Impact of Non-obstructive left main disease on the progression of coronary artery disease: A PARADIGM substudy

Abstract

Background: The aim of the study is examine the impact of non-obstructive (< 50%stenosis) left main (LM) disease on the natural history of coronary artery disease using serial coronary computed tomography angiography (CTA). Methods: CTAs from the PARADIGM (Progression of atherosclerotic plaque determined by computed tomographic angiography imaging) study, a prospective multinational registry of patients who underwent serial CTA at a ≥2 year interval were analyzed. Those without evidence of CAD on their baseline scan were excluded, as were those with obstructive left main disease. Coronary artery vessels and their branches underwent quantification of: plaque volume and composition; diameter stenosis; presence of high-risk plaque. Results: Of 944 (62 ± 9 years, 60% male) who had evidence of CAD at baseline, 444 (47%) had LM disease. Those with LM disease had a higher baseline plaque volume (194.8 ± 221mm3 versus 72.9 ± 84.3mm3, p < 0.001) and a higher prevalence of high-risk plaque (17.5% versus 13%, p < 0.001) than those without LM disease. On multivariable general linear model, patients with LM disease had greater annual rates of progression of total (26.5 ± 31.4mm3/yr versus 14.9 ± 20.1mm3/yr, p < 0.001) and calcified plaque volume (17 ± 24mm3/yr versus 7 ± 11mm3/yr, p < 0.001), with no difference in fibrous, fibrofatty or necrotic core plaque components. Conclusion: The presence of non-obstructive LM disease is associated with greater rates of plaque progression and a higher prevalence of high-risk plaque throughout the entire coronary artery tree compared to CAD without LM involvement. Our data suggests that non-obstructive LM disease may be a marker for an aggressive phenotype of CAD that may benefit from more intensive treatment strategies.

Significance of Insignificant Left Main Disease

“…Rather than serving to dismiss the relevance of intermediate LM disease, however, the very relationship between adverse outcomes and the clinical covariates confounding this association serve to underscore the role of intermediate LM disease as a marker of patient vulnerability. As postulated previously by Weir-McCall et al, 8 atherosclerotic disease of the LM coronary artery may indicate an aggressive phenotype of coronary artery disease warranting respect and possibly intensified medical therapy. Indeed, the mere presence of calcification in the LM distribution in asymptomatic patients has been associated with adverse outcomes.…”

Therapeutic and diagnostic targeting of fibrosis in metabolic, proliferative and viral disorders

“…Patients with LMCA presented with a more calcified, more fibrous and more necrotic plaque, as well as with increased progression at follow-up scans. This exemplifies the value of CTA, as it contributed to the realization that the severity of LMCA is a marker for more aggressive progression of coronary artery disease [292]. Efforts to correlate CTA imaging features with histology-derived information may help to further improve the diagnostic power of this imaging modality [293,294].…”

Outcomes With Intermediate Left Main Disease: Analysis From the ISCHEMIA Trial

“…In our study, intermediate LMD was associated with overall worse clinical outcomes, but in the fully adjusted models taking into account the extent of CAD, patients with intermediate LMD had a higher risk of stroke but not other end points, suggesting that the prognostic value of intermediate LMD is, in part, a reflection of greater burden of atherosclerosis. 18…”

“…In our study, intermediate LMD was associated with overall worse clinical outcomes, but in the fully adjusted models taking into account the extent of CAD, patients with intermediate LMD had a higher risk of stroke but not other end points, suggesting that the prognostic value of intermediate LMD is, in part, a reflection of greater burden of atherosclerosis. 18 Finally, given this greater burden of atherosclerosis and potential progression to significant LMD, we explored whether there is heterogeneity of treatment effect of invasive and conservative strategy based on LM stenosis severity. In our study, 7% of those with intermediate LMD on CCTA were considered to have significant obstructive (≥50% stenosis on quantitative coronary angiography) LMD on coronary angiography, perhaps emphasizing the differences between the two imaging modalities.…”