Lipoprotein subclasses are associated with Hepatic steatosis: insights from the prospective multicenter imaging study for the evaluation of chest pain (PROMISE) clinical trial.

Objectives: To determine the relationship between lipoprotein particle size/number with hepatic steatosis (HS), given its association with traditional lipoproteins and coronary atherosclerosis. Methods: Individuals with available CT data and blood samples enrolled in the PROMISE trial were studied. HS was defined based on CT attenuation. Lipoprotein particle size/number were measured by nuclear magnetic resonance spectroscopy. Principal components analysis (PCA) was used for dimensionality reduction. The association of PCA factors and individual lipoprotein particle size/number with HS were assessed in multivariable regression models. Associations were validated in an independent cohort of 59 individuals with histopathology defined HS. Results: Individuals with HS (n=410/1,509) vs those without (n=1,099/1,509), were younger (59±8 vs 61±8 years) and less often females (47.6 % vs 55.9 %). All PCA factors were associated with HS: factor 1 (OR:1.36, 95 %CI:1.21-1.53), factor 3 (OR:1.75, 95 %CI:1.53-2.02) and factor 4 (OR:1.49; 95 %CI:1.32-1.68) were weighted heavily with small low density lipoprotein (LDL) and triglyceride-rich (TRL) particles, while factor 2 (OR:0.86, 95 %CI:0.77-0.97) and factor 5 (OR:0.74, 95 %CI:0.65-0.84) were heavily loaded with high density lipoprotein (HDL) and larger LDL particles. These observations were confirmed with the analysis of individual lipoprotein particles in PROMISE. In the validation cohort, association between HS and large TRL (OR: 8.16, 95 %CI:1.82-61.98), and mean sizes of TRL- (OR: 2.82, 95 %CI:1.14-9.29) and HDL (OR:0.35, 95 %CI:0.13-0.72) were confirmed. Conclusions: Large TRL, mean sizes of TRL-, and HDL were associated with radiographic and histopathologic HS. The use of lipoprotein particle size/number could improve cardiovascular risk assessment in HS.

Risk factors for cardiovascular disease among individuals with hepatic steatosis.

Cardiovascular disease (CVD) is the leading cause of mortality in adults with hepatic steatosis (HS). However, risk factors for CVD in HS are unknown. We aimed to identify factors associated with coronary artery disease (CAD) and incident major adverse cardiovascular events (MACE) in individuals with HS. We performed a nested cohort study of adults with HS detected on coronary computed tomography in the PROspective Multicenter Imaging Study for Evaluation of chest pain (PROMISE) trial. Obstructive CAD was defined as ≥50% coronary stenosis. MACE included hospitalization for unstable angina, nonfatal myocardial infarction, or all-cause death. Multivariate modeling, adjusted for age, sex, atherosclerotic CVD (ASCVD) risk score and body mass index, identified factors associated with obstructive CAD. Cox regression, adjusted for ASCVD risk score, determined the predictors of MACE. A total of 959 of 3,756 (mean age 59.4 years, 55.0% men) had HS. Obstructive CAD was present in 15.2% (145 of 959). Male sex (adjusted odds ratio [aOR] = 1.83, 95% confidence interval [CI] 1.18-1.2.84; p = 0.007), ASCVD risk score (aOR = 1.05, 95% CI 1.03-1.07; p < 0.001), and n-terminal pro-b-type natriuretic peptide (NT-proBNP; aOR = 1.90, 95% CI 1.38-2.62; p < 0.001) were independently associated with obstructive CAD. In the 25-months median follow-up, MACE occurred in 4.4% (42 of 959). Sedentary lifestyle (adjusted hazard ratio [aHR] = 2.53, 95% CI 1.27-5.03; p = 0.008) and NT-proBNP (aOR = 1.50, 95% CI 1.01-2.25; p = 0.046) independently predicted MACE. Furthermore, the risk of MACE increased by 3% for every 1% increase in ASCVD risk score (aHR = 1.03, 95% CI 1.01-1.05; p = 0.02). Conclusion: In individuals with HS, male sex, NT-pro-BNP, and ASCVD risk score are associated with obstructive CAD. Furthermore, ASCVD, NT-proBNP, and sedentary lifestyle are independent predictors of MACE. These factors, with further validation, may help risk-stratify adults with HS for incident CAD and MACE.

Coronary Atherosclerosis, Cardiac Troponin, and Interleukin-6 in Patients With Chest Pain: The PROMISE Trial Results.

BACKGROUND: Increased inflammation and myocardial injury can be observed in the absence of myocardial infarction or obstructive coronary artery disease (CAD). OBJECTIVES: The authors determined whether biomarkers of inflammation and myocardial injury-interleukin (IL)-6 and high-sensitivity cardiac troponin (hs-cTn)-were associated with the presence and extent of CAD and were independent predictors of major adverse cardiovascular events (MACEs) in stable chest pain. METHODS: Using participants from the PROMISE trial, the authors measured hs-cTn I and IL-6 concentrations and analyzed computed tomography angiography (CTA) images in the core laboratory for CAD characteristics: significant stenosis (≥70%), high-risk plaque (HRP), Coronary Artery Disease Reporting and Data System (CAD-RADS) categories, segment involvement score (SIS), and coronary artery calcium (CAC) score. The primary endpoint was a composite MACE (death, myocardial infarction, or unstable angina). RESULTS: The authors included 1,796 participants (age 60.2 ± 8.0 years; 47.5% men, median follow-up 25 months). In multivariable linear regression adjusted for atherosclerotic cardiovascular disease (ASCVD) risk, hs-cTn was associated with HRP, stenosis, CAD-RADS, and SIS. IL-6 was only associated with stenosis and CAD-RADS. hs-cTn above median (1.5 ng/L) was associated with MACEs in univariable analysis (HR: 2.1 [95% CI: 1.3-3.6]; P = 0.006), but not in multivariable analysis adjusted for ASCVD and CAD. IL-6 above median (1.8 ng/L) was associated with MACEs in multivariable analysis adjusted for ASCVD and HRP (HR: 1.9 [95% CI: 1.1-3.3]; P = 0.03), CAC (HR: 1.9 [95% CI: 1.0-3.4]; P = 0.04), and SIS (HR: 1.8 [95% CI: 1.0-3.2]; P = 0.04), but not for stenosis or CAD-RADS. In participants with nonobstructive CAD (stenosis 1%-69%), the presence of both hs-cTn and IL-6 above median was strongly associated with MACEs (HR: 2.5-2.7 after adjustment for CAD characteristics). CONCLUSIONS: Concentrations of hs-cTn and IL-6 were associated with CAD characteristics and MACEs, indicating that myocardial injury and inflammation may each contribute to pathways in CAD pathophysiology. This association was most pronounced among participants with nonobstructive CAD representing an opportunity to tailor treatment in this at-risk group. (PROspective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550).

First report of intravascular ultrasound-guided intravascular lithotripsy to treat an underexpanded stent in the superficial femoral artery.

BACKGROUND/OBJECTIVE: To evaluate the safety and utility of a new in Europe intravascular ultrasound (IVUS) catheter in a case of peripheral arterial disease caused by in-stent restenosis of the superficial femoral artery. METHOD: Pre-therapeutic computed tomographic angiography identified severe stent restenosis related to device underexpansion, which was caused by an underlying eccentric severely calcified stenosis leading to suboptimal device deployment. The OptiCross 18 (30 MHz Peripheral Imaging Catheter, Boston Scientific, USA) is a short rail imaging catheter. It consists of two main assemblies: The imaging core is composed of a hi-torque, flexible, rotating drive cable with a radial looking 30 MHz ultrasonic transducer at the distal tip. An electro-mechanical connector interface at the proximal end of the catheter makes the connection to the Motordrive Unit (MDU5 PLUSTM) Instrument. The MDU5 PLUS-catheter interface consists of an integrated mechanical drive socket and electrical connection. RESULTS: The use of the IVUS-guided imaging revealed in-stent restenosis, fracture, and protrusion of the calcified plaque in the stent and confirmed the preoperative computed tomography angiography which showed stent compression. Use of intravascular litotripsy catheter (intravascular lithotripsy Shockwave Medical, Santa Clara, California) and drug coated balloon led to improvement in stent expansion, having minimal patent diameter of 5.77 mm. The patient's subsequent clinical course was uneventful, and clinically had palpable pulses in the foot and ankle-brachial index of 1. CONCLUSIONS: Whether acoustic pulse application might affect device structure in the long term remains to be determined, use of the novel IVUS system demonstrated excellent visibility of the etiology of the in-stent restenosis improving the perioperative diagnostic modalities of suboptimal endovascular outcome.

Multicenter Mid-Term Outcomes of the Chimney Technique in the Elective Treatment of Degenerative Pararenal Aortic Aneurysms.

PURPOSE: Chimney endovascular abdominal aortic aneurysm repair (CHEVAR) has predominantly been described as an alternative technique for the management of urgent presentations of degenerative pararenal aortic aneurysms (dPAAs). However, the role of CHEVAR in the treatment of asymptomatic patients remains unknown. The aim of current multinational study was to evaluate the outcomes of elective CHEVAR of dPAAs. MATERIAL AND METHODS: Retrospective analysis of 267 consecutive dPAA patients treated with elective CHEVAR at 13 European and US centers from 2008 to 2014. Primary endpoints were 30 days and out of hospital CHEVAR-related mortality. Secondary endpoints included persistent type Ia endoleak or endotension, angiographically confirmed occlusion and/or high-grade chimney graft (CG) or involved splanchnic vessel stenosis identified at index procedure and/or during follow-up, as well as CHEVAR-related re-intervention. RESULTS: Mean follow-up time was 25.5±13.3 months. The 442 visceral vessels were involved and mean number of CGs per patient was 1.63±0.7. 436 targeted vessels were successfully cannulated. The aortic graft intentionally covered 6 renal arteries and immediate technical success was 98.6%. The 30 days mortality was 1.9% (n=5), while the in-hospital complication rate was 10.1% (n=27) including 3 strokes, 1 permanent dialysis, and 1 intestinal ischemia. No 30 day type Ia endoleaks were detected and 3.2% of CGs (n=14, including the intentionally covered) had evidence of occlusion and/or stenosis. The overall CHEVAR-related mortality was 2.2% (n=6). Freedom from primary and secondary type Ia endoleak/endotension rates at 3 years was 93.0% and 98.0%, respectively. Primary and secondary CG patency was 87.0% and 89.0%. Primary and secondary endovascular freedom from any endpoint at 3 years was 81.0% and 94.0% respectively. CONCLUSION: Elective use of CHEVAR in the management of dPAAs seems to be durable. These results are comparable to published outcomes with other total endovascular strategies, which justifies an expanded role for CHEVAR in the treatment of asymptomatic patients presenting with dPAAs.

Differences in Cardiovascular Risk, Coronary Artery Disease, and Cardiac Events Between Black and White Individuals Enrolled in the PROMISE Trial.

IMPORTANCE: Race and ethnicity have been studied as risk factors in cardiovascular disease. How risk factors, epicardial coronary artery disease, and cardiac events differ between Black and White individuals undergoing noninvasive testing for coronary artery disease is not known. OBJECTIVE: To assess differences in cardiovascular risk burden, coronary plaque, and major adverse cardiac events between Black and White individuals assigned to receive coronary computed tomography angiography (CCTA) or functional testing for stable chest pain. DESIGN, SETTING, AND PARTICIPANTS: A nested observational cohort study within the PROMISE trial was conducted at 193 outpatient sites in North America. A total of 1071 non-Hispanic Black (hereafter Black) and 7693 non-Hispanic White (hereafter White) participants with stable chest pain undergoing noninvasive cardiovascular testing were included. This analysis was conducted from February 13, 2015, to November 2, 2021. MAIN OUTCOMES AND MEASURES: The primary end point was the composite of death, myocardial infarction, or hospitalization for unstable angina over a median follow-up of 24.4 months. RESULTS: Among 1071 Black individuals (12.2%) (women, 646 [60.3%]; mean [SD] age, 59 [8] years) and 7693 White individuals (87.8%) (women, 4029 [52.4%]; mean [SD] age, 61.1 [8.4] years), Black participants had a higher cardiovascular risk burden (more hypertension and diabetes), yet there was a similarly low major adverse cardiovascular events rate over a median 2-year follow-up (32 [3.0%] vs 243 [3.2%]; P = .84). Sensitivity analyses restricted to the 79.8% (6993 of 8764) individuals with a normal or mildly abnormal noninvasive testing result and the 54.3% (4559 of 8396) not receiving statin therapy yielded similar findings. In comparison of Black and White individuals in the CCTA group (n = 3323), significant coronary stenosis (hazard ratio [HR], 7.21; 95% CI, 1.94-26.76 vs HR, 4.30; 95% CI, 2.62-7.04) and high-risk plaque (HR, 3.47; 95% CI, 1.00-12.06 vs HR, 2.21; 95% CI, 1.37-3.57) were associated with major adverse cardiovascular events in both Black and White patients. However, with respect to epicardial coronary artery disease burden, Black individuals had a less-prevalent coronary artery calcium score greater than 0 (45.1% vs 63.2%; P < .001), coronary stenosis greater than or equal to 50% (32 [8.7%] vs 430 [14.6%]; P = .001), and high-risk plaque (139 [37.6%] vs 1547 [52.4%]; P < .001). CONCLUSIONS AND RELEVANCE: The findings of this study suggest that, despite a greater cardiovascular risk burden in Black persons, rates of coronary artery calcium, stenosis, and high-risk plaque observed via CCTA were lower in Black persons than White persons. This result suggests differences in cardiovascular risk burden and coronary plaque in Black and White individuals with stable chest pain.

Risk Stratification With the Use of Coronary Computed Tomographic Angiography in Patients With Nonobstructive Coronary Artery Disease.

OBJECTIVES: The purpose of this study was to develop a risk prediction model for patients with nonobstructive CAD. BACKGROUND: Among stable chest pain patients, most cardiovascular (CV) events occur in those with nonobstructive coronary artery disease (CAD). Thus, developing tailored risk prediction approaches in this group of patients, including CV risk factors and CAD characteristics, is needed. METHODS: In PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) computed tomographic angiography patients, a core laboratory assessed prevalence of CAD (nonobstructive 1% to 49% left main or 1% to 69% stenosis any coronary artery), degree of stenosis (minimal: 1% to 29%; mild: 30% to 49%; or moderate: 50% to 69%), high-risk plaque (HRP) features (positive remodeling, low-attenuation plaque, and napkin-ring sign), segment involvement score (SIS), and coronary artery calcium (CAC). The primary end point was an adjudicated composite of unstable angina pectoris, nonfatal myocardial infarction, and death. Cox regression analysis determined independent predictors in nonobstructive CAD. RESULTS: Of 2,890 patients (age 61.7 years, 46% women) with any CAD, 90.4% (n = 2,614) had nonobstructive CAD (mean age 61.6 yrs, 46% women, atherosclerotic cardiovascular disease [ASCVD] risk 16.2%). Composite events were independently predicted by ASCVD risk (hazard ratio [HR]: 1.03; p = 0.001), degree of stenosis (30% to 69%; HR: 1.91; p = 0.011), and presence of ≥2 HRP features (HR: 2.40; p = 0.008). Addition of ≥2 HRP features to: 1) ASCVD and CAC; 2) ASCVD and SIS; or 3) ASCVD and degree of stenosis resulted in a statistically significant improvement in model fit (p = 0.0036; p = 0.0176; and p = 0.0318; respectively). Patients with ASCVD ≥7.5%, any HRP, and mild/moderate stenosis had significantly higher event rates than those who did not meet those criteria (3.0% vs. 6.2%; p = 0.007). CONCLUSIONS: Advanced coronary plaque features have incremental value over total plaque burden for the discrimination of clinical events in low-risk stable chest pain patients with nonobstructive CAD. This may be a first step to improve prevention in this cohort with the highest absolute risk for CV events.

Association of Metabolic Phenotypes With Coronary Artery Disease and Cardiovascular Events in Patients With Stable Chest Pain.

OBJECTIVE: Obesity and metabolic syndrome are associated with major adverse cardiovascular events (MACE). However, whether distinct metabolic phenotypes differ in risk for coronary artery disease (CAD) and MACE is unknown. We sought to determine the association of distinct metabolic phenotypes with CAD and MACE. RESEARCH DESIGN AND METHODS: We included patients from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) who underwent coronary computed tomography (CT) angiography. Obesity was defined as a BMI ≥30 kg/m2 and metabolically healthy as less than or equal to one metabolic syndrome component except diabetes, distinguishing four metabolic phenotypes: metabolically healthy/unhealthy and nonobese/obese (MHN, MHO, MUN, and MUO). Differences in severe calcification (coronary artery calcification [CAC] ≥400), severe CAD (≥70% stenosis), high-risk plaque (HRP), and MACE were assessed using adjusted logistic and Cox regression models. RESULTS: Of 4,381 patients (48.4% male, 60.5 ± 8.1 years of age), 49.4% were metabolically healthy (30.7% MHN and 18.7% MHO) and 50.6% unhealthy (22.3% MUN and 28.4% MUO). MHO had similar coronary CT findings as compared with MHN (severe CAC/CAD and HRP; P > 0.36 for all). Among metabolically unhealthy patients, those with obesity had similar CT findings as compared with nonobese (P > 0.10 for all). However, both MUN and MUO had unfavorable CAD characteristics as compared with MHN (P ≤ 0.017 for all). A total of 130 events occurred during follow-up (median 26 months). Compared with MHN, MUN (hazard ratio [HR] 1.61 [95% CI 1.02-2.53]) but not MHO (HR 1.06 [0.62-1.82]) or MUO (HR 1.06 [0.66-1.72]) had higher risk for MACE. CONCLUSIONS: In patients with stable chest pain, four metabolic phenotypes exhibit distinctly different CAD characteristics and risk for MACE. Individuals who are metabolically unhealthy despite not being obese were at highest risk in our cohort.

Small whole heart volume predicts cardiovascular events in patients with stable chest pain: insights from the PROMISE trial.

OBJECTIVES: The size of the heart may predict major cardiovascular events (MACE) in patients with stable chest pain. We aimed to evaluate the prognostic value of 3D whole heart volume (WHV) derived from non-contrast cardiac computed tomography (CT). METHODS: Among participants randomized to the CT arm of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE), we used deep learning to extract WHV, defined as the volume of the pericardial sac. We compared the WHV across categories of cardiovascular risk factors and coronary artery disease (CAD) characteristics and determined the association of WHV with MACE (all-cause death, myocardial infarction, unstable angina; median follow-up: 26 months). RESULTS: In the 3798 included patients (60.5 ± 8.2 years; 51.5% women), the WHV was 351.9 ± 57.6 cm3/m2. We found smaller WHV in no- or non-obstructive CAD, women, people with diabetes, sedentary lifestyle, and metabolic syndrome. Larger WHV was found in obstructive CAD, men, and increased atherosclerosis cardiovascular disease (ASCVD) risk score (p < 0.05). In a time-to-event analysis, small WHV was associated with over 4.4-fold risk of MACE (HR (per one standard deviation) = 0.221; 95% CI: 0.068-0.721; p = 0.012) independent of ASCVD risk score and CT-derived CAD characteristics. In patients with non-obstructive CAD, but not in those with no- or obstructive CAD, WHV increased the discriminatory capacity of ASCVD and CT-derived CAD characteristics significantly. CONCLUSIONS: Small WHV may represent a novel imaging marker of MACE in stable chest pain. In particular, WHV may improve risk stratification in patients with non-obstructive CAD, a cohort with an unmet need for better risk stratification. KEY POINTS: • Heart volume is easily assessable from non-contrast cardiac computed tomography. • Small heart volume may be an imaging marker of major adverse cardiac events independent and incremental to traditional cardiovascular risk factors and established CT measures of CAD. • Heart volume may improve cardiovascular risk stratification in patients with non-obstructive CAD.

Association of Hepatic Steatosis With Major Adverse Cardiovascular Events, Independent of Coronary Artery Disease.

BACKGROUND & AIMS: Hepatic steatosis has been associated with increased risk of major adverse cardiovascular events (MACE) but it is not clear whether steatosis is independently associated with risk of MACE. We investigated whether steatosis is associated with risk of MACE independently of the presence and extent of baseline coronary artery disease, assessed by comprehensive contrast-enhanced computed tomography angiography (CTA). METHODS: We conducted a nested cohort study of 3756 subjects (mean age, 60.6 years; 48.4% men) who underwent coronary CTA at 193 sites in North America, from July 2010 through September 2013, as part of the PROMISE study, which included noninvasive cardiovascular analyses of symptomatic outpatients without coronary artery disease. Independent core laboratory readers measured hepatic and splenic attenuation, using non-contrast computed tomography images to identify steatosis, and evaluated coronary plaques and stenosis in coronary CTA images. We collected data on participants' cardiovascular risk factors, presence of metabolic syndrome, and body mass index. The primary endpoint was an adjudicated composite of MACE (death, myocardial infarction, or unstable angina) during a median follow-up time of 25 months. RESULTS: Among the 959 subjects who had steatosis (25.5% of the cohort), 42 had MACE (4.4%), whereas among the 2797 subjects without steatosis, 73 had MACE (2.6%) (hazard ratio [HR] for MACE in subjects with steatosis, 1.69; 95% CI, 1.16-2.48; P = .006 for MACE in subjects with vs without steatosis). This association remained after adjustment for atherosclerotic cardiovascular disease risk scores, significant stenosis, and metabolic syndrome (adjusted HR, 1.72; 95% CI, 1.16-2.54; P = .007) or obesity (adjusted HR, 1.75; 95% CI, 1.19-2.59; P = .005). Steatosis remained independently associated with MACE after adjustment for all CTA measures of plaques and stenosis. CONCLUSIONS: Hepatic steatosis is associated with MACE independently of other cardiovascular risk factors or extent of coronary artery disease. Strategies to reduce steatosis might reduce risk of MACE. ClinicalTrials.gov no: NCT01174550.

Coronary artery bypass grafting and perioperative stroke: imaging of atherosclerotic plaques in the ascending aorta with ungated high-pitch CT-angiography.

Perioperative stroke is a devastating complication after coronary artery bypass graft (CABG) surgery, with atherosclerosis of the ascending aorta as important risk factor. During surgical manipulation, detachment of plaques can lead to consecutive embolization into brain-supplying arteries. High-pitch computed tomography angiography (HP-CTA) represents a non-invasive imaging modality, which provides the opportunity for comprehensive imaging of the ascending aorta, including plaque detection and advanced characterization. In our present retrospective study on 719 individuals, who had undergone HP-CTA within 6 months prior to CABG, atherosclerotic disease of the ascending aorta was evaluated with respect to perioperative stroke rates. For image analysis, the ascending aorta was divided into a proximal and distal part, consisting of four segments, and evaluated for presence and distribution of calcified and mixed plaques. All patients with perioperative stroke presented with atherosclerotic disease of the ascending aorta. The stroke rate was significantly associated with the presence and extent of atherosclerotic disease. Patients burdened with mixed plaques presented with significantly higher perioperative stroke rates. This study demonstrates that HP-CTA allows accurate evaluation of plaque extent and composition in the ascending aorta, and therefore may improve risk stratification of stroke prior to CABG.

Safety and efficiency of low-field magnetic resonance imaging in patients with cardiac rhythm management devices.

PURPOSE: Low-field magnetic resonance imaging (MRI), i.e. MRI with a static magnetic field strength <0.5 T, has been reported to be safe in patients with pacemakers, however there are no data about the safety of low-field MRI in patients with implantable cardioverter defibrillators (ICD) and/or cardiac resynchronization therapy (CRT). We aimed to investigate the safety and diagnostic efficiency of routine low-field MRI in patients with different devices for cardiac rhythm management (i.e. pacemakers and ICD, including devices with CRT). METHOD: MRI scans of 446 regions of interest were evaluated with field strength of 0.2 T in 338 patients (62% male; age at MRI scan 76.1 ± 9.2 years; time since device implantation 4.1 ± 3.2 years) with cardiac rhythm management devices (298 pacemakers, 25 ICD, 8 CRT-ICD, and 7 CRT pacemakers). This analysis included 62 pacemaker-dependent patients (18.3%), 52 patients with 1.5-Tesla-MR conditional pacemakers (15.4%) and 13 patients with abandoned leads (3.9%). RESULTS: Except for one examination, which was interrupted because of recurrent severe nausea, all MRI scans could be analyzed efficiently. No induction of arrhythmia or inhibition of pacemaker function occurred. Compared to the device interrogation before MRI, there were no significant changes in battery voltage, pacing capture threshold, sensing of intrinsic ECG, lead impedance, as well as shock impedance in ICD devices after completed examination. CONCLUSIONS: Low-field MRI examinations (0.2 T) were efficient and safe regarding clinical and technical complications in patients with devices for cardiac rhythm management, even in case of pacemaker-dependency or the presence of abandoned leads.

Non-invasive fractional flow reserve derived from coronary computed tomography angiography in patients with acute chest pain: Subgroup analysis of the ROMICAT II trial.

BACKGROUND: Non-invasive fractional flow reserve (FFRCT) derived from coronary computed tomography angiography (CTA) permits hemodynamic evaluation of coronary stenosis and may improve efficiency of assessment in stable chest pain patients. We determined feasibility of FFRCT in the population of acute chest pain patients and assessed the relationship of FFRCT with outcomes of acute coronary syndrome (ACS) and revascularization and with plaque characteristics. METHODS: We included 68 patients (mean age 55.8 ±â€¯8.4 years, 71% men) from the ROMICAT II trial who had ≥50% stenosis on coronary CTA or underwent additional non-invasive stress test. We evaluated coronary stenosis and high-risk plaque on coronary CTA. FFRCT was measured in a core laboratory. RESULTS: We found correlation between anatomic severity of stenosis and FFRCT ≤0.80 vs. FFRCT >0.80 (severe stenosis 84.8% vs. 15.2%; moderate stenosis 33.3% vs. 66.7%; mild stenosis 33.3% vs. 66.7% patients). Patients with severe stenosis had lower FFRCT values (median 0.64, 25th-75th percentile 0.50-0.75) as compared to patients with moderate (median 0.84, 25th-75th percentile, p < 0.001) or mild stenosis (median 0.86, 25th-75th percentile 0.78-0.88, p < 0.001). The relative risk of ACS and revascularization in patients with positive FFRCT ≤0.80 was 4.03 (95% CI 1.56-10.36) and 3.50 (95% CI 1.12-10.96), respectively. FFRCT ≤0.80 was associated with the presence of high-risk plaque (odds ratio 3.91, 95% CI 1.55-9.85, p = 0.004) after adjustment for stenosis severity. CONCLUSION: Abnormal FFRCT was associated with the presence of ACS, coronary revascularization, and high-risk plaque. FFRCT measurements correlated with anatomic severity of stenosis on coronary CTA and were feasible in population of patients with acute chest pain.

Coronary Computed Tomography Angiography-Specific Definitions of High-Risk Plaque Features Improve Detection of Acute Coronary Syndrome.

Background High-risk plaque (HRP) features as detected by coronary computed tomography angiography (CTA) predict acute coronary syndrome (ACS). We sought to determine whether coronary CTA-specific definitions of HRP improve discrimination of patients with ACS as compared with definitions from intravascular ultrasound (IVUS). Methods and Results In patients with suspected ACS, randomized to coronary CTA in the ROMICAT II (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography II) trial, we retrospectively performed semiautomated quantitative analysis of HRP (including remodeling index, plaque burden as derived by plaque area, low computed tomography attenuation plaque volume) and degree of luminal stenosis and analyzed the performance of traditional IVUS thresholds to detect ACS. Furthermore, we derived CTA-specific thresholds in patients with ACS to detect culprit lesions and applied those to all patients to calculate the discriminatory ability to detect ACS in comparison to IVUS thresholds. Of 472 patients, 255 patients (56±7.8 years; 63% men) had coronary plaque. In 32 patients (6.8%) with ACS, culprit plaques (n=35) differed from nonculprit plaques (n=172) with significantly greater values for all HRP features except minimal luminal area (significantly lower; all P<0.01). IVUS definitions showed good performance while minimal luminal area (odds ratio: 6.82; P=0.014) and plaque burden (odds ratio: 5.71; P=0.008) were independently associated with ACS but not remodeling index (odds ratio: 0.78; P=0.673). Optimized CTA-specific thresholds for plaque burden (area under the curve: 0.832 versus 0.676) and degree of stenosis (area under the curve: 0.826 versus 0.721) showed significantly higher diagnostic performance for ACS as compared with IVUS-based thresholds (all P<0.05) with borderline significance for minimal luminal area (area under the curve: 0.817 versus 0.742; P=0.066). Conclusions CTA-specific definitions of HRP features may improve the discrimination of patients with ACS as compared with IVUS-based definitions. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov . Unique identifier: NCT01084239.

Differences in the association of total versus local coronary artery calcium with acute coronary syndrome and culprit lesions in patients with acute chest pain: The coronary calcium paradox.

BACKGROUND AND AIMS: Total coronary artery calcium (CAC) burden is associated with an increased cardiovascular risk, while local CAC may represent stable plaques. We determined differences in relationship of total CAC with acute coronary syndrome (ACS) and local CAC with culprit lesions in patients with suspected ACS. METHODS: We performed computed tomography (CT) for CAC and CT angiography to assess the presence of significant stenosis and high-risk plaque (positive remodeling, low CT attenuation, napkin-ring sign, spotty calcium) in 37 patients with ACS and 223 controls. Total and segmental Agatston scores were measured. Culprit lesions were assessed in subjects with ACS. RESULTS: Patients (n = 260) with vs. without ACS had higher total CAC score (median 229, 25th-75th percentile 75-517 vs. 27, 25th-75th percentile 0-99, p<0.001), higher prevalence of significant stenosis (78% vs. 7%, p<0.001) and high-risk plaque (95% vs. 59%, p<0.001). In those with ACS, culprit (n = 41) vs. non-culprit (n = 200) lesions, had similar segmental CAC score (median 22, 25th-75th percentile 4-71 vs. 14, 25th-75th percentile 0-51; p=0.37), but higher prevalence of significant stenosis (81% vs. 11%, p<0.001) and high-risk plaque (76% vs. 51%, p=0.005). Significant stenosis (odds ratio 40.2, 95%CI 15.6-103.9, p<0.001) and high-risk plaque (odds ratio 3.4, 95%CI 1.3-9.1, p=0.02), but not segmental CAC score (odds ratio 1.0, 95%CI 1.0-1.0, p=0.47), were associated with culprit lesions of ACS. CONCLUSIONS: Total CAC burden was associated with ACS but segmental CAC was not associated with culprit lesions. Our findings suggest that total but not local CAC is a marker of ACS risk and support the hypothesis that extensive local CAC is a marker of plaque stability.

Obesity promotes resistance to anti-VEGF therapy in breast cancer by up-regulating IL-6 and potentially FGF-2.

Anti-vascular endothelial growth factor (VEGF) therapy has failed to improve survival in patients with breast cancer (BC). Potential mechanisms of resistance to anti-VEGF therapy include the up-regulation of alternative angiogenic and proinflammatory factors. Obesity is associated with hypoxic adipose tissues, including those in the breast, resulting in increased production of some of the aforementioned factors. Hence, we hypothesized that obesity could contribute to anti-VEGF therapy's lack of efficacy. We found that BC patients with obesity harbored increased systemic concentrations of interleukin-6 (IL-6) and/or fibroblast growth factor 2 (FGF-2), and their tumor vasculature was less sensitive to anti-VEGF treatment. Mouse models revealed that obesity impairs the effects of anti-VEGF on angiogenesis, tumor growth, and metastasis. In one murine BC model, obesity was associated with increased IL-6 production from adipocytes and myeloid cells within tumors. IL-6 blockade abrogated the obesity-induced resistance to anti-VEGF therapy in primary and metastatic sites by directly affecting tumor cell proliferation, normalizing tumor vasculature, alleviating hypoxia, and reducing immunosuppression. Similarly, in a second mouse model, where obesity was associated with increased FGF-2, normalization of FGF-2 expression by metformin or specific FGF receptor inhibition decreased vessel density and restored tumor sensitivity to anti-VEGF therapy in obese mice. Collectively, our data indicate that obesity fuels BC resistance to anti-VEGF therapy via the production of inflammatory and angiogenic factors.

Use of High-Risk Coronary Atherosclerotic Plaque Detection for Risk Stratification of Patients With Stable Chest Pain: A Secondary Analysis of the PROMISE Randomized Clinical Trial.

Importance: Coronary computed tomographic angiography (coronary CTA) can characterize coronary artery disease, including high-risk plaque. A noninvasive method of identifying high-risk plaque before major adverse cardiovascular events (MACE) could provide practice-changing optimizations in coronary artery disease care. Objective: To determine whether high-risk plaque detected by coronary CTA was associated with incident MACE independently of significant stenosis (SS) and cardiovascular risk factors. Design, Setting, and Participants: This prespecified nested observational cohort study was part of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial. All stable, symptomatic outpatients in this trial who required noninvasive cardiovascular testing and received coronary CTA were included and followed up for a median of 25 months. Exposures: Core laboratory assessment of coronary CTA for SS and high-risk plaque (eg, positive remodeling, low computed tomographic attenuation, or napkin-ring sign). Main Outcomes and Measures: The primary end point was an adjudicated composite of MACE (defined as death, myocardial infarction, or unstable angina). Results: The study included 4415 patients, of whom 2296 (52%) were women, with a mean age of 60.5 years, a median atherosclerotic cardiovascular disease (ASCVD) risk score of 11, and a MACE rate of 3% (131 events). A total of 676 patients (15.3%) had high-risk plaques, and 276 (6.3%) had SS. The presence of high-risk plaque was associated with a higher MACE rate (6.4% vs 2.4%; hazard ratio, 2.73; 95% CI, 1.89-3.93). This association persisted after adjustment for ASCVD risk score and SS (adjusted hazard ratio [aHR], 1.72; 95% CI, 1.13-2.62). Adding high-risk plaque to the ASCVD risk score and SS assessment led to a significant continuous net reclassification improvement (0.34; 95% CI, 0.02-0.51). Presence of high-risk plaque increased MACE risk among patients with nonobstructive coronary artery disease relative to patients without high-risk plaque (aHR, 4.31 vs 2.64; 95% CI, 2.25-8.26 vs 1.49-4.69). There were no significant differences in MACE in patients with SS and high-risk plaque as opposed to those with SS but not high-risk plaque (aHR, 8.68 vs. 9.31; 95% CI, 4.25-17.73 vs 4.21-20.61). High-risk plaque was a stronger predictor of MACE in women (aHR, 2.41; 95% CI, 1.25-4.64) vs men (aHR, 1.40; 95% CI, 0.81-2.39) and younger patients (aHR, 2.33; 95% CI, 1.20-4.51) vs older ones (aHR, 1.36; 95% CI, 0.77-2.39). Conclusions and Relevance: High-risk plaque found by coronary CTA was associated with a future MACE in a large US population of outpatients with stable chest pain. High-risk plaque may be an additional risk stratification tool, especially in patients with nonobstructive coronary artery disease, younger patients, and women. The importance of findings is limited by low absolute MACE rates and low positive predictive value of high-risk plaque. Trial Registration: clinicaltrials.gov Indentifier: NCT01174550.

Quantitative coronary plaque analysis predicts high-risk plaque morphology on coronary computed tomography angiography: results from the ROMICAT II trial.

Semi-automated software can provide quantitative assessment of atherosclerotic plaques on coronary CT angiography (CTA). The relationship between established qualitative high-risk plaque features and quantitative plaque measurements has not been studied. We analyzed the association between quantitative plaque measurements and qualitative high-risk plaque features on coronary CTA. We included 260 patients with plaque who underwent coronary CTA in the Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography (ROMICAT) II trial. Quantitative plaque assessment and qualitative plaque characterization were performed on a per coronary segment basis. Quantitative coronary plaque measurements included plaque volume, plaque burden, remodeling index, and diameter stenosis. In qualitative analysis, high-risk plaque was present if positive remodeling, low CT attenuation plaque, napkin-ring sign or spotty calcium were detected. Univariable and multivariable logistic regression analyses were performed to assess the association between quantitative and qualitative high-risk plaque assessment. Among 888 segments with coronary plaque, high-risk plaque was present in 391 (44.0%) segments by qualitative analysis. In quantitative analysis, segments with high-risk plaque had higher total plaque volume, low CT attenuation plaque volume, plaque burden and remodeling index. Quantitatively assessed low CT attenuation plaque volume (odds ratio 1.12 per 1 mm3, 95% CI 1.04-1.21), positive remodeling (odds ratio 1.25 per 0.1, 95% CI 1.10-1.41) and plaque burden (odds ratio 1.53 per 0.1, 95% CI 1.08-2.16) were associated with high-risk plaque. Quantitative coronary plaque characteristics (low CT attenuation plaque volume, positive remodeling and plaque burden) measured by semi-automated software correlated with qualitative assessment of high-risk plaque features.