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.     

Hybrid Revascularization for Multivessel Coronary Artery Disease

ObjectivesThe aim of this study was to assess the feasibility of hybrid coronary revascularization (HCR) in patients with multivessel coronary artery disease (MVCAD) referred for standard coronary artery bypass grafting (CABG).BackgroundConventional CABG is still the treatment of choice in patients with MVCAD. However, the limitations of standard CABG and the unsatisfactory long-term patency of saphenous grafts are commonly known.MethodsA total of 200 patients with MVCAD involving the left anterior descending artery (LAD) and a critical (>70%) lesion in at least 1 major epicardial vessel (except the LAD) amenable to both PCI and CABG and referred for conventional surgical revascularization were randomly assigned to undergo HCR or CABG (in a 1:1 ratio). The primary endpoint was the evaluation of the safety of HCR. The feasibility was defined by the percent of patients with a complete HCR procedure and the percent of patients with conversions to standard CABG. The occurrence of major adverse cardiac events such as death, myocardial infarction, stroke, repeated revascularization, and major bleeding within the 12-month period after randomization was also assessed.ResultsMost of the pre-procedural characteristics were similar in the 2 groups. Of the patients in the hybrid group, 93.9% had complete HCR and 6.1% patients were converted to standard CABG. At 12 months, the rates of death (2.0% vs. 2.9 %, p = NS), myocardial infarction (6.1% vs. 3.9%, p = NS), major bleeding (2% vs. 2%, p = NS), and repeat revascularization (2% vs. 0%, p = NS) were similar in the 2 groups. In both groups, no cerebrovascular incidents were observed.ConclusionsHCR is feasible in select patients with MVCAD referred for conventional CABG. (Safety and Efficacy Study of Hybrid Revascularization in Multivessel Coronary Artery Disease [POL-MIDES]; NCT01035567).     

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.     

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.     

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.     

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.     

Association of Epicardial Adipose Tissue With Progression of Coronary Artery Calcification Is More Pronounced in the Early Phase of Atherosclerosis: Results From the Heinz Nixdorf Recall Study

ObjectivesThis study sought to determine whether epicardial adipose tissue (EAT) volume predicts the progression of coronary artery calcification (CAC) score in the general population.BackgroundEAT predicts coronary events and is suggested to influence the development of atherosclerosis.MethodsWe included 3,367 subjects (mean age 59 ± 8 years; 47% male) from the population-based Heinz Nixdorf Recall study without known coronary artery disease at baseline. CAC was quantified from noncontrast cardiac electron beam computed tomography at baseline and after 5 years. EAT was defined as fat volume inside the pericardial sac and was quantified from axial computed tomography images. Association of EAT volume with CAC progression (log[CAC(follow-up) + 1] − log[CAC(baseline) + 1]) was depicted as percent progression of CAC + 1 per SD of EAT.ResultsSubjects with progression of CAC above the median had higher EAT volume than subjects with less CAC change (101.1 ± 47.1 ml vs. 84.4 ± 43.4 ml; p < 0.0001). In regression analysis, 6.3% (95% confidence interval [CI]: 2.3% to 10.4%; p = 0.0019) of progression of CAC + 1 was attributable to 1 SD of EAT, which persisted after adjustment for risk factors (6.1% [95% CI: 1.2% to 11.2%]; p = 0.014). For subjects with a CAC score of >0 to ≤100, progression of CAC + 1 by 20% (95% CI: 11% to 31%; p < 0.0001) was attributable to 1 SD of EAT. Effect sizes decreased with CAC at baseline, with no relevant link for subjects with a CAC score ≥400 (0.2% [95% CI: −3.5% to 4.2%]; p = 0.9). Likewise, subjects age <55 years at baseline showed the strongest association of EAT with CAC progression (20.6% [95% CI: 9.7% to 32.5%]; p < 0.0001). Interestingly, the effect of EAT on CAC progression was more pronounced in subjects with low body mass index (BMI), and decreased with degree of adiposity (BMI ≤25 kg/m²: 19.8% [95% CI: 9.2% to 31.4%]; p = 0.0001, BMI >40 kg/m²: 0.8% [95% CI: −26.7% to 38.9%]; p = 0.96).ConclusionsEAT is associated with the progression of CAC, especially in young subjects and subjects with low CAC score, suggesting that EAT may promote early atherosclerosis development.     

Faster increase in body mass index between ages 8 and 13 is associated with risk factors for cardiovascular morbidity and mortality

Background and aimsExcess childhood weight is associated with cardiovascular disease (CVD) in adulthood. Whether this is mediated through adult body mass index (BMI) and associated risk factors such as metabolic derangements remains unclear. The aim was to examine whether childhood BMI velocity (Δkg m⁻² per year) was associated with adult CVD mortality and to examine how adult BMI and cardiometabolic risk factors contribute to the association.Methods and resultsSubjects were 1924 Icelanders born between 1921 and 1935 and living in Reykjavik when recruited into a longitudinal study from 1967 to 1991. From ages 8–13 years, BMI velocity was calculated to quantify the association between childhood growth and adult CVD mortality. Deaths from recruitment to 31 December 2009 were extracted from the national register. There were 202 CVD deaths among men and 90 CVD deaths among women (mean follow-up: 25.9 years). Faster BMI velocity from ages 8–13 years was associated with CVD mortality when comparing those in the highest versus lowest tertile with corresponding hazard ratio (HR) (95% confidence interval (CI)): 1.49 (1.03, 2.15) among men and 2.32 (1.32, 4.08) among women after adjustment for mid-life BMI and CVD risk factors. Faster childhood BMI velocity was associated with elevated CVD risk factors among men at mid-life but these associations were less pronounced among women.ConclusionFaster increase in BMI from ages 8–13 years was associated with an increased CVD mortality risk. Children with early growth spurts coupled with excess weight gain during this transition period from childhood into adolescence should be closely monitored to ensure better health in adulthood.     

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.     

Baru almond improves lipid profile in mildly hypercholesterolemic subjects: A randomized,controlled, crossover study

Backgroud and aimThe usual consumption of nuts reduces cardiovascular diseases (CVD) risk by improving serum lipids and oxidation status. Baru almonds (Dipteryxalata Vog.), a native species of Brazilian Savannah, have considerable contents of monounsaturated fatty acids (MUFA), dietary fiber, vitamin E and zinc, which could exert positive effects in serum lipids and markers of oxidation. However, there is no study about the effect of their consumption on human health. Thus, the aim of this study was to evaluate the effect of baru almonds supplementation on lipid profile and oxidation of mildly hypercholesterolemic subjects.Methods and ResultsA randomized, crossover, placebo controlled study was performed with 20 mildly hypercholesterolemic subjects (total cholesterol (TC) mean ±SEM = 5.8 ± 0.2 mmol/L). The assay had 2 periods of 6 weeks each and a 4-week washout period between the treatments. Subjects were randomly allocated in alternated periods receiving the following treatments per period: supplementation with 20 g/day of baru almonds or placebo (1 corn starch capsule/day). Compared to placebo, supplementation of baru almonds reduced TC (−8.1 ± 2.4%, P = 0.007), low-density lipoprotein cholesterol (LDL-c) (−9.4 ± 2.4%, P = 0.006) and non-high-density lipoprotein cholesterol (non-HDL-c) (−8.1 ± 3.0%, P = 0.013). There were no significant changes on the oxidation biomarkers evaluated.ConclusionDietary supplementation of mildly hypercholesterolemic subjects with baru almonds improved serum lipid parameters, so that this food might be included in diets for reducing the CVD risk.Clinical Trial registryBrazilian Registry of Clinical Trials (ReBEC) (website: http://www.ensaiosclinicos.gov.br). Register number: RBR-4zdy9p.     

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.