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.

2018 ACC/HRS/NASCI/SCAI/SCCT Expert Consensus Document on Optimal Use of Ionizing Radiation in Cardiovascular Imaging-Best Practices for Safety and Effectiveness, Part 2: Radiological Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection.

The stimulus to create this document was the recognition that ionizing radiation-guided cardiovascular procedures are being performed with increasing frequency, leading to greater patient radiation exposure and, potentially, to greater exposure to clinical personnel. While the clinical benefit of these procedures is substantial, there is concern about the implications of medical radiation exposure. ACC leadership concluded that it is important to provide practitioners with an educational resource that assembles and interprets the current radiation knowledge base relevant to cardiovascular procedures. By applying this knowledge base, cardiovascular practitioners will be able to select procedures optimally, and minimize radiation exposure to patients and to clinical personnel. "Optimal Use of Ionizing Radiation in Cardiovascular Imaging - Best Practices for Safety and Effectiveness" is a comprehensive overview of ionizing radiation use in cardiovascular procedures and is published online. To provide the most value to our members, we divided the print version of this document into 2 focused parts. "Part I: Radiation Physics and Radiation Biology" addresses radiation physics, dosimetry and detrimental biologic effects. "Part II: Radiologic Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection" covers the basics of operation and radiation delivery for the 3 cardiovascular imaging modalities (x-ray fluoroscopy, x-ray computed tomography, and nuclear scintigraphy). For each modality, it includes the determinants of radiation exposure and techniques to minimize exposure to both patients and to medical personnel.

2018 ACC/HRS/NASCI/SCAI/SCCT Expert Consensus Document on Optimal Use of Ionizing Radiation in Cardiovascular Imaging-Best Practices for Safety and Effectiveness, Part 1: Radiation Physics and Radiation Biology: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways Developed in Collaboration With Mended Hearts.

The stimulus to create this document was the recognition that ionizing radiation-guided cardiovascular procedures are being performed with increasing frequency, leading to greater patient radiation exposure and, potentially, to greater exposure for clinical personnel. Although the clinical benefit of these procedures is substantial, there is concern about the implications of medical radiation exposure. The American College of Cardiology leadership concluded that it is important to provide practitioners with an educational resource that assembles and interprets the current radiation knowledge base relevant to cardiovascular procedures. By applying this knowledge base, cardiovascular practitioners will be able to select procedures optimally, and minimize radiation exposure to patients and to clinical personnel. Optimal Use of Ionizing Radiation in Cardiovascular Imaging: Best Practices for Safety and Effectiveness is a comprehensive overview of ionizing radiation use in cardiovascular procedures and is published online. To provide the most value to our members, we divided the print version of this document into 2 focused parts. Part I: Radiation Physics and Radiation Biology addresses the issue of medical radiation exposure, the basics of radiation physics and dosimetry, and the basics of radiation biology and radiation-induced adverse effects. Part II: Radiological Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection covers the basics of operation and radiation delivery for the 3 cardiovascular imaging modalities (x-ray fluoroscopy, x-ray computed tomography, and nuclear scintigraphy) and will be published in the next issue of the Journal.

A clinical model to identify patients with high-risk coronary artery disease.

OBJECTIVES: This study sought to develop a clinical model that identifies patients with and without high-risk coronary artery disease (CAD). BACKGROUND: Although current clinical models help to estimate a patient's pre-test probability of obstructive CAD, they do not accurately identify those patients with and without high-risk coronary anatomy. METHODS: Retrospective analysis of a prospectively collected multinational coronary computed tomographic angiography (CTA) cohort was conducted. High-risk anatomy was defined as left main diameter stenosis ≥50%, 3-vessel disease with diameter stenosis ≥70%, or 2-vessel disease involving the proximal left anterior descending artery. Using a cohort of 27,125, patients with a history of CAD, cardiac transplantation, and congenital heart disease were excluded. The model was derived from 24,251 consecutive patients in the derivation cohort and an additional 7,333 nonoverlapping patients in the validation cohort. RESULTS: The risk score consisted of 9 variables: age, sex, diabetes, hypertension, current smoking, hyperlipidemia, family history of CAD, history of peripheral vascular disease, and chest pain symptoms. Patients were divided into 3 risk categories: low (≤7 points), intermediate (8 to 17 points) and high (≥18 points). The model was statistically robust with area under the curve of 0.76 (95% confidence interval [CI]: 0.75 to 0.78) in the derivation cohort and 0.71 (95% CI: 0.69 to 0.74) in the validation cohort. Patients who scored ≤7 points had a low negative likelihood ratio (<0.1), whereas patients who scored ≥18 points had a high specificity of 99.3% and a positive likelihood ratio (8.48). In the validation group, the prevalence of high-risk CAD was 1% in patients with ≤7 points and 16.7% in those with ≥18 points. CONCLUSIONS: We propose a scoring system, based on clinical variables, that can be used to identify patients at high and low pre-test probability of having high-risk CAD. Identification of these populations may detect those who may benefit from a trial of medical therapy and those who may benefit most from an invasive strategy.

Is metabolic syndrome predictive of prevalence, extent, and risk of coronary artery disease beyond its components? Results from the multinational coronary CT angiography evaluation for clinical outcome: an international multicenter registry (CONFIRM).

Although metabolic syndrome is associated with increased risk of cardiovascular disease and events, its added prognostic value beyond its components remains unknown. This study compared the prevalence, severity of coronary artery disease (CAD), and prognosis of patients with metabolic syndrome to those with individual metabolic syndrome components. The study cohort consisted of 27125 consecutive individuals who underwent ≥ 64-detector row coronary CT angiography (CCTA) at 12 centers from 2003 to 2009. Metabolic syndrome was defined as per NCEP/ATP III criteria. Metabolic syndrome patients (n = 690) were matched 1:1:1 to those with 1 component (n = 690) and 2 components (n = 690) of metabolic syndrome for age, sex, smoking status, and family history of premature CAD using propensity scoring. Major adverse cardiac events (MACE) were defined by a composite of myocardial infarction (MI), acute coronary syndrome, mortality and late target vessel revascularization. Patients with 1 component of metabolic syndrome manifested lower rates of obstructive 1-, 2-, and 3-vessel/left main disease compared to metabolic syndrome patients (9.4% vs 13.8%, 2.6% vs 4.5%, and 1.0% vs 2.3%, respectively; p < 0.05), while those with 2 components did not (10.5% vs 13.8%, 2.8% vs 4.5% and 1.3% vs 2.3%, respectively; p > 0.05). At 2.5 years, metabolic syndrome patients experienced a higher rate of MACE compared to patients with 1 component (4.4% vs 1.6%; p = 0.002), while no difference observed compared to individuals with 2 components (4.4% vs 3.2% p = 0.25) of metabolic syndrome. In conclusion, Metabolic syndrome patients have significantly greater prevalence, severity, and prognosis of CAD compared to patients with 1 but not 2 components of metabolic syndrome.

Patient-centered imaging: shared decision making for cardiac imaging procedures with exposure to ionizing radiation.

The current paper details the recommendations arising from an NIH-NHLBI/NCI-sponsored symposium held in November 2012, aiming to identify key components of a radiation accountability framework fostering patient-centered imaging and shared decision-making in cardiac imaging. Symposium participants, working in 3 tracks, identified key components of a framework to target critical radiation safety issues for the patient, the laboratory, and the larger population of patients with known or suspected cardiovascular disease. The use of ionizing radiation during an imaging procedure should be disclosed to all patients by the ordering provider at the time of ordering, and reinforced by the performing provider team. An imaging protocol with effective dose ≤3 mSv is considered very low risk, not warranting extensive discussion or written informed consent. However, a protocol effective dose >20 mSv was proposed as a level requiring particular attention in terms of shared decision-making and either formal discussion or written informed consent. Laboratory reporting of radiation dosimetry is a critical component of creating a quality laboratory fostering a patient-centered environment with transparent procedural methodology. Efforts should be directed to avoiding testing involving radiation, in patients with inappropriate indications. Standardized reporting and diagnostic reference levels for computed tomography and nuclear cardiology are important for the goal of public reporting of laboratory radiation dose levels in conjunction with diagnostic performance. The development of cardiac imaging technologies revolutionized cardiology practice by allowing routine, noninvasive assessment of myocardial perfusion and anatomy. It is now incumbent upon the imaging community to create an accountability framework to safely drive appropriate imaging utilization.

Progressive radiation dose reduction from coronary computed tomography angiography in a statewide collaborative quality improvement program: results from the Advanced Cardiovascular Imaging Consortium.

BACKGROUND: A best-practice intervention previously demonstrated significant dose reduction over a period of one year. We sought to evaluate whether this reduction would be incremental and sustained by promoting new scanner technology in the context of an ongoing quality improvement program during a 3-year period in a statewide registry of coronary computed tomography angiography. METHODS AND RESULTS: In this prospective, controlled, nonrandomized study involving 11 901 patients at 15 Michigan centers participating in the Advanced Cardiovascular Imaging Consortium, radiation doses and image quality were compared between the following periods: control (May to June 2008) versus follow-up I (July 2008 to June 2009) and follow-up I versus follow-up II (July 2009 to April 2011). Intervention during these study periods included continuous education, feedback, and mandatory participation in this initiative. The median radiation dose remained unchanged from control to follow-up I: dose-length product of 697 (interquartile range, 407-1163) to 675 (interquartile range, 418-1146) mGy·cm (P=0.93). With the introduction of newer technology in follow-up I period, there was incremental 31% decrease during follow-up II to median dose-length product of 468 (interquartile range, 292-811) mGy·cm (P<0.0001). No significant change was noted in the percentage of diagnostic quality scans from follow-up I (92%) to follow-up II (92.7%). CONCLUSIONS: Although ongoing application of a best-practice algorithm was associated with sustaining previously achieved targets, the use of newer scanner technology resulted in incremental radiation dose reduction in a statewide coronary computed tomography angiography registry without image quality degradation. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00640068.

Coronary computed tomography angiography after stress testing: results from a multicenter, statewide registry, ACIC (Advanced Cardiovascular Imaging Consortium).

OBJECTIVES: This study was conducted to evaluate the correlation between stress test results and coronary computed tomography angiography (CCTA) findings and comparative diagnostic performance of the 2 modalities in patients undergoing invasive coronary angiography (ICA). BACKGROUND: Recent data suggest that only a third of patients undergoing ICA have obstructive coronary artery disease (CAD); accurate pre-ICA risk stratification is needed. METHODS: At 47 centers participating in the ACIC (Advanced Cardiovascular Imaging Consortium) in Michigan, patients without known CAD who were undergoing CCTA within 3 months of a stress test were studied. Demographics, risk factors, symptoms, and stress test results were correlated with obstructive CAD (>50% stenosis) on CCTA and ICA. RESULTS: Among 6,198 patients (age 56 ± 12 years, 48% men), >50% stenosis was seen in 1,158 (18.7%) on CCTA. Independent predictors included male sex (odds ratio [OR]: 2.37, 95% confidence interval [CI]: 1.83 to 3.06), current smoking (OR: 2.23, 95% CI: 1.57 to 3.17), older age (OR per 10-year increment: 2.14, 95% CI: 1.89 to 2.41), hypertension (OR: 1.8, 95% CI: 1.37 to 2.34), and typical angina (OR: 1.48, 95% CI: 1.03 to 2.12). Stress test results were not predictive. Among patients undergoing ICA (n = 621), there was a strong correlation of ICA with CCTA findings (OR: 9.09, 95% CI: 5.57 to 14.8, p < 0.001), but not stress results (OR: 0.79, 95% CI: 0.56 to 1.11, p = 0.17). CONCLUSIONS: Stress test findings did not predict obstructive CAD on CCTA, observed in <20% of patients in this large study group. The strong association of CCTA with ICA suggests that it may serve as an effective "gatekeeper" to invasive testing in patients needing adjudication of stress test results. (Advanced Cardiovascular Imaging Consortium: A Collaborative Quality Improvement Project [ACIC]; NCT00640068).

Prevalence and severity of coronary artery disease and adverse events among symptomatic patients with coronary artery calcification scores of zero undergoing coronary computed tomography angiography: results from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry.

OBJECTIVES: The purpose of this study was to describe the prevalence and severity of coronary artery disease (CAD) in relation to prognosis in symptomatic patients without coronary artery calcification (CAC) undergoing coronary computed tomography angiography (CCTA). BACKGROUND: The frequency and clinical relevance of CAD in patients without CAC are unclear. METHODS: We identified 10,037 symptomatic patients without CAD who underwent concomitant CCTA and CAC scoring. CAD was assessed as <50%, ≥50%, and ≥70% stenosis. All-cause mortality and the composite endpoint of mortality, myocardial infarction, or late coronary revascularization (≥90 days after CCTA) were assessed. RESULTS: Mean age was 57 years, 56% were men, and 51% had a CAC score of 0. Among patients with a CAC score of 0, 84% had no CAD, 13% had nonobstructive stenosis, and 3.5% had ≥50% stenosis (1.4% had ≥70% stenosis) on CCTA. A CAC score >0 had a sensitivity, specificity, and negative and positive predictive values for stenosis ≥50% of 89%, 59%, 96%, and 29%, respectively. During a median of 2.1 years, there was no difference in mortality among patients with a CAC score of 0 irrespective of obstructive CAD. Among 8,907 patients with follow-up for the composite endpoint, 3.9% with a CAC score of 0 and ≥50% stenosis experienced an event (hazard ratio: 5.7; 95% confidence interval: 2.5 to 13.1; p < 0.001) compared with 0.8% of patients with a CAC score of 0 and no obstructive CAD. Receiver-operator characteristic curve analysis demonstrated that the CAC score did not add incremental prognostic information compared with CAD extent on CCTA for the composite endpoint (CCTA area under the curve = 0.825; CAC + CCTA area under the curve = 0.826; p = 0.84). CONCLUSIONS: In symptomatic patients with a CAC score of 0, obstructive CAD is possible and is associated with increased cardiovascular events. CAC scoring did not add incremental prognostic information to CCTA.

SCCT guidelines on radiation dose and dose-optimization strategies in cardiovascular CT.

Over the last few years, computed tomography (CT) has developed into a standard clinical test for a variety of cardiovascular conditions. The emergence of cardiovascular CT during a period of dramatic increase in radiation exposure to the population from medical procedures and heightened concern about the subsequent potential cancer risk has led to intense scrutiny of the radiation burden of this new technique. This has hastened the development and implementation of dose reduction tools and prompted closer monitoring of patient dose. In an effort to aid the cardiovascular CT community in incorporating patient-centered radiation dose optimization and monitoring strategies into standard practice, the Society of Cardiovascular Computed Tomography has produced a guideline document to review available data and provide recommendations regarding interpretation of radiation dose indices and predictors of risk, appropriate use of scanner acquisition modes and settings, development of algorithms for dose optimization, and establishment of procedures for dose monitoring.

Radiation dose from coronary CT angiography: five years of progress.

Radiation doses from coronary CT angiography have been scrutinized as a consequence of rising concern over cumulative lifetime radiation dose from diagnostic imaging and potential cancer risk. In response to this, the past 5 years have witnessed progressive refinements in CT technology and new dose reduction protocols, including electrocardiography-based tube current modulation, lower peak tube voltage, prospective or axial scanning, high-pitch spiral scanning, and iterative CT data reconstruction. As a direct result, compared with radiation exposure levels initially reported from 64-detector coronary CT angiography without dose modulation (range, 16-20 mSv), doses have decreased by approximately 50% every 2 years since 2005. Recent high-pitch spiral scan studies have documented doses ≤ 1 mSv. In routine clinical practice, registries show somewhat higher radiation dose levels, but nonetheless a similar rate of improvement with marked dose reduction enabled by dissemination of updated CT scanner technology. The current challenge is to continue the past rate of progress by incorporating research into practice and to facilitate improved technology.

Radiation dose from cardiac computed tomography before and after implementation of radiation dose-reduction techniques.

CONTEXT: Cardiac computed tomography angiography (CCTA) can accurately diagnose coronary artery disease, but radiation dose from this procedure is of concern. OBJECTIVES: To determine whether a collaborative radiation dose-reduction program would be associated with reduced radiation dose in patients undergoing CCTA in a statewide registry over a 1-year period and to define its effect on image quality. DESIGN, SETTING, AND PATIENTS: A prospective, controlled, nonrandomized study conducted during a control period (July-August 2007), an intervention period (September 2007-April 2008), and a follow-up period (May-June 2008) at 15 hospital imaging centers participating in the Advanced Cardiovascular Imaging Consortium in Michigan, which included small community hospitals and large academic medical centers. A total of 4995 sequential patients undergoing CCTA for suspected coronary artery disease were enrolled; 4862 patients (97.3%) had complete radiation data for analysis. INTERVENTION: A best-practice CCTA scan model was used, which included minimized scan range, heart rate reduction, electrocardiographic-gated tube current modulation, and reduced tube voltage in suitable patients. MAIN OUTCOME MEASURES: Primary outcomes included dose-length product and effective radiation dose from all phases of the CCTA scan. Secondary outcomes were image quality assessed by a 4-point scale (1 indicated excellent; 2, good; 3, adequate; and 4, nondiagnostic) and frequency of diagnostic-quality scans. RESULTS: Compared with the control period, patients' estimated median radiation dose in the follow-up period was reduced by 53.3% (dose-length product decreased from 1493 mGy x cm [interquartile range {IQR}, 855-1823 mGy x cm] to 697 mGy x cm [IQR, 407-1163 mGy x cm]; P < .001) and effective dose from 21 mSv (IQR, 12-26 mSv) to 10 mSv (IQR, 6-16 mSv) (P < .001). The greatest reduction in dose occurred at low-volume sites. There were no significant changes in median image quality assessment during the control period compared with the follow-up period (median image quality of 2 [images rated as good] vs median image quality of 2; P = .13) or frequency of diagnostic-quality scans (554/620 patients [89%] vs 769/835 patients [92%]; P = .07). CONCLUSION: Consistent application of currently available dose-reduction techniques was associated with a marked reduction in estimated radiation doses in a statewide CCTA registry, without impairment of image quality. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00640068.

Vascular endothelial growth factor-165 gene therapy promotes cardiomyogenesis in reperfused myocardial infarction.

BACKGROUND: Vascular endothelial growth factor (VEGF)-165 promotes cardiomyogenesis in chronic myocardial ischemia and nonreperfused myocardial infarction (MI). It is unknown whether this effect is present in reperfused MI. We sought to investigate the effect of VEGF-165 gene therapy on cardiomyogenesis after reperfused MI. METHODS AND RESULTS: Twenty-four Yucatan minipigs underwent thoracotomy and a vascular clamp was placed in the left circumflex artery. Reperfusion was reestablished after 90 minutes, and VEGF-165 gene therapy or placebo was administered. A replication-deficient recombinant human adenovirus serotype 5 was used for gene transfer (Ad5-VEGF165). The same viral vector devoid of VEGF gene (Ad5-beta-galactosidase) was used as placebo. Two administration routes were tested, intramyocardial (IM) injection and circumflex intracoronary (IC) infusion. The pigs were assigned to one of the following groups: IM Ad5-VEGF165 (n = 6), IM Ad5-betaGal (n = 6), IC Ad5-VEGF165 (n = 6), and IC Ad5-betaGal (n = 6). All pigs received 5-bromo-2'-deoxyuridine (BrdU) 250 mg IV twice a week to label cells undergoing DNA replication. The hearts were explanted at 4 weeks. BrdU-labeled cardiomyocytes in the peri-infarct area were counted by a pathologist blinded to group assignment. The number of BrdU-labeled cardiomyocytes per million cells was 4-fold higher in the group receiving IM VEGF-165 (64 +/- 11.4) vs. IM placebo (16 +/- 10.6), P = 0.034. No difference in infarct size or ventricular function was observed between the groups. CONCLUSIONS: IM VEGF-165 gene therapy promotes cardiomyogenesis in reperfused MI. However, no benefit in infarct size or cardiac function was observed at 4 weeks. The origin of these cells remains unknown and needs to be determined.

Interpreting the evidence: how accurate is coronary computed tomography angiography?

Coronary CT angiography (CTA) has evolved rapidly into a powerful diagnostic tool. More than 30 accuracy studies have reported accuracy results in >2000 patients. A meta-analysis of 29 studies found per-patient accuracy of 96% sensitivity, 74% specificity, 83% positive predictive value, and 94% negative predictive value. Several clinical studies support the safety and accuracy of coronary CTA for acute chest pain, after inconclusive stress testing, and in preoperative evaluation of patients before cardiac valve surgery. Accuracy studies suffer from selection bias because of the inclusion only of patients previously selected to undergo invasive angiography. This increases the incidence of true disease, raising apparent sensitivity and lowering negative predictive value, although the latter remains high at 94%. CTA has relatively low accuracy for the quantitative assessment of stenosis severity. CTA accuracy studies show high figures for sensitivity and negative predictive value in detection of coronary lesions. CTA less accurately shows lesion severity, and intermediate-grade lesions require physiologic evaluation. Clinical studies support the effectiveness of CTA for exclusion of significant coronary disease.