Teruo Noguchi

Percutaneous transluminal coronary angioplasty of chronic total occlusions. determinants of primary success and long-term clinical outcome

This study was conducted to assess the determinants of the procedural success and long‐term clinical benefits of percutaneous transluminal balloon angioplasty (PTCA) of chronic total occlusion (CTO) in recent years. Two hundred and twenty‐six consecutive patients who underwent PTCA of CTO were divided into two groups according to the procedural success (n = 134) or failure (n = 92). Both groups were analyzed in terms of the initial success, predictors of procedural failure, and clinical outcome. The procedural success rate was noted to have improved to more than 70% since 1995. A multiple logistic regression analysis revealed that the presence of calcification, the length of the occlusion and the presence of multivessel disease were independent predictors of procedural failure. Cardiac death and the need for coronary surgery were significantly less frequent in patients with procedural success than in those with procedural failure. In properly selected cases, the success rate of PTCA of CTO is acceptable. Long‐term clinical benefit is suggested by the high rate of freedom from coronary surgery and the low cardiac death rate in the patients who underwent successful revascularization. Cathet. Cardiovasc. Intervent. 49:258–264, 2000.

High-intensity signals in coronary plaques on noncontrast T1-weighted magnetic resonance imaging as a novel determinant of coronary events.

OBJECTIVES The aim of this study was to determine whether coronary high-intensity plaques (HIPs) visualized by noncontrast T1-weighted imaging can predict future coronary events. BACKGROUND Coronary HIPs are associated with characteristics of vulnerable plaques, including positive remodeling, lower Hounsfield units, and ultrasound attenuation. However, it remains unclear whether the presence of HIPs is associated with increased risk for coronary events. METHODS The signal intensity of coronary plaques was prospectively examined in 568 patients with suspected or known coronary artery disease (CAD) who underwent noncontrast T1-weighted imaging to determine the plaque-to-myocardium signal intensity ratio (PMR). RESULTS During the follow-up period (median 55 months), coronary events were observed in 55 patients. Receiver-operating characteristic curve analysis identified a PMR of 1.4 as the optimal cutoff for predicting prognosis. Multivariate Cox regression analysis identified the presence of plaques with PMRs ≥1.4 as the significant independent predictor of coronary events (hazard ratio: 3.96; 95% confidence interval: 1.92 to 8.17; p < 0.001) compared with the presence of CAD (hazard ratio: 3.56; 95% confidence interval: 1.76 to 7.20; p < 0.001) and other traditional risk factors. Among the 4 groups based on PMR cutoff and the presence of CAD, coronary event-free survival was lowest in the group with PMRs ≥1.4 and CAD and highest in the group with PMRs <1.4 but no CAD. Importantly, the group with PMRs ≥1.4 and no CAD had an intermediate rate of coronary events, similar to the group with PMRs <1.4 and CAD. CONCLUSIONS HIPs identified in a noninvasive, quantitative manner are significantly associated with coronary events and may thus represent a novel predictive factor.

Characterization of Hyperintense Plaque With Noncontrast T1-Weighted Cardiac Magnetic Resonance Coronary Plaque Imaging: Comparison With Multislice Computed Tomography and Intravascular Ultrasound

OBJECTIVES This study sought to characterize coronary hyperintense plaques (HIP) using noncontrast T(1)-weighted imaging (T1WI) in cardiac magnetic resonance, which was then compared with multislice computed tomography and intravascular ultrasound. BACKGROUND Carotid plaque components such as intraplaque hemorrhages and/or lipid-rich necrotic cores can be detected as HIP by noncontrast T1WI. Although coronary HIPs have been successfully detected using this technique, the properties of hyperintense signals in coronary plaques have not yet been systematically evaluated. METHODS Thirty-eight lesions from 37 patients with angina pectoris who demonstrated >70% coronary stenosis on multislice computed tomography were evaluated by noncontrast T1WI using a 1.5-T magnetic resonance imager, and 25 lesions were evaluated by intravascular ultrasound. Signal intensity of coronary plaque to cardiac muscle ratio >1.0 was defined as HIP. We divided 25 lesions into the 2 groups, according to the presence or absence of HIP: HIP (n = 18) and non-HIP (n = 7) groups. RESULTS In comparison with the non-HIP group, the HIP group demonstrated significantly higher coronary plaque to cardiac muscle ratio (1.7 +/- 0.7 vs. 0.9 +/- 0.1, p < 0.01), higher frequency of positive remodeling as observed by both multislice computed tomography (89% vs. 0%, p<0.0001) and intravascular ultrasound (94% vs. 14%, p < 0.001) and ultrasound attenuation (100% vs. 14.3%, p < 0.0001). The frequency of spotty calcification tended to be higher in HIP (89% vs. 50%, p = 0.079). The HIP group also exhibited a significantly lower computed tomography density (-23.2 +/- 20.7 Hounsfield units [HU] vs. 9.6 +/- 20.5 HU, p < 0.01). In addition, the incidence of transient slow-flow phenomena was significantly higher in the HIP group than in the non-HIP group (83% vs. 14%, p < 0.01). CONCLUSIONS The typical HIP case was associated with ultrasound attenuation, positive remodeling, remarkably low computed tomography density, and a high incidence of slow-flow phenomena. Noncontrast T1WI in cardiac magnetic resonance imaging may be useful for the assessment of coronary plaque characterization in patients with coronary artery disease.

C-Terminal Truncation of Cardiac Troponin I Causes Divergent Effects on ATPase and Force Implications for the Pathophysiology of Myocardial Stunning

Abstract— Myocardial stunning is a form of reversible myocardial ischemia/reperfusion injury associated with systolic and diastolic contractile dysfunction. In the isolated rat heart model, myocardial stunning is characterized by specific C-terminal proteolysis of the myofilament protein, troponin I (cTnI) that yields cTnI1-193. To determine the effect of this particular C-terminal truncation of cTnI, without the confounding factor of other stunning-induced protein modifications, a series of solution biochemical assays has been undertaken using the human homologue of mouse/rat cTnI1-193, cTnI1-192. Affinity chromatography and actin sedimentation experiments detected little, or no, difference between the binding of cTnI (cTnI1-209) and cTnI1-192 to actin-tropomyosin, troponin T, or troponin C. Both cTnI and cTnI1-192 inhibit the actin-tropomyosin–activated ATPase activity of myosin subfragment 1 (S1), and this inhibition is released by troponin C in the presence of Ca2+. However, cTnI1-192, when reconstituted as part of the troponin complex (cTn1-192), caused a 54±11% increase in the maximum Ca2+-activated actin-tropomyosin-S1 ATPase activity, compared with troponin reconstituted with cTnI (cTn). Furthermore, cTn1-192 increased Ca2+ sensitivity of both the actin-tropomyosin-activated S1 ATPase activity and the Ca2+-dependent sliding velocity of reconstituted thin filaments, in an in vitro motility assay, compared with cTn. In an in vitro force assay, the actin-tropomyosin filaments bearing cTn1-192 developed only 76±4% (P <0.001) of the force obtained with filaments composed of reconstituted cTn. We suggest that cTnI proteolysis may contribute to the pathophysiology of myocardial stunning by altering the Ca2+-sensing and chemomechanical properties of the myofilaments.

Thin Filament-Based Modulation of Contractile Performance in Human Heart Failure

Background—The contribution of the sarcomere’s thin filament to the contractile dysfunction of human cardiomyopathy is not well understood. Methods and Results—We have developed techniques to isolate and functionally characterize intact (native) thin filaments obtained from failing and nonfailing human ventricular tissue. By use of in vitro motility and force assays, native thin filaments from failing ventricular tissue exhibited a 19% increase in maximal velocity but a 27% decrease in maximal contractile force compared with nonfailing myocardium. Native thin filaments isolated from human myocardium after left ventricular assist device support demonstrated a 37% increase in contractile force. Dephosphorylation of failing native thin filaments resulted in a near-normalization of thin-filament function, implying a phosphorylation-mediated mechanism. Tissue expression of the protein kinase C isoforms &agr;, &bgr;1, and &bgr;2 was increased in failing human myocardium and reduced after left ventricular assist device support. Conclusions—These novel findings demonstrate that (1) the thin filament is a key modulator of contractile performance in the failing human heart, (2) thin-filament function is restored to near normal levels after LVAD support, and (3) the alteration of thin-filament function in failing human myocardium is mediated through phosphorylation, most likely through activation of protein kinase C.

Myosin from failing and non-failing human ventricles exhibit similar contractile properties.

In non-failing human myocardium, V1 myosin comprises a small amount (<10%) of the total myosin content, whereas end-stage failing hearts contain nearly 100% V3 myosin. It has been suggested that this shift in V1 myosin isoform content may contribute to the contractile deficit in human myocardial failure. To test this hypothesis, myosin was isolated from human failing and non-failing ventricles, and non-failing atria. Performance was assessed in in vitro motility and isometric force assays. Consistent with prior reports, a small amount of V1 myosin was present in both non-failing (6.2 +/- 1.0%) and failing (3.5 +/- 1.4%) ventricular tissues. No difference in isometric force or unloaded shortening velocity was observed for failing and non-failing ventricular myosin irrespective of myosin isoform content. Atrial tissue expressing predominantly V1 myosin (66.7 +/- 4.1%) generated half the force but greater velocity compared with ventricular tissue, expressing predominantly V3 myosin. In additional experiments, rabbit cardiac myosin was used in a calcium regulated assay system to determine if V1 and V3 isoforms differentially affect thin filament activation. Half-maximal calcium activation was similar for the two cardiac isoforms. A 1:9 mixture of V1/V3 myosin, simulating isoform composition in non-failing human myocardium, was indistinguishable from 100% V3 myosin (simulating the failing state) with regard to velocity of shortening and average force. These data suggest that the myosin isoform shift reported in human myocardial failure does not significantly contribute to the contractile deficit of this disease.

Effect of Cardiac Myosin Binding Protein-C on Mechanoenergetics in Mouse Myocardium

We examined the effect of cardiac myosin binding protein-C (cMyBP-C) on contractile efficiency in isovolumically contracting left ventricle (LV) and on internal viscosity and oscillatory work production in skinned myocardial strips. A 6-week diet of 0.15% 6-n-propyl-2-thiouracil (PTU) was fed to wild-type (+/+PTU) and homozygous-truncated cMyBP-C (t/tPTU) mice starting at age ≈8 weeks and leading to a myosin heavy chain (MHC) isoform profile of 10% &agr;-MHC and 90% β-MHC in both groups. Western blot analysis confirmed that cMyBP-C was present in the +/+PTU and effectively absent in the t/tPTU. Total LV mechanical energy per beat was quantified as pressure-volume area (PVA). O2 consumption (VO2) per beat was plotted against PVA at varying LV volumes. The reciprocal of the slope of the linear VO2–PVA relation represents the contractile efficiency of converting O2 to mechanical energy. Contractile efficiency was significantly enhanced in t/tPTU (26.1±2.6%) compared with +/+PTU (17.1±1.6%). In skinned myocardial strips, maximum isometric tension was similar in t/tPTU (18.7±2.1 mN · mm−2) and +/+PTU (21.9±4.0 mN · mm−2), but maximum oscillatory work induced by sinusoidal length perturbations occurred at higher frequencies in t/tPTU (7.31±1.17 Hz) compared with +/+PTU (4.48±0.60 Hz) and was significantly more sensitive to phosphate concentration in the t/tPTU. Under rigor conditions, the internal viscous load was significantly lower in the t/tPTU compared with +/+PTU, ie, ≈40% lower at 1 Hz. These results collectively suggest that contractile efficiency is enhanced in the t/tPTU, probably through a reduced loss of mechanical energy by a viscous load normally provided by cMyBP-C and through a gain of phosphate-dependent oscillatory work normally inhibited by cMyBP-C.

Prognostic impact of spontaneous coronary artery dissection in young female patients with acute myocardial infarction: A report from the Angina Pectoris–Myocardial Infarction Multicenter Investigators in Japan

BACKGROUND We sought to compare the prognosis of patients with spontaneous coronary artery dissection (SCAD) and atherosclerosis as the cause of acute myocardial infarction (AMI), especially in young females. METHODS AND RESULTS A total of 20,195 patients with AMI at 20 institutions between 2000 and 2013 were retrospectively studied. Major adverse cardiac event (MACE: cardiac death, AMI or urgent revascularization) was the endpoint. The overall prevalence of SCAD was 0.31% (n=63; female, 94%). SCAD developed following emotional stress in 29% of patients. Revascularization was performed in 56% (35 of 63 patients), and SCAD recurrence developed in the originally involved vessel in 6 of 35 patients with revascularization, compared to none among 28 patients after conservative therapy (p=0.002). We compared the clinical characteristics of young female AMI patients aged ≤50years in the SCAD (n=45) and no-SCAD groups (atherosclerotic AMI, n=55). During a median follow-up of 50months, SCAD recurred in 27% of patients, of which 42% was in the first 30days. Kaplan-Meier analysis showed a significantly higher incidence of MACE in the SCAD group compared to the no-SCAD group (hazard ratio, 6.91; 95% confidence interval, 2.5 to 24.3; p<0.001), although the rate of successful percutaneous coronary intervention for SCAD was as high as 92%. CONCLUSIONS Young female patients with SCAD represent a high-risk subgroup of patients with AMI and require close follow-up.

The First Clinical Pilot Study of Intravenous Adrenomedullin Administration in Patients With Acute Myocardial Infarction

Adrenomedullin (AM) is a 52-amino-acid vasodilator peptide that was originally isolated from human pheochromocytoma. In the previous experimental study with rat ischemia/reperfusion model, AM reduced infarct size and inhibited myocyte apoptosis. AM also suppressed the production of oxygen-free radicals. The present study was designed to evaluate the feasibility of intravenous administration of AM in patients with acute myocardial infarction. We studied 10 patients with first acute myocardial infarction [male to female ratio: 9 to 1, age: 65 ± 9 (mean ± SD) years, peak creatine phosphokinase level: 4215 ± 1933 (SD) U/L], who were hospitalized within 12 hours of symptom onset. Proceeding reperfusion therapy, AM infusion was initiated and continued at concentration of 0.0125-0.025 μg·kg−1·min−1 for 12 hours. Follow-up coronary angiography and left ventriculography were performed at 3 months. Cardiac magnetic resonance was examined at 1 month and 3 months after AM therapy. During infusion of AM, hemodynamics kept stable except 2 patients. Wall motion index in the infarct area at 3 months was significantly improved compared with that at baseline, and infarct size evaluated by cardiac magnetic resonance was significantly decreased at 3 months. In conclusion, intravenous administration of AM, which possesses a variety of potential cardiovascular protective actions, can be adjunctive to percutaneous coronary intervention.

High-intensity signals in carotid plaques on T1-weighted magnetic resonance imaging predict coronary events in patients with coronary artery disease.

OBJECTIVES The purpose of this study was to determine whether high-intensity carotid plaques visualized by a noncontrast T1-weighted imaging technique, magnetization-prepared rapid acquisition with gradient echo (MPRAGE), predict future coronary events in patients with clinically stable coronary artery disease (CAD). BACKGROUND Coronary plaque vulnerability to rupture can be assessed by examining for the presence of atherosclerosis and measuring intima media thickness (IMT) in surrogate vessels such as the carotid arteries. We previously showed that MPRAGE successfully identifies vulnerable carotid plaques as high-intensity signals. It remains unclear, however, if the presence of carotid high-intensity plaques (HIP) is associated with an increased risk of coronary events. METHODS We examined the signal intensity of carotid plaques in 217 patients with clinically stable CAD using MPRAGE with magnetic resonance imaging and measured IMT with ultrasonography. A carotid HIP was defined as a signal >200% that of the adjacent muscle. All patients were divided into 2 groups according to the presence or absence of HIP, namely, the HIP group (n = 116) and the non-HIP group (n = 101), and were followed up for as long as 72 months. RESULTS The presence of HIP was significantly associated with cardiac events compared to the non-HIP group (log-rank p < 0.0001). Furthermore, multivariate Cox regression analysis identified the presence of HIP as the strongest independent predictor of cardiac events (hazard ratio: 3.15; 95% confidence interval: 1.93 to 5.58, p < 0.0001) compared with IMT (hazard ratio: 1.62, 95% confidence interval: 0.97 to 2.44, p = 0.055) and other coronary risk factors. CONCLUSIONS Characterization of carotid plaques using magnetic resonance imaging with MPRAGE provides more clinically relevant information for the risk assessment of CAD patients than IMT.