Yasutsugu Shiono

Comparison of cardiac MRI and 18F-FDG positron emission tomography manifestations and regional response to corticosteroid therapy in newly diagnosed cardiac sarcoidosis with complete heart block

BACKGROUND Complete heart block (CHB) caused by myocardial inflammation is a serious consequence of cardiac sarcoidosis (CS) that requires early diagnosis for effective anti-inflammatory treatment. OBJECTIVE This study aimed to clarify the cardiac magnetic resonance imaging (MRI) and (18)F-fluoro-2-deoxyglucose positron emission tomography ((18)F-FDG PET) manifestations of newly diagnosed CS with CHB and to assess whether certain imaging features could predict responders to corticosteroid therapy. METHODS Fifteen newly diagnosed CS patients with CHB and 17 without CHB were examined. We defined abnormal (18)F-FDG uptake on (18)F-FDG PET and increased T2-weighted signal on cardiac MRI as signs of myocardial inflammation and delayed enhancement (DE) on cardiac MRI as a sign of myocardial fibrosis. Ten CHB+ patients were then treated with corticosteroids. RESULTS The CHB+ group showed higher (18)F-FDG uptake and increased T2-weighted signal in the interventricular septum, which involves the electrical pathway of atrioventricular conduction, than the CHB- group (P = .001 and P < .0001, respectively), whereas there was no group difference in DE (P = .232). Six corticosteroid-treated patients recovered from CHB; all had exhibited increased T2-weighted signal, (18)F-FDG uptake, and DE in the interventricular septum before therapy. In contrast, among the 4 patients without recovery, 2 showed no abnormal (18)F-FDG uptake and 3 had no increased T2-weighted signal in the interventricular septum, but all showed DE. The 2 patients without recovery with abnormal (18)F-FDG uptake showed wall thinning in the interventricular septum. CONCLUSION Focal inflammation in the interventricular septum was associated with CHB and might predict recovery from CHB after corticosteroids if it coexists with preserved wall thickness.

Long-Term Outcome After Deferral of Revascularization in Patients With Intermediate Coronary Stenosis and Gray-Zone Fractional Flow Reserve

BACKGROUND A strategy of deferred percutaneous coronary intervention for coronary stenosis with fractional flow reserve (FFR) 0.75-0.80, termed the gray zone, remains a matter of debate. The aim of this study was to assess the safety of deferring revascularization for patients with FFR 0.75-0.80 compared with those with FFR >0.80. METHODS AND RESULTS We assessed 3-year clinical outcome in 150 patients with angiographically intermediate stenosis who had revascularization deferred on the basis of FFR ≥ 0.75 (FFR 0.75-0.80, n=56; FFR >0.80, n=94). Target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction (MI), and ischemia-driven target vessel revascularization (TVR) was evaluated during follow-up. Cardiac death was observed in 1 patient with FFR 0.75-0.80. There was no target vessel-related MI in either group. The incidence of ischemia-driven TVR was higher in patients with FFR 0.75-0.80 than in those with FFR >0.80 (14% vs. 3%, P=0.020). TVF-free survival was significantly worse for the patients with FFR 0.75-0.80 than those with FFR >0.80 (hazard ratio, 5.2; 95% confidence intervals: 1.4-19.5; P=0.015). CONCLUSIONS Patients with FFR 0.75-0.80 were at higher risk of TVF mainly due to TVR than those with FFR >0.80.

Impact of Eicosapentaenoic Acid Treatment on the Fibrous Cap Thickness in Patients with Coronary Atherosclerotic Plaque: An Optical Coherence Tomography Study

AIM Previous clinical trials have demonstrated the effectiveness of eicosapentaenoic acid (EPA) in preventing cardiovascular events. The aim of the present study was to investigate the effects of EPA treatment on the accumulation of coronary atherosclerotic plaque using optical coherence tomography (OCT). METHODS A total of 46 acute coronary syndrome (ACS) patients without dyslipidemia were divided into two groups: those who received 1,800 mg/day of EPA (n = 15) or the control group (n = 31). Serial OCT examinations were performed at baseline and after eight months of follow-up. The target for the OCT analysis was non-culprit plaque with a percent diameter of stenosis of 30% to 70% in non-culprit vessels of ACS. RESULTS Between the baseline and follow-up visits, the serum EPA levels increased (50 ± 26 mg/dL to 200 ± 41 mg/dL, p ＜ 0.001) in the EPA group, although they did not change in the control group. According to the OCT analysis, the lipid arc did not change in the EPA group (131 ± 52 degrees to 126 ± 54 degrees, p = 0.106) or the control group (137 ± 50 degrees to 138 ± 50 degrees, p=0.603). In contrast, the fibrous cap thickness significantly increased in both the EPA group (169 ± 70 μm to 201 ± 49 μm, p ＜ 0.001) and the control group (164 ± 63 μm to 174 ± 72 μm, p=0.018); however, the relative change in the fibrous cap thickness was significantly greater in the EPA group than in the control group (131 ± 35% vs. 106 ± 15%, p = 0.001). CONCLUSIONS In the present study, the administration of EPA for eight months significantly increased the fibrous cap thickness in patients with coronary atherosclerotic plaque.

Prognostic Value of Microvascular Resistance Index Immediately After Primary Percutaneous Coronary Intervention on Left Ventricular Remodeling in Patients With Reperfused Anterior Acute ST-Segment Elevation Myocardial Infarction

OBJECTIVES This study sought to investigate the relationship between the degree of microvascular dysfunction assessed by a dual-sensor guidewire (pressure and Doppler velocity) and left ventricular (LV) remodeling after successful primary percutaneous coronary intervention (PPCI) for a first anterior acute myocardial infarction (AMI). BACKGROUND Microvascular dysfunction after AMI is associated with progressive LV dilation. METHODS In 24 consecutive patients, the microvascular resistance index (MVRI) immediately after PPCI was calculated as the ratio of the mean distal pressure to average peak flow velocity during maximal hyperemia. Cardiac magnetic resonance was performed to determine LV volumes at baseline and 8-month follow-up. LV remodeling was defined as an increase in left ventricular end-diastolic volume (LVEDV) of ≥20%. RESULTS In patients with an MVRI greater than the median value of 2.96 mm Hg·cm(-1)·s, the LVEDV increased significantly from 117.1 ± 20.7 ml at baseline to 146.5 ± 21.4 ml (p = 0.006) at 8 months, whereas it did not change between baseline and 8 months (108.2 ± 21.2 ml vs. 111.6 ± 29.9 ml, p = 0.620) in patients with an MVRI ≤2.96 mm Hg·cm(-1)·s. LV remodeling was more frequent in the group with an MVRI >2.96 mm Hg·cm(-1)·s (64% vs. 15%, p = 0.033). Furthermore, there was a positive correlation between MVRI and the percentage of increase or decrease in LVEDV (r = 0.42, p = 0.042). Logistic regression analysis showed that MVRI was the strongest univariate predictor of LV remodeling. The best cutoff value of MVRI was 2.96 mm Hg·cm(-1)·s with a sensitivity of 78% and a specificity of 73%. CONCLUSIONS MVRI immediately after PPCI predicts LV remodeling in patients with reperfused anterior AMI.

Impact of glucose fluctuation and monocyte subsets on coronary plaque rupture

BACKGROUND AND AIMS It remains unclear whether glycemic fluctuation can affect plaque rupture in acute myocardial infarction (AMI). Here we investigate the impact of glucose fluctuation on plaque rupture, as observed by optical coherence tomography (OCT), and monocyte subsets in patients with AMI. METHODS AND RESULTS We studied 37 consecutive patients with AMI. All patients underwent OCT examination, which revealed 24 patients with plaque rupture and 13 patients without plaque rupture at the culprit site. Peripheral blood sampling was performed on admission. Three monocyte subsets (CD14(+)CD16(-), CD14(bright)CD16(+), and CD14(dim)CD16(+)) were assessed by flow cytometry. Glycemic variability, expressed as the mean amplitude of glycemic excursion (MAGE), was determined by a continuous glucose monitoring system 7 days after the onset of AMI. MAGE was significantly higher in the rupture patients than in the non-rupture patients (P=0.036). Levels of CD14(bright)CD16(+) monocytes from the rupture patients were significantly higher than those from the non-rupture patients (P=0.042). Of interest, levels of CD14(bright)CD16(+) monocytes correlated positively and significantly with MAGE (r=0.39, P=0.02). CONCLUSION Dynamic glucose fluctuation may be associated with coronary plaque rupture, possibly through the preferential increase in CD14(bright)CD16(+) monocyte levels.

Optical Coherence Tomography Predictors for Edge Restenosis After Everolimus-Eluting Stent Implantation

Background—Stent edge restenosis (SER) remains a potential limitation of drug-eluting stents. The aim of this study was to determine optical coherence tomography (OCT) predictors for angiographic late SER after everolimus-eluting stent implantation. Methods and Results—We retrospectively analyzed 319 patients who underwent OCT immediately after everolimus-eluting stent implantation and scheduled 9- to 12-month follow-up angiography. The binary angiographic SER rate was 10% (32/319) in the patients, 8.4% (32/382) in lesions, and 4.4% (33/744) in stent edge segments. In the stent edge segments at post stenting, OCT-derived lipidic plaque (61% versus 20%; P<0.001) was more often observed in the SER group, and OCT-measured minimum lumen area (4.13±2.61 versus 5.58±2.46 mm2; P=0.001) was significantly smaller in the SER group compared with the non-SER group. Multivariate analysis identified lipidic plaque (odds ratio: 5.99; 95% confidence interval: 2.89–12.81; P<0.001) and minimum lumen area (odds ratio: 0.64; 95% confidence interval: 0.42–0.96; P=0.029) as independent predictors of binary SER. Receiver-operating characteristic analysis demonstrated that lipid arc of 185° (sensitivity: 71%; specificity: 72%; area under the curve: 0.761) and minimum lumen area of 4.10 mm2 (sensitivity: 67%; specificity: 77%; area under the curve: 0.787) were optimal cutoff values for predicting ischemia-driven SER. Conclusions—The present OCT study demonstrated that lipidic plaque and minimum lumen area in the stent edge segments at post stenting were associated with late SER after everolimus-eluting stent implantation. OCT provides valuable information to determine an appropriate landing zone for stent implantation.

Clinical implications of three-vessel fractional flow reserve measurement in patients with coronary artery disease

Aims There are limited data on the clinical implications of total physiologic atherosclerotic burden assessed by invasive physiologic studies in patients with coronary artery disease. We investigated the prognostic implications of total physiologic atherosclerotic burden assessed by total sum of fractional flow reserve (FFR) in three vessels (3V-FFR). Methods and results A total of 1136 patients underwent FFR measurement in three vessels (3V FFR-FRIENDS study, NCT01621438). The patients were classified into high and low 3V-FFR groups according to the median value of 3V-FFR (2.72). The primary endpoint was major adverse cardiac events (MACE, a composite of cardiac death, myocardial infarction and ischaemia-driven revascularization) at 2 years. Mean angiographic percent diameter stenosis and FFR were 43.7 ± 19.3% and 0.90 ± 0.08, respectively. There was a negative correlation between 3V-FFR and estimated 2-year MACE rate (P < 0.001). The patients in low 3V-FFR group showed a higher risk of 2-year MACE than those in the high 3V-FFR group [(7.1% vs. 3.8%, hazard ratio (HR) 2.205, 95% confidence interval (CI) 1.201-4.048, P = 0.011]. The higher 2-year MACE rate was mainly driven by the higher rate of ischaemia-driven revascularization in the low 3V-FFR group (6.2% vs. 2.7%, HR 2.568, 95% CI 1.283-5.140, P = 0.008). In a multivariable adjusted model, low 3V-FFR was an independent predictor of MACE (HR 2.031, 95% CI 1.078-3.830, P = 0.029). Conclusion Patients with high total physiologic atherosclerotic burden assessed by 3V-FFR showed higher risk of 2-year clinical events than those with low total physiologic atherosclerotic burden. The difference was mainly driven by ischaemia-driven revascularization for both functionally significant and insignificant lesions at baseline. Three-vessel FFR might be used as a prognostic indicator in patients with coronary artery disease. Clinical trial registration 3V FFR-FRIENDS study (https://clinicaltrials.gov/ct2/show/NCT01621438, NCT01621438).

Feasibility of Optical Coronary Tomography in Quantitative Measurement of Coronary Arteries With Lipid-Rich Plaque

BACKGROUND The aim of the present study was to evaluate the feasibility of optical coherence tomography (OCT) for measurement of vessel area in coronary arteries with lipid-rich plaque as compared with intravascular ultrasound (IVUS). METHODS AND RESULTS: We investigated 80 coronary artery segments with lipid-rich plaque on OCT and non-attenuated plaque on IVUS. According to the lipid arc on OCT, the plaques were classified into 4 groups: group 1, lipid arc ≤90°; group 2, 90°270°. Vessel circular arcs that could not be identified due to OCT signal attenuation were interpolated using an approximating algorithm. OCT-measured vessel area was well-correlated with IVUS-measured vessel area (R=0.834, P<0.001). On Bland-Altman plot, there was a good agreement between OCT-measured vessel area and IVUS-measured vessel area, although mean difference and limits of agreement increased with increase of lipid arc (mean difference in groups 1-4: -0.21, -0.31, -1.02, and -2.13 mm(2); lower limit: -1.49, -3.22, -5.24, and -9.25 mm(2); and upper limit: 1.07, 2.60, 3.20, and 4.99 mm(2)). Intra-observer (R=0.97-0.99, P<0.001) and inter-observer (R=0.97-0.99, P<0.001) reproducibility for OCT measurement of vessel area was excellent. CONCLUSIONS Like IVUS, OCT can be used to measure vessel area in coronary arteries with lipid-rich plaque.

Impact of myocardial supply area on the transstenotic hemodynamics as determined by fractional flow reserve

The aim of this study was to investigate the impact of myocardial area supplied by the coronary artery on fractional flow reserve (FFR).

Difference in neointimal appearance between early and late restenosis after sirolimus-eluting stent implantation assessed by optical coherence tomography.

ObjectivesLate in-stent restenosis (ISR) is an important clinical issue in the drug-eluting stent era. Autopsy studies have reported different underlying mechanisms between early ISR and late ISR. The aim of the present study was to compare the neointimal tissue appearance between early ISR (<1 year) and late ISR (>1 year) after sirolimus-eluting stent (SES) implantation using optical coherence tomography (OCT). Materials and methodsWe examined the neointimal tissue appearance in 48 ISR lesions after SES implantation [30 early ISR lesions (8±1 months after stenting) and 18 late ISR lesions (34±14 months after stenting)] by OCT. ISR was defined as percent diameter stenosis more than 50% within the stented segment in angiography. Lipid-rich neointima was characterized by signal-poor regions with diffuse borders. Thin-cap fibroatheroma (TCFA)-like neointima was defined by lipid-rich neointima with cap thickness 65 &mgr;m or less. ResultsIn the OCT findings, heterogeneous neointima was more often observed in the late ISR group compared with the early ISR group (89 vs. 43%, P=0.002). Although the frequency of intraluminal thrombus was not different between the two groups (P=0.085), the frequency of lipid-rich neointima (83 vs. 27%, P<0.001), TCFA-like neointima (39 vs. 10%, P=0.028), microchannels within neointima (67 vs. 27%, P=0.007), and neointimal disruption (33 vs. 3%, P=0.008) was significantly higher in the late ISR group. ConclusionIn the present OCT study, it was found that atherosclerotic progression of neointima, such as lipid-rich neointima, TCFA-like neointima, microchannels, and neointimal disruption, was more often observed in late ISR lesions after SES implantation compared with early ISR ones.