Gary S. Mintz

BACKGROUND: Preventive percutaneous coronary intervention (PCI) of non–flow-limiting lesions (fractional flow reserve >0.80) that are high-risk plaques has emerged as a potential strategy to reduce cardiac events. However, identifying which lesions derive the greatest benefit from preventive PCI compared with optimal medical therapy alone remains challenging. This post hoc analysis evaluates the role of the near-infrared spectroscopy–derived lipid core burden index in identifying high-risk plaques that may benefit from preventive PCI. METHODS: Among the 1606 patients enrolled in the PREVENT trial (Preventive Coronary Intervention on Stenosis with Functionally Insignificant Vulnerable Plaque) from September 2015 to September 2021, an investigator-initiated, multicenter, open-label, randomized controlled trial, this post hoc analysis included 598 patients (mean age, 64.1±8.8 years; 27.9% women) comprising 632 lesions with a plaque burden >70% and a minimal lumen area 315. The primary outcome was a composite of death from cardiac causes, target-vessel myocardial infarction, ischemia-driven target-vessel revascularization, or hospitalization for unstable or progressive angina. RESULTS: LRPs were present in 223 patients (37.3%) with 234 lesions. During median follow-up of 5.6 years, primary outcome events occurred more frequently in patients with LRPs than in those with non-LRPs (12.5% versus 4.7%; unadjusted hazard ratio, 2.08; 95% CI, 1.03–4.19; P =0.039) in the overall population. Within the LRP group, preventive PCI was associated with a lower risk of the primary outcome compared with optimal medical therapy alone (7.3% vs. 17.6%; adjusted hazard ratio, 0.23; 95% CI, 0.13–0.41; P P =0.97). A significant interaction was found between treatment strategy and the presence of LRP ( P _interaction <0.001). CONCLUSIONS: In this post hoc analysis of the PREVENT trial, preventive PCI was associated with a lower risk of the primary composite outcome in patients with near-infrared spectroscopy–defined LRPs, whereas no significant association was observed in those with non-LRPs despite their large plaque burden and small minimal lumen area. These findings suggest the importance of plaque composition, beyond morphological severity alone, in guiding preventive PCI. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02316886.

BACKGROUND: Intravascular imaging (IVI) during percutaneous coronary intervention (PCI) improves outcomes. Pullback pressure gradient characterizes coronary artery disease patterns as focal or diffuse; however, the benefit of IVI across this spectrum remains incompletely understood. We aimed to evaluate clinical outcomes after PCI with or without IVI guidance in patients with focal and diffuse disease defined by pullback pressure gradient. METHODS: Prospective, multicenter, single-arm study of 811 patients (840 vessels) undergoing PCI. Pullback pressure gradient was calculated from manual fractional flow reserve pullbacks to define focal (pullback pressure gradient ≥0.62) or diffuse coronary artery disease. IVI use was at the operator’s discretion. The primary outcome was target vessel failure at 1-year follow-up. RESULTS: IVI-guided PCI was performed in 41% of patients. In the overall cohort, target vessel failure was lower with IVI guidance (adjusted hazard ratio, 0.60 [95% CI, 0.36–0.99]; P =0.044), with a lower incidence of cardiac death ( P =0.042). The results were consistent irrespective of the baseline coronary artery disease pattern ( P _interaction =0.128). Among patients with focal disease, IVI-guided PCI was associated with a significantly lower incidence of target vessel failure compared with non-IVI-guided PCI (hazard ratio, 0.41 [95% CI, 0.18–0.91]; P =0.029). There was no statistical difference in target vessel failure with the use of IVI among patients with diffuse disease (hazard ratio, 0.91 [95% CI, 0.48–1.73]; P =0.771). CONCLUSIONS: In patients undergoing physiology-guided PCI, the use of IVI reduced clinical events at 1 year. These findings suggest that the benefit of IVI extends across the full spectrum of coronary artery disease.

Background: Coronary microvascular dysfunction (CMD) contributes to myocardial ischemia in patients both without obstructive coronary artery disease (e.g., MINOCA/INOCA) and in those with co-existing epicardial stenosis. While its etiology includes structural and functional causes. hematologic parameters have been linked to cardiovascular outcomes. However, the relationship between red blood cell (RBC) markers and microvascular resistance remains poorly characterized. We aim to evaluate whether RBC parameters are correlated with the angiography-derived index of microcirculatory resistance (angio-IMR). Methods: This retrospective study evaluated the association between red blood cell (RBC) parameters and angio-IMR in patients with intermediate coronary artery disease (30%−70% stenosis). Data were analyzed from 604 patients, comprising 733 lesions; red blood cell parameters were obtained during hospitalization prior to angiography. Coronary microcirculatory resistance was derived using the AngioPlus mQFR system. Multivariable linear regression models adjusted for confounders. Subgroup analyses assessed effect modification by diabetes status, and sensitivity analyses excluded hematocrit outliers, and analyses stratified by vessel (left anterior descending (LAD), left circumflex (LCx), right coronary artery (RCA)). Results: Higher RBC, Hct and Hgb were independently associated with elevated angio-IMR after full adjustment (RBC: β = 0.182, P < 0.001; Hct: β = 0.019, P < 0.001; Hgb: β = 0.006, P < 0.001). Results remained robust after excluding Hct outliers (β = 0.020, P < 0.001) and consistent across diabetic ( P = 0.007) and non-diabetic subgroups ( P = 0.012). The association was significant in non-LAD vessels (Hct: β = 0.022, P < 0.001) but not in LAD lesions (Hct: β = 0.008, P = 0.357). Conclusion: Elevated RBC parameters are independently associated with increased microcirculatory resistance, particularly in non-LAD vessels. These findings suggest that RBC parameters may serve as clinically relevant markers of microvascular dysfunction, warranting further investigation into their prognostic and therapeutic implications.

BACKGROUND: Calcified nodules (CNs) remain a major challenge in percutaneous coronary intervention (PCI). We sought to compare procedural and clinical outcomes after orbital atherectomy (OA) versus intravascular lithotripsy (IVL)-facilitated PCI in patients with CNs. METHODS: We identified patients with optical coherence tomography (OCT)-defined CNs who underwent PCI with either OA or IVL between 2012 and 2022 and had both pre- and post-PCI OCT images available. The imaging end point was the minimal stent area on final post-PCI OCT. The clinical end point was 2-year target-lesion failure, a composite of cardiac death, target-vessel myocardial infarction, or clinically driven target-lesion revascularization. A multivariable Cox proportional hazards regression model was used to estimate hazard ratio and 95% CI. Sensitivity analyses were performed using propensity score matching, incorporating covariates such as age, sex, diabetes, and pre-PCI calcium burden assessed by OCT (length, arc, and thickness). RESULTS: Among 4856 patients with evaluable pre- and post-PCI OCT images, 493 patients (10.2%) had CNs, and 167 patients underwent PCI with either OA (n=83) or IVL (n=84). The 2 groups had similar baseline demographic and lesion characteristics. After PCI, final minimal stent area was comparable between the 2 groups (OA, 5.6 mm ² [interquartile range, 4.8–6.7] versus IVL, 5.5 mm ² [interquartile range, 4.8–7.0]; P =0.75). At a median follow-up of 2.4 years, there was no difference in target-lesion failure between the OA and IVL groups (12.0% versus 9.8%, respectively; log-rank P =0.64; adjusted hazard ratio, 1.10 [95% CI, 0.28–4.31]; P =0.89). Overall results remained consistent in the propensity score-matched population (n=68 per group), with similar minimal stent area (5.6 mm ² [4.8–6.7] versus 5.5 mm ² [4.7–6.8]; P =0.73) and comparable 2-year target-lesion failure rate (9.8% versus 8.8%; log-rank P =0.82). CONCLUSIONS: In patients with OCT-defined CNs, OA- and IVL-assisted PCI resulted in comparable post-PCI minimal stent area and 2-year clinical outcomes.

BACKGROUND: Coronary stenting alters vessel dynamics, displacing hinge movement closer to stent edges. We aimed to investigate whether calcified nodules (CNs) are more frequent at stent edges associated with calcium. METHODS: In vessels with previously implanted stents evaluated by optical coherence tomography, 4 different calcified lesions were studied: stent-edge calcified lesions with or without a CN, and unstented native calcified lesions with or without a CN. RESULTS: In 801 patients, 989 stent-edge calcified lesions and 354 unstented native calcified lesions were identified. Stent-edge calcified lesions exhibited a higher prevalence of CNs versus native calcified lesions (15.7% versus 5.1%; P P =0.01), mainly driven by target lesion revascularization. CONCLUSIONS: Stent-edge calcium may predispose to the development of a CN. Stent-edge CNs were associated with a higher major adverse cardiac events rate than stent edges without a CN, whether treated or untreated.

BACKGROUND: Clinical guidelines recommend different revascularization strategies for nonculprit lesions in patients with ST-segment–elevation myocardial infarction (STEMI) versus non-STEMI (NSTEMI). Whether the prevalence of untreated high-risk vulnerable plaques differs in STEMI and NSTEMI and affects their outcomes is unknown. METHODS: In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree II), a multicenter, prospective natural history study, patients with recent myocardial infarction underwent 3-vessel coronary angiography with coregistered near-infrared spectroscopy and intravascular ultrasound after successful percutaneous coronary intervention of obstructive lesions from 2014 through 2017. Two-feature high-risk plaques were defined as those with both plaque burden ≥70% and maximum lipid core burden index over any 4-mm segment ≥324.7. The primary end point was major adverse cardiovascular events arising from untreated nonculprit lesions during a median 3.7-year follow-up. RESULTS: Of 898 patients, 199 (22.2%) with 849 nonculprit lesions had STEMI and 699 (77.8%) with 2784 nonculprit lesions had NSTEMI. By intravascular ultrasound, the median nonculprit lesion length was 17.4 mm (interquartile range, 16.3–18.5) in STEMI and 17.7 mm (interquartile range, 17.1–18.4) in NSTEMI ( P =0.63), and the median minimal lumen area was 5.5 mm ² (interquartile range, 5.3–5.7 mm ² ) in STEMI and 5.5 mm ² (interquartile range, 5.3–5.6 mm ² ) in NSTEMI ( P =0.99). At the lesion level, the prevalence of 2-feature high-risk nonobstructive nonculprit plaques was slightly higher in patients with STEMI than in patients with NSTEMI (12.8% versus 10.1%; P =0.03). At the patient level, however, the prevalence of 2-feature high-risk plaques was similar in STEMI versus NSTEMI (38.8% versus 32.7%; P =0.11). The prevalence of patients with 1 or more lesions meeting at least 1 high-risk plaque criterion was also similar (plaque burden ≥70%, 63.3% versus 57.8% [ P =0.16]; maximum lipid core burden index over any 4-mm segment ≥324.7, 63.3% versus 57.6% [ P =0.15]). The 4-year rates of nonculprit lesion–related major adverse cardiovascular events were similar in STEMI versus NSTEMI (8.6% versus 7.8%; hazard ratio, 1.02 [95% CI, 0.57–1.81]; P =0.95), as were the rates of all major adverse cardiovascular events (14.2% versus 13.0%; hazard ratio, 1.06 [95% CI, 0.68–1.64]; P =0.80). CONCLUSIONS: In the PROSPECT II study, the per-patient prevalence of high-risk vulnerable plaques was comparable in STEMI versus NSTEMI, as was the overall long-term incidence of nonculprit lesion–related and all major adverse cardiovascular events. These results support a similar revascularization strategy for nonculprit lesions in patients with STEMI or NSTEMI after culprit lesion management. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02171065.

BACKGROUND: Patients with acute myocardial infarction and angiographically obstructive non-culprit lesions are at high risk for recurrent major adverse cardiac events (MACEs). However, it remains largely unknown whether events are due to stenosis severity or due to the underlying high-risk lesion morphology. METHODS: Between January 2017 and December 2021, 1312 patients with acute myocardial infarction underwent optical coherence tomography of all the 3 main epicardial arteries after successful percutaneous coronary intervention. Patients and lesions were categorized according to the presence or absence of (1) 1 or more non-culprit angiographic obstructive stenoses with a visual diameter stenosis of ≥50% and (2) 1 or more lesions with an underlying high-risk morphology defined as an optical coherence tomography thin-cap fibroatheroma (TCFA). Patients were followed for up to 5 years (median 4.1 [interquartile range: 3.0–5.0] years). MACEs comprised cardiac death, non-fatal myocardial infarction, and unplanned coronary revascularization. RESULTS: Overall, 492 patients had at least 1 obstructive non-culprit lesion, 352 had a single lesion, and 140 had multiple obstructive non-culprit lesions. The presence and number of angiographic obstructive non-culprit lesions correlated with the proportion and number of optical coherence tomography–derived TCFAs. At the lesion level, the prevalence of TCFA was twice as high in obstructive lesions compared with nonobstructive lesions. Patients with obstructive non-culprit lesions had an increased risk of overall MACEs (17.7% versus 12.8%; hazard ratio, 1.39 [95% CI, 1.02–1.91]) and non-culprit lesion–related MACEs (8.7% versus 3.9%; HR, 2.13 [95% CI, 1.26–3.59). Results were similar when patients were categorized on the basis of the underlying TCFA. A proportionally higher rate of overall and non-culprit lesion–related MACEs was observed as the number of obstructive stenoses or TCFAs in non-culprit segments increased. The lesion-specific HRs for obstructive lesion and TCFA were 2.03 (95% CI, 1.06–3.89) and 2.39 (95% CI, 1.29–4.43), respectively. Optical coherence tomography–derived TCFA, but not angiographic obstructive stenosis, was independently predictive of recurrent MACEs in both patient-level and lesion-level multivariable models in which these 2 characteristics were introduced simultaneously. CONCLUSIONS: The long-term prognostic implications of the presence and extent of angiographic obstructive non-culprit lesions in patients with acute myocardial infarction are primarily due to their correlation with the underlying high-risk morphology, which confers an increased risk of recurrent MACEs.

Plaque erosion (PE) with secondary thrombosis is one of the key mechanisms of acute coronary syndrome (ACS) which often leads to drastic cardiovascular events. Identification and prediction of PE are of fundamental significance for disease diagnosis, prevention and treatment. In vivo optical coherence tomography (OCT) data of eight eroded plaques and eight non-eroded plaques were acquired to construct three-dimensional fluid–structure interaction models and obtain plaque biomechanical conditions for investigation. Plaque stenosis severity, plaque burden, plaque wall stress (PWS) and strain (PWSn), flow shear stress (FSS), and ΔFSS (FSS variation in time) were extracted for comparison and prediction. A logistic regression model was used to predict plaque erosion. Our results indicated that the combination of mean PWS and mean ΔFSS gave best prediction (AUC = 0.866, 90% confidence interval (0.717, 1.0)). The best single predictor was max ΔFSS (AUC = 0.819, 90% confidence interval (0.624, 1.0)). The average of maximum FSS values from eroded plaques was 76% higher than that from the non-eroded plaques (127.96 vs. 72.69 dyn/cm²) while the average of mean FSS from erosion sites of the eight eroded plaques was 48.6% higher than that from sites without erosion (71.52 vs. 48.11 dyn/cm²). The average of mean PWS from plaques with erosion was 22.83% lower than that for plaques without erosion (83.2 kPa vs. 107.8 kPa). This pilot study suggested that combining plaque stress, strain and flow shear stress could help better identify patients with potential plaque erosion, enabling possible early intervention therapy. Further studies are needed to validate our findings.