Doctor of Medicine, Osaka University (2008)
This study investigated sex differences in coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) in patients with angina in the absence of obstructive coronary artery disease.Coronary microvascular dysfunction is associated with worse long-term outcomes, especially in women. Coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) are 2 methods of assessing the coronary microcirculation.We prospectively enrolled 117 women and 40 men with angina in the absence of obstructive coronary artery disease. We performed CFR, IMR, fractional flow reserve, and quantitative coronary angiography in the left anterior descending artery. Coronary flow was assessed with a thermodilution method by obtaining mean transit time (Tmn) (an inverse correlate to absolute flow) at rest and hyperemia.All patients had minimal atherosclerosis by quantitative coronary angiography (% diameter stenosis: 23.2 ± 12.3%), and epicardial disease was milder in women (fractional flow reserve: 0.88 ± 0.04 vs. 0.87 ± 0.04; p = 0.04). IMR was similar between the sexes (20.7 ± 9.8 vs. 19.1 ± 8.0; p = 0.45), but CFR was lower in women (3.8 ± 1.6 vs. 4.8 ± 1.9; p = 0.004). This was primarily due to a shorter resting Tmn in women (p = 0.005), suggesting increased resting coronary flow, whereas hyperemic Tmn was identical (p = 0.79). In multivariable analysis, female sex was an independent predictor of lower CFR and shorter resting Tmn.Despite similar microvascular function in women and men by IMR, CFR is lower in women. This discrepancy appears to be due to differences in resting coronary flow between the sexes. The effect of sex differences should be considered in interpretation of physiological indexes using resting coronary flow.
View details for DOI 10.1016/j.jcin.2015.03.045
View details for PubMedID 26404195
Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) significantly improves outcomes compared with angio-guided PCI in patients with multivessel coronary artery disease. However, there is a theoretical concern that in patients with reduced left ventricular ejection fraction (EF) FFR may be less accurate and FFR-guided PCI less beneficial.From the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) trial database, we compared FFR values between patients with reduced EF (both ≤40%, n=90 and ≤50%, n=252) and preserved EF (>40%, n=825 and >50%, n=663) according to the angiographic stenosis severity. We also compared differences in 1year outcomes between FFR- vs. angio-guided PCI in patients with reduced and preserved EF.Both groups had similar FFR values in lesions with 50-70% stenosis (p=0.49) and with 71-90% stenosis (p=0.89). The reduced EF group had a higher mean FFR compared to the preserved EF group across lesions with 91-99% stenosis (0.55 vs. 0.50, p=0.02), although the vast majority of FFR values remained ≤0.80. There was a similar reduction in the composite end point of death, nonfatal myocardial infarction, and repeat revascularization with FFR-guided compared to angio-guided PCI for both the reduced (14.5% vs. 19.0%, relative risk=0.76, p=0.34) and the preserved EF group (13.8 vs. 17.0%, relative risk=0.81, p=0.25). The results were similar with an EF cutoff of 40%.Reduced EF has no influence on the FFR value unless the stenosis is very tight, in which case a theoretically explainable, but clinically irrelevant overestimation might occur. As a result, FFR-guided PCI remains beneficial regardless of EF.
View details for DOI 10.1016/j.ijcard.2015.11.169
View details for PubMedID 26670174
Although a myocardial bridge (MB) is often regarded as a benign coronary variant, recent studies have associated MB with focal myocardial ischemia. The physiological consequences of MB on ventricular function during stress have not been well established.We enrolled 58 patients with MB of the left anterior descending artery, diagnosed by intravascular ultrasound. Patients underwent invasive physiological evaluation of the MB by diastolic fractional flow reserve during dobutamine challenge and exercise echocardiography. Septal and lateral longitudinal strain (LS) were assessed at rest and immediately after exercise and compared with strain of matched controls. Absolute and relative changes in strain were also calculated. The mean age was 42.5±16.0 years. Fifty-five patients had a diastolic fractional flow reserve ≤0.76. At rest, there was no significant difference between the 2 groups in septal LS (19.0±1.8% for patients with MB versus 19.2±1.5% for control, P=0.53) and lateral LS (20.1±2.0% versus 20.0±1.6%, P=0.83). With stress, compared with controls, patients with MB had a lower peak septal LS (18.9±2.6% versus 21.7±1.6%, P<0.001) and lower absolute (-0.1±2.1% versus 2.5±1.3%, P<0.001) and relative change (-0.6±11.2% versus 13.1±7.8%, P<0.001) in septal LS, whereas there was no significant difference in lateral LS. In multivariate analysis, diastolic fractional flow reserve and length were independent determinants of lower changes in septal LS.Patients with a hemodynamically significant MB, determined by invasive diastolic fractional flow reserve, have significantly lower change in septal LS on exercise echocardiography, suggesting that septal LS may be useful for noninvasively assessing the hemodynamic significance of an MB.
View details for DOI 10.1161/JAHA.115.002496
View details for PubMedID 26581225
Local production of C-reactive protein (CRP) in human coronary arterial plaque was reported as a possible marker for local inflammation and vulnerable plaque. Integrated backscatter intravascular ultrasound (IB-IVUS) plaque tissue characterization may detect vulnerable plaque with high local plaque inflammation. Thus, the aim of this study was to clarify the relationship between IB-IVUS-based plaque characteristics and local high-sensitivity C-reactive protein (hs-CRP) production in stable and unstable plaque.Eighteen patients (nine unstable angina/non-ST-segment elevation myocardial infarction and nine stable angina) were prospectively enrolled. Using the microcatheter, blood samples from the proximal and distal sites of the culprit lesion were obtained to measure local CRP production. Translesional hs-CRP was defined as distal hs-CRP minus proximal hs-CRP of the culprit lesion. Gray-scale and IB-IVUS analyses were carried out at the target lesion. The translesional hs-CRP level tended to be higher in the unstable angina group than in the stable angina group (0.026±0.033 vs. 0.003±0.007 mg/dl, P=0.050). Gray-scale IVUS-derived indices did not correlate with translesional hs-CRP. However, % lipid pool area by IB-IVUS correlated positively (r=0.54, P=0.02) and % fibrosis area correlated negatively with the translesional hs-CRP level (r=-0.52, P=0.03).Lipid pool area detected by IB-IVUS is correlated positively with the translesional hs-CRP level.
View details for DOI 10.1097/MCA.0000000000000250
View details for Web of Science ID 000357641400010
View details for PubMedID 25886998
Systolic global longitudinal strain (GLS) is emerging as a useful metric of ventricular function in heart failure and usually assessed using post-processing software. The purpose of this study was to investigate whether longitudinal strain (LS) derived using manual-tracings of ventricular lengths (manual-LS) can be reliable and time efficient when compared to LS obtained by post-processing software (software-LS). Apical 4-chamber view images were retrospectively examined in 50 healthy controls, 100 patients with dilated cardiomyopathy (DCM), and 100 with hypertrophic cardiomyopathy (HCM). We measured endocardial and mid-wall manual-LS and software-LS, using peak of average regional curve [software-LS(a)] and global ventricular lengths [software-LS(l)] according to definition of Lagragian strain. We compared manual-LS and software-LS by using Bland-Altman plot and coefficient of variation (COV). In addition, test-retest was also performed for further assessment of variability in measurements. While manual-LS was obtained in all subjects, software-LS could be obtained in 238 subjects (95 %). The time spent for obtaining manual-LS was significantly shorter than for the software-LS (94 ± 39 s vs. 141 ± 79 s, P < 0.001). Overall, manual-LS had an excellent correlation with both software-LS (a) (R(2) = 0.93, P < 0.001) and software-LS(l) (R(2) = 0.84, P < 0.001). The bias (95 %CI) between endocardial manual-LS and software-LS(a) was 0.4 % [-2.8, 3.6 %] in absolute and 3.5 % [-17.0, 24.0 %] in relative difference while it was 0.4 % [-2.5, 3.3 %] and 3.4 % [-16.2, 23.1 %], respectively with software-LS(l). Mid-wall manual-LS and mid-wall software-LS(a) also had good agreement [a bias (95 % CI) for absolute value of 0.1 % [-2.1, 2.5 %] in HCM, and 0.2 % [-2.2, 2.6 %] in controls]. The COV for manual and software derived LS were below 6 %. Test-retest showed good variability for both methods (COVs were 5.8 and 4.7 for endocardial and mid-wall manual-LS, and 4.6 and 4.9 for endocardial and mid-wall software-LS(a), respectively. Manual-LS appears to be as reproducible as software-LS; this may be of value especially when global strain is the metric of interest.
View details for DOI 10.1007/s10554-015-0804-x
View details for PubMedID 26578468
No systematic validation study is available with optical frequency domain imaging (OFDI), directly compared with frequency domain optical coherence tomography (FD-OCT) and intravascular ultrasound (IVUS). Controversy also remains about the impact of different stent contour tracing methods by OFDI/FD-OCT. In vitro: coronary phantom models (1.51-5.04 mm) were imaged with OFDI, FD-OCT, and IVUS, demonstrating excellent quantitative precision with a slight overestimation of mean lumen diameter (difference 0.01-0.02 mm). In vivo: corresponding 64 OFDI/IVUS images of stented coronary segments from 20 swines were analyzed. Minimum lumen area by OFDI was larger than IVUS at baseline (P < 0.001), whereas it was smaller than IVUS at follow-up. When stent was traced at leading edges of struts by OFDI, minimum stent area was similar between OFDI and IVUS (P = 0.60). When traced at the highest intensity points of struts by OFDI, it was significantly larger in OFDI than in IVUS (P < 0.001). Three modalities have clinically acceptable precision across the wide range of lumen diameters. In vivo measurements by OFDI and IVUS could slightly be discrepant depending on the parameters and time points. In stent assessment by OFDI, the 2 methods led to a small but systematic difference; therefore, consistency in methodology is advised for comparative studies.
View details for DOI 10.1007/s12928-015-0349-x
View details for PubMedID 26271203
This study investigated the association between arterial remodeling and geographic distribution of cardiac allograft vasculopathy (CAV), and outcomes after heart transplantation.CAV is characterized by a combination of coronary intimal thickening and pathological vessel remodeling, which varies at different locations in coronary arteries.In 100 transplant recipients, serial volumetric intravascular ultrasonography (IVUS) was performed at baseline and 1 year post-transplantation in the first 50 mm of the left anterior descending artery (LAD). IVUS indices were evaluated in the entire segment and 3 equally divided LAD segments. Paradoxical vessel remodeling was defined as [Δvessel volume/Δintimal volume <0].After 1 year, death or re-transplantation occurred in 20 patients over a median follow-up period of 4.7 years. Paradoxical vessel remodeling was observed in 57%, 41%, 50%, and 40% for the entire vessel, proximal, middle, and distal LAD segments, respectively. Kaplan-Meier analysis revealed a significantly lower event-free rate of survival in patients with paradoxical vessel remodeling involving the proximal LAD segment, which was not present when involving the entire LAD or mid and distal LAD segments. In multivariate analysis, paradoxical vessel remodeling of the proximal LAD segment was independently associated with death or re-transplantation (hazard ratio [HR]: 11.18; 95% confidence interval [CI]: 2.39 to 83.23; p = 0.0015).Despite the diffuse nature of CAV, paradoxical vessel remodeling of the proximal LAD segment at 1 year was the primary determinant of long-term mortality or re-transplantation. Assessment of arterial remodeling combined with coronary intimal thickening may enhance identification of high-risk patients who may benefit from closer follow-up and targeted medical therapies.
View details for DOI 10.1016/j.jchf.2015.07.013
View details for PubMedID 26577615
Increased level of serum catecholamines in the acute phase was reported to be a feature of takotsubo cardiomyopathy (TC). We report a TC case with pheochromocytoma, which caused a stir in the diagnosis of TC and suggests the importance of screening for a catecholamine-producing tumor. A female patient was referred to our emergency department due to ongoing chest pain. Coronary angiography showed no abnormality; however, subsequent left ventriculography showed basal hyperkinesis and apical ballooning, which completely recovered in 2 weeks. She experienced significant emotional stress on the eve of her admission, to which the diagnosis of TC was attributed. Although serum catecholamine levels on admission in our case were higher than on day 14, the value on day 14 was much higher than the normal range in our patient. The screening abdominal computed tomography scan revealed a left adrenal mass, which was diagnosed as pheochromocytoma by 24-hour urinary excretion of catecholamine and (131)I-MIBG scintigraphy. The mass was successfully resected and pathological findings supported the diagnosis. In our case, emotional stress was thought to be the direct trigger to develop TC by exceeding the threshold of catecholamine-induced cardiomyopathy. Screening for a catecholamine-producing tumor through careful history-taking and measuring catecholamines at a follow-up stage were important clinical aspects in this case and may well be for others.
View details for PubMedID 24907091
Nicorandil, an ATP sensitive potassium channel opener, may reduce the incidence of microvascular dysfunction after percutaneous coronary intervention (PCI) by dilating coronary resistance vessels. The aim of the study was evaluation of the impact of the administration of intravenous nicorandil on measuring the index of microcirculatory resistance (IMR) in PCI to patients with stable angina pectoris (SAP).Intravascular ultrasound (IVUS), fractional flow reserve (FFR), IMR and blood examination (CK-MB), cardiac troponin I (cTnI) immediately post-PCI (and 24 hours later) were performed in 62 consecutive patients with SAP undergoing PCI. FFR and IMR were measured simultaneously with a single coronary pressure wire. IMR was defined as Pd/coronary flow (or Pd* mean transit time) at peak hyperaemia. Patients were randomised to the control (n=29), or nicorandil group (n=33). In the nicorandil group, nicorandil was intravenously administered as a 6 mg bolus injection just before PCI and as a constant infusion at 6 mg/hour for 24 hours thereafter. All volumetric IVUS parameters and FFR were similar between the two groups both pre- and post-PCI. However, IMR immediately post-PCI and cTnI 24 hours post-PCI were significantly higher in the control group compared to the nicorandil group (IMR: 25.4±12.1 vs. 17.9±9.1 units, and cTnI: 0.21±0.13 vs. 0.12±0.08 ng/mL, for control vs. nicorandil). The incidence for cTnI elevation more than fivefold the normal range (>0.20 ng/mL) was significantly larger in the control group than in the nicorandil group (41% vs. 12%, p<0.01). Additionally, the control group showed a closer correlation between plaque volume reduction during stenting as assessed by volumetric IVUS, and cTnI elevation than the nicorandil group (r=0.55 vs. 0.42, p<0.001 for control vs. nicorandil).In patients undergoing successful coronary stenting for stable angina, administration of nicorandil is associated with reduced microvascular dysfunction induced by PCI.
View details for DOI 10.4244/EIJV9I9A178
View details for PubMedID 24457276
View details for DOI 10.2217/ica.13.88
A case of acute myocardial infarction (AMI) due to thrombus in the left coronary cusp to the ascending aorta is described. There was no clinical evidence of coagulopathy, immunodisability, or local erosive lesion of the aortic and sinus of Valsalva wall macroscopically. Secondary polycythemia, induced by heavy smoking, was the likely cause of the myocardial infarction. Although this may be a rare case, intraaortic thrombus should be considered in the differential diagnosis of the causes of AMI.
View details for Web of Science ID 000324872700018
View details for PubMedID 23913610
The previous OLIVUS trial reported a positive role in achieving a lower rate of coronary atheroma progression through the administration of olmesartan, an angiotension-II receptor blocking agent (ARB), for stable angina pectoris (SAP) patients requiring percutaneous coronary intervention (PCI). However, the benefits between ARB administration on long-term clinical outcomes and serial atheroma changes by IVUS remain unclear. Thus, we examined the 4-year clinical outcomes from OLIVUS according to treatment strategy with olmesartan.Serial volumetric IVUS examinations (baseline and 14 months) were performed in 247 patients with hypertension and SAP. When these patients underwent PCI for culprit lesions, IVUS was performed in their non-culprit vessels. Patients were randomly assigned to receive 20-40mg of olmesartan or control, and treated with a combination of β-blockers, calcium channel blockers, glycemic control agents and/or statins per physician's guidance. Four-year clinical outcomes and annual progression rate of atherosclerosis, assessed by serial IVUS, were compared with major adverse cardio- and cerebrovascular events (MACCE).Cumulative event-free survival was significantly higher in the olmesartan group than in the control group (p=0.04; log-rank test). By adjusting for validated prognosticators, olmesartan administration was identified as a good predictor of MACCE (p=0.041). On the other hand, patients with adverse events (n=31) had larger annual atheroma progression than the rest of the population (23.8% vs. 2.1%, p<0.001).Olmesartan therapy appears to confer improved long-term clinical outcomes. Atheroma volume changes, assessed by IVUS, seem to be a reliable surrogate for future major adverse cardio- and cerebrovascular events in this study cohort.
View details for DOI 10.1016/j.atherosclerosis.2011.10.013
View details for Web of Science ID 000298374800022
View details for PubMedID 22119063