Coronary Atherosclerosis Phenotypes in Focal and Diffuse Disease
Selected in JACC: Cardiovascular Imaging by A. N. Calik
This multicenter, prospective, single-arm study determined that Focal CAD had a higher plaque burden and was predominantly lipid-rich with a high prevalence of TCFA, whereas calcifications were more prevalent in diffuse CAD.
References
Authors
Koshiro Sakai, Takuya Mizukami, Jonathon Leipsic, Marta Belmonte, Jeroen Sonck, Bjarne L. Nørgaard, Hiromasa Otake, Brian Ko, Bon-kwon Koo, Michael Maeng, Jesper Møller Jensen, Dimitri Buytaert, Daniel Munhoz, Daniele Andreini, Hirofumi Ohashi, Toshiro Shinke, Charles A. Taylor, Emanuele Barbato, Nils P. Johnson, Bernard De Bruyne, Carlos Collet
Reference
https://doi.org/10.1016/j.jcmg.2023.05.018
Published
July, 2023
Link
Read the abstractReviewer
My Comment
Why this study – the rationale/objective?
Invasive and non-invasive imaging techniques that measure volume, extension, and composition can be used to determine the burden of atherosclerotic plaque. While calcifications are considered measures of plaque stability, large plaque burden, lipid-rich plaques (LRPs), and thin-cap fibroatheroma (TCFA) have been found to be predictors of plaque rupture and adverse clinical outcomes. Based on the intravascular physiologic evaluation, the pullback pressure gradient (PPG) is a quantitative index to classify coronary artery disease (CAD) patterns as focal or diffuse CAD. Whilst diffuse CAD is characterized by gradual gradient changes, focal disease is indicated by large pressure gradients. Because the relationship between plaque morphology and local hemodynamics is still poorly understood, the current study investigates the pathophysiological interaction between physiological patterns and plaque features in patients with CAD utilizing a combination of non-invasive and invasive imaging methods.
How was it executed – the methodology?
The present study is a subanalysis of the P3 (Precise Percutaneous Coronary Intervention Plan)(1), a multicenter, prospective, single-arm study conducted in 5 countries. Patients with stable CAD and invasive fractional flow reserve (FFR) ≤ 0.80 were included in the study. All patients underwent coronary computed tomography angiography (CTA) with quantitative plaque analysis and an invasive procedure with motorized intracoronary pressure recordings [FFR pullback: PPG ranges from 0 (diffuse disease) to 1 (focal disease)] for longitudinal vessel evaluation followed by optical coherence tomography (OCT). This substudy aimed to differentiate atherosclerotic plaque morphologies between localized and diffuse CAD as determined by coronary hemodynamics utilizing PPG derived from hyperemic pullback pressure curves.
Central illustration: Association Between Coronary Artery Disease Patterns and Plaque Characteristics Based on Invasive and Noninvasive Imaging
Source: JACC Cardiovascular Imaging
What is the main result?
A total of 259 patients were screened from February 2019 to December 2020, with 117 patients (120 vessels) included. Coronary CTA plaque analysis was performed in all cases, while OCT plaque analysis was feasible in 57% (68 of 120). Patients with focal CAD had a lower mean age, were more likely to be male, and one-fifth of the patient group had diabetes. Diffuse CAD was prevalent in the left anterior descending artery. The median PPG was 0.66. Patients with focal disease CAD had more severe lesions, as evidenced by a smaller MLA in 3D-QCA and a lower FFR. Based on CTA plaque analysis, the mean plaque burden (at the MLA) was significantly higher in patients with focal CAD. Patients with diffuse CAD had a higher Agatston score, longer calcium length, and greater calcified plaque burden than patients with focal CAD.
Additionally, PPG was strongly associated with plaque burden and characteristics at the MLA. The higher the PPG, the greater the plaque burden at the MLA, the greater the low-attenuation plaque and noncalcified plaque burden, and the lower the calcified plaque burden. Based on OCT plaque analysis, LRPs were found in 57% of cases, with circumferential LRP being substantially more prevalent in individuals with focal CAD. PPG predicted the existence of circumferential LRP with an area under the curve of 0.82 (95% CI: 0.66-0.99). Fibrous caps overlaying fibroatheromas were thinner in arteries with focal CAD, and TCFA was more prevalent (47.4% focal vs 10.2% diffuse; P =0.002) than in vessels with diffuse disease. Independent of FFR values, and diabetes mellitus, PPG was strongly associated with the presence of circumferential LRP, TCFA, and plaque rupture.
Critical reading and the relevance for clinical practice
The critical finding of the current study is the unique plaque characteristics observed in patients with focal vs diffuse CAD. Atherosclerotic lesions in vessels with localized disease (high PPG) showed a larger plaque burden and were primarily lipid-rich, with a high rate of TCFA, whereas calcifications were the hallmark of vessels with diffuse disease (low PPG). Unlike previous similar studies conducted using only FFR, this study evaluated lesion characteristics using PPG, quantifying the longitudinal distribution of epicardial resistance and adding a dimension to single-point FFR. The PPG will make it possible to link coronary physiological patterns to plaque features. In addition to assessing lesion significance with FFR, the pullback manoeuvre provides extra information on the probability of successful PCI and helps identify the risk of adverse events. The findings show that FFR-PPG helps us understand the lesions' atherosclerotic phenotyping following physiologic assessment; focal disease, with a predominantly lipidic atherosclerotic pattern, and diffuse disease, with a more stable atherosclerotic and calcified pattern. From a clinical perspective, the focal disease is more responsive to treatments like PCI, and patients in this subgroup, characterized by lipidic plaque phenotype, can benefit from interventions.
On the other hand, diffuse disease, which is less suitable for PCI and tends to be stable, may benefit more from conservative management. The PPG can aid in standardizing the diagnosis of CAD patterns and help identify individuals who respond differently to coronary interventions. In short, this substudy comparing atherosclerotic plaque phenotypes between focal and diffuse CAD based on coronary hemodynamics revealed that vessels exhibiting focal disease (high PPG) had a more significant amount of plaque accumulation, primarily consisting of lipid-rich plaques (LRPs) with a high occurrence of thin-cap fibroatheromas (TCFA). Conversely, vessels with diffuse disease (low PPG) mainly had calcified plaques. Besides, an association between PPG and cap thickness was noted, with thinner caps observed in lesions with higher focal pressure gradients. When applying the findings of this study to our daily practice, it is crucial to consider that the lack of comparable plaque assessment for non-hemodynamically significant lesions (FFR > 0.80) prevents us from extending these results to a less diseased population. Another limitation of this study is that it only captures a momentary view of the atherosclerosis process. Since there is a need for more prospective data, it is unlikely to evaluate the progression of the disease or examine the clinical outcomes associated explicitly with focal and diffuse disease.
Lastly, it is essential to note that the current study primarily examined the relationship between coronary hemodynamics and plaque characteristics. The actual impact of these findings on clinical outcomes is yet to be determined and requires further investigation.
References
- Sonck J, Nagumo S, Norgaard Bjarne L, et al. Clinical validation of a virtual planner for coronary interventions based on coronary CT angiography. J Am Coll Cardiol Img. 2022;15:1242–1255.
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