Takumi Higuma

A Combined Optical Coherence Tomography and Intravascular Ultrasound Study on Plaque Rupture, Plaque Erosion, and Calcified Nodule in Patients With ST-Segment Elevation Myocardial Infarction: Incidence, Morphologic Characteristics, and Outcomes After Percutaneous Coronary Intervention.

OBJECTIVES This study sought to evaluate the incidence of plaque rupture (PR), plaque erosion (PE), and calcified nodule (CN) using optical coherence tomography (OCT) in patients with ST-segment elevation myocardial infarction (STEMI); to compare detailed morphologic plaque characteristics of PR, PE, and CN with optical coherence tomography and intravascular ultrasound; and to compare the post-procedure outcomes among PR, PE, and CN. BACKGROUND The incidence and detailed morphologic characteristics of PR, PE, and CN in STEMI patients and their outcome after percutaneous coronary intervention (PCI) are unknown. METHODS A total of 112 STEMI patients who underwent PCI within 24 h [corrected] from symptom onset were included. Both optical coherence tomography and intravascular ultrasound were performed following aspiration thrombectomy. RESULTS The incidence of PR, PE, and CN was 64.3%, 26.8%, and 8.0%, respectively. PE and CN, compared with PR, had more fibrous plaque (p < 0.001 and p < 0.001) and less thin-cap fibroatheroma (p < 0.001 and p < 0.001) as well as smaller plaque burden (p = 0.003 and p = 0.001) and remodeling index (p = 0.003 and p < 0.001). PE had greater plaque eccentricity index than PR and CN (p < 0.001 and p < 0.001). CN had greater calcified arc and shallower calcium than PR (p < 0.001 and p < 0.001) or PE (p < 0.001 and p < 0.001). More than one-half of CN had negative remodeling. PE had a lower incidence of no-reflow phenomenon after PCI than PR (p = 0.011). CONCLUSIONS PE was the underlying mechanism in one-fourth of STEMI. PE was characterized by eccentric fibrous plaque. CN was characterized by superficial large calcium and negative remodeling. PE was associated with less microvascular damage after PCI.

Mechanism of ST elevation and ventricular arrhythmias in an experimental Brugada syndrome model.

Background—Although phase 2 reentry is said to be responsible for initiation of ventricular tachycardia (VT) in Brugada syndrome, information about the activation sequence during VT is limited. Methods and Results—We developed an experimental Brugada syndrome model using a canine isolated right ventricular preparation cross-circulated with arterial blood of a supporter dog and examined the VT mechanism. Two plaque electrodes (35×30 mm) containing 96 bipolar electrodes were attached to the endocardium and epicardium. Saddleback and coved types of ST elevation in transmural ECG were induced by pilsicainide, a pure sodium channel blocker, and pinacidil, a KATP channel opener. Eighteen polymorphic VT episodes were recorded in 9 of the 12 preparations associated with ST elevation. Fourteen episodes spontaneously developed in 5 preparations after an extrasystole during basic drive pacing. Analysis of local recovery times revealed increased dispersion especially in epicardium, and the extrasystole originated from a site with a short recovery time, suggesting that phase 2 reentry was its mechanism. The other 4 VTs in 4 preparations were induced by premature stimulation. Analysis of the activation sequences during VT revealed reentry between epicardium and endocardium or reentry around an arc of a functional block confined to epicardium or endocardium with bystander activation of the other. Conclusions—Electrical heterogeneity in the recovery phase was induced in this experimental Brugada syndrome model, which can be a substrate for the development of phase 2 reentry and the subsequent reentry around an arc of the functional block, resulting in sustained VT.

Efficacy and safety of low-dose pioglitazone after primary coronary angioplasty with the use of bare metal stent in patients with acute myocardial infarction and with type 2 diabetes mellitus or impaired glucose tolerance.

Thiazolidinediones (TZDs) have beneficial effects on markers of cardiovascular risk in patients with type 2 diabetes mellitus (DM). This study aimed to investigate the efficacy and safety of low-dose pioglitazone (15 mg per day) in patients with acute myocardial infarction (AMI) and type 2 DM or impaired glucose tolerance (IGT) treated with coronary angioplasty using bare metal stent (BMS). In 56 patients, pioglitazone was orally administered for 6 months after stenting (pioglitazone group). The incidence of in-stent restenosis (ISR) and left ventricular end-diastolic volume index (LVEDVI) at acute phase and 6 months after stenting in these patients were retrospectively compared with those in the other 37 patients (control group) treated without pioglitazone. No adverse events including death, emergency bypass surgery, and reinfarction, occurred in any patients in the hospital. There was no congestive heart failure (CHF) during a follow-up period in the pioglitazone group. At 6 months after stenting, the overall angiographic ISR rate was significantly lower in the pioglitazone group than in the control group (28.6% vs 48.6%, P = 0.049). In patients with hemoglobin A1c (HbA1c) <7.0% at follow-up, the ISR rate was also significantly lower in the pioglitazone group than in controls (21.3% vs 44.8%, P = 0.03). Delta-LVEDVI (defined as follow-up LVEDVI minus acute LVEDVI) was similar between the pioglitazone group and control group (0.13 vs 5.16 ml/m2, P = 0.482). Low-dose pioglitazone seems to have a potential to reduce ISR and does not adversely affect LV remodeling after AMI treated with coronary angioplasty using BMS in patients with type 2 DM or IGT.

Effects of pravastatin and rosuvastatin on the generation of adiponectin in the visceral adipose tissue in patients with coronary artery disease

Pravastatin increases the plasma adiponectin level. We examined whether this is a statins’ class effect or specific to pravastatin. Of 50 patients undergoing cardiac surgery for coronary artery disease (CAD, n = 36) and valvular heart disease (VHD, n = 14), 23 with CAD and serum LDL‐cholesterol level >100 mg/dL were randomized to pravastatin at 10 mg/day (PRAVA, n = 12) or rosuvastatin at 2.5 mg/day (ROSUVA, n = 11) for 2 months, and the other 13 with CAD and LDL‐cholesterol ≤100 mg/dL were not treated with statin (Non‐statin, n = 13). Patients with VHD did not have CAD and were not treated with statin. Blood was sampled at baseline and surgery. Visceral (VIS) and subcutaneous (SC) adipose tissues were harvested during surgery. At baseline, the plasma adiponectin level was low in patients with CAD compared with that of patients with VHD. At surgery, adiponectin level in PRAVA was increased to the level in VHD, whereas those in ROSUVA and Non‐statin were unchanged. VIS contents and gene expressions of adiponectin in PRAVA and VHD were similar to each other and were both higher than those in Non‐statin and ROSUVA. SC content and gene expression of adiponectin were similar among 4 groups. Protein carbonyl (PC) level, an indicator of oxidative stress, in VIS was lower in PRAVA and VHD than in ROSUVA and Non‐statin. There was a negative correlation between the plasma adiponectin and VIS PC levels (r = −0.41, P < 0.05). Thus, pravastatin increases adiponectin generation, whereas rosuvastatin does not.

Increased serum anandamide level at ruptured plaque site in patients with acute myocardial infarction

Inflammation caused by activated macrophages and T lymphocytes may trigger plaque rapture in acute coronary syndrome (ACS). Anandamide and 2‐arachidonylglycerol (2‐AG) are macrophage‐derived signal lipids and may be involved in the pathogenesis of ACS, but no clinical relevant data have been reported. In 43 acute myocardial infarction (AMI) patients (66 ± 2 years), blood samples were obtained from the aortic root and the infarct‐related coronary artery (IRA) using a PercuSurge system during primary percutaneous coronary intervention (PCI). In six patients with stable effort angina (SEA) (56 ± 6 years), blood samples were obtained from the site of stenosis during elective PCI. In 25 of the 43 AMI patients, anandamide was detected in the serum. Serum anandamide level was 35 ± 20 pmol/mL in the aorta and was significantly increased to 401 ± 134 pmol/mL in the IRA (P < 0.01). 2‐AG was undetectable in most of the patients. In patients with SEA, neither anandamide nor 2‐AG was detected in the serum at the plaque site. In AMI patients with anandamide detected, left ventricular ejection fraction at 2 weeks after PCI was increased by 3.7 ± 2.1% compared with that at the acute phase, while it was decreased by 3.0 ± 1.8% in those without anandamide detected (P < 0.05). The serum anandamide level at the culprit lesion was elevated compared with the systemic level in a significant number of AMI patients, indicating the synthesis of anandamide at the IRA. Anandamide was suggested to be derived from ruptured plaque and may exert beneficial effects in humans.

Decreased plasma and cardiac matrix metalloproteinase activities in patients with coronary artery disease and treated with pravastatin

Matrix metalloproteinase (MMP), which is activated by oxidative stress, plays an important role in the development of ventricular remodeling in coronary artery disease. Pravastatin is shown to reduce oxidative stress. We tested the hypothesis that cardiac oxidative stress and MMP activity are reduced in patients with coronary artery disease and treated with pravastatin. Forty-eight patients who underwent coronary artery bypass graft surgery (CABG) were studied. Twenty-four patients had the serum low-density lipoprotein (LDL) cholesterol level >2.59 mM, and were treated with pravastatin (10 mg/day) for 2 months before CABG (pravastatin group). The other 24 had LDL cholesterol< or =2.59 mM, and were untreated (control group). The plasma and pericardial MMP-2 and MMP-9 activities were measured by gelatin zymography, and MMP-2 and MMP-9 levels, and pericardial 8-iso-prostagrandin F2alpha (8-iso-PGF2alpha) level, a maker of oxidative stress, by enzyme-linked immunosorbent assay. The plasma and pericardial MMP-2 and MMP-9 activities and levels were all lower by 20-30% in pravastatin than in control group (all P<0.05). The pericardial 8-iso-PGF2alpha level was lower in pravastatin than in control group (38+/-4 vs 64+/-7 pg/ml, P<0.05). The pericardial MMP-2 and MMP-9 activities were positively correlated with the pericardial 8-iso-PGF2alpha level (r=0.57 and 0.47, respectively, both P<0.01). Thus, cardiac oxidative stress and MMP activities are reduced in patients with coronary artery disease and treated with pravastatin, which may be beneficial in preventing and reducing ventricular remodeling.

Impact of telmisartan on coronary stenting in patients with acute myocardial infarction compared with enalapril

OBJECTIVE To determine whether telmisartan reduces in-stent restenosis (ISR) after coronary angioplasty using bare metal stent (BMS) in patients with acute myocardial infarction (AMI) compared with an angiotensin converting enzyme (ACE) inhibitor. BACKGROUND The efficacy of inhibition of renin-angiotensin-aldosterone system in patients with AMI has been established, and the prescription of ACE inhibitor is recommended as class I indication for all AMI patients, whereas that of angiotensin II receptor blocker (ARB) as class IIa. Telmisartan is a unique ARB since it has a peroxisome proliferator-activated receptor (PPAR) gamma activating effect which is known to reduce neointimal tissue proliferation after coronary stenting. METHODS In 64 patients, telmisartan (20-40 mg per day) was orally administered for 6 months after stenting (telmisartan group). The incidence of ISR after stenting in these patients was retrospectively compared with those in the other 60 patients administrated enalapril (2.5-5 mg per day) (enalapril group). RESULTS There were no adverse events such as death, re-infarction and emergency bypass surgery in telmisartan group during a follow-up period for 6 months. The ISR rate was lower in telmisartan group (18.8%) than in enalapril group (33.3%) (p=0.06). However, percent diameter stenosis (%DS) at follow-up in telmisartan group was significantly smaller than in enalapril group (26.7+/-18.6% vs 38.0+/-23.9%, p=0.004). Late lumen loss was also significantly smaller in telmisartan group than in enalapril group (0.97+/-0.48 mm vs 1.19+/-0.68 mm, p=0.039). CONCLUSIONS Telmisartan not only is tolerable in patients with AMI but has a potential to reduce neointimal tissue proliferation after AMI treated with coronary angioplasty using BMS compared with enalapril.

Nicorandil suppresses the increases in plasma level of matrix metalloproteinase activity and attenuates left ventricular remodeling in patients with acute myocardial infarction

Nicorandil, a hybrid KATP channel opener and nicotinamide nitrate, reduces no-reflow phenomenon and improves cardiac function in patients with acute myocardial infarction (AMI). We repoted that nicorandil suppresses radical formation in patients with AMI undergoing primary percutaneous coronary intervention (PCI). In the present study, we tested the hypothesis that nicorandil treatment suppresses MMP activities and predicts ventricular remodeling in AMI. Sixty-two patients with AMI were randomized into nicorandil pretreatment (n = 31) and control (n = 31) groups after admission and underwent primary PCI. Nicorandil was administered as a bolus injection (4 mg) followed by constant infusion (8 mg/h) for 24 h just after admission. On days 1, 2, and 14 after the onset of AMI, the plasma levels of matrix metalloproteinase (MMP)-2 and MMP-9 were measured by enzyme-linked immunosorbent assay and the activities by gelatin zymography. There were no differences in the baseline clinical characteristics between the two groups. On day 1, there were no differences in both MMP-2 and MMP-9 levels and their activities between the two groups. However, both MMP-2 and MMP-9 levels and their activities were significantly lower in nicorandil than in control group on day 2 (MMP-2 level, 1 014 ± 39 vs 1 174 ± 44 ng/ml; MMP-9 level, 17 ± 1 vs 23 ± 2 ng/ml; both P < 005) and on day l4 (MMP-2 level, 970 ± 38 vs 1 221 ± 44 ng/ml; MMP-9 level, 17 ± 1 vs 23 ± 1 ng/ml; both P < 0.05). Left ventricular end-diastolic volume index (LVEDVI) at acute phase was not different between the two groups. At 6 months after AMI, LVEDVI was significantly smaller in nicorandil than in the control group (83 ± 4 vs 96 ± 4 ml/m2, P < 0.05). The change in LVEDVI from acute phase to 6 months was positively correlated with MMP-2 and MMP-9 levels and activities. Nicorandil suppresses the increases in MMP levels and activities and prevents the development of ventricular remodeling in AMI.

V-H-A Pattern as a criterion for the differential diagnosis of atypical AV nodal reentrant tachycardia from AV reciprocating tachycardia.

Background: During ventricular extrastimulation, His bundle potential (H) following ventricular (V) and followed by atrial potentials (A), i.e., V‐H‐A, is observed in the His bundle electrogram when ventriculo‐atrial (VA) conduction occurs via the normal conduction system. We examined the diagnostic value of V‐H‐A for atypical form of atrioventricular nodal reentrant tachycardia (AVNRT), which showed the earliest atrial activation site at the posterior paraseptal region during the tachycardia.

Morphological predictors for no reflow phenomenon after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction caused by plaque rupture

Aims Myocardial no reflow after percutaneous coronary intervention (PCI) is associated with poor outcome. Patients with ST-segment elevation myocardial infarction (STEMI) caused by plaque rupture are at high risk for no reflow. However, specific morphologic characteristics associated with no reflow are unknown in this population. The aim of this study is to identify the morphological characteristics of culprit plaques associated with no reflow in patients with STEMI caused by plaque rupture using both optical coherence tomography (OCT) and intravascular ultrasound (IVUS). Methods and results We enrolled 145 patients with STEMI who underwent both OCT and IVUS within 12 h of symptom onset. Among these patients, we excluded those with plaque erosion and calcified nodule and included 72 patients who had plaque rupture as an underlying mechanism for STEMI. Myocardial no reflow, defined as Thrombolysis in Myocardial Infarction flow grade 0–2 and/or myocardial blush grade 0–1 after PCI, was observed in 28 patients (38.9%). Onset to recanalization time was similar between the groups with and without no reflow. Receiver-operating curve analysis revealed OCT-derived lipid index > 3500 [area under curve (AUC) 0.77, P < 0.001] and IVUS-derived plaque burden > 81.5% (AUC 0.70, P = 0.002) were the best discriminators for myocardial no reflow. Conclusion No reflow occurred in nearly 40% of patients with STEMI caused by plaque rupture. Large lipid index and plaque burden were critical morphological discriminators between no reflow and normal flow.