Tadayuki Uetani

The correlation between lipid volume in the target lesion, measured by integrated backscatter intravascular ultrasound, and post-procedural myocardial infarction in patients with elective stent implantation

AIMS The aim of this study was to perform quantitative analysis of the plaques of target lesions by integrated backscatter intravascular ultrasound (IB-IVUS) and to investigate the association between these data and the risk of post-procedural myocardial injury after stenting. METHODS AND RESULTS One hundred and fourteen consecutive patients who received elective stent implantations following IB-IVUS analysis were enrolled. The volume of each plaque component (lipid, fibrous, and calcified) was calculated for the target lesion. Creatine kinase-MB (CK-MB) and troponin-T (TnT) were also evaluated 18 h after procedure. We defined a post-procedural TnT level higher than three times the normal limit as a post-procedural myocardial injury. Lipid, fibrous, and calcified volumes were greater in patients with myocardial injury than in those without myocardial injury. Lipid and fibrous volumes correlated with post-procedural cardiac biomarkers, and the lipid volume fraction (lipid volume/total plaque volume) also correlated with post-procedural TnT and CK-MB. The fibrous volume fraction for plaques was found to be inversely correlated with post-procedural TnT and CK-MB. Hence, lipid volume and volume fraction were concluded to be independent predictors of post-procedural myocardial injury. CONCLUSION A larger plaque volume and lipid-rich plaque may be indicative of embolic events after stent implantation, resulting in myocardial injury.

Impact of omega-3 polyunsaturated fatty acids on coronary plaque instability: An integrated backscatter intravascular ultrasound study

OBJECTIVE To assess the impact of omega-3 polyunsaturated fatty acids (ω3 PUFAs) on coronary plaque instability. METHODS Serum content of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) was measured in 336 of 368 consecutive patients suspected of having coronary artery disease who underwent coronary angiography. Conventional and integrated backscatter intravascular ultrasound (IB-IVUS) parameters were analyzed in 116 patients with 128 coronary plaques, using a 43-MHz (motorized pullback 0.5mm/s) intravascular catheter (View It, Terumo Co., Japan). Lipid-rich plaques were classified into two categories according to their components. RESULTS Patients with acute coronary syndrome had significantly lower levels of ω3 PUFAs (especially of EPA and DPA) than those without it. IB-IVUS analyses showed that ω3 PUFAs correlated inversely with % lipid volume and positively with % fibrous volume. Patients with low EPA levels, low DPA levels, and low DHA levels had a significantly higher % lipid volume (p=0.048, p=0.008, and p=0.036, respectively) and a significantly lower % fibrous volume (p=0.035, p=0.008, and p=0.034, respectively) than those with high levels of these fatty acids. Even after adjustment for confounders, the presence of both low EPA and low DPA levels proved to be an independent predictor for lipid-rich plaques in any of the two categories. CONCLUSIONS A lower serum content of ω3 PUFAs (especially of EPA and DPA) was significantly associated with lipid-rich plaques, suggesting the contribution to the incidence of acute coronary syndrome.

Abnormal glucose regulation is associated with lipid-rich coronary plaque: relationship to insulin resistance.

OBJECTIVES This study sought to determine lipid and fibrous volume of coronary atherosclerotic plaques in subjects with abnormal glucose regulation (AGR) by integrated backscatter (IB) intravascular ultrasound (IVUS) during percutaneous coronary intervention. BACKGROUND Abnormal glucose regulation, including impaired glucose regulation (IGR) and diabetes mellitus (DM), has emerged as an important determinant of cardiovascular risk. We hypothesized that AGR would be associated with coronary plaque instability. METHODS Conventional intravascular ultrasound and IB-IVUS using a 40-MHz (motorized pullback 1 mm/s) intravascular catheter was performed in 172 consecutive patients. The percentage of fibrous area and the percentage of lipid area were automatically calculated by IB-IVUS. Three-dimensional analysis of IB-IVUS images was performed to determine the percentage of lipid volume (%LV) and fibrous volume (%FV). Following the World Health Organization criteria, the subjects were classified into the DM group, the IGR group, and the normal glucose regulation group. The cutoff point for the lipid-rich plaque was defined as %LV >44% or %FV <52%, which was the 75th percentile of %LV or the 25th percentile of %FV in this study population. Insulin resistance (IR) was defined as the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS There were no significant differences in the baseline characteristics except for glucometabolic parameters. The conventional IVUS analysis indicated that the DM group had a significantly increased plaque volume (and percent plaque volume). In the IB-IVUS analysis, as compared with the normal glucose regulation group, the DM and the IGR groups showed a significant increase in %LV (36 +/- 14% and 37 +/- 13% vs. 29 +/- 14%, p = 0.02) and a significant decrease in %FV (59 +/- 11% and 58 +/- 11% vs. 64 +/- 11%, p = 0.03). The lipid-rich plaque rate was significantly associated with an increasing HOMA-IR in the tertile (p = 0.008). On logistic regression analysis after adjusting for confounding and coronary risk factors, the DM group (odds ratio 3.52, 95% confidence interval 1.13 to 11.0, p = 0.03) and the IGR group (odds ratio 3.92, 95% confidence interval 1.13 to 13.6, p = 0.03) were significantly associated with the lipid-rich plaque. CONCLUSIONS Coronary lesions in patients with AGR are associated with more lipid-rich plaque content, which may be related to the increased IR in these patients.

The Association Between Plaque Characterization by CT Angiography and Post-Procedural Myocardial Infarction in Patients With Elective Stent Implantation

OBJECTIVES This study sought to evaluate the association between volumetric characterization of target lesions by multidetector computed tomography (MDCT) angiography and the risk of post-procedural myocardial injury after elective stent implantation. BACKGROUND Previous reports have shown that plaque characterization of the target lesion may provide useful information for stratifying the risk of coronary stenting. METHODS A total of 189 consecutive patients were enrolled; they underwent elective stent implantation after volumetric plaque analysis with 64-slice MDCT. Each plaque component and lumen (filled with dye) was defined as follows: 1) low-attenuation plaque (LAP) (<50 HU); 2) moderate-attenuation plaque (MAP) (50 to 150 HU); 3) lumen (151 to 500 HU); and 4) high-attenuation plaque (HAP) (>500 HU). The volume of each plaque component in the target lesion was calculated using Color Code Plaque. Post-procedural creatine kinase-MB isoform and troponin-T (TnT) at 18 h after percutaneous coronary intervention were also evaluated. RESULTS The volumes of LAP (87.9+/-94.8 mm3 vs. 47.4+/-43.7 mm3, p<0.01) and MAP (111.6+/-77.5 mm3 vs. 89.8+/-67.1 mm3, p<0.05) were larger in patients with post-procedural myocardial injury (defined as positive TnT) than in those with negative TnT. The volumes of LAP and MAP and fraction of LAP in total plaque (LAP volume/total plaque volume) correlated with biomarkers; the MAP fraction was inversely correlated with biomarkers. The volume of LAP was an independent predictor of positive TnT after adjusting for patient background, conventional IVUS parameters, and procedural factors. CONCLUSIONS Post-procedural myocardial injury was associated with the volume and fraction of LAP as detected by MDCT. The volume of LAP was an independent predictor of positive TnT. Plaque analysis by MDCT would be a useful method for predicting post-procedural myocardial injury after percutaneous coronary intervention.

Impact of renal function on coronary plaque composition

BACKGROUND Recent studies have demonstrated that patients with chronic kidney disease are at high risk of atherosclerosis. Recently it has been found that coronary plaque components can be evaluated by integrated backscatter intravascular ultrasound (IB-IVUS), and lipid-rich plaque is associated with vulnerable plaque. The aim of the study was to investigate the relationship between renal function and tissue characterization of coronary plaque composition at the target stenotic site for percutaneous coronary intervention (PCI). METHODS We prospectively performed IB-IVUS before elective PCI in 89 consecutive patients with stable angina. According to estimated glomerular filtration rate (eGFR), they were divided into two groups (eGFR <60 ml/min/ 1.73 m(2) or eGFR > or =60 ml/min/1.73 m(2)). The tissue characteristics of the coronary plaque at each target stenotic site were evaluated by three-dimensional (3D) IB-IVUS just before PCI procedure. RESULTS The patients with eGFR <60 ml/min/1.73 m(2) had higher percentage of lipid volume and lower percentage of fibrous volume compared to the patients with eGFR > or = 60 ml/min/1.73 m(2) on the 3D IB-IVUS images (36.7 +/- 10.6% versus 28.7 +/- 9.3%, P < 0.001 and 59.1 +/- 8.7% versus 66.3 +/- 8.3%, P < 0.001, respectively). eGFR showed a significant negative correlation with lipid volume and had a significant positive correlation with fibrous volume in coronary plaques (r = -0.44, P < 0.0001, and r = 0.46, P < 0.0001, respectively). CONCLUSIONS Impaired renal function was related to higher percentage of lipid volume and lower percentage of fibrous volume in coronary plaque. Our findings may explain the increasing risk of cardiovascular events in patients with renal dysfunction.

Cardiac 64-Multislice Computed Tomography Reveals Increased Epicardial Fat Volume in Patients With Acute Coronary Syndrome

Inflammatory cytokines released from epicardial fat around coronary arteries may modulate the coronary arteries and promote coronary atherosclerosis. We assessed the hypothesis that epicardial fat volume (EFV) is increased in patients with acute coronary syndrome (ACS). EFV was measured in 80 Japanese patients hospitalized for ACS using 64-multislice computed tomography. The ACS group included 51 patients with ST-segment elevated myocardial infarction and 29 patients with non-ST-segment elevated myocardial infarction. All patients underwent emergency coronary angioplasty and 64-multislice computed tomographic scanning during hospitalization. The control group included 90 consecutive outpatients with suspected ACS whose coronary computed tomographic results were normal. EFV was larger in patients with ACS than in the control group (117 ± 47 vs 95 ± 33 ml, p <0.001). Multivariate regression analysis showed that EFV was associated with age, body mass index, and visceral fat area in the control group. However, these correlations did not appear in the ACS group. Multivariate logistic regression analysis showed that EFV >100 ml was independently associated with ACS (odds ratio 2.84, 95% confidence interval 1.17 to 6.87, p = 0.021). Receiver operator characteristic analysis determined a cut-off value of 100.3 ml with a sensitivity of 75% and a specificity of 60% for ACS (area under the curve 0.692, 95% confidence interval 0.596 to 0.777, p <0.001). Compared to subcutaneous adipose tissue, epicardial adipose tissue showed inflammatory cell infiltrates on a micrograph. In conclusion, the present study demonstrated significantly increased EFV in patients with ACS. A large amount of epicardial fat may be a risk factor for ACS.

Accuracy of 64-slice multidetector computed tomography for classification and quantitation of coronary plaque: Comparison with integrated backscatter intravascular ultrasound

BACKGROUND Noninvasive assessment of coronary plaque is important for coronary risk stratification. Whereas integrated backscatter intravascular ultrasound (IB-IVUS) has proven effective for analysis of the tissue components of coronary plaque, plaque assessment by 64-slice multidetector computed tomography (MDCT) has not been established. We therefore evaluated the accuracy of MDCT compared with IB-IVUS for identification of coronary plaque components and determination of plaque volume. METHODS Thirty-one sites in 17 coronary vessels (7 left anterior descending, 5 left circumflex, and 5 right coronary arteries) with substantial stenosis were visualized by both 64-slice MDCT and IB-IVUS. Coronary plaque was evaluated by MDCT and the findings were compared with those of IB-IVUS at the same sites and for the same vessel lengths. Plaque was classified as low-attenuated, fibrous, or calcified, and the volume of each plaque component and total plaque volume were calculated. RESULTS Total plaque volume per vessel determined by MDCT was significantly correlated with that determined by IB-IVUS (r=0.704, P<0.05, n=17). However, the volumes of individual plaque components determined by the two approaches were not correlated. The predominant plaque morphology as determined by the two approaches was consistent in 12 of the 17 vessels (70.6%), whereas calcified and low-attenuated plaques were overestimated by MDCT in the remaining vessels. CONCLUSIONS MDCT is a promising approach for noninvasive detection of different types of coronary plaque and may therefore contribute to coronary risk stratification. The ability of MDCT to determine the volume of individual plaque components, however, is limited.

Ca2+-dependent Modulation of Intracellular Mg2+ Concentration with Amiloride and KB-R7943 in Pig Carotid Artery

It has long been recognized that magnesium is associated with several important diseases, including diabetes, hypertension, cardiovascular, and cerebrovascular diseases. In the present study, we measured the intracellular free Mg2+ concentration ([Mg2+]i) using 31P nuclear magnetic resonance (NMR) in pig carotid artery smooth muscle. In normal solution, application of amiloride (1 mm) decreased [Mg2+]i by ∼12% after 100 min. Subsequent washout tended to further decrease [Mg2+]i. In contrast, application of amiloride significantly increased [Mg2+]i (by ∼13% after 100 min) under Ca2+-free conditions, where passive Mg2+ influx is facilitated. The treatments had little effect on intracellular ATP and pH (pHi). Essentially the same Ca2+-dependent changes in [Mg2+]i were produced with KB-R7943, a selective blocker of reverse mode Na+-Ca2+ exchange. Application of dimethyl amiloride (0.1 mm) in the presence of Ca2+ did not significantly change [Mg2+]i, although it inhibited Na+-H+ exchange at the same concentration. Removal of extracellular Na+ caused a marginal increase in [Mg2+]i after 100–200 min, as seen in intestinal smooth muscle in which Na+-Mg2+ exchange is known to be the primary mechanism of maintaining a low [Mg2+]i against electrochemical equilibrium. In Na+-free solution (containing Ca2+), neither amiloride nor KB-R7943 decreased [Mg2+]i, but they rather increased it. The results suggest that these inhibitory drugs for Na+-Ca2+ exchange directly modulate Na+-Mg2+ exchange in a Ca2+-dependent manner, and consequently produce the paradoxical decrease in [Mg2+]i in the presence of Ca2+.

Impact of Insulin Resistance on Post-Procedural Myocardial Injury and Clinical Outcomes in Patients Who Underwent Elective Coronary Interventions With Drug-Eluting Stents

OBJECTIVES This study sought to evaluate the associations between homeostatic indexes of insulin resistance (HOMA-IR) and post-procedural myocardial injury and clinical outcome after a percutaneous coronary intervention (PCI) with a drug-eluting stent. BACKGROUND Insulin resistance increases the risk of cardiovascular events. However, the association between insulin resistance and clinical outcome after coronary intervention is unclear. METHODS We evaluated 516 consecutive patients who underwent elective PCI with drug-eluting stents. Blood samples were collected from venous blood after overnight fasting, and fasting plasma glucose and insulin levels were measured. HOMA-IR was calculated according to the homeostasis model assessment. Post-procedural myocardial injury was evaluated by analysis of troponin T and creatine kinase-myocardial band isozyme levels hours after PCI. Cardiac event was defined as the composite endpoint of cardiovascular death, myocardial infarction, and any revascularization. RESULTS With increasing tertiles of HOMA-IR, post-procedural troponin T and creatine kinase-myocardial band levels increased. In the multiple regression analysis, HOMA-IR was independently associated with troponin T elevation. During a median follow-up of 623 days, patients with the highest tertiles of HOMA-IR had the highest risk of cardiovascular events. The Cox proportional hazard models identified HOMA-IR as independently associated with worse clinical outcome after adjustment for clinical and procedural factors. CONCLUSIONS These results indicated the impact of insulin resistance on post-procedural myocardial injury and clinical outcome after elective PCI with drug-eluting stent deployment. Evaluation of insulin resistance may provide useful information for predicting clinical outcomes after elective PCI.

Association of cardiorespiratory fitness with characteristics of coronary plaque: Assessment using integrated backscatter intravascular ultrasound and optical coherence tomography

BACKGROUND Cardiorespiratory fitness (CRF) can predict future cardiovascular disease. Rupture of vulnerable plaque which often has a large lipid core with a thin fibrous cap causes acute coronary syndrome including sudden cardiac death. We tested our hypothesis that preserved CRF is associated with low lipid composition and thick fibrous cap thickness of coronary lesions. METHODS We prospectively performed both integrated backscatter intravascular ultrasound (IB-IVUS) and optical coherence tomography (OCT) for 77 non-culprit coronary lesions in 77 consecutive angina pectoris patients who underwent percutaneous coronary intervention (PCI). Percentage of achieved of predicted peak oxygen consumption (%PPeak Vo(2)) calculated based on measured peak Vo(2) using a cardiopulmonary exercise test performed post PCI was adapted as an indicator of patient CRF. RESULTS Patients were divided into two groups [those with preserved CRF (%PPeak Vo(2) >82%) (Group I) or others (Group II)]. Coronary plaques of Group I patients had significantly smaller lipid volume, greater fibrous volume, and thicker fibrous cap thickness than those of Group II (32 ± 14% vs. 45 ± 13%, p<0.001; 57 ± 11% vs. 49 ± 11%, p<0.001; and 177.7 ± 20.9 μm vs. 143.7 ± 36.9 μm, p<0.001). In multivariate linear regression analysis, %PPeak Vo(2) showed a significantly negative correlation with lipid volume and a positive correlation with fibrous volume and fibrous cap thickness (β=-0.418, p=0.001; β=0.361, p=0.006; and β=0.339, p=0.008). CONCLUSIONS High %PPeak Vo(2) was associated with low lipid volume, high fibrous volume and thick fibrous cap thickness in coronary lesions. These results may well suggest an attenuated risk of cardiovascular events in patients with preserved CRF.