Author + information
- Stefano Sdringola, MD∗,
- Nils P. Johnson, MD, MS∗,
- Jagat Narula, MD, PhD† and
- K. Lance Gould, MD∗∗ ()
- ∗Weatherhead PET Center for Preventing and Reversing Atherosclerosis, Division of Cardiology, Department of Medicine, University of Texas Medical School and Memorial Hermann Hospital, Houston, Texas
- †Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York
- ↵∗Address for correspondence:
Dr. K. Lance Gould, Weatherhead PET Center for Preventing and Reversing Atherosclerosis, University of Texas Medical School at Houston, 6431 Fannin Street, Room 4.256 MSB, Houston, Texas 77030.
a large atherosclerotic plaque burden and severe luminal stenosis are associated with unfavorable outcomes in coronary artery disease (cad). On the one hand, critical luminal obstruction has remained the gold standard for clinical decisions on coronary revascularization. On the other hand, expansion of plaque volume has been proposed as a prerequisite for acute coronary syndrome (ACS) events, including sudden death and acute myocardial infarction (MI) (1). In this iPIX, we discuss serial assessment of absolute coronary flow and coronary flow reserve, demonstrating the relationship between plaque progression by positron emission tomography (PET) perfusion imaging and major adverse coronary events.
Traditional belief holds that plaques resulting in ACS are generally subcritically occluded. PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), a large, multicenter serial imaging study, recently demonstrated substantial plaque expansion before the occurrence of ACS. The fateful lesions evolved from 32 ± 21% diameter stenosis to 65 ± 16% over a follow-up period of 3.4 years; intravascular ultrasound–verified cross-sectional plaque area burden (>70%) and minimum luminal area (<4 mm2) were 2 (of the 3) most important determinants of outcomes. Histopathological comparison of a large number of stable, vulnerable, and disrupted plaques revealed that plaque rupture was associated with significant luminal stenosis (1). In this study, the plaques that ruptured were substantially more occlusive than the plaques vulnerable to rupture. The authors therefore proposed that the high-risk plaques would need to expand further before they ruptured.
For stable coronary disease, a critical severity threshold of luminal stenosis identifies patients with improved outcomes by revascularization (2). In this context, percutaneous coronary intervention (PCI) based on routine measurement of fractional flow reserve (FFR) in patients with multivessel CAD improved outcomes compared with PCI based on the angiogram. In the original FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) trial, the patients randomly assigned to FFR-guided PCI had a lower 2-year rate of death, MI, and need for repeat revascularization than patients with angiographically guided PCI. In the logical extension of this study, the FAME II trial established the superiority of an FFR-guided PCI strategy over optimal medical therapy in patients with an FFR ≤0.8. Although designed for a follow-up of 2 years, enrollment in the FAME II trial was terminated early due to substantial treatment difference. The difference in the composite endpoint was predominantly driven by a significantly lower rate of urgent revascularization in the PCI arm (hazard ratio: 0.13; 95% confidence interval: 0.06 to 0.30; p < 0.001). The need for an urgent revascularization was not based on demonstration of ischemia or an increase in serum biomarkers, and there were very few hard endpoints.
The facts presented here are based on a 1-time-point invasive assessment, serial intravascular imaging, or postmortem analysis. It is reasonable to propose that a noninvasive imaging strategy should provide prognostic information to help decide on timely interventions. For this iPIX, several cases of serially assessing absolute coronary flow and flow reserve or relative stress perfusion by PET show progression of CAD to an adverse event and/or indication for revascularization (Figs. 1 to 3)⇓⇓.
Drs. Sdringola, Johnson, and Gould received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis. Drs. Johnson and Gould have a non-financial, mutual non-disclosure agreement with Volcano Corporation to discuss coronary physiology, Volcano Corporation manufactures FFR and CFR wires. Dr. Gould is the 510(k) applicant for cfrQuant, a software package for quantifying absolute flow using cardiac positron emission tomography. All royalties will go to a University of Texas scholarship fund. The University of Texas has a commercial, nonexclusive agreement with Positron Corporation to distribute and market cfrQuant in exchange for royalties. However, Dr. Gould retains the ability to distribute cost-free versions to selected collaborators for research. Dr. Narula has reported that he has no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation