Predictors of Rapid Plaque Progression: An Optical Coherence Tomography Study

ObjectivesThis study sought to identify morphological predictors of rapid plaque progression.BackgroundTwo patterns of plaque progression have been described: slow linear progression and rapid step-wise progression. The former pattern will cause stable angina when the narrowing reaches a critical threshold, whereas the latter pattern may lead to acute coronary syndromes or sudden cardiac death.MethodsPatients who underwent optical coherence tomography (OCT) imaging during the index procedure and follow-up angiography with a minimum interval of 6 months were selected. Nonculprit lesions with a diameter stenosis of ≥30% on index angiography were assessed. Lesion progression was defined as a decrease of angiographic minimum lumen diameter ≥0.4 mm at follow-up (mean, 7.1 months). Baseline morphological characteristics of plaques with rapid progression were evaluated by OCT. In a subgroup with follow-up OCT imaging for plaques with rapid progression, morphological changes from baseline to follow-up were assessed.ResultsAmong 517 lesions in 248 patients, 50 lesions showed rapid progression. These lesions had a significantly higher prevalence of lipid-rich plaque (76.0% vs. 50.5%, respectively), thin-cap fibroatheroma (TCFA) (20.0% vs. 5.8%, respectively), layered plaque (60.0% vs. 34.0%, respectively), macrophage accumulation (62.0% vs. 42.4%, respectively), microvessel (46.0% vs. 29.1%, respectively), plaque rupture (12.0% vs. 4.7%, respectively), and thrombus (6.0% vs. 1.1%, respectively) at baseline compared with those without rapid progression. Multivariate analysis identified lipid-rich plaque (odds ratio [OR]: 2.17; 95% confidence interval [CI]: 1.02 to 4.62; p = 0.045]), TCFA (OR: 5.85; 95% CI: 2.01 to 17.03; p = 0.001), and layered plaque (OR: 2.19; 95% CI: 1.03 to 4.17; p = 0.040) as predictors of subsequent rapid lesion progression. In a subgroup analysis for plaques with rapid progression, a new layer was detected in 25 of 41 plaques (61.0%) at follow-up.ConclusionsLipid-rich plaques, TCFA, and layered plaques were predictors of subsequent rapid plaque progression. A new layer, a signature of previous plaque disruption and healing, was detected in more than half of the lesions with rapid progression at follow-up. (Massachusetts General Hospital Optical Coherence Tomography Registry; NCT01110538)     

Healed Culprit Plaques in Patients With Acute Coronary Syndromes

BackgroundHealed plaques, morphologically characterized by a layered phenotype, are frequently found in subjects with sudden cardiac death. However, in vivo data are lacking.ObjectivesThe purpose of this study was to determine the prevalence, morphological characteristics, and clinical significance of healed culprit plaques in patients with acute coronary syndromes (ACS) using optical coherence tomography (OCT).MethodsA total of 376 ACS patients (252 ST-segment elevation myocardial infarction [MI] and 124 non–ST-segment elevation acute coronary syndrome) who had undergone pre-intervention OCT imaging of the culprit lesion were enrolled. Patients were stratified according to the presence of layered phenotype, defined as layers of different optical density at OCT. Clinical and laboratory data, OCT characteristics, and 1-year outcome were compared between the 2 groups.ResultsAmong 376 patients, 108 (28.7%) healed plaques were identified. Hyperlipidemia, diabetes, and history of MI were more frequent in patients with healed plaques (44.4% vs. 33.2%; p = 0.041; 35.2% vs. 23.5%; p = 0.021; and 15.7% vs. 6.3%; p = 0.009, respectively). High-sensitivity C-reactive protein was significantly higher in patients with healed plaques (median 4.98 mg/l [interquartile range: 1.00 to 11.32 mg/l] vs. 3.00 mg/l [interquartile range: 0.30 to 10.15 mg/l]; p = 0.029). Plaque rupture (64.8% vs. 53.0%; p = 0.039), thin cap fibroatheroma (56.5% vs. 42.5%; p = 0.016), and macrophage accumulation (81.1% vs. 63.4%; p = 0.001) were common in the layered group. OCT also revealed greater area stenosis in plaques with layered phenotype (79.2 ± 9.5% vs. 74.3 ± 14.3%; p = 0.001). The incidence of major adverse cardiovascular events was similar between the 2 groups, except that the all-cause rehospitalization rate was higher among healed plaques (32.7% vs. 16.5%; p = 0.013).ConclusionsHealed plaques, a signature of prior plaque destabilization, were found at the culprit site in more than one-quarter of ACS patients. Such patients more frequently were diabetic, were hyperlipidemic, or had a history of MI. Healed plaques frequently showed OCT features of vulnerability with evidence of local and systemic inflammation. The combination of plaque vulnerability, local inflammation, and greater plaque burden in addition to systemic inflammation may outweigh the protective mechanism of plaque healing and predispose those plaques to develop occlusive thrombus.     

Increased Vulnerability and Distinct Layered Phenotype at Culprit and Nonculprit Lesions in STEMI Versus NSTEMI

ObjectivesThis study aimed to investigate the pancoronary plaque vulnerability (including culprit and nonculprit lesions) and layered phenotype in patients with ST-segment elevation myocardial infarction (STEMI) vs non-STEMI (NSTEMI).BackgroundPancoronary vulnerability should account for distinct clinical manifestations of acute myocardial infarction (AMI). Layered plaque is indicative of previous coronary destabilization and thrombosis.MethodsA total of 464 patients with AMI who underwent 3-vessel optical coherence tomography imaging were consecutively studied and divided into a STEMI group (318 patients; 318 culprit and 1,187 nonculprit plaques) and a NSTEMI group (146 patients; 146 culprit and 560 nonculprit plaques). Patients were followed up for a median period of 2 years.ResultsCompared with NSTEMI, culprit lesions in STEMI had more plaque rupture, thrombus, thin-cap fibroatheroma (TCFA), calcification, macrophage accumulation, and microvessels. The prevalence of plaque rupture (8.2% vs 4.8%; P = 0.018), microvessels (57.5% vs 45.2%; P < 0.001), and calcification (40.7% vs 30.2%; P = 0.003) at nonculprit lesions was higher in STEMI than NSTEMI. The layer area and thickness at the culprit and nonculprit lesions were significantly larger in STEMI than in NSTEMI. Multivariate analyses showed that culprit layer area (odds ratio: 1.443; 95% CI: 1.138-1.830; P = 0.002) was predictive of STEMI (vs NSTEMI), in addition to culprit TCFA, culprit thrombus, and non–left circumflex artery location of the culprit lesion. Although the type of AMI was not related to clinical outcomes, high-sensitivity C-reactive protein, culprit calcified nodule, and nonculprit TCFA predicted the 2-year major adverse cardiovascular events in patients with AMI.ConclusionsPatients with STEMI had increased plaque vulnerability (ie, more plaque rupture and microvessels) and distinct layered phenotype at the culprit and nonculprit lesions compared with patients with NSTEMI. Culprit lesion features of large layer area, TCFA, thrombus, and non–left circumflex artery location predicted the clinical presentation of STEMI.     

Air Pollution and Coronary Plaque Vulnerability and Instability: An Optical Coherence Tomography Study

ObjectivesWe assessed the relationship between exposure to air pollutants and mechanisms of coronary instability evaluated by optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS).BackgroundAir pollution is an emerging key player in determining the residual risk of coronary events. However, pathophysiological mechanisms linking air pollution and coronary events have been not adequately investigated.MethodsPatients with ACS undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT, and the presence of macrophage infiltrates (MØI) and thin-cap fibroatheroma (TCFA) at the culprit site was also assessed. Based on each case’s home address, exposure to several pollutants was evaluated, including particulate matter 2.5 (PM2.5), PM10, and carbon monoxide (CO). Only patients with >2 years of available data on air pollution exposure prior to ACS were enrolled.ResultsWe included 126 patients (median age: 67.0 years of age; IQR: 55.5-76.0; 97 male patients [77.0%]). Sixty-six patients (52.4%) had PR as the mechanism of plaque instability. Patients with PR were exposed to significantly higher PM2.5 levels than to IFC, and PM2.5 was independently associated with PR (odds ratio: 1.194; 95% CI: 1.036 to 1.377; P = 0.015). Moreover, exposure to higher levels of PM2.5 was independently associated with the presence of TCFA and of MØI at the culprit site. Interestingly, PM2.5, PM10, and Co levels were positively and significantly correlated with serum levels of C-reactive protein.ConclusionsWe provide novel insights into the missing link between air pollution and increased risk of coronary events. In particular, exposure to higher concentrations of air pollutants is associated with the presence of vulnerable plaque features and with plaque rupture as a mechanism of coronary instability. An enhanced systemic and plaque inflammatory activation may explain these findings.     

Pancoronary Plaque Characteristics in STEMI Caused by Culprit Plaque Erosion Versus Rupture: 3-Vessel OCT Study

ObjectivesThis study sought to investigate nonculprit plaque characteristics in patients with ST-segment elevation myocardial infarction (STEMI) presenting with plaque erosion (PE) and plaque rupture (PR). Pancoronary vulnerability was considered at nonculprit sites: 1) the CLIMA (Relationship Between OCT Coronary Plaque Morphology and Clinical Outcome) study (NCT02883088) defined high-risk plaques with simultaneous presence of 4 optical coherence tomography (OCT) features (minimum lumen area <3.5 mm²; fibrous cap thickness [FCT] <75 μm; maximum lipid arc >180º; and macrophage accumulation); and 2) the presence of plaque ruptures or thin-cap fibroatheromas (TCFA).BackgroundPE is a unique clinical entity associated with better outcomes than PR. There is limited evidence regarding pancoronary plaque characteristics of patients with culprit PE versus culprit PR.MethodsBetween October 2016 and September 2018, 523 patients treated by 3-vessel OCT at the time of primary percutaneous intervention were included with 152 patients excluded from final analysis.ResultsOverall, 458 nonculprit plaques were identified in 202 STEMI patients with culprit PE; and 1,027 nonculprit plaques were identified in 321 STEMI patients with culprit PR. At least 1 CLIMA-defined OCT nonculprit high-risk plaque was seen in 11.4% of patients with culprit PE, but twice as many patients were seen with culprit PR (25.2%; p < 0.001). This proportion was also seen when individual high-risk features were analyzed separately. When patients with PE were divided by a heterogeneous substrate (fibrous or lipid-rich plaque) underlying the culprit site, the prevalence of nonculprits with FCT <75 μm, macrophages, and TCFA showed a significant gradient from PE_(Fibrous) to PE_{lipid-rich plaque (LRP)} to PR. Interestingly, nonculprit rupture was rarely found in patients with culprit PE_(Fibrous) (1.9%), although it was exhibited with comparable prevalence in patients with culprit PE_(LRP) (16.3%) versus PR (17.8%). Culprit PE predicted decreased pancoronary vulnerability independent of conventional risk factors.ConclusionsSTEMI patients with culprit PE have a limited pancoronary vulnerability that may explain better outcomes in these patients than in STEMI patients with culprit PR.     

Association between food and nutrients intakes and coronary plaque vulnerability in patients with coronary heart disease: An optical coherence tomography study

Background and aimsDietary intakes play important roles in the prevention and treatment of coronary heart disease (CHD). Coronary plaque vulnerability is the key mechanism leading to CHD progression. We aimed to explore the association between dietary intakes and plaque vulnerability via optical coherence tomography (OCT).Methods and resultsA total of 314 CHD patients were included in this study. Dietary intake status was assessed by semi-quantitative food frequency questionnaire and plaque vulnerability was measured by OCT. The results showed that vegetables were negatively associated with macrophage infiltration, thin cap fibroatheroma (TCFA) and thrombus [odds ratio (OR) = 0.48, 0.38, 0.38, 95% confidence interval (95% CI) = 0.24–0.93, 0.17–0.84, 0.15–0.94, all P < 0.05]; fruits were negatively associated with lipid plaque, TCFA, rupture and thrombus (OR = 0.17, 0.11, 0.12, 0.20, 95% CI = 0.07–0.39, 0.04–0.29, 0.05–0.28, 0.08–0.55, all P < 0.05); salt was positively associated with lipid plaque and TCFA (OR = 2.59, 2.83, 95% CI = 1.14–5.90, 1.23–6.51, all P < 0.05). Regarding nutrients intakes, dietary fiber was negatively associated with macrophage infiltration (OR = 0.34, 95% CI = 0.14–0.85, P = 0.021); folate was negatively associated with lipid plaque, TCFA and rupture (OR = 0.22, 0.16, 0.20, 95% CI = 0.09–0.58, 0.06–0.41, 0.08–0.51, all P < 0.05); vitamin C was negatively associated with TCFA, rupture and thrombus (OR = 0.26, 0.22, 0.05, 95% CI = 0.07–0.95, 0.07–0.65, 0.01–0.25, all P < 0.05); sodium was positively associated with lipid plaque, TCFA, rupture and thrombus (OR = 3.43, 3.96, 2.73, 4.84, 95% CI = 1.51–7.80, 1.66–9.45, 1.18–6.27, 1.76–9.28, all P < 0.05).ConclusionSalt and sodium were dietary risk factors for plaque vulnerability, whereas vegetables, fruits, dietary fiber, folate and vitamin C were dietary protective factors for plaque vulnerability.     

The role of the plasma glycosylated hemoglobin A1c/Apolipoprotein A-l ratio in predicting cardiovascular outcomes in acute coronary syndrome

Background and aimsGlucose and lipid metabolism are major prognostic indicators of coronary heart disease. The ratio of plasma glycosylated hemoglobin A1c (HbA1c) to apolipoprotein A-l (ApoA-l) is an indirect measure of insulin resistance. The study aimed to evaluate whether the HbA1c/ApoA-1 ratio can predict the prognosis in patients with the acute coronary syndrome (ACS).Methods and resultsA total of 476 ACS patients diagnosed by coronary angiography were enrolled in this longitudinal, observational, retrospective study. Plasma HbA1c, fasting blood glucose and lipid profile were measured. Patients were stratified according to the tertiles of HbA1c/ApoA-l levels. Cox proportional hazard model was used to examine the predictive value of HbA1c/ApoA-l for study endpoints. The association between the Log HbA1c/ApoA-l ratio and major adverse cardiovascular events (MACEs) was estimated using multiple logistic regression. Baseline characteristics showed a mean age of 66 ± 8 years, and 52.5% were hypertensive, 26.8% diabetic, and 54.5% current or prior smokers. During a mean follow-up period of 22.3 ± 1.7 months, 59 deaths occurred. After adjusting for age, gender, smoking, hypertension, diabetes, and coronary artery disease severity, patients in the highest HbA1c/ApoA-l ratio tertile had a 4.36-fold increased risk of mortality compared with those in the lowest tertile. The multivariate logistic regression showed that the Log HbA1c/ApoA-l ratio was associated with MACEs (Odds ratio 2.95, p = 0.013).ConclusionAfter adjusting for traditional cardiovascular risk factors and ACS severity scores, the HbA1c/ApoA-1 ratio remained an independent predictor of all-cause mortality and MACEs in the ACS patients undergoing angiography.     

Automated Pixel-Wise Quantitative Myocardial Perfusion Mapping by CMR to Detect Obstructive Coronary Artery Disease and Coronary Microvascular Dysfunction: Validation Against Invasive Coronary Physiology

ObjectivesThis study sought to assess the performance of cardiovascular magnetic resonance (CMR) myocardial perfusion mapping against invasive coronary physiology reference standards for detecting coronary artery disease (CAD, defined by fractional flow reserve [FFR] ≤0.80), microvascular dysfunction (MVD) (defined by index of microcirculatory resistance [IMR] ≥25) and the ability to differentiate between the two.BackgroundDifferentiation of epicardial (CAD) and MVD in patients with stable angina remains challenging. Automated in-line CMR perfusion mapping enables quantification of myocardial blood flow (MBF) to be performed rapidly within a clinical workflow.MethodsFifty patients with stable angina and 15 healthy volunteers underwent adenosine stress CMR at 1.5T with quantification of MBF and myocardial perfusion reserve (MPR). FFR and IMR were measured in 101 coronary arteries during subsequent angiography.ResultsTwenty-seven patients had obstructive CAD and 23 had nonobstructed arteries (7 normal IMR, 16 abnormal IMR). FFR positive (epicardial stenosis) areas had significantly lower stress MBF (1.47 ± 0.48 ml/g/min) and MPR (1.75 ± 0.60) than FFR-negative IMR-positive (MVD) areas (stress MBF: 2.10 ± 0.35 ml/g/min; MPR: 2.41 ± 0.79) and normal areas (stress MBF: 2.47 ± 0.50 ml/g/min; MPR: 2.94 ± 0.81). Stress MBF ≤1.94 ml/g/min accurately detected obstructive CAD on a regional basis (area under the curve: 0.90; p < 0.001). In patients without regional perfusion defects, global stress MBF <1.82 ml/g/min accurately discriminated between obstructive 3-vessel disease and MVD (area under the curve: 0.94; p < 0.001).ConclusionsThis novel automated pixel-wise perfusion mapping technique can be used to detect physiologically significant CAD defined by FFR, MVD defined by IMR, and to differentiate MVD from multivessel coronary disease. A CMR-based diagnostic algorithm using perfusion mapping for detection of epicardial disease and MVD warrants further clinical validation.     

Optical Coherence Tomography Fractional Flow Reserve and Cardiovascular Outcomes in Patients With Acute Coronary Syndrome

BackgroundOptical coherence tomography–derived fractional flow reserve (OCT-FFR) correlates strongly with wire-based FFR; however, its clinical significance remains uncertain.ObjectivesThis study sought to investigate the relationship between post–percutaneous coronary intervention (PCI) OCT-FFR and long-term clinical outcomes in acute coronary syndrome (ACS).MethodsThis retrospective, multicenter, observational cohort study included consecutive patients with ACS who underwent OCT-guided emergency PCI. We analyzed post-PCI OCT images and calculated OCT-FFR to identify independent factors associated with target vessel failure (TVF) after PCI.ResultsAmong 364 enrolled patients, 54 experienced TVF during a median follow-up of 36 (IQR: 26-48) months. Vessel-level OCT-FFR was significantly lower in the TVF group than in the non-TVF group (0.87 vs 0.94; P < 0.001). In the multivariable Cox regression analysis, low vessel-level OCT-FFR (HR per 0.1 increase: 0.38; 95% CI: 0.29-0.49; P < 0.001) and thin-cap fibroatheroma in the nonculprit lesion were independently associated with TVF. The TVF rate of vessels with both low vessel-level OCT-FFR (<0.90) and thin-cap fibroatheroma in the nonculprit lesion was 8.1 times higher than that of all other vessels (69.3% vs 12.4%; HR: 8.13; 95% CI: 4.33-15.25; log-rank P < 0.001). Furthermore, adding vessel-level OCT-FFR to baseline characteristics and post-PCI OCT findings improved discriminatory and reclassification ability in identifying patients with subsequent TVF.ConclusionsVessel-level OCT-FFR was an independent factor associated with TVF after PCI in patients with ACS. Adding the OCT-FFR measurement to post-PCI OCT findings may enable better discrimination of patients with subsequent TVF after PCI for ACS. (Relationship between Intracoronary Optical Coherence Tomography Derived Virtual Fractional Flow Reserve and cardiovascular outcome on Acute coronary syndrome; UMIN000043858)     

Intravascular Polarimetry in Patients With Coronary Artery Disease

ObjectivesThe aims of this first-in-human pilot study of intravascular polarimetry were to investigate polarization properties of coronary plaques in patients and to examine the relationship of these features with established structural characteristics available to conventional optical frequency domain imaging (OFDI) and with clinical presentation.BackgroundPolarization-sensitive OFDI measures birefringence and depolarization of tissue together with conventional cross-sectional optical frequency domain images of subsurface microstructure.MethodsThirty patients undergoing polarization-sensitive OFDI (acute coronary syndrome, n = 12; stable angina pectoris, n = 18) participated in this study. Three hundred forty-two cross-sectional images evenly distributed along all imaged coronary arteries were classified into 1 of 7 plaque categories according to conventional OFDI. Polarization features averaged over the entire intimal area of each cross section were compared among plaque types and with structural parameters. Furthermore, the polarization properties in cross sections (n = 244) of the fibrous caps of acute coronary syndrome and stable angina pectoris culprit lesions were assessed and compared with structural features using a generalized linear model.ResultsThe median birefringence and depolarization showed statistically significant differences among plaque types (p < 0.001 for both, one-way analysis of variance). Depolarization differed significantly among individual plaque types (p < 0.05), except between normal arteries and fibrous plaques and between fibrofatty and fibrocalcified plaques. Caps of acute coronary syndrome lesions and ruptured caps exhibited lower birefringence than caps of stable angina pectoris lesions (p < 0.01). In addition to clinical presentation, cap birefringence was also associated with macrophage accumulation as assessed using normalized SD.ConclusionsIntravascular polarimetry provides quantitative metrics that help characterize coronary arterial tissues and may offer refined insight into coronary arterial atherosclerotic lesions in patients.     

Identification of High-Risk Plaques Destined to Cause Acute Coronary Syndrome Using Coronary Computed Tomographic Angiography and Computational Fluid Dynamics

ObjectivesThe authors investigated the utility of noninvasive hemodynamic assessment in the identification of high-risk plaques that caused subsequent acute coronary syndrome (ACS).BackgroundACS is a critical event that impacts the prognosis of patients with coronary artery disease. However, the role of hemodynamic factors in the development of ACS is not well-known.MethodsSeventy-two patients with clearly documented ACS and available coronary computed tomographic angiography (CTA) acquired between 1 month and 2 years before the development of ACS were included. In 66 culprit and 150 nonculprit lesions as a case-control design, the presence of adverse plaque characteristics (APC) was assessed and hemodynamic parameters (fractional flow reserve derived by coronary computed tomographic angiography [FFR_CT], change in FFR_CT across the lesion [△FFR_CT], wall shear stress [WSS], and axial plaque stress) were analyzed using computational fluid dynamics. The best cut-off values for FFR_CT, △FFR_CT, WSS, and axial plaque stress were used to define the presence of adverse hemodynamic characteristics (AHC). The incremental discriminant and reclassification abilities for ACS prediction were compared among 3 models (model 1: percent diameter stenosis [%DS] and lesion length, model 2: model 1 + APC, and model 3: model 2 + AHC).ResultsThe culprit lesions showed higher %DS (55.5 ± 15.4% vs. 43.1 ± 15.0%; p < 0.001) and higher prevalence of APC (80.3% vs. 42.0%; p < 0.001) than nonculprit lesions. Regarding hemodynamic parameters, culprit lesions showed lower FFR_CT and higher △FFR_CT, WSS, and axial plaque stress than nonculprit lesions (all p values <0.01). Among the 3 models, model 3, which included hemodynamic parameters, showed the highest c-index, and better discrimination (concordance statistic [c-index] 0.789 vs. 0.747; p = 0.014) and reclassification abilities (category-free net reclassification index 0.287; p = 0.047; relative integrated discrimination improvement 0.368; p < 0.001) than model 2. Lesions with both APC and AHC showed significantly higher risk of the culprit for subsequent ACS than those with no APC/AHC (hazard ratio: 11.75; 95% confidence interval: 2.85 to 48.51; p = 0.001) and with either APC or AHC (hazard ratio: 3.22; 95% confidence interval: 1.86 to 5.55; p < 0.001).ConclusionsNoninvasive hemodynamic assessment enhanced the identification of high-risk plaques that subsequently caused ACS. The integration of noninvasive hemodynamic assessments may improve the identification of culprit lesions for future ACS. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary CT Angiography and Computational Fluid Dynamic [EMERALD]; NCT02374775)     

Clinical Characteristics and Prognosis of MINOCA Caused by Atherosclerotic and Nonatherosclerotic Mechanisms Assessed by OCT

BackgroundMyocardial infarction with nonobstructive coronary artery (MINOCA) is a heterogeneous syndrome caused by different pathophysiologic mechanisms. There is limited evidence regarding prognosis of patients with MINOCA caused by different mechanisms.ObjectivesThe present study aimed to assess the underlying mechanisms of MINOCA by optical coherence tomography (OCT) and to correlate with clinical outcomes.MethodsPatients with MINOCA were divided into 2 groups based on OCT findings: atherosclerotic MINOCA (Ath-MINOCA) and nonatherosclerotic MINOCA (non-Ath-MINOCA). Major adverse cardiac events (MACE) were defined as cardiac death, nonfatal MI, target lesion revascularization, stroke, and rehospitalization for unstable or progressive angina.ResultsAmong 7,423 patients with a clinical diagnosis of MI who underwent angiography, 190 of 294 MINOCA were studied using OCT. The causes of Ath-MINOCA (n = 99, 52.1%) were plaque erosion (n = 64, 33.7%), plaque rupture (n = 33, 17.4%), and calcified nodule (n = 2, 1.1%) whereas the causes of non-Ath-MINOCA (n = 91, 47.9%) were spontaneous coronary artery dissection (n = 8, 4.2%), coronary spasm (n = 9, 4.7%), and unclassified cause (n = 74, 38.9%). The 1-year MACE was 15.3% for Ath-MINOCA vs 4.5% for non-Ath-MINOCA (P = 0.015). An atherosclerotic cause was an independent predictor of MACE (HR: 5.36 [95% CI: 1.08-26.55]; P = 0.040), mainly driven by target lesion revascularization and rehospitalization, despite the composite endpoint including cardiac death and MI showing no difference.ConclusionsOCT identified a cause in 61.1% of MINOCA, in which Ath-MINOCA represents an important and distinct MINOCA subset. Ath-MINOCA were more common and associated with worse outcomes. (Incidence Rate of Heart Failure After Acute Myocardial Infarction With Optimal Treatment; NCT03297164; Paradigm Shift in the Treatment of Patients With ACS; NCT02041650)     

Bypass Grafting and Native Coronary Artery Disease Activity

ObjectivesThe aim of this study was to describe the potential of ¹⁸F-sodium fluoride (¹⁸F-NaF) positron emission tomography (PET) to identify graft vasculopathy and to investigate the influence of coronary artery bypass graft (CABG) surgery on native coronary artery disease activity and progression.BackgroundAs well as developing graft vasculopathy, CABGs have been proposed to accelerate native coronary atherosclerosis.MethodsPatients with established coronary artery disease underwent baseline ¹⁸F-NaF PET, coronary artery calcium scoring, coronary computed tomographic angiography, and 1-year repeat coronary artery calcium scoring. Whole-vessel coronary microcalcification activity (CMA) on ¹⁸F-NaF PET and change in calcium scores were quantified in patients with and without CABG surgery.ResultsAmong 293 participants (mean age 65 ± 9 years, 84% men), 48 (16%) underwent CABG surgery 2.7 years [IQR: 1.4-10.4 years] previously. Although all arterial and the majority (120 of 128 [94%]) of vein grafts showed no ¹⁸F-NaF uptake, 8 saphenous vein grafts in 7 subjects had detectable CMA. Bypassed native coronary arteries had 3 times higher CMA values (2.1 [IQR: 0.4-7.5] vs 0.6 [IQR: 0-2.7]; P < 0.001) and greater progression of 1-year calcium scores (118 Agatston unit [IQR: 48-194 Agatston unit] vs 69 [IQR: 21-142 Agatston unit]; P = 0.01) compared with patients who had not undergone CABG, an effect confined largely to native coronary plaques proximal to the graft anastomosis. In sensitivity analysis, bypassed native coronary arteries had higher CMA (2.0 [IQR: 0.4-7.5] vs 0.8 [IQR: 0.3-3.2]; P < 0.001) and faster disease progression (24% [IQR: 16%-43%] vs 8% [IQR: 0%-24%]; P = 0.002) than matched patients (n = 48) with comparable burdens of coronary artery disease and cardiovascular comorbidities in the absence of bypass grafting.ConclusionsNative coronary arteries that have been bypassed demonstrate increased disease activity and more rapid disease progression than nonbypassed arteries, an observation that appears independent of baseline atherosclerotic plaque burden. Microcalcification activity is not a dominant feature of graft vasculopathy.     

Feasibility of Coronary Access in Patients With Acute Coronary Syndrome and Previous TAVR

ObjectivesThe aim of this study was to characterize the feasibility of coronary angiography (CA) and percutaneous coronary intervention (PCI) in acute settings among patients who have undergone transcatheter aortic valve replacement (TAVR).BackgroundImpaired coronary access after TAVR may be challenging and particularly in acute settings could have deleterious consequences.MethodsIn this international registry, data from patients with prior TAVR requiring urgent or emergent CA were retrospectively collected. A total of 449 patients from 25 sites with acute coronary syndromes (89.1%) and other acute cardiovascular situations (10.9%) were included.ResultsSuccess rates were high for CA of the right coronary artery (98.3%) and left coronary artery (99.3%) and were higher among patients with short stent-frame prostheses (SFPs) than in those with long SFPs for CA of the right coronary artery (99.6% vs 95.9%; P = 0.005) but not for CA of the left coronary artery (99.7% vs 98.7%; P = 0.24). PCI of native coronary arteries was successful in 91.4% of cases and independent of valve type (short SFP 90.4% vs long SFP 93.4%; P = 0.44). Guide engagement failed in 6 patients, of whom 3 underwent emergent coronary artery bypass grafting and another 3 died in the hospital. Among patients requiring revascularization of native vessels, independent predictors of 30-day all-cause mortality were prior diabetes, cardiogenic shock, and failed PCI but not valve type or success of coronary engagement.ConclusionsCA or PCI after TAVR in acute settings is usually successful, but selective coronary engagement may be more challenging in the presence of long SFPs. Among patients requiring PCI, prior diabetes, cardiogenic shock, and failed PCI were predictors of early mortality.     

Long-Term Follow-Up in Patients With Stable Angina and Unobstructed Coronary Arteries Undergoing Intracoronary Acetylcholine Testing

ObjectivesThe aim of this study was to investigate the prognosis of a large cohort of patients with stable angina and unobstructed coronaries undergoing acetylcholine spasm testing.BackgroundCoronary artery spasm can be found in up to 60% of patients with symptoms of myocardial ischemia despite unobstructed coronary arteries.MethodsConsecutive symptomatic patients with unobstructed coronary arteries undergoing acetylcholine testing to detect epicardial or microvascular coronary spasm were prospectively enrolled. After a median follow-up period of 7.2 years (6.5 to 7.9 years), data regarding mortality, nonfatal myocardial infarction, stroke, repeat coronary angiography, recurrent symptoms, and quality of life were obtained in 736 patients (57% women, mean age 62 ± 12 years).ResultsIn total, 55 deaths (7.5%), 8 nonfatal myocardial infarctions (1.4%), and 12 strokes (2.2%) occurred during the follow-up period. Recurrent symptoms were reported by 64% of patients, and repeat coronary angiography was performed in 12% of cases. Multivariate analysis revealed epicardial spasm as a predictor of nonfatal myocardial infarction (hazard ratio: 14.469; 95% confidence interval: 1.735 to 120.646) and repeat angiography (hazard ratio: 1.703; 95% confidence interval: 1.062 to 2.732), whereas patients with microvascular spasm more often had recurrent angina at follow-up (hazard ratio: 1.311; 95% confidence interval: 1.013 to 1.697).ConclusionsIn this long-term follow-up study, the overall prognosis of patients with coronary spasm was favorable. Patients with epicardial spasm were at increased risk for myocardial infarction and repeat angiography, while microvascular spasm was associated with recurrent angina. Acetylcholine testing may help identify patients at increased risk for adverse cardiac events among this overall low-risk population.     

Peak Troponin and CMR to Guide Management in Suspected ACS and Nonobstructive Coronary Arteries

BackgroundPatients presenting with acute coronary syndrome (ACS) and nonobstructive coronary arteries are a diagnostic dilemma. Cardiac magnetic resonance (CMR) has an overall diagnostic yield of ～75%; however, in ～25% of patients, CMR does not identify any myocardial injury. Identifying the underlying diagnosis has important clinical implications for patients’ management and outcome.ObjectivesThe authors sought to assess whether the combination of CMR and peak troponin levels in patients with ACS and nonobstructive coronary arteries would lead to increased diagnostic yield.MethodsConsecutive patients with ACS and nonobstructive coronary arteries without an obvious cause underwent CMR. The primary endpoint of the study was the diagnostic yield of CMR. The Youden index was used to find the optimal diagnostic cut point for peak troponin T to combine with CMR to improve diagnostic yield. Logistic or Cox regression models were used to estimate predictors of a diagnosis by CMR.ResultsA total of 719 patients met the inclusion criteria. The peak troponin T threshold for optimal diagnostic sensitivity and specificity was 211 ng/L. Overall, CMR has a diagnostic yield of 74%. CMR performed <14 days from presentation and with a peak troponin of ≥211 ng/L (n = 198) leads to an improved diagnostic yield (94% vs 72%) compared with CMR performed ≥14 days (n = 245). When CMR was performed <14 days and with a peak troponin of <211 ng/L, the diagnostic yield was 76% (n = 86) compared with 53% (n = 190) when performed ≥14 days. An increase in 1 peak troponin decile increases the odds of the CMR identifying a diagnosis by 20% (OR: 1.20; P = 0.008, 95% CI: 1.05-1.36).ConclusionsThe combination of CMR performed <14 days from presentation and peak troponin T ≥211 ng/L leads to a very high diagnostic yield (94%) on CMR. The diagnostic yield remains high (72%) even when CMR is performed ≥14 days from presentation, but reduces to 53% when peak troponin T was <211 ng/L.     

Alignment of Transcatheter Aortic-Valve Neo-Commissures (ALIGN TAVR): Impact on Final Valve Orientation and Coronary Artery Overlap

ObjectivesThe aim of this study was to evaluate the impact of initial deployment orientation of SAPIEN 3, Evolut, and ACURATE-neo transcatheter heart valves on their final orientation and neocommissural overlap with coronary arteries.BackgroundCoronary artery access and redo transcatheter aortic valve replacement (TAVR) following initial TAVR may be influenced by transcatheter heart valve orientation. In this study the impact of transcatheter heart valve deployment orientation on commissural alignment was evaluated.MethodsPre-TAVR computed tomography and procedural fluoroscopy were analyzed in 828 patients who underwent TAVR (483 SAPIEN 3, 245 Evolut, and 100 ACURATE-neo valves) from March 2016 to September 2019 at 5 centers. Coplanar fluoroscopic views were coregistered to pre-TAVR computed tomography to determine commissural alignment. Severe overlap between neocommissural posts and coronary arteries was defined as 0° to 20° apart. The SAPIEN 3 had 1 commissural post crimped at 3, 6, 9, and 12 o’clock. The Evolut “Hat” marker and ACURATE-neo commissural post at deployment were classified as center back (CB), inner curve (IC), outer curve (OC), or center front (CF) and matched with final orientation.ResultsInitial SAPIEN 3 crimped orientation had no impact on commissural alignment. Evolut “Hat” at OC or CF at initial deployment had less severe overlap than IC or CB (p < 0.001) against the left main (15.7% vs. 66.0%) and right coronary (7.1% vs. 51.1%) arteries. Tracking Evolut “Hat” at OC of the descending aorta (n = 107) improved OC at deployment from 70.2% to 91.6% (p = 0.002) and reduced coronary artery overlap by 36% to 60% (p < 0.05). ACURATE-neo commissural post at CB or IC during deployment had less coronary artery overlap compared to CF or OC (p < 0.001), with intentional alignment successful in 5 of 7 cases.ConclusionsThis is the first systematic evaluation of commissural alignment in TAVR. More than 30% to 50% of cases had overlap with 1 or both coronary arteries. Initial SAPIEN 3 orientation had no impact on alignment, but specific initial orientations of Evolut and ACURATE improved alignment. Optimizing valve alignment to avoid coronary artery overlap will be important in coronary artery access and redo TAVR.     

Association of Sex,Reduced Myocardial Flow Reserve,and Long-Term Mortality Across Spectrum of Atherosclerotic Disease

BackgroundCoronary vasomotor dysfunction (defined by reduced myocardial blood flow reserve [MBFR]) is associated with high cardiac risk in both men and women in absence of significant coexisting epicardial disease. Whether there is a sex-specific difference in prognostic value of reduced MBFR in patients with a greater burden of coexisting epicardial atherosclerotic disease is not well understood.ObjectivesThe purpose of this study was to examine the association of sex, MBFR, and mortality in consecutive patients with suspected or known coronary artery disease undergoing positron emission tomography myocardial perfusion imaging.MethodsUnique consecutive patients undergoing rubidium (Rb)-82 rest/stress positron emission tomography myocardial perfusion imaging from 2010-2016 were followed for a median of 3.2 years. Multivariable Cox models were built to describe the interaction of sex and MBFR on all-cause and cardiac death for the overall population and stratified by extent of calcified atherosclerosis (none: coronary artery calcium score = 0, subclinical: coronary artery calcium >0, clinical: prior myocardial infarction/percutaneous coronary intervention) and abnormal perfusion (no significant obstructive disease: summed stress score = 0, 1%-9.9%, and ≥10%) at baseline.ResultsAmong 12,594 patients, 52.8% were women. Compared with men, women had a lower prevalence of known coronary artery disease (16.5% vs 29.5%; P < 0.001) and were less likely to undergo revascularization after myocardial perfusion imaging (4.9% vs 9.7%; P < 0.001), but were more likely to have a reduced MBFR of <2 (56.2% vs 50.6%; P < 0.001). There were 1,699 (13.5%) all-cause and 490 (3.9%) cardiac deaths. In fully adjusted Cox models, reduced MBFR was independently associated with higher risk of death (HR per 0.1-U decrease: 1.09 [95% CI: 1.08-1.10]; P < 0.001), but female sex was not (HR: 0.95 [95% CI: 0.85-1.05]; P = 0.27). There was no significant interaction between sex and MBFR on death (P = 0.22) and cardiac death (P = 0.35) overall or in subgroups of patients with clinical, subclinical, and no atherosclerosis or across categories of perfusion abnormality at baseline.ConclusionsThe association between reduced MBFR and higher risk of all-cause and cardiac death did not differ by sex, regardless of extent of coexisting atherosclerosis or perfusion abnormality.     

Myocarditis in Relation to Angiographic Findings in Patients With Provisional Diagnoses of MINOCA

ObjectivesThe aim of this study was to determine the prevalence of myocarditis among patients presenting with myocardial infarction with nonobstructive coronary arteries (MINOCA) in relation to the angiographic severity of nonobstructive coronary artery disease (CAD).BackgroundMINOCA represents about 6% of all cases of acute myocardial infarction. Myocarditis is a diagnosis that may be identified by cardiac magnetic resonance (CMR) imaging in patients with a provisional diagnosis of MINOCA.MethodsA systematic review was performed to identify studies reporting the results of CMR findings in MINOCA patients with nonobstructive CAD or normal coronary arteries. Study-level and individual patient data meta-analyses were performed using fixed- and random-effects methods.ResultsTwenty-seven papers were included, with 2,921 patients with MINOCA; CMR findings were reported in 2,866 (98.1%). Myocarditis prevalence was 34.5% (95% confidence interval [CI]: 27.2% to 42.2%) overall and was numerically higher in studies that defined MINOCA as myocardial infarction with angiographically normal coronary arteries compared with a definition that permitted nonobstructive CAD (45.9% vs. 32.3%; p = 0.16). In a meta-analysis of individual patient data from 9 of the 27 studies, the pooled prevalence of CMR-confirmed myocarditis was greater in patients with angiographically normal coronary arteries than in those with nonobstructive CAD (51% [95% CI: 47% to 56%] vs. 23% [95% CI: 18% to 27%]; p < 0.001). Men and younger patients with MINOCA were more likely to have myocarditis. Angiographically normal coronary arteries were associated with increased odds of myocarditis after adjustment for age and sex (adjusted odds ratio: 2.30; 95% CI: 1.12 to 4.71; p = 0.023).ConclusionsPatients with a provisional diagnosis of MINOCA are more likely to have CMR findings consistent with myocarditis if they have angiographically normal coronary arteries.     

Long-Term Prognosis of Patients With Coronary Microvascular Disease Using Stress Perfusion Cardiac Magnetic Resonance

ObjectivesThis study investigated the prognosis of coronary microvascular disease (CMD) as determined by stress perfusion cardiac magnetic resonance (CMR) in patients with ischemic symptoms but without significant coronary artery disease (CAD).BackgroundPatients with CMD have poorer prognosis with various cardiac diseases. The myocardial perfusion reserve index (MPRI) derived from noninvasive stress perfusion CMR has been established to diagnose microvascular angina with a threshold MPRI <1.4. The prognosis of CMD as determined by MPRI is unknown.MethodsChest pain patients without epicardial CAD or myocardial disease from January 2009 to December 2017 were retrospectively included from 3 imaging centers in Hong Kong (HK). Stress perfusion CMR examinations were performed using either adenosine or adenosine triphosphate. Adequate stress was assessed by achieving splenic switch-off sign. Measurement of MPRI was performed in all stress perfusion CMR scans. Patients were followed for major adverse cardiovascular events defined as all-cause death, acute coronary syndrome (ACS), epicardial CAD development, heart failure hospitalization and non-fatal stroke.ResultsA total of 218 patients were studied (mean age 59 ± 12 years; 49.5% male) and the average MPRI of that cohort was 1.56 ± 0.33. Females and a history of hyperlipidemia were predictors of lower MPRI. Major adverse cardiovascular events (MACE) occurred in 15.6% of patients during a median follow-up of 5.5 years (interquartile range: 4.6 to 6.8 years). The optimal cutoff value of MPRI in predicting MACE was found with a threshold MPRI ≤1.47. Patients with MPRI ≤1.47 had three-fold increased risk of MACE compared with those with MPRI >1.47 (hazard ratio [HR]: 3.14; 95% confidence interval [CI]: 1.58 to 6.25; p = 0.001). Multivariate Cox regression after adjusting for age and hypertension demonstrated that MPRI was an independent predictor of MACE (HR: 0.10; 95% CI: 0.03 to 0.34; p < 0.001).ConclusionsStress perfusion CMR-derived MPRI is an independent imaging marker that predicts MACE in patients with ischemic symptom and no overt CAD over the medium term.