRI-driven strategy, Maganti pointed out, can look for myocardial viability, myocardium at risk, and also any signs of mechanical complications.

There have been increasing reports of mechanical complications and other unusual symptoms of late STEMI presentation in the past year as a result of COVID-19, as Dauerman acknowledged to TCTMD. This paper, while not directly related to the pandemic, he said, does carry some timely information.

“I think that one initial concept with the COVID pandemic was that maybe we should use more fibrinolysis, because primary PCI might be delayed. I think that this paper emphasizes that smaller delays in primary PCI and total symptom time don't mean there isn't still a benefit for primary PCI,” he explained. “And so even if there's a built-in delay related to COVID pandemic precautions, or to patients presenting later, as long as they're having symptoms and are within 48 hours and have persistent ST elevation, those patients should be treated with a primary PCI approach as the default strategy.”