Invasive Measurements Confirm Quick Recovery of Microcirculation After Primary PCI

After successful primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI), reperfusion is often impaired by microcirculatory dysfunction. However, the microvessels begin to recover within 1 day and return to near-normal by 6 months, according to a hemodynamic studypublished in the November 4, 2014, issue of the Journal of the American College of Cardiology.

Importantly, microvascular dysfunction may distort early measurement of fractional flow reserve (FFR), causing underestimation of ischemic risk, the authors say.

Methods
Researchers led by Adrian P. Banning, MBBS, MD, of Oxford University Hospitals (Oxford, England), studied 82 STEMI patients who underwent invasive coronary physiology assessment with a pressure wire (Certus; St. Jude Medical) during primary PCI at a single center between October 2010 and October 2011. On the day after PCI, 74% of patients received repeat invasive assessment and 55% had late gadolinium-enhanced cardiac magnetic resonance imaging (MRI), while at 6 months 56% and 50% underwent the respective procedures.
Mean age was 62 years, and 78% of patients were men. Most patients were treated via the transradial approach, 65% had thrombectomy, and 85% received abciximab.

Blood Flow Metrics Affected by Early Obstruction

Of 45 patients who had cardiac MRI, 47% had microvascular obstruction at 1 day, with a mean value of 7.6% of LV mass. Those with obstruction were more likely to have diabetes and the LAD as the infarct artery. In addition, TIMI flow grade 3 was reached in 86% of patients with microvascular obstruction compared with 100% of those without the condition (P = .06), and complete ST-segment resolution was achieved in 38% of patients with obstruction vs 71% of those without (P = .03).

Mean coronary flow reserve—the ratio of transit times at baseline and during hyperemia—was lower in patients with vs. without microvascular obstruction at the index PCI (P = .02) and at day 1 (P = .04) but not at 6 months (P = .10). Similarly, in patients with obstruction there was a trend toward higher mean index of microvascular resistance during PCI and at day 1 (P = .07 for both).

On the day after PCI, patients with vs without microvascular obstruction had lower LVEF, more myocardial edema, and larger infarct size as measured by cardiac MRI. The differences in LVEF and infarct size were maintained at 6 months (table 1).

 Table 1. Cardiac MRI Measures

Overall, FFR of the infarct artery decreased from 0.93 ± 0.05 after PCI to 0.92 ± 0.06 at 1 day and to 0.89 ± 0.06 at 6 months (P = .048 and P = .003 for the respective intervals). However, the decline between PCI and 6 months was significant among those with microvascular obstruction (P = .006) but not those without the condition (P = .21), demonstrating interaction between the presence of obstruction and the timing of FFR (P = .03).

According to the paper, “the drop of FFR [in the infarct artery] cannot be explained by angiographic restenosis as the degree of vessel stenosis remained stable over the study period.”

Both 6-month infarct size on cardiac MRI and change in FFR from PCI to 6 months increased with the degree of microvascular obstruction (P = .004 and P = .03 for trend, respectively).

The extent of myocardial edema seen on the first day after PCI was related to coronary flow reserve and index of microvascular resistance at 1 day and to the extent of detectable scar measured by cardiac MRI at 6 months. However, early edema did not have any clear effect on the shift in FFR during follow-up.

Microcirculation Improves Over Time

The partial reversibility of post-STEMI microvascular dysfunction over time has been shown in previous research, William F. Fearon, MD, of Stanford University Medical Center (Stanford, CA), told TCTMD in an email. “What this study adds is serial measurements… in combination with invasive assessment of the microvasculature with [index of microvascular resistance] and [coronary flow reserve],” he said. “By doing this, the authors show that FFR changes even within 1 day after STEMI and continues to change between 1 day and 6 months.

“Although challenging (because it would have meant another invasive procedure), it would have been informative to see whether the FFR had already reached its 6-month value by 3 to 6 days,” Dr. Fearon continued, pointing out that the shift in FFR is more common in patients with microvascular obstruction, which tends to improve over time.

Overall, Dr. Fearon said, the changes seen in the study “make sense and confirm the findings of previous investigators” regarding improvements in microvascular function after STEMI, particularly for smaller MIs.

“I think the future for invasive assessment of the microvasculature at the time of STEMI will involve using [index of microvascular resistance] to identify a high-risk subset with the most microvascular damage and the greatest to gain from an intervention, such as regenerative stem-cell therapy,” he added.

Hold Off on FFR

In an accompanying editorial, Gilles Rioufol, MD, PhD, and Gérard Finet, MD, PhD, both of Hospices Civils de Lyon (Bron, France), say a lesson to be drawn from the study is that FFR values evolve—with the resolution of epicardial stenosis, these values decreased significantly over time.

Dr. Fearon agreed, noting that “for this reason, measuring FFR in the culprit vessel at the time of acute STEMI has been contraindicated [because the value] may be falsely elevated due to transient microvascular damage, which once it has resolved will allow greater hyperemic flow and a subsequently lower FFR down the same vessel.”

He added that other investigators have shown that most of the improvement in microvascular dysfunction occurs during the first week and measuring FFR no earlier than 3 to 6 days after STEMI in the culprit vessel correlates well with noninvasive assessment of ischemia.

Drs. Rioufol and Finet conclude that a “single invasive measure of microcirculation… now seems an unsatisfactory way of identifying patients at high risk of [microvascular obstruction]. Even so, invasive assessment remains an important focus of research, as the moment of [primary PCI] is a unique opportunity for detecting reperfusion lesions and setting up the therapeutic measures needed to treat them.”

 


Sources:
1. Cuculi F, De Maria GL, Meier P, et al. Impact of microvascular obstruction on the assessment of coronary flow reserve, index of microcirculatory resistance, and fractional flow reserve after ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2014;64:1894-1904.

2. Rioufol G, Finet G. Invasive coronary microcirculation assessment during myocardial infarction: one step forward or two steps back [editorial]? J Am Coll Cardiol. 2014;64:1905-1907.

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Disclosures
  • Dr. Banning reports being partially funded by the NIHR Oxford Biomedical Research Unit and receiving an unrestricted research grant from Boston Scientific.
  • Drs. Rioufol and Finet report no relevant conflicts of interest.
  • Dr. Fearon reports receiving research grants from St. Jude Medical.

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