Comparative differences in the atherosclerotic disease burden between the epicardial coronary arteries: quantitative plaque analysis on coronary computed tomography angiography.

AIMS: Anatomic series commonly report the extent and severity of coronary artery disease (CAD), regardless of location. The aim of this study was to evaluate differences in atherosclerotic plaque burden and composition across the major epicardial coronary arteries. METHODS AND RESULTS: A total of 1271 patients (age 60 ± 9 years; 57% men) with suspected CAD prospectively underwent coronary computed tomography angiography (CCTA). Atherosclerotic plaque volume was quantified with categorization by composition (necrotic core, fibrofatty, fibrous, and calcified) based on Hounsfield Unit density. Per-vessel measures were compared using generalized estimating equation models. On CCTA, total plaque volume was lowest in the LCx (10.0 ± 29.4 mm3), followed by the RCA (32.8 ± 82.7 mm3; P < 0.001), and LAD (58.6 ± 83.3 mm3; P < 0.001), even when correcting for vessel length or volume. The prevalence of ≥2 high-risk plaque features, such as positive remodelling or spotty calcification, occurred less in the LCx (3.8%) when compared with the LAD (21.4%) or RCA (10.9%, P < 0.001). In the LCx, the most stenotic lesion was categorized as largely calcified more often than in the RCA and LAD (55.3% vs. 39.4% vs. 32.7%; P < 0.001). Median diameter stenosis was also lowest in the LCx (16.2%) and highest in the LAD (21.3%; P < 0.001) and located more distal along the LCx when compared with the RCA and LAD (P < 0.001). CONCLUSION: Atherosclerotic plaque, irrespective of vessel volume, varied across the epicardial coronary arteries; with a significantly lower burden and different compositions in the LCx when compared with the LAD and RCA. These volumetric and compositional findings support a diverse milieu for atherosclerotic plaque development and may contribute to a varied acute coronary risk between the major epicardial coronary arteries.

Validation of Wall Shear Stress Assessment in Non-invasive Coronary CTA versus Invasive Imaging: A Patient-Specific Computational Study.

Endothelial shear stress (ESS) identifies coronary plaques at high risk for progression and/or rupture leading to a future acute coronary syndrome. In this study an optimized methodology was developed to derive ESS, pressure drop and oscillatory shear index using computational fluid dynamics (CFD) in 3D models of coronary arteries derived from non-invasive coronary computed tomography angiography (CTA). These CTA-based ESS calculations were compared to the ESS calculations using the gold standard with fusion of invasive imaging and CTA. In 14 patients paired patient-specific CFD models based on invasive and non-invasive imaging of the left anterior descending (LAD) coronary arteries were created. Ten patients were used to optimize the methodology, and four patients to test this methodology. Time-averaged ESS (TAESS) was calculated for both coronary models applying patient-specific physiological data available at the time of imaging. For data analysis, each 3D reconstructed coronary artery was divided into 2 mm segments and each segment was subdivided into 8 arcs (45°).TAESS and other hemodynamic parameters were averaged per segment as well as per arc. Furthermore, the paired segment- and arc-averaged TAESS were categorized into patient-specific tertiles (low, medium and high). In the ten LADs, used for optimization of the methodology, we found high correlations between invasively-derived and non-invasively-derived TAESS averaged over segments (n = 263, r = 0.86) as well as arcs (n = 2104, r = 0.85, p < 0.001). The correlation was also strong in the four testing-patients with r = 0.95 (n = 117 segments, p = 0.001) and r = 0.93 (n = 936 arcs, p = 0.001).There was an overall high concordance of 78% of the three TAESS categories comparing both methodologies using the segment- and 76% for the arc-averages in the first ten patients. This concordance was lower in the four testing patients (64 and 64% in segment- and arc-averaged TAESS). Although the correlation and concordance were high for both patient groups, the absolute TAESS values averaged per segment and arc were overestimated using non-invasive vs. invasive imaging [testing patients: TAESS segment: 30.1(17.1-83.8) vs. 15.8(8.8-63.4) and TAESS arc: 29.4(16.2-74.7) vs 15.0(8.9-57.4) p < 0.001]. We showed that our methodology can accurately assess the TAESS distribution non-invasively from CTA and demonstrated a good correlation with TAESS calculated using IVUS/OCT 3D reconstructed models.

Quantitative assessment of coronary plaque volume change related to triglyceride glucose index: The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry.

BACKGROUND: The association between triglyceride glucose (TyG) index and coronary atherosclerotic change remains unclear. We aimed to evaluate the association between TyG index and coronary plaque progression (PP) using serial coronary computed tomography angiography (CCTA). METHODS: A total of 1143 subjects (aged 60.7 ± 9.3 years, 54.6% male) who underwent serial CCTA with available data on TyG index and diabetic status were analyzed from The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry. PP was defined as plaque volume (PV) (mm3) at follow-up minus PV at index > 0. Annual change of PV (mm3/year) was defined as PV change divided by inter-scan period. Rapid PP was defined as the progression of percent atheroma volume (PV divided by vessel volume multiplied by 100) ≥ 1.0%/year. RESULTS: The median inter-scan period was 3.2 (range 2.6-4.4) years. All participants were stratified into three groups based on TyG index tertiles. The overall incidence of PP was 77.3%. Baseline total PV (group I [lowest]: 30.8 (0.0-117.7), group II: 47.2 (6.2-160.4), and group III [highest]: 57.5 (8.4-154.3); P < 0.001) and the annual change of total PV (group I: 5.7 (0.0-20.2), group II: 7.6 (0.5-23.5), and group III: 9.4 (1.4-27.7); P = 0.010) were different among all groups. The risk of PP (odds ratio [OR] 1.648; 95% confidence interval [CI] 1.167-2.327; P = 0.005) and rapid PP (OR 1.777; 95% CI 1.288-2.451; P < 0.001) was increased in group III compared to that in group I. TyG index had a positive and significant association with an increased risk of PP and rapid PP after adjusting for confounding factors. CONCLUSION: TyG index is an independent predictive marker for the progression of coronary atherosclerosis. Clinical registration ClinicalTrials.gov NCT02803411.

Baseline Predictors of Low-Density Lipoprotein Cholesterol and Systolic Blood Pressure Goal Attainment After 1 Year in the ISCHEMIA Trial.

BACKGROUND: Risk factor control is the cornerstone of managing stable ischemic heart disease but is often not achieved. Predictors of risk factor control in a randomized clinical trial have not been described. METHODS AND RESULTS: The ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) randomized individuals with at least moderate inducible ischemia and obstructive coronary artery disease to an initial invasive or conservative strategy in addition to optimal medical therapy. The primary aim of this analysis was to determine predictors of meeting trial goals for LDL-C (low-density lipoprotein cholesterol, goal <70 mg/dL) or systolic blood pressure (SBP, goal <140 mm Hg) at 1 year post-randomization. We included all randomized participants in the ISCHEMIA trial with baseline and 1-year LDL-C and SBP values by January 28, 2019. Among the 3984 ISCHEMIA participants (78% of 5179 randomized) with available data, 35% were at goal for LDL-C, and 65% were at goal for SBP at baseline. At 1 year, the percent at goal increased to 52% for LDL-C and 75% for SBP. Adjusted odds of 1-year LDL-C goal attainment were greater with older age (odds ratio [OR], 1.11 [95% CI, 1.03-1.20] per 10 years), lower baseline LDL-C (OR, 1.19 [95% CI, 1.17-1.22] per 10 mg/dL), high-intensity statin use (OR, 1.30 [95% CI, 1.12-1.51]), nonwhite race (OR, 1.32 [95% CI, 1.07-1.63]), and North American enrollment compared with other regions (OR, 1.32 [95% CI, 1.06-1.66]). Women were less likely than men to achieve 1-year LDL-C goal (OR, 0.68 [95% CI, 0.58-0.80]). Adjusted odds of 1-year SBP goal attainment were greater with lower baseline SBP (OR, 1.27 [95% CI, 1.22-1.33] per 10 mm Hg) and with North American enrollment (OR, 1.35 [95% CI, 1.04-1.76]). CONCLUSIONS: In ISCHEMIA, older age, male sex, high-intensity statin use, lower baseline LDL-C, and North American location predicted 1-year LDL-C goal attainment, whereas lower baseline SBP and North American location predicted 1-year SBP goal attainment. Future studies should examine the effects of sex disparities, international practice patterns, and provider behavior on risk factor control.

Longitudinal quantitative assessment of coronary plaque progression related to body mass index using serial coronary computed tomography angiography.

AIMS: This study explored the coronary plaque volume change (PVC) according to the change of percent body mass index (BMI) and categorical BMI group using serial coronary computed tomography angiography (CCTA). METHODS AND RESULTS: A total of 1568 subjects who underwent serial CCTA with available BMI at baseline (CCTA1) and follow-up (CCTA2) were included. Median inter-scan period was 3.3 (interquartile range: 2.6-4.6) years. Quantitative assessment of coronary plaque was performed at both scans. All participants were categorized into three BMI (kg/m2) groups: normal: <25.0; overweight: 25.0-29.9; and obesity: ≥30.0. During follow-up, there were no significant differences in annualized PVC according to the 5% change of BMI in all BMI groups. Among 1424 (90.8%) subjects in the same BMI group at CCTA1 and CCTA2, a significant difference in annualized (PVC) was observed among the three groups. In 144 (9.2%) subjects with the change in their BMI group at CCTA2 compared their results at CCTA1, annualized PVC was not different compared with subjects in the same BMI group during follow-up. The percent change of BMI was not significantly related to the annualized PVC after adjusting confounding factors. Male gender [odds ratio (OR): 1.38; 95% confidence interval (CI): 1.05-1.81; P = 0.022], baseline plaque volume (OR: 1.07; 95% CI: 1.05-1.09; P < 0.001), and baseline overweight or obesity (OR: 1.35; 95% CI: 1.04-1.77; P = 0.027) were independently associated with coronary plaque progression. CONCLUSION: Over the near term, longitudinal small changes in BMI were not associated with changes in coronary plaque volume although baseline BMI was. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02803411.

Longitudinal assessment of coronary plaque volume change related to glycemic status using serial coronary computed tomography angiography: A PARADIGM (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging) substudy.

BACKGROUND: Data on the impact of glycemic status on coronary plaque progression have been limited. This study evaluated the association between glycemic status and coronary plaque volume change (PVC) using coronary computed tomography angiography (CCTA). METHODS: A total of 1296 subjects (61 ±â€¯9, 56.9% male) who underwent serial CCTA with available glycemic status were enrolled and analyzed from the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry. The median inter-scan period was 3.2 (2.6-4.4) years. Quantitative assessment of coronary plaques was performed at both scans. All participants were categorized into the following groups according to glycemic status: normal, pre-diabetes (pre-DM), and diabetes mellitus (DM). RESULTS: During the follow-up, significant differences in PVC (normal: 51.3 ±â€¯83.3 mm3 vs. pre-DM: 51.0 ±â€¯84.3 mm3 vs. DM: 72.6 ±â€¯95.0 mm3; p < 0.001) and annualized PVC (normal: 14.9 ±â€¯24.9 mm3 vs. pre-DM: 15.7 ±â€¯23.8 mm3 vs. DM: 21.0 ±â€¯27.7 mm3; p = 0.001) were observed among the 3 groups. Compared with normal individuals, individuals with pre-DM showed no significant differences in the adjusted odds ratio (OR) for plaque progression (PP) (1.338, 95% confidence interval [CI] 0.967-1.853; p = 0.079). However, the adjusted OR for PP was higher in DM individuals than in normal individuals (1.635, 95% CI 1.126-2.375; p = 0.010). CONCLUSION: DM had an incremental impact on coronary PP, but pre-DM appeared to have no significant association with an increased risk of coronary PP after adjusting for confounding factors. CLINICAL TRIAL REGISTRATION: ClinicalTrials.govNCT02803411.

Quantification of Coronary Atherosclerosis in the Assessment of Coronary Artery Disease.

BACKGROUND: Diagnosis of coronary artery disease and management strategies have relied solely on the presence of diameter stenosis ≥50%. We assessed whether direct quantification of plaque burden (PB) and plaque characteristics assessed by coronary computed tomography angiography could provide additional value in terms of predicting rapid plaque progression. METHODS AND RESULTS: From a 13-center, 7-country prospective observational registry, 1345 patients (60.4±9.4 years old; 57.1% male) who underwent repeated coronary computed tomography angiography >2 years apart were enrolled. For conventional angiographic analysis, the presence of stenosis ≥50%, number of vessel involved, segment involvement score, and the presence of high-risk plaque feature were determined. For quantitative analyses, PB and annual change in PB (△PB/y) in the entire coronary tree were assessed. Clinical outcomes (cardiac death, nonfatal myocardial infarction, and coronary revascularization) were recorded. Rapid progressors, defined as a patient with ≥median value of △PB/y (0.33%/y), were older, more frequently male, and had more clinical risk factors than nonrapid progressors (all P<0.05). After risk adjustment, addition of baseline PB improved prediction of rapid progression to each angiographic assessment of coronary artery disease, and the presence of high-risk plaque further improved the predictive performance (all P<0.001). For prediction of adverse outcomes, adding both baseline PB and △PB/y showed best predictive performance (C statistics, 0.763; P<0.001). CONCLUSIONS: Direct quantification of atherosclerotic PB in addition to conventional angiographic assessment of coronary artery disease might be beneficial for improving risk stratification of coronary artery disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02803411.

Anatomically correct three-dimensional coronary artery reconstruction using frequency domain optical coherence tomographic and angiographic data: head-to-head comparison with intravascular ultrasound for endothelial shear stress assessment in humans.

AIMS: To develop a methodology that permits accurate 3-dimensional (3D) reconstruction from FD-OCT and angiographic data enabling reliable evaluation of the ESS distribution, and to compare the FD-OCT-derived models against the established models based on angiography/IVUS. METHODS AND RESULTS: Fifteen patients (17 coronary arteries) who underwent angiography, FD-OCT and IVUS examination during the same procedure were studied. The FD-OCT and IVUS lumen borders were placed onto the 3D luminal centreline derived from angiographic data. Three-dimensional geometry algorithms and anatomical landmarks were used to estimate the orientation of the borders appropriately. ESS was calculated using computational fluid dynamics. In 188 corresponding consecutive 3-mm segments, FD-OCT- and IVUS-derived models were highly correlated for lumen area (r=0.96) and local ESS (r=0.89) measurements. FD-OCT-based 3D reconstructions had a high diagnostic accuracy for detecting regions exposed to proatherogenic low ESS identified on the IVUS-based 3D models, considered as the gold standard (receiver operator characteristic area under the curve: 94.9%). CONCLUSIONS: FD-OCT-based 3D coronary reconstruction provides anatomically correct models and permits reliable ESS computation. ESS assessment in combination with the superior definition of plaque characteristics by FD-OCT is expected to provide valuable insights into the effect of the haemodynamic environment on the development and destabilisation of high-risk plaques.

A new methodology for accurate 3-dimensional coronary artery reconstruction using routine intravascular ultrasound and angiographic data: implications for widespread assessment of endothelial shear stress in humans.

AIMS: To develop and validate a new methodology that allows accurate 3-dimensional (3-D) coronary artery reconstruction using standard, simple angiographic and intravascular ultrasound (IVUS) data acquired during routine catheterisation enabling reliable assessment of the endothelial shear stress (ESS) distribution. METHODS AND RESULTS: Twenty-two patients (22 arteries: 7 LAD; 7 LCx; 8 RCA) who underwent angiography and IVUS examination were included. The acquired data were used for 3-D reconstruction using a conventional method and a new methodology that utilised the luminal 3-D centreline to place the detected IVUS borders and anatomical landmarks to estimate their orientation. The local ESS distribution was assessed by computational fluid dynamics. In corresponding consecutive 3 mm segments, lumen, plaque and ESS measurements in the 3-D models derived by the centreline approach were highly correlated to those derived from the conventional method (r>0.98 for all). The centreline methodology had a 99.5% diagnostic accuracy for identifying segments exposed to low ESS and provided similar estimations to the conventional method for the association between the change in plaque burden and ESS (centreline method: slope= -1.65%/Pa, p=0.078; conventional method: slope= -1.64%/Pa, p=0.084; p =0.69 for difference between the two methodologies). CONCLUSIONS: The centreline methodology provides geometrically correct models and permits reliable ESS computation. The ability to utilise data acquired during routine coronary angiography and IVUS examination will facilitate clinical investigation of the role of local ESS patterns in the natural history of coronary atherosclerosis.

In-vivo assessment of the natural history of coronary atherosclerosis: vascular remodeling and endothelial shear stress determine the complexity of atherosclerotic disease progression.

PURPOSE OF REVIEW: Atherosclerotic disease progression is determined by localized plaque growth, which is induced by systemic and local hemodynamic factors, and the nature of the wall remodeling response. The purpose of this review is to summarize the processes underlying the heterogeneity of coronary atherosclerosis progression in relation to the local hemodynamic and arterial remodeling environment. RECENT FINDINGS: Multiple competing biological processes in the extracellular matrix define the extent of vascular remodeling and disease progression. The remodeling phenomenon is not consistent but is characterized by great phenotypical heterogeneity which reflects the complex effect of systemic, genetic and hemodynamic factors on the arterial wall response to plaque formation and progression. The exaggeration of expansive remodeling (i.e., excessive expansive remodeling) likely contributes to the transformation of an initially favorable action into an excessive course of vessel expansion, continued disease progression and plaque instability. Extremely low endothelial shear stress and excessive expansive remodeling establish a vicious cycle which leads to the formation of severe plaques with high-risk characteristics. SUMMARY: The dynamic interplay between the local hemodynamic environment and the wall remodeling behavior determines the complexity of the natural history of atherosclerosis and explains the development of localized plaque vulnerability.

The Critical Care Safety Study: The incidence and nature of adverse events and serious medical errors in intensive care.

OBJECTIVE: Critically ill patients require high-intensity care and may be at especially high risk of iatrogenic injury because they are severely ill. We sought to study the incidence and nature of adverse events and serious errors in the critical care setting. DESIGN: We conducted a prospective 1-year observational study. Incidents were collected with use of a multifaceted approach including direct continuous observation. Two physicians independently assessed incident type, severity, and preventability as well as systems-related and individual performance failures. SETTING: Academic, tertiary-care urban hospital. PATIENTS: Medical intensive care unit and coronary care unit patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcomes of interest were the incidence and rates of adverse events and serious errors per 1000 patient-days. A total of 391 patients with 420 unit admissions were studied during 1490 patient-days. We found 120 adverse events in 79 patients (20.2%), including 66 (55%) nonpreventable and 54 (45%) preventable adverse events as well as 223 serious errors. The rates per 1000 patient-days for all adverse events, preventable adverse events, and serious errors were 80.5, 36.2, and 149.7, respectively. Among adverse events, 13% (16/120) were life-threatening or fatal; and among serious errors, 11% (24/223) were potentially life-threatening. Most serious medical errors occurred during the ordering or execution of treatments, especially medications (61%; 170/277). Performance level failures were most commonly slips and lapses (53%; 148/277), rather than rule-based or knowledge-based mistakes. CONCLUSIONS: Adverse events and serious errors involving critically ill patients were common and often potentially life-threatening. Although many types of errors were identified, failure to carry out intended treatment correctly was the leading category.

From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II.

Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document will focus on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I.

Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document focuses on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

Economic consequences of routine coronary angiography in low- and intermediate-risk patients with unstable angina pectoris.

In low- and intermediate-risk patients with unstable angina pectoris (UAP) and non-ST-elevation acute myocardial infarction (NSTEAMI), routine early invasive management with coronary angiography does not decrease the risk of death or AMI. The economic consequences of this strategy in low- and intermediate-risk patients are unknown. We applied a risk prediction rule to a multihospital practice database and to the population of the Thrombolysis In Myocardial Ischemia trial, phase IIIB (TIMI 3B), which compared early invasive with conservative therapy for UAP and NSTEAMI. We then analyzed the effect of an early invasive strategy with regard to the composite end point of death, AMI, or rehospitalization for ischemia at rest. A logistic regression model was used to compare outcomes in patients with high versus low or intermediate risk scores. The costs and benefits of early invasive management in low- or intermediate-risk patients were assessed. In the practice database, 56% of patients with UAP and NSTEAMI who had low or intermediate risk scores underwent early cardiac catheterization, although early invasive management of these lower risk patients has not been associated with a reduction in the rate of death or MI. In TIMI 3B, when rehospitalization for ischemia at rest was added to the composite end point, invasive management was superior to conservative management at 42 days (p = 0.005) and at 1 year (p = 0.03). If all low- or intermediate-risk patients randomized to conservative therapy in that trial had been treated instead with an early invasive strategy, an estimated 5.4% of rehospitalizations would have been avoided. Within TIMI 3B, such a routine invasive strategy would have resulted in an additional cost of 2,695,700 US dollars with no effect on death or AMI, but it would have led to 34 fewer rehospitalizations. This expenditure of 79,285 US dollars per hospitalization prevented far exceeds the monetary cost of rehospitalization (14,000 US dollars). Although common in clinical practice, routine early invasive management of low- or intermediate-risk patients with UAP generates substantial health-care costs without a mortality benefit or decrease in the risk of AMI. Unless the incremental benefit in quality of life from prevented rehospitalizations for UAP is judged to be worth the large incremental cost (79,285 US dollars per hospitalization prevented), such a strategy is unlikely to be cost effective.

Optimizing ambulatory ECG monitoring of T-wave alternans for arrhythmia risk assessment.

Considerable scientific data support the potential value of T-wave alternans (TWA) as an index of vulnerability to ventricular fibrillation. This chapter summarizes our state of knowledge regarding the use of routine ambulatory ECGs to evaluate TWA and discusses recent methodologic approaches designed to optimize AECG-based TWA analysis for arrhythmia risk stratification. Newer methods, including the nonspectral technique of Modified Moving Average analysis, appear promising in detecting TWA during the changing conditions associated with daily activities. The Modified Moving Average approach does not require specialized electrodes and is not encumbered by the need to achieve target heart rates, as is the case for conventional spectral-based methods. Guidelines are provided for evaluating latent cardiac electrical instability using AECG-based TWA testing. These recent developments make possible the TWA analysis of ambulatory ECGs not only in prospective trials but also in vast stores of archival data.

Mental stress-induced ischemia and all-cause mortality in patients with coronary artery disease: Results from the Psychophysiological Investigations of Myocardial Ischemia study.

BACKGROUND: Ischemia during laboratory mental stress tests has been linked to significantly higher rates of adverse cardiac events. Previous studies have not been designed to detect differences in mortality rates. METHODS AND RESULTS: To determine whether mental stress-induced ischemia predicts death, we evaluated 196 patients from the Psychophysiological Investigations of Myocardial Ischemia (PIMI) study who had documented coronary artery disease and exercise-induced ischemia. Participants underwent bicycle exercise and psychological stress testing with radionuclide imaging. Cardiac function data and psychological test results were collected. Vital status was ascertained by telephone and by querying Social Security records 3.5+/-0.4 years and 5.2+/-0.4 years later. Of the 17 participants who had died, new or worsened wall motion abnormalities during the speech test were present in 40% compared with 19% of survivors (P=0.04) and significantly predicted death (rate ratio=3.0; 95% CI, 1.04 to 8.36; P=0.04). Ejection fraction changes during the speech test were similar in patients who died and in survivors (P=0.9) and did not predict death even after adjusting for resting ejection fraction (P=0.63), which was similar in both groups (mean, 56.4 versus 59.7; P=0.24). Other indicators of ischemia during the speech test (ST-segment depression, chest pain) did not predict death, nor did psychological traits, hemodynamic responses to the speech test, or markers of the presence and severity of ischemia during daily life and exercise. CONCLUSIONS: In patients with coronary artery disease and exercise-induced ischemia, the presence of mental stress-induced ischemia predicts subsequent death.