Kavanagh, P A U L

Abstract Purpose Spatial distribution of coronary artery calcium (CAC) may provide additional prognostic value in patients undergoing SPECT and PET myocardial perfusion imaging (MPI). We aimed to automatically identify CAC in proximal segments from attenuation correction CT (CTAC) scans using artificial intelligence (AI) and to evaluate prognostic significance in two large international multicenter registries. Methods From hybrid MPI/CT imaging (N=43,099) across 15 sites, we included 4,552 most relevant patients with 1) no prior coronary artery disease; 2) AI-derived mild CAC scores (1-99); and 3) normal perfusion (stress total perfusion deficit <5%). The independent associations between AI-identified proximal CAC and major adverse cardiovascular events (MACE) and all-cause mortality (ACM) were evaluated using multivariable Cox regression, likelihood ratio test (LRT), and continuous net reclassification index (NRI). Results Among the patients with mild CAC and normal perfusion (mean age 65±12 years, 51% male), 1,730 (38%) had proximal CAC. Over 3.6 (inter-quartile interval 2.1, 5.2) years follow-up, 599 (13%) and 444 (10%) patients had MACE or ACM, respectively. Proximal CAC was associated with an increased risk of MACE (adjusted hazard ratio [HR] 1.24, 95% CI 1.03–1.48, P=0.02) and ACM (adjusted HR 1.25, 95% CI 1.01–1.53, P=0.04) after the adjustment of CAC score and density, clinical risk factors, and perfusion deficit. Proximal CAC improved the risk stratification of MACE (LRT P=0.02; NRI 12%) and ACM (LRT P=0.04; NRI 12%). Conclusion In patients with mild CAC and normal perfusion, AI detection of proximal CAC identified a higher-risk group for adverse outcomes, highlighting its prognostic utility. Graphical Abstract From patients who underwent hybrid myocardial perfusion imaging (MPI) from 15 sites, we analyzed those without prior coronary artery disease (CAD), mild coronary artery calcium (CAC) scores (1-99), and normal perfusion (stress total perfusion deficit <5%). A previously developed AI model was used to identify CAC lesions in proximal coronary segments on CT attenuation correction maps (CTAC). We evaluated associations with major adverse cardiovascular events (MACE) and all-cause mortality (ACM), showing risk stratification of proximal CAC and improvement by net reclassification index (NRI). CAC lesion color: green, left anterior descending artery (LAD) with left main artery; red, left circumflex artery (LCX); yellow, right coronary artery (RCA). Adjusted hazard ratios (HRs) are shown with 95% confidence intervals.

Abstract Aims Left bundle branch block (LBBB) is associated with mechanical dyssynchrony, heterogeneous perfusion, and adverse left ventricular (LV) remodelling. However, not all patients with LBBB develop cardiomyopathy, and dyssynchrony can occur without conduction defects. The role of microvascular dysfunction remains uncertain. We aimed to assess how mechanical dyssynchrony and perfusion heterogeneity relate to LV remodelling and function in patients with and without LBBB. Methods and results We analysed 233 patients with LBBB and 932 matched controls who underwent PET myocardial perfusion imaging, assessing mechanical dyssynchrony (phase entropy), LV volumes, and ejection fraction (EF); coronary vascular resistance (CVR), myocardial blood flow (MBF), myocardial flow reserve (MFR) as markers of microvascular function; and septal-to-lateral MBF ratio (SLR) as a measure of regional perfusion heterogeneity. Compared with controls, LBBB patients had greater dyssynchrony (56% vs. 40%), larger LV volumes, and lower EF (54% vs. 67%) (all P &lt; 0.001), as well as higher stress CVR (37 vs. 34 mmHg/mL·min−1·g−1), and lower MBF (2.4 vs. 2.6 mL/min/g), MFR (2.4 vs. 2.6), and SLR (0.95 vs. 1.00) (all P &lt; 0.05). Among patients with dyssynchrony, SLR &lt;1.0 identified greater remodelling. In multivariable regression, phase entropy and SLR independently predicted LV volumes and EF, with adverse effects of SLR reduction amplified in LBBB (interaction P &lt; 0.01). In Cox analysis, phase entropy (HR:1.02, P = 0.01), MFR (HR:0.62, P &lt; 0.001), and LVEF (HR:0.97, P &lt; 0.001) were independently associated with death or heart failure hospitalization, whereas LBBB was not. Conclusion Mechanical dyssynchrony and perfusion heterogeneity independently predict adverse LV remodelling, irrespective of LBBB. Integrated imaging improves cardiomyopathy stratification.

Abstract Aims Left bundle branch block (LBBB) is associated with mechanical dyssynchrony, heterogeneous perfusion, and adverse left ventricular (LV) remodeling. However, not all patients with LBBB develop cardiomyopathy, and dyssynchrony can occur without conduction defects. The role of microvascular dysfunction remains uncertain. We aimed to assess how mechanical dyssynchrony and perfusion heterogeneity relate to LV remodeling and function in patients with and without LBBB. Methods and results We retrospectively analyzed 233 patients with isolated LBBB and 932 matched controls who underwent PET myocardial perfusion imaging, assessing mechanical dyssynchrony (phase entropy), myocardial blood flow (MBF), coronary vascular resistance (CVR), myocardial flow reserve (MFR), septal-to-lateral MBF ratio (SLR) for perfusion heterogeneity, LV volumes, and ejection fraction (EF). Compared to controls, patients with LBBB had greater dyssynchrony (56% vs. 40%), larger LV volumes, and lower EF (54% vs. 67%) (all p <0.001), and had higher stress CVR (37 vs. 34 mmHg/mL·min⁻¹·g⁻¹), lower stress MBF (2.4 vs. 2.6 mL/min/g), reduced MFR (2.4 vs. 2.6), and lower SLR (0.95 vs. 1.00) (all p <0.05). Among patients with dyssynchrony, SLR<1.0 identified those with more adverse remodeling. In multivariable regression, phase entropy and SLR independently predicted LV volumes and EF, with adverse effects of SLR reduction amplified in LBBB (interaction p <0.01). In the Cox proportional hazards analysis, phase entropy (HR:1.02, p =0.01), MFR (HR:0.62, p <0.001), and LVEF (HR:0.97, p <0.001) were independently associated with mortality and heart failure hospitalization, whereas LBBB was not. Conclusions Mechanical dyssynchrony and perfusion heterogeneity independently predict adverse LV remodeling, irrespective of LBBB. Integrated imaging enhances cardiomyopathy stratification.