Quantification of Myocardial Blood Flow in Absolute Terms Using 82Rb PET Imaging: The RUBY-10 Study

ObjectivesThe purpose of this study was to compare myocardial blood flow (MBF) and myocardial flow reserve (MFR) estimates from rubidium-82 positron emission tomography (⁸²Rb PET) data using 10 software packages (SPs) based on 8 tracer kinetic models.BackgroundIt is unknown how MBF and MFR values from existing SPs agree for ⁸²Rb PET.MethodsRest and stress ⁸²Rb PET scans of 48 patients with suspected or known coronary artery disease were analyzed in 10 centers. Each center used 1 of 10 SPs to analyze global and regional MBF using the different kinetic models implemented. Values were considered to agree if they simultaneously had an intraclass correlation coefficient >0.75 and a difference <20% of the median across all programs.ResultsThe most common model evaluated was the Ottawa Heart Institute 1-tissue compartment model (OHI-1-TCM). MBF values from 7 of 8 SPs implementing this model agreed best. Values from 2 other models (alternative 1-TCM and Axially distributed) also agreed well, with occasional differences. The MBF results from other models (e.g., 2-TCM and retention) were less in agreement with values from OHI-1-TCM.ConclusionsSPs using the most common kinetic model—OHI-1-TCM—provided consistent results in measuring global and regional MBF values, suggesting that they may be used interchangeably to process data acquired with a common imaging protocol.     

Intravascular Ultrasound-Derived Minimal Lumen Area Criteria for Functionally Significant Left Main Coronary Artery Stenosis

ObjectivesThis study sought to evaluate the intravascular ultrasound (IVUS) minimal lumen area (MLA) for functionally significant left main coronary artery (LMCA) stenosis using fractional flow reserve (FFR) as the standard.BackgroundThe evaluation of significant LMCA stenosis remains challenging.MethodsWe identified 112 patients with isolated ostial and shaft intermediate LMCA stenosis (angiographic diameter stenosis of 30% to 80%) who underwent IVUS and FFR measurement.ResultsThe FFR was ≤0.80 in 66 LMCA lesions (59%); these exhibited smaller reference vessels, smaller minimal lumen diameter, greater diameter of stenosis, longer lesion length, smaller MLA, larger plaque burden, and more frequent plaque rupture. The independent factors of an FFR of ≤0.80 were plaque rupture (odds ratio [OR]: 4.47; 95% Confidence Interval (CI): 1.35 to 14.8; p = 0.014); body mass index (OR: 1.19; 95% CI: 1.00 to 1.41; p = 0.05), age (OR: 0.95; 95% CI: 0.90 to 1.00; p = 0.031), and IVUS MLA (OR: 0.37; 95% CI: 0.25 to 0.56; p < 0.001). The optimal IVUS MLA cutoff value for an FFR of ≤0.80 was 4.5 mm² (77% sensitivity, 82% specificity, 84% positive predictive value, 75% negative predictive value, area under the curve: 0.83, 95% CI: 0.76 to 0.96; p < 0.001) overall and 4.1 to 4.5 mm² in various subgroups. Adjustment for the body surface area, body mass index, and left ventricular mass did not improve the diagnostic accuracy of the IVUS MLA.ConclusionsIn patients with isolated ostial and shaft intermediate LMCA stenosis, an IVUS-derived MLA of ≤4.5 mm² is a useful index of an FFR of ≤0.80.     

The 24-Month Prognosis of Patients With Positive or Intermediate Results in the Intracoronary Ergonovine Provocation Test

ObjectivesThis study was an observational, multicenter registry to determine clinical characteristics and 24-month prognosis of patients who underwent intracoronary ergonovine provocation tests.BackgroundThe clinical characteristics and prognosis of patients who underwent the ergonovine provocation for vasospastic angina were not fully elucidated.MethodsA total of 2,129 patients in the VA-KOREA (Vasospastic Angina in Korea) registry were classified into positive (n = 454), intermediate (n = 982), and negative (n = 693) groups by intracoronary ergonovine provocation tests. The 24-month incidences of cardiac death, new-onset arrhythmia, and acute coronary syndrome were determined (mean 26.7 ± 8.8 months).ResultsThe number of smokers, frequency of angina before angiography, high-sensitivity C-reactive protein, and triglyceride were higher in the positive group than in other groups. The clinical characteristics of the intermediate and the negative groups were very similar. In the positive group, the incidences of diffuse, focal, and mixed spasm were 65.9%, 23.6%, and 10.6%. Coronary spasm was more frequently provoked on atherosclerotic segments. The 24-month incidences of cardiac death, arrhythmia, and acute coronary syndrome were low (0.9%, 1.6%, and 1.9%, respectively) in the positive group, and there was no cardiac death in the intermediate group (p = 0.02). In the positive group, frequent angina, current smoking, and multivessel spasm were independent predictors for adverse events.ConclusionsThe 24-month prognosis of the positive group in the intracoronary ergonovine provocation test was relatively worse than that of the intermediate group. More intensive clinical attention should be paid to vasospastic angina patients with high-risk factors including frequent angina before angiography, current smoking, and multivessel spasm.     

Coronary Vessel Wall Contrast Enhancement Imaging as a Potential Direct Marker of Coronary Involvement: Integration of Findings From CAD and SLE Patients

ObjectivesThis study investigated the feasibility of visual and quantitative assessment of coronary vessel wall contrast enhancement (CE) for detection of symptomatic atherosclerotic coronary artery disease (CAD) and subclinical coronary vasculitis in autoimmune inflammatory disease (systemic lupus erythematosus [SLE]), as well as the association with aortic stiffness, an established marker of risk.BackgroundCoronary CE by cardiac magnetic resonance (CMR) is a novel noninvasive approach to visualize gadolinium contrast uptake within the coronary artery vessel wall.MethodsA total of 75 subjects (CAD: n = 25; SLE: n = 27; control: n = 23) underwent CMR imaging using a 3-T clinical scanner. Coronary arteries were visualized by a T2-prepared steady state free precession technique. Coronary wall CE was visualized using inversion-recovery T1 weighted gradient echo sequence 40 min after administration of 0.2 mmol/kg gadobutrol. Proximal coronary segments were visually examined for distribution of CE and quantified for contrast-to-noise ratio (CNR) and total CE area.ResultsCoronary CE was prevalent in patients (93%, n = 42) with a diffuse pattern for SLE and a patchy/regional distribution in CAD patients. Compared with control subjects, CNR values and total CE area in patients with CAD and SLE were significantly higher (mean CNR: 3.9 ± 2.5 vs. 6.9 ± 2.5 vs. 6.8 ± 2.0, respectively; p < 0.001; total CE area: median 0.8 [interquartile range (IQR): 0.6 to 1.2] vs. 3.2 [IQR: 2.6 to 4.0] vs. 3.3 [IQR: 1.9 to 4.5], respectively; p < 0.001). Both measures were positively associated with aortic stiffness (CNR: r = 0.61, p < 0.01; total CE area: 0.36, p = 0.03), hypercholesterolemia (r = 0.68, p < 0.001; r = 0.61, p < 0.001) and hypertension (r = 0.40, p < 0.01; r = 0.32, p < 0.05).ConclusionsWe demonstrate that quantification of coronary CE by CNR and total CE area is feasible for detection of subclinical and clinical uptake of gadolinium within the coronary vessel wall. Coronary vessel wall CE may become an instrumental novel direct marker of vessel wall injury and remodeling in subpopulations at risk.     

Validation and Comparison of the Long-Term Prognostic Capability of the SYNTAX Score-II Among 1,528 Consecutive Patients Who Underwent Left Main Percutaneous Coronary Intervention

ObjectivesThis study sought to evaluate the long-term prognostic capacity of the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score II (SS-II) and compare it with other risk scores among patients undergoing left main percutaneous coronary intervention (LM-PCI).BackgroundRecently, the SS-II was developed in an attempt to individualize and help the decision-making process between PCI and coronary artery bypass graft (CABG) surgery in the management of complex coronary artery disease (CAD). However, there is a paucity of data regarding the utility of SS-II in patients undergoing LM-PCI.MethodsData from 1,528 consecutive patients from a single center undergoing unprotected LM-PCI were prospectively collected. The SS-II and other scores were then derived using patients’ baseline clinical characteristics. Patients were stratified according to tertiles of SS-II for PCI: SS-II ≤21 (n = 508), SS-II >21 and ≤28 (n = 480), and >28 (n = 540). Predictive capability for long-term mortality was compared between angiographic scores and scores combining both angiographic and clinical variables.ResultsAt a mean follow-up of 4.4 years, mortality in the first, second, and third SS-II tertiles was 1.8%, 3.5%, and 9.4%, respectively (p < 0.0001). Multivariate analysis showed SS-II to be a strong independent predictor of mortality (hazard ratio: 1.76, 95% confidence interval: 1.10 to 2.82; p = 0.02) after LM-PCI. When compared with the angiographic SS, scores combining both clinical and angiographic variables, such as the SS-II, were superior in terms of long-term prognostication.ConclusionsResults of this large series of consecutive patients who underwent unprotected LM-PCI suggested that the SS-II has better long-term prognostic power in terms of mortality compared with the original purely angiographic SS.     

Diagnostic Accuracy of Myocardial Magnetic Resonance Perfusion to Diagnose Ischemic Stenosis With Fractional Flow Reserve as Reference: Systematic Review and Meta-Analysis

ObjectivesThis paper systematically analyzed the performance of magnetic resonance (MR) perfusion to diagnose coronary artery disease (CAD) with fractional flow reserve (FFR) as the reference standard.BackgroundMyocardial MR perfusion has passed the stage of a research technique and has demonstrated the ability to detect functional or ischemic stenosis of coronary arteries. However, the evidence is limited to single-center studies and small sample sizes.MethodsWe searched PubMed and Embase databases for all published studies that evaluated the accuracy of MR perfusion to diagnose CAD versus FFR. We used an exact binomial rendition of the bivariate mixed-effects regression model with test type as a random-effects covariate to synthesize the available data. Based on Bayes’ theorem, the post-test probability was calculated to guide MR perfusion’s clinical utility.ResultsWe identified 14 studies evaluating 1,073 arteries and 650 patients. The pooled sensitivity and specificity were 0.90 (95% confidence interval [CI]: 0.86 to 0.93) and 0.87 (95% CI: 0.82 to 0.90) at the patient level and 0.89 (95% CI: 0.83 to 0.92) and 0.86 (95% CI: 0.77 to 0.92) at the artery and territory levels, respectively. The area under the summary receiver-operating characteristic at the patient level was 0.95 (95% CI: 0.92 to 0.96) and 0.93 (95% CI: 0.91 to 0.95) at the artery and territory levels, respectively. MR perfusion could increase the post-test probability of CAD >80% in patients with a pre-test probability of >37% and can decrease post-test probability of CAD <20% with a pre-test probability of <72%.ConclusionsWith FFR as the reference standard, the diagnostic ability of MR perfusion to detect ischemic CAD is high.     

Prevalence of Coronary Microvascular Dysfunction Among Patients With Chest Pain and Nonobstructive Coronary Artery Disease

ObjectivesThis study assessed the prevalence of coronary microvascular abnormalities in patients presenting with chest pain and nonobstructive coronary artery disease (CAD).BackgroundCoronary microvascular abnormalities mediate ischemia and can lead to an increased risk of cardiovascular events.MethodsUsing an intracoronary Doppler guidewire, endothelial-dependent microvascular function was examined by evaluating changes in coronary blood flow in response to acetylcholine, whereas endothelial-independent microvascular function was examined by evaluating changes in coronary flow velocity reserve in response to intracoronary adenosine. Patients were divided into 4 groups depending on whether they had a normal (+) or abnormal (−) coronary blood flow (CBF) in response to acetylcholine (Ach) and a normal (+) or abnormal (−) coronary flow velocity reserve (CFR) in response to adenosine (Adn): CBFAch+, CFRAdn+ (n = 520); CBFAch−, CFRAdn+ (n = 478); CBFAch+, CFRAdn− (n = 173); and CBFAch−, CFRAdn− (n = 268).ResultsTwo-thirds of all patients had some sort of microvascular dysfunction. Women were more prevalent in each group (56% to 82%). Diabetes was uncommon in all groups (7% to 12%), whereas hypertension and hyperlipidemia were relatively more prevalent in each group, although rates for most conventional cardiovascular risk factors did not differ significantly between groups. There were no significant differences in the findings of noninvasive functional testing between groups. In a multivariable analysis, age was the only variable that independently predicted abnormal microvascular function.ConclusionsPatients with chest pain and nonobstructive CAD have a high prevalence of coronary microvascular abnormalities. These abnormalities correlate poorly with conventional cardiovascular risk factors and are dissociated from the findings of noninvasive functional testing.     

Myeloperoxidase levels predict accelerated progression of coronary atherosclerosis in diabetic patients: Insights from intravascular ultrasound

ObjectiveWhile inflammation has been proposed to contribute to the adverse cardiovascular outcome in diabetic patients, the specific pathways involved have not been elucidated. The leukocyte derived product, myeloperoxidase (MPO), has been implicated in all stages of atherosclerosis. The relationship between MPO and accelerated disease progression observed in diabetic patients has not been studied.MethodsWe investigated the relationship between MPO and disease progression in diabetic patients. 881 patients with angiographic coronary artery disease underwent serial evaluation of atherosclerotic burden with intravascular ultrasound. Disease progression in diabetic (n = 199) and non-diabetic (n = 682) patients, stratified by baseline MPO levels was investigated.ResultsMPO levels were similar in patients with and without diabetes (1362 vs. 1255 pmol/L, p = 0.43). No relationship was observed between increasing quartiles of MPO and either baseline (p = 0.81) or serial changes (p = 0.43) in levels of percent atheroma volume (PAV) in non-diabetic patients. In contrast, increasing MPO quartiles were associated with accelerated PAV progression in diabetic patients (p = 0.03). While optimal control of lipid and the use of high-dose statin were associated with less disease progression, a greater benefit was observed in diabetic patients with lower compared with higher MPO levels at baseline.ConclusionsIncreasing MPO levels are associated with greater progression of atherosclerosis in diabetic patients. This finding indicates the potential importance of MPO pathways in diabetic cardiovascular disease.     

A Registry-Based Randomized Trial Comparing Radial and Femoral Approaches in Women Undergoing Percutaneous Coronary Intervention: The SAFE-PCI for Women (Study of Access Site for Enhancement of PCI for Women) Trial

ObjectivesThis study sought to determine the effect of radial access on outcomes in women undergoing percutaneous coronary intervention (PCI) using a registry-based randomized trial.BackgroundWomen are at increased risk of bleeding and vascular complications after PCI. The role of radial access in women is unclear.MethodsWomen undergoing cardiac catheterization or PCI were randomized to radial or femoral arterial access. Data from the CathPCI Registry and trial-specific data were merged into a final study database. The primary efficacy endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding or vascular complications requiring intervention. The primary feasibility endpoint was access site crossover. The primary analysis cohort was the subgroup undergoing PCI; sensitivity analyses were conducted in the total randomized population.ResultsThe trial was stopped early for a lower than expected event rate. A total of 1,787 women (691 undergoing PCI) were randomized at 60 sites. There was no significant difference in the primary efficacy endpoint between radial or femoral access among women undergoing PCI (radial 1.2% vs. 2.9% femoral, odds ratio [OR]: 0.39; 95% confidence interval [CI]: 0.12 to 1.27); among women undergoing cardiac catheterization or PCI, radial access significantly reduced bleeding and vascular complications (0.6% vs. 1.7%; OR: 0.32; 95% CI: 0.12 to 0.90). Access site crossover was significantly higher among women assigned to radial access (PCI cohort: 6.1% vs. 1.7%; OR: 3.65; 95% CI: 1.45 to 9.17); total randomized cohort: (6.7% vs. 1.9%; OR: 3.70; 95% CI: 2.14 to 6.40). More women preferred radial access.ConclusionsIn this pragmatic trial, which was terminated early, the radial approach did not significantly reduce bleeding or vascular complications in women undergoing PCI. Access site crossover occurred more often in women assigned to radial access. (SAFE-PCI for Women; NCT01406236)     

Outcomes After Percutaneous Coronary Intervention With Stents in Patients Treated With Thoracic External Beam Radiation for Cancer

ObjectivesThe aim of this study was to assess outcomes after percutaneous coronary intervention (PCI) with stents in patients treated with thoracic external beam radiation therapy (EBRT).BackgroundThoracic EBRT for cancer is associated with long-term cardiotoxic sequelae. The impact of EBRT on patients requiring coronary stents is unclear.MethodsWe analyzed outcomes after PCI in cancer survivors treated with curative thoracic EBRT before and after stenting between 1998 and 2012. Reference groups were propensity-matched cohorts with stenting but no EBRT. Primary endpoint was target lesion revascularization (TLR), a clinical surrogate for restenosis. Secondary endpoints included myocardial infarction (MI) and cardiac and overall mortality.ResultsWe identified 115 patients treated with EBRT a median 3.6 years after stenting (group A) and 45 patients treated with EBRT a median 2.2 years before stenting (group B). Long-term mean TLR rates in group A (3.2 vs. 6.6%; hazard ratio: 0.6; 95% confidence interval: 0.2 to 1.6; p = 0.31) and group B (9.2 vs. 9.7%; hazard ratio: 1.2; 95% confidence interval: 0.4 to 3.4; p = 0.79) were similar to rates in corresponding control patients (group A: 1,390 control patients; group B: 439 control patients). Three years post-PCI, group A had higher overall mortality (48.6% vs. 13.9%; p < 0.001) but not MI (4.8% vs. 4.3%; p = 0.93) or cardiac mortality (2.3% vs. 3.6%; p = 0.66) rates versus control patients. There were no significant differences in MI, cardiac, or overall mortality rates in group B.ConclusionsThoracic EBRT is not associated with increased stent failure rates when used before or after PCI. A history of PCI should not preclude the use of curative thoracic EBRT in cancer patients or vice versa. Optimal treatment of cancer should be the goal.