Ischemic Burden Reduction and Long-Term Clinical Outcomes After Chronic Total Occlusion Percutaneous Coronary Intervention.

OBJECTIVES: The authors sought to evaluate the impact of ischemic burden reduction after chronic total occlusion (CTO) percutaneous coronary intervention (PCI) on long-term prognosis and cardiac symptom relief. BACKGROUND: The clinical benefit of CTO PCI is questioned. METHODS: In a high-volume CTO PCI center, 212 patients prospectively underwent quantitative [15O]H2O positron emission tomography perfusion imaging before and three months after successful CTO PCI between 2013-2019. Perfusion defects (PD) (in segments) and hyperemic myocardial blood flow (hMBF) (in ml · min-1 · g-1) allocated to CTO areas were related to prognostic outcomes using unadjusted (Kaplan-Meier curves, log-rank test) and risk-adjusted (multivariable Cox regression) analyses. The prognostic endpoint was a composite of all-cause death and nonfatal myocardial infarction. RESULTS: After a median [interquartile range] of 2.8 years [1.8 to 4.3 years], event-free survival was superior in patients with ≥3 versus <3 segment PD reduction (p < 0.01; risk-adjusted p = 0.04; hazard ratio [HR]: 0.34 [95% confidence interval (CI): 0.13 to 0.93]) and with hMBF increase above (Δ≥1.11 ml · min-1 · g-1) versus below the population median (p < 0.01; risk-adjusted p < 0.01; HR: 0.16 [95% CI: 0.05 to 0.54]) after CTO PCI. Furthermore, event-free survival was superior in patients without versus any residual PD (p < 0.01; risk-adjusted p = 0.02; HR: 0.22 [95% CI: 0.06 to 0.76]) or with a residual hMBF level >2.3 versus ≤2.3 ml · min-1 · g-1 (p < 0.01; risk-adjusted p = 0.03; HR: 0.25 [95% CI: 0.07 to 0.91]) at follow-up positron emission tomography. Patients with residual hMBF >2.3 ml · min-1 · g-1 were more frequently free of angina and dyspnea on exertion at long-term follow-up (p = 0.04). CONCLUSIONS: Patients with extensive ischemic burden reduction and no residual ischemia after CTO PCI had lower rates of all-cause death and nonfatal myocardial infarction. Long-term cardiac symptom relief was associated with normalization of hMBF levels after CTO PCI.

Association of High-Density Calcified 1K Plaque With Risk of Acute Coronary Syndrome.

Importance: Plaque morphologic measures on coronary computed tomography angiography (CCTA) have been associated with future acute coronary syndrome (ACS). However, the evolution of calcified coronary plaques by noninvasive imaging is not known. Objective: To ascertain whether the increasing density in calcified coronary plaque is associated with risk for ACS. Design, Setting, and Participants: This multicenter case-control cohort study included individuals enrolled in ICONIC (Incident Coronary Syndromes Identified by Computed Tomography), a nested case-control study of patients drawn from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, which included 13 study sites in 8 countries. Patients who experienced core laboratory-verified ACS after baseline CCTA (n = 189) and control individuals who did not experience ACS after baseline CCTA (n = 189) were included. Patients and controls were matched 1:1 by propensity scores for age; male sex; presence of hypertension, hyperlipidemia, and diabetes; family history of premature coronary artery disease (CAD); current smoking status; and CAD severity. Data were analyzed from November 2018 to March 2019. Exposures: Whole-heart atherosclerotic plaque volume was quantitated from all coronary vessels and their branches. For patients who underwent invasive angiography at the time of ACS, culprit lesions were coregistered to baseline CCTA lesions by a blinded independent reader. Low-density plaque was defined as having less than 130 Hounsfield units (HU); calcified plaque, as having more than 350 HU and subcategorized on a voxel-level basis into 3 strata: 351 to 700 HU, 701 to 1000 HU, and more than 1000 HU (termed 1K plaque). Main Outcomes and Measures: Association between calcium density and future ACS risk. Results: A total of 189 patients and 189 matched controls (mean [SD] age of 59.9 [9.8] years; 247 [65.3%] were male) were included in the analysis and were monitored during a mean (SD) follow-up period of 3.9 (2.5) years. The overall mean (SD) calcified plaque volume (>350 HU) was similar between patients and controls (76.4 [101.6] mm3 vs 99.0 [156.1] mm3; P = .32), but patients who experienced ACS exhibited less 1K plaque (>1000 HU) compared with controls (3.9 [8.3] mm3 vs 9.4 [23.2] mm3; P = .02). Individuals within the highest quartile of 1K plaque exhibited less low-density plaque, as a percentage of total plaque, when compared with patients within the lower 3 quartiles (12.6% [10.4%] vs 24.9% [20.6%]; P < .001). For 93 culprit precursor lesions detected by CCTA, the volume of 1K plaque was lower compared with the maximally stenotic lesion in controls (2.6 [7.2] mm3 vs 7.6 [20.3] mm3; P = .01). The per-patient and per-lesion results were similar between the 2 groups when restricted to myocardial infarction cases. Conclusions and Relevance: Results of this study suggest that, on a per-patient and per-lesion basis, 1K plaque was associated with a lower risk for future ACS and that measurement of 1K plaque may improve risk stratification beyond plaque burden.

Adverse Plaque Characteristics Relate More Strongly With Hyperemic Fractional Flow Reserve and Instantaneous Wave-Free Ratio Than With Resting Instantaneous Wave-Free Ratio.

OBJECTIVES: The current substudy of the PACIFIC (Prospective Comparison of Cardiac PET/CT, SPECT/CT Perfusion Imaging and CT Coronary Angiography With Invasive Coronary Angiography) trial explores the impact of computed tomography (CT)-derived unfavorable plaque features on both hyperemic and non-hyperemic flow indices. BACKGROUND: Next to lesion severity, plaque vulnerability as assessed using coronary CT angiography affects fractional flow reserve (FFR), which is associated with imminent acute coronary syndromes. Instantaneous wave-free ratio (iFR) has recently emerged as an alternative for FFR to interrogate coronary lesions for ischemia. It is, however, unknown whether vasodilator-free assessment with iFR is associated with plaque stability similarly as FFR. METHODS: Of 120 patients (62% men, age 58.3 ± 8.6 years) with suspected coronary artery disease, 257 vessels were prospectively evaluated. Each patient underwent 256-slice coronary CT angiography to assess stenosis severity and plaque features (positive remodeling [PR], low attenuation plaque [LAP], spotty calcification [SC], and napkin ring sign [NRS]), as well as intracoronary pressure measurements (FFR, iFR, Pd/Pa, and pressure ratio during adenosine within the wave-free period [iFRa]). CT-derived plaque characteristics were related to these invasive pressure measurements. RESULTS: Atherosclerotic plaques were present in 170 (66%) coronary arteries. On a per-vessel basis, luminal stenosis severity was significantly associated with impaired FFR, iFR, Pd/Pa, and iFRa. Multivariable analysis revealed that FFR and iFR were independently related to ≥70% stenosis (-0.10, p < 0.001 and -0.09, p = 0.003, respectively) and plaque volume (-0.02, p = 0.020 and -0.02, p = 0.030, respectively). Additionally, PR and SC were also independent predictors of an impaired FFR (-0.10, p < 0.001 and -0.07, p = 0.021, respectively), but adverse plaque characteristics were not independently related to the vasodilator-free iFR. CONCLUSIONS: CT-derived vulnerable plaque characteristics are independently associated with hyperemic flow indices as assessed with FFR and iFRa, but not with non-hyperemic indices such as iFR and Pd/Pa. These findings suggest that the effects of hyperemia on pressure-derived indices might depend not only on hemodynamic stenosis severity but also on plaque characteristics.

Quantitative measurement of lipid rich plaque by coronary computed tomography angiography: A correlation of histology in sudden cardiac death.

BACKGROUND AND AIMS: Recent advancements in coronary computed tomography angiography (CCTA) have allowed for the quantitative measurement of high-risk lipid rich plaque. Determination of the optimal threshold for Hounsfield units (HU) by CCTA for identifying lipid rich plaque remains unknown. We aimed to validate reliable cut-points of HU for quantitative assessment of lipid rich plaque. METHODS: 8 post-mortem sudden coronary death hearts were evaluated with CCTA and histologic analysis. Quantitative plaque analysis was performed in histopathology images and lipid rich plaque area was defined as intra-plaque necrotic core area. CCTA images were analyzed for quantitative plaque measurement. Low attenuation plaque (LAP) was defined as any pixel < 30, 45, 60, 75, and 90 HU cut-offs within a coronary plaque. The area of LAP was calculated in each cross-section. RESULTS: Among 105 cross-sections, 37 (35.2%) cross-sectional histology images contained lipid rich plaque. Although the highest specificity for identifying lipid rich plaque was shown with <30 HU cut-off (88.2%), sensitivity (e.g. 55.6% for <75 HU, 16.2% for <30 HU) and negative predictive value (e.g. 75.9% for <75 HU, 65.9% for <30 HU) tended to increase with higher HU cut-offs. For quantitative measurement, <75 HU showed the highest correlation coefficient (0.292, p = 0.003) and no significant differences were observed between lipid rich plaque area and LAP area between histology and CT analysis (Histology: 0.34 ±â€¯0.73 mm2, QCT: 0.37 ±â€¯0.71 mm2, p = 0.701). CONCLUSIONS: LAP area by CCTA using a <75 HU cut-off value demonstrated high sensitivity and quantitative agreement with lipid rich plaque area by histology analysis.

Impact of Revascularization on Absolute Myocardial Blood Flow as Assessed by Serial [15O]H2O Positron Emission Tomography Imaging: A Comparison With Fractional Flow Reserve.

BACKGROUND: The main goal of coronary revascularization is to restore myocardial perfusion in case of ischemia, causing coronary artery disease. Yet, little is known on the effect of revascularization on absolute myocardial blood flow (MBF). Therefore, the present prospective study assesses the impact of coronary revascularization on absolute MBF as measured by [15O]H2O positron emission tomography and fractional flow reserve (FFR) in patients with stable coronary artery disease. METHODS AND RESULTS: Fifty-three patients (87% men, mean age 58.7±9.0 years) with suspected coronary artery disease were included prospectively. All patients underwent serial [15O]H2O positron emission tomography perfusion imaging at baseline and after revascularization by either percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery. FFR was routinely measured at baseline and directly post-PCI. After revascularization, regional rest and stress MBF improved from 0.77±0.16 to 0.86±0.25 mL/min/g and from 1.57±0.59 to 2.48±0.91 mL/min/g, respectively, yielding an increase in coronary flow reserve from 2.02±0.69 to 2.94±0.94 (P<0.01 for all). Mean FFR at baseline improved post-PCI from 0.61±0.17 to 0.89±0.08 (P<0.01). After PCI, an increase in FFR paralleled improvement in absolute myocardial perfusion as reflected by stress MBF and coronary flow reserve (r = 0.74 and r = 0.71, respectively, P<0.01 for both). PCI demonstrated a greater improvement of regional stress MBF as compared with coronary artery bypass graft surgery (1.14±1.11 versus 0.66±0.69 mL/min/g, respectively, P=0.02). However, patients undergoing bypass grafting had a more advanced stage of coronary artery disease and more incomplete revascularizations. CONCLUSION: Successful coronary revascularization has a significant and positive impact on absolute myocardial perfusion as assessed by serial quantitative [15O]H2O positron emission tomography. Notably, improvement of FFR after PCI was directly related to the increase in hyperemic MBF.

Development and Validation of a Simple-to-Use Nomogram for Predicting 5-, 10-, and 15-Year Survival in Asymptomatic Adults Undergoing Coronary Artery Calcium Scoring.

OBJECTIVES: The purpose of this study was to develop and validate a simple-to-use nomogram for prediction of 5-, 10-, and 15-year survival among asymptomatic adults. BACKGROUND: Simple-to-use prognostication tools that incorporate robust methods such as coronary artery calcium scoring (CACS) for predicting near-, intermediate- and long-term mortality are warranted. METHODS: In a consecutive series of 9,715 persons (mean age: 53.4 ± 10.5 years; 59.3% male) undergoing CACS, we developed a nomogram using Cox proportional hazards regression modeling that included: age, sex, smoking, hypertension, dyslipidemia, diabetes, family history of coronary artery disease, and CACS. We developed a prognostic index (PI) summing the number of risk points corresponding to weighted covariates, which was used to configure the nomogram. Validation of the nomogram was assessed by discrimination and calibration applied to a separate cohort of 7,824 adults who also underwent CACS. RESULTS: A total of 936 and 294 deaths occurred in the derivation and validation sets at a median follow-up of 14.6 years (interquartile range: 13.7 to 15.5 years) and 9.4 years (interquartile range: 6.8 to 11.5 years), respectively. The developed model effectively predicted 5-, 10-, and 15-year probability of survival. The PI displayed high discrimination in the derivation and validation sets (C-index 0.74 and 0.76, respectively), indicating suitable external performance of our nomogram model. The predicted and actual estimates of survival in each dataset according to PI quartiles were similar (though not identical), demonstrating improved model calibration. CONCLUSIONS: A simple-to-use nomogram effectively predicts 5-, 10- and 15-year survival for asymptomatic adults undergoing screening for cardiac risk factors. This nomogram may be considered for use in clinical care.

Relative flow reserve derived from quantitative perfusion imaging may not outperform stress myocardial blood flow for identification of hemodynamically significant coronary artery disease.

BACKGROUND: Quantitative myocardial perfusion imaging is increasingly used for the diagnosis of coronary artery disease. Quantitative perfusion imaging allows to noninvasively calculate fractional flow reserve (FFR). This so-called relative flow reserve (RFR) is defined as the ratio of hyperemic myocardial blood flow (MBF) in a stenotic area to hyperemic MBF in a normal perfused area. The aim of this study was to assess the value of RFR in the detection of significant coronary artery disease. METHODS AND RESULTS: From a clinical population of patients with suspected coronary artery disease who underwent oxygen-15-labeled water cardiac positron emission tomography and invasive coronary angiography, 92 patients with single- or 2-vessel disease were included. Intermediate lesions (diameter stenosis, 30%-90%; n=75) were interrogated by FFR. Thirty-eight (41%) vessels were deemed hemodynamically significant (>90% stenosis or FFR≤0.80). Hyperemic MBF, coronary flow reserve, and RFR were lower for vessels with a hemodynamically significant lesion (2.01±0.78 versus 2.90±1.16 mL·min(-1)·g(-1); P<0.001, 2.27±1.03 versus 3.10±1.29; P<0.001, and 0.67±0.23 versus 0.93±0.15; P<0.001, respectively). The correlation between RFR and FFR was moderate (r=0.54; P<0.01). Receiver operator characteristic curve analysis showed an area under the curve of 0.82 for RFR, which was not significantly higher compared with that for hyperemic MBF and coronary flow reserve (0.76; P=0.32 and 0.72; P=0.08, respectively). CONCLUSIONS: Noninvasive estimation of FFR by quantitative perfusion positron emission tomography by calculating RFR is feasible, yet only a trend toward a slight improvement of diagnostic accuracy compared with hyperemic MBF assessment was determined.