Feasibility and safety of transradial balloon aortic valvuloplasty in patients with severe aortic stenosis.

Balloon aortic valvuloplasty (BAV) was developed as a technique to treat aortic stenosis (AS) and is associated with significant improvements in aortic valve area and trans-aortic valve gradient in the early and immediate periods after the procedure. BAV is commonly performed using a trans-femoral retrograde approach; however, trans-femoral access is associated with frequent access-site bleeding. Among 146 patients with symptomatic severe AS who were treated with BAV in our institution, 123 patients received BAV treatment via a trans-radial approach using a 7-Fr Glidesheath. The balloon size was 16-20 mm for all patients. Echocardiograms were obtained before and after BAV. Patients who received BAV alone (n = 119) were followed up for 3 months, and major adverse events (stroke, re-hospitalization for heart failure, and death) and procedural complications were recorded. At post-procedural echocardiography, the mean trans-valvular gradient (49.7 ± 21.5-42.5 ± 17.6 mmHg; p < 0.0001) was reduced significantly. All patients in this study did not die or require valve surgery within the first 7 days after BAV. Successful BAV was obtained in 45.6% of the patients. No patients had severe aortic insufficiency or BAV access-site bleeding. Three patients died suddenly and 4 patients were readmitted for heart failure. Trans-radial BAV is safe and may be useful as a bridging therapy for trans-catheter aortic valve replacement or surgical aortic valve replacement.

Admission free-fatty acid level is a predictor of the mid-term worsening renal function in patients with ST-segment elevation myocardial infarction.

Whether free fatty acids (FFAs), which are generators of reactive oxygen species and substrates of cytotoxic lipid peroxidation products in proximal tubules of the kidney, can be a predictor of worsening renal function (WRF) is not fully elucidated. A total of 110 patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention within 24 h after symptom onset were included. The exclusion criteria were out-of-hospital cardiac arrest, vasospastic angina, hemodialysis, and/or lack of data. FFAs and serum cystatin C were measured on admission, and urinary liver-type fatty acid-binding protein (L-FABP) was measured 3 h after admission. WRF, defined as an increase in serum creatinine by ≥ 0.3 mg/dL for 2-year follow-up, was observed in 16 patients (15%). A multivariate logistic regression analysis (a stepwise algorithm) revealed that the FFA level was an independent predictor of WRF (P = 0.024). The FFA level was associated with WRF adjusted after serum cystatin C (odds ratio [OR]: 1.378 per 1 mEq/L, P = 0.017), L-FABP (OR: 1.370 per 1 mEq/L, P = 0.016), or the Mehran contrast-induced nephropathy (CIN) risk score (OR: 1.362 per 1 mEq/L, P = 0.021). The FFA level was inversely associated with the change in estimated glomerular filtration rate level for 2 years (R2 = 0.051, P = 0.018). The FFA level on admission was associated with the mid-term WRF in patients with STEMI.

Direct Oral Anticoagulant Therapy for Isolated Distal Deep Vein Thrombosis Associated with Cancer in Routine Clinical Practice.

BACKGROUND: The efficacy and bleeding complications of direct oral anticoagulant (DOAC) therapy for isolated distal deep vein thrombosis (IDDVT) associated with cancer in routine clinical practice remain unclear. Moreover, prior studies on prolonged therapy for IDDVT are limited. METHODS: This retrospective study enrolled 1641 consecutive patients with acute venous thromboembolism (VTE) who had received oral anticoagulant therapy, including warfarin or DOAC, between April 2014 and September 2018 in our institutions. In these patients, 200 patients with cancer-associated IDDVT were evaluated. RESULTS: Mean follow-up period was 780 ± 593 days. Major bleeding and VTE recurrence were observed in 22 (11.0%) and 11 (5.5%) patients, respectively. In multivariate analysis, statistically significant factors correlated with major bleeding were advanced cancer stage, high performance status, stomach cancer, and gallbladder cancer; those correlated with all-cause death were advanced cancer stage, high performance status, liver dysfunction, pancreatic cancer, and major bleeding. Cumulative events of major bleeding and recurrence between patients with prolonged DOAC therapy (≥90 days) and those with nonprolonged therapy were not significantly different. CONCLUSIONS: Preventing major bleeding is important because it is a significant risk factor for all-cause death. Major bleeding and recurrent events were comparable between prolonged and nonprolonged therapy.

Prognostic impact of muscle and fat mass in patients with heart failure.

BACKGROUND: Cachexia, characterized by loss of muscle with or without loss of fat mass, is a poor prognostic factor in patients with heart failure (HF). However, there is limited investigation on the prognostic impact of muscle and fat mass separately in HF. We hypothesized that muscle and fat mass have different effects on the prognosis of HF. METHODS: This was an observational cohort study of 418 patients (59% were men) admitted with a diagnosis of HF (71 ± 13 years [mean ± standard deviation]), with left ventricular ejection fraction (LVEF) of 39 ± 16%, including 31.3%, 14.8%, and 53.8% of patients with preserved LVEF (LVEF ≥ 50%), mid-range LVEF (40-50%), and reduced (<40%) LVEF, respectively. Dual-energy X-ray absorptiometry was performed with the patients in the stable state after decongestion therapy. RESULTS: The mean body mass index of patients was 22.1 ± 4.6 kg/m2 , and the mean appendicular skeletal mass (ASM) index was 6.88 ± 1.23 kg/m2 in men and 5.59 ± 0.92 in women; 54.1% of the patients showed reduced muscle mass defined by the international cut-off value (7.0 kg/m2 for men and 5.4 for women). The mean fat mass was 20.4 ± 7.2% in men and 27.2 ± 8.6% in women. During a median follow-up of 37 months, 92 (22.0%) of 418 patients with HF died (1 and 3 year mortality: 8.4% and 17.3%, respectively). Lower values of both skeletal muscle and fat mass were independently associated with increased risk of mortality adjusted for age, sex, haemoglobin, New York Heart Association functional class, and height squared (hazard ratio with 95% confidence interval of 0.825 [0.747-0.908] per 1 kg increase of ASM, P < 0.001, and 0.954 [0.916-0.993] per 1 kg increase of fat mass, P = 0.018, respectively). CONCLUSIONS: More than half of the patients with HF showed reduced muscle mass. Lower values of both muscle and fat mass were associated with higher mortality in HF.

Characteristics and clinical outcomes of patients with de-escalation from prasugrel to clopidogrel after acute myocardial infarction - Insights from the prospective Japan Acute Myocardial Infarction Registry (JAMIR).

BACKGROUND: De-escalation of P2Y12 inhibitor may occur for various clinical reasons in patients with acute myocardial infarction (AMI). We aimed to assess the characteristics and outcomes of patients who underwent a de-escalation strategy in real-world clinical practice. METHODS AND RESULTS: We studied 2604 AMI patients initially treated with prasugrel using the Japan Acute Myocardial Infarction Registry (JAMIR) database. Of these, 110 (4%) were discharged on clopidogrel [de-escalation group; switching 4 days after admission (median)] and the remaining 2494 continued prasugrel at discharge (continuation group). The de-escalation group had higher incidence of heart failure or history of cerebrovascular disease, and were more likely to receive mechanical circulatory support, and oral anticoagulation than the continuation group. During mean follow-up of 309±133 days post-discharge, no significant differences were observed in ischemic events (2.2% vs. 2.8%, p = 0.74) or major bleeding (1.1% vs. 1.6%, p = 0.72) between the de-escalation and continuation groups. CONCLUSIONS: Although, patients with de-escalation from prasugrel to clopidogrel had higher bleeding risk profile than those continued on prasugrel, post discharge ischemic and bleeding events were similar between patients with and without de-escalation. De-escalation strategy may be an option for AMI patients with high risk for bleeding.

Direct Oral Anticoagulant Therapy for Cancer-Associated Venous Thromboembolism in Routine Clinical Practice.

BACKGROUND: The efficacy and bleeding complications of direct oral anticoagulant (DOAC) therapy for cancer-associated venous thromboembolism (VTE) in routine clinical practice remain unclear. Moreover, data on long-term outcomes in patients with cancer-associated VTE who received DOAC therapy are limited.Methods and Results:This retrospective study enrolled 1,096 consecutive patients with acute VTE who received warfarin or DOAC therapy between April 2014 and May 2017. The mean follow-up period was 665±490 days. The number of cancer-associated VTE patients who received DOAC therapy was 334. Patients who could not be followed up and those prescribed off-label under-dose DOAC were excluded. Finally, 303 patients with cancer-associated VTE were evaluated. The number of cases of major bleeding and VTE recurrence was 54 (17.8%) and 26 (8.6%), respectively. In the multivariate analysis, the factors correlated with major bleeding were high cancer stage, high performance status, liver dysfunction, diabetes mellitus, and stomach cancer; those correlated with recurrent VTE were initial diagnosis of pulmonary embolism, uterine cancer, and previous cerebral infarction. Major bleeding was an independent risk factor of all-cause death. In the Kaplan-Meier analysis, those who received prolonged DOAC therapy had lower composite major bleeding and recurrent VTE risks than those who did not. CONCLUSIONS: In DOAC therapy for cancer-associated VTE, major bleeding prevention is important because it is an independent risk factor of death.

Acute anterior myocardial infarction with pectus carinatum.

We presented a case of acute anterior myocardial infarction caused by left anterior descending artery occlusion in a patient with pectus carinatum. The electrocardiogram (ECG) on admission showed counterclockwise rotation and T wave inversion only in leads V1-V2. Computed tomography revealed that this patient with pectus carinatum had greater septal angle. Electrocardiographic counterclockwise rotation due to greater septal angle in pectus carinatum led to atypical ECG findings of acute myocardial infraction.

Stress Perfusion Coronary Flow Reserve Versus Cardiac Magnetic Resonance for Known or Suspected CAD.

BACKGROUND: Phase-contrast (PC) cine magnetic resonance imaging (MRI) of the coronary sinus is a noninvasive method to quantify coronary flow reserve (CFR). OBJECTIVES: This study sought to compare the prognostic value of CFR by cardiac magnetic resonance (CMR) and stress perfusion CMR to predict major adverse cardiac events (MACE). METHODS: Participants included 276 patients with known coronary artery disease (CAD) and 400 with suspected CAD. CFR was calculated as myocardial blood flow during adenosine triphosphate infusion divided by myocardial blood flow at rest using PC cine MRI of the coronary sinus. RESULTS: During a median follow-up of 2.3 years, 47 patients (7%) experienced MACE. Impaired CFR (<2.0) and >10% ischemia on stress perfusion CMR were significantly associated with MACE in patients with known CAD (hazard ratio [HR]: 5.17 and HR: 5.10, respectively) and suspected CAD (HR: 14.16 and HR: 6.50, respectively). The area under the curve for predicting MACE was 0.773 for CFR and 0.731 for stress perfusion CMR (p = 0.58) for patients with known CAD, and 0.885 for CFR and 0.776 for stress perfusion CMR (p = 0.059) in the group with suspected CAD. In patients with known CAD, sensitivity, specificity, and positive and negative predictive values to predict MACE were 64%, 91%, 38%, and 97%, respectively, for CFR, and 82%, 59%, 15%, and 97%, respectively, for stress perfusion CMR. In the suspected CAD group, these values were 65%, 99%, 80%, and 97%, respectively, for CFR, and 72%, 83%, 22%, and 98%, respectively, for stress perfusion CMR. CONCLUSIONS: The predictive values of CFR and stress perfusion CMR for MACE were comparable in patients with known CAD. In patients with suspected CAD, CFR showed higher HRs and areas under the curve than stress perfusion CMR, suggesting that CFR assessment by PC cine MRI might provide better risk stratification for patients with suspected CAD.

Clinical Implications of Electrocardiograms for Patients With Type A Acute Aortic Dissection.

Type A acute aortic dissection (AAD) is a serious cardiovascular emergency requiring urgent surgery. Timely accurate diagnosis is essential, but often challenging, because of the wide spectrum of clinical presentations. In patients with type A AAD, chest pain is the most common symptom; furthermore, ischemic ST-T changes such as ST-segment elevation or depression or negative T waves are frequently observed on presentation ECG. These clinical presentations of type A AAD are difficult to differentiate from those of acute coronary syndrome (ACS), which could lead to delayed diagnosis and treatment of type A AAD or misdiagnosis of ACS followed by inappropriate treatment. Of note, ischemic ST-T changes have been shown to be associated with poor outcomes in patients with type A AAD. Because ECG is simple, inexpensive, noninvasive, readily available, and rapidly interpretable at the time of presentation, risk stratification based on ECG findings is considered very useful clinically. ECG findings of type A AAD thus have clinically important diagnostic, therapeutic, and prognostic implications; however, the relationships among these factors remain poorly understood. We review the prevalence of ECG abnormalities, clinical features associated with such changes, and the prognostic importance in patients with type A AAD.

Combined impact of chronic kidney disease and contrast-induced nephropathy on long-term outcomes in patients with ST-segment elevation acute myocardial infarction who undergo primary percutaneous coronary intervention.

Contrast-induced nephropathy (CIN) and chronic kidney disease (CKD) are associated with poor outcomes after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI); however, its combined prognostic significance remains unclear. We enrolled 577 patients with AMI undergoing primary PCI within 12 h after symptom onset and measured serum creatinine on admission and the next 3 days. CKD was defined as admission estimated glomerular filtration rate <60 ml/min/1.73 m2, and CIN was defined as creatinine increase ≥0.5 mg/dl or ≥25 % from baseline within the first 72 h. Patients were stratified according to the presence or absence of CKD and CIN. In patients with no CKD and no CIN (n = 244), no CKD but CIN (n = 152), CKD but no CIN (n = 127), and both CKD and CIN (n = 54), the 3-year major adverse cardiovascular events (MACE: a combination of all-cause mortality, nonfatal reinfarction, or heart failure requiring rehospitalization) were 8, 9, 13, and 35 %, respectively (p < 0.001). Multivariate analysis showed that as compared with no CKD and no CIN, hazard ratios (95 % CI) for MACE associated with no CKD but CIN, CKD but no CIN, and both CKD and CIN were 0.91 (0.44-1.84; p = 0.79), 1.11 (0.5-2.23; p = 0.77), and 2.98 (1.48-6.04; p = 0.002), respectively. In patients with AMI undergoing primary PCI, the combination of CKD and CIN is significantly associated with adverse long-term outcomes.

ST-segment category at acute presentation is associated with the time course of coronary artery disease progression in patients with acute coronary syndromes.

BACKGROUND: Several studies have shown higher early mortality for ST-segment elevation acute coronary syndrome (STEACS), but late mortality remains consistently higher for non-ST-segment elevation acute coronary syndrome (NSTEACS). We hypothesized that ST-segment category at acute presentation is associated with the time course of coronary artery disease progression (CP) of nonculprit lesions in patients with acute coronary syndrome (ACS). METHODS: A total of 226 patients (182 men, age 65 ± 10 years) with STEACS (n = 95) or NSTEACS (n = 131) who underwent percutaneous coronary intervention (PCI) during initial hospitalization were studied. All patients underwent serial coronary angiograms (CAGs) performed immediately before PCI and at 7 ± 3 months and 60 ± 10 months after presentation. CP was defined as an increase in stenosis severity >15% of a nonculprit lesion between 2 serial CAGs. RESULTS: The rate of CP between the first and second CAGs did not differ by ST-segment category at acute presentation. Compared to STEACS, NSTEACS had a higher rate of CP between the second and final CAGs (27.4 vs. 42.7%, P = 0.018). Multivariate analysis showed that the independent predictors of CP between the second and final CAGs were NSTEACS (odds ratio 2.709, P = 0.003), estimated glomerular filtration rate <60 ml/min/1.73 m2 (odds ratio 2.447, P = 0.015), and diabetes mellitus (odds ratio 2.135, P = 0.021). CONCLUSIONS: Irrespective of conventional risk factors and angiographic findings, ST-segment category at initial presentation is associated with the persistency of widespread coronary disease activity following presentation in ACS patients undergoing PCI. This may partly explain the time-dependent differences in outcomes of patients with STEACS and NSTEACS.

Symptomatic radiation-induced cardiac disease in long-term survivors of esophageal cancer.

PURPOSE: To evaluate clinical and dosimetric factors retrospectively affecting the risk of symptomatic cardiac disease (SCD) in esophageal cancer patients treated with radiotherapy. PATIENTS AND METHODS: A total of 343 patients with newly diagnosed esophageal cancer were managed with concurrent chemoradiotherapy or radiotherapy alone. Of these, 58 patients were followed at our hospital for at least 4 years. Median clinical follow-up was 79 months. Cardiac toxicity was determined by Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0. The maximum and mean doses to the heart and percentage of the volume were calculated from the dose-volume histograms. RESULTS: SCD manifested in 11 patients. The heart diseases included three pericardial effusions, one pericardial effusion with valvular disease and paroxysmal atrial tachycardia, three atrial fibrillations, one sinus tachycardia, one coronary artery disease, one chest pain with strongly suspected coronary artery disease, and one congestive heart failure. The actual incidence of SCD was 13.8 % at 5 years. Univariate and multivariate analyses of continuous variables revealed that the risk of developing an SCD depended on the volume of the heart receiving a dose greater than 45 Gy (V45), 50 Gy (V50), and 55 Gy (V55). No other clinical factors were found to influence the risk of SCD. For V45, V50, and V55, the lowest significant cutoff values were 15, 10, and 5 %, respectively. CONCLUSION: High-dose and large-volume irradiation of the heart increased the risk of SCD in long-term survivors. Using modern radiotherapy techniques, it is important to minimize the heart dose-volume parameters without reducing the tumor dose.

Simultaneous fat and bone assessment in hospitalized heart failure patients using non-contrast-enhanced computed tomography.

BACKGROUND: Heart failure (HF) is associated with adverse metabolic influences and provokes fat loss as well as bone and muscle loss at the terminal stages. Pericardial fat is an ectopic fat depot that can potentially affect the myocardium, but the role of pericardial fat in HF is unclear. We sought to characterize pericardial fat in HF, particularly in association with bone tissue using cardiac computed tomography (CT). METHODS: In 61 consecutive hospitalized HF patients with left ventricular ejection fraction ≤50%, pericardial fat volume (PFV), CT density in the thoracic vertebrae, and ectopic calcification in the aortic valve were assessed simultaneously using electrocardiogram-gated non-contrast-enhanced CT. RESULTS: The mean PFV was 93.5±50.6cm(3), which might reflect the total body fat measured with dual energy X-ray absorptiometry (Pearson's r=0.48, p=0.01). The PFV index, defined as the PFV/body surface area, was significantly higher among older patients (>65 years; 63.5±30.6cm(3)/m(2) vs. 42.7±17.1cm(3)/m(2), p<0.01) and among patients with atrial fibrillation (AF; 70.9±36.4cm(3)/m(2) vs. 48.8±21.2cm(3)/m(2), p<0.01) and hypertension (60.7±29.3cm(3)/m(2) vs. 41.5±18.2cm(3)/m(2), p<0.01) compared to patients without these conditions. The PFV indices were comparable between the patients with and without ischemic etiology, diabetes, and renal dysfunction. Patients with increased PFV indices (above the median) exhibited lower CT density in the thoracic vertebrae (134±41 Hounsfield units vs. 161±57 Hounsfield units, p=0.04), and were more likely to have aortic valve calcification (48% vs. 18%, p=0.02) and N-telopeptide (bone resorption marker; 20.7±5.2nmolBCE/mmolCr vs. 25.5±5.9nmolBCE/mmolCr, p=0.03) levels than those without increased PFV indices. CONCLUSIONS: We simultaneously assessed the pericardial fat and bone tissue of HF patients with CT and successfully characterized AF, hypertension, and advanced age as factors that are associated with increased PFV. PFV was correlated with bone tissues and alterations in bone turnover.

Utility of noninvasive endothelial function test for prediction of deep vein thrombosis after total hip or knee arthroplasty.

BACKGROUND: Venous thromboembolism (VTE) is a common and sometimes lethal postoperative complication of arthroplasty. Endothelial dysfunction is important in the pathogenesis of thrombus formation. Reactive hyperemia-peripheral arterial tonometry (RH-PAT) can noninvasively evaluate endothelial function. This study investigated the predictive value of RH-PAT for deep vein thrombosis (DVT) after lower limb arthroplasty. METHODS AND RESULTS: A prospective observational study of 126 osteoarthritic patients who underwent total knee arthroplasty (TKA) or hip arthroplasty (THA) was conducted. The RH-PAT index (RHI) was measured on the day before surgery, and presence of DVT was checked by ultrasonography or phlebography before and after surgery. Following arthroplasty, DVT was diagnosed in 51 patients (40.5%). RHI in the DVT group (0.58±0.25) was significantly lower than in the non-DVT group (0.71±0.25, P=0.004). RHI was a significant and independent predictor of postoperative DVT in multivariate logistic regression analyses and improved a net reclassification index (23.8%, P=0.022). Subgroup analyses according to operation site with adjustment for Qthrombosis score demonstrated that RHI significantly predicted postoperative DVT in the THA group (odds ratio per 0.1, 0.77; 95% confidence interval 0.60-0.98; P=0.03), but did not reach statistical significance in the TKA group. CONCLUSIONS: Low RHI was significantly associated with DVT after lower limb arthroplasty. Endothelial dysfunction, as assessed by RH-PAT, is potentially useful for identifying patients at high risk for VTE especially after THA.

Frequency and implication of ST-T abnormalities on hospital admission electrocardiograms in patients with type A acute aortic dissection.

Although patients with Stanford type A acute aortic dissection often show ST-T abnormalities at presentation, the frequency and implication of such findings remain unclear. To clarify these points, admission electrocardiograms from 233 patients admitted ≤6 hours after symptom onset who underwent emergency surgery for type A acute aortic dissection were studied. The prevalence of electrocardiographic (ECG) patterns was 51% for ST-T abnormalities (4% for ST-segment elevation and 47% for ST-segment depression and/or negative T waves), 30% for normal ECG findings or no significant ST-T changes, and 19% for ECG confounders such as bundle branch block or left ventricular hypertrophy. Patients with ST-T abnormalities had higher prevalence of pericardial effusion (48% vs 9% and 38%), cardiac tamponade (28% vs 3% and 18%), moderate or severe aortic regurgitation (28% vs 7% and 18%), shock on admission (34% vs 3% and 13%), coronary ostial involvement (14% vs 1% and 2%), concomitant coronary artery bypass surgery (9% vs 1% and 0%), and in-hospital mortality (11% vs 1% and 4%) compared with patients with normal ECG findings or no significant ST-T changes and those who had ECG confounders (p <0.05 for all). On multivariate analysis, ST-T abnormalities were the only independent predictor of in-hospital mortality (odds ratio 3.87, 95% confidence interval 1.02 to 14.7, p = 0.035). In conclusion, about 50% of patients who underwent emergency surgery for type A acute aortic dissection had ST-T abnormalities, characterized predominantly by ST-segment depression or negative T waves, in the acute phase. ST-T abnormalities were associated with more complicated features and independently predicted in-hospital death.

Relation between hyperinsulinemia and nonculprit plaque characteristics in nondiabetic patients with acute coronary syndromes.

OBJECTIVES: We sought to assess whether hyperinsulinemia is associated with percentage lipid and coronary plaque burden in nondiabetic patients with acute coronary syndromes (ACS). BACKGROUND: Hyperinsulinemia carries an increased risk of cardiovascular disease even in pre-diabetic patients, but the precise mechanisms of its effects remain unclear. METHODS: Nonculprit coronary lesions associated with mild-to-moderate stenosis in 82 nondiabetic patients with ACS were examined by integrated backscatter intravascular ultrasound (IB-IVUS), using a 40-MHz intravascular catheter. Conventional IVUS and IB-IVUS measurements from the worst 10-mm segment (1-mm intervals) were calculated. All patients underwent a 75-g oral glucose tolerance test (OGTT) to calculate the area under the insulin concentration-time curve (AUC insulin) from 0 to 120 min. RESULTS: Patients in the high tertile of AUC insulin had a significantly greater percentage lipid area and absolute lipid volume than did patients in the intermediate and low tertiles (tertile 3 vs. tertile 2 vs. tertile 1; 37.6 ± 16.6% vs. 25.8 ± 11.9% vs. 27.5 ± 14.7%, p < 0.01 by analysis of variance [ANOVA], and 29.9 ± 22.6 mm(3) vs. 15.3 ± 12.6 mm(3) vs. 17.7 ± 12.7 mm(3), p < 0.01 by ANOVA, respectively) and a smaller percentage fibrosis area (55.0 ± 11.5% vs. 61.7 ± 9.4% vs. 60.7 ± 9.4%, p = 0.03 by ANOVA). Multiple regression analysis showed that the high tertile of AUC insulin was independently associated with an increased percentage lipid area (p < 0.05). On conventional IVUS analysis, external elastic membrane cross-sectional area was significantly increased with greater plaque volume in patients in the high tertile of AUC insulin (both p < 0.05 by ANOVA). CONCLUSIONS: Hyperinsulinemia is associated with an increased lipid content and a greater plaque volume of nonculprit intermediate lesions in nondiabetic patients with ACS, suggesting that plaque vulnerability is increased in this subgroup of patients.

Impact of concomitant use of proton-pump inhibitors and thienopyridine derivatives on the antiplatelet effects.

BACKGROUND: Although there has been an intense debate whether concomitant use of proton-pump inhibitors (PPIs) attenuates the antiplatelet effects of thienopyridine derivatives, the drug-drug interaction remains unclear in Japanese patients with coronary artery disease. METHODS AND RESULTS: Platelet function test was performed in 461 patients who were scheduled for or had undergone stent implantation, treated with 100mg/day of aspirin and a thienopyridine (200mg/day of ticlopidine or 75 mg/day of clopidogrel) for at least 14 days. Adenosine diphosphate-induced platelet aggregation was evaluated with screen filtration pressure method, and the upper quartile of high platelet reactivity was defined as high on-treatment platelet reactivity (HPR). PPI use was at physician's discretion. Patients taking a thienopyridine plus a PPI (n=166) were older and had a higher incidence of acute coronary syndromes on admission compared with patients taking a thienopyridine without a PPI (n=295). The rate of HPR was higher in patients taking a thienopyridine plus a PPI than in patients taking a thienopyridine without a PPI (31% vs 21%, p=0.01). On multivariate logistic regression analysis, independent predictors of HPR were concomitant PPI use [odds ratio (OR): 1.66, 95% confidence interval (CI): 1.03-2.68], diabetes mellitus (OR: 1.76, CI: 1.11-2.81), and calcium channel blockers use (OR: 1.93, CI: 1.18-3.18). However, there was no significant difference in the rate of extremely high platelet reactivity [58 patients (12.5%) with PATI<4.0 µM] between patients treated with a thienopyridine plus a PPI and those without a PPI (14% vs 11%, NS). CONCLUSION: HPR was frequently observed in Japanese patients treated with thienopyridines plus PPIs compared to those without PPIs. Further prospective studies are needed to estimate the risk of adverse cardiovascular events associated with concomitant use of PPIs and thienopyridines.

An early and simple predictor of severe left main and/or three-vessel disease in patients with non-ST-segment elevation acute coronary syndrome.

Clopidogrel should be initiated as soon as possible in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) except those who urgently require coronary artery bypass grafting (CABG). The present study assessed the ability to predict severe left main coronary artery and/or 3-vessel disease (LM/3VD) that would most likely require urgent CABG based on only clinical factors on admission in 572 patients with NSTE-ACS undergoing coronary angiography. Severe LM/3VD was defined as ≥75% stenosis of LM and/or 3VD with ≥90% stenosis in ≥2 proximal lesions of the left anterior descending coronary artery and other major epicardial arteries. Patients were divided into the 3 groups according to angiographic findings: no LM/3VD (n = 460), LM/3VD but not severe LM/3VD (n = 57), and severe LM/3VD (n = 55). Severe LM/3VD was associated with a higher rate of urgent CABG compared to no LM/3VD and LM/3VD but not severe LM/3VD (46%, 2%, and 2%, p <0.001). On multivariate analysis, degree of ST-segment elevation in lead aVR was the strongest predictor of severe LM/3VD (odds ratio 29.1, p <0.001), followed by positive troponin T level (odds ratio 1.27, p = 0.044). ST-segment elevation ≥1.0 mm in lead aVR best identified severe LM/3VD with 80% sensitivity, 93% specificity, 56% positive predictive value, and 98% negative predictive value. In conclusion, ST-segment elevation ≥1.0 mm in lead aVR on admission electrocardiogram is highly suggestive of severe LM/3VD in patients with NSTE-ACS. Selected patients with this finding might benefit from promptly undergoing angiography, withholding clopidogrel to allow early CABG.

Impact of statin pretreatment on the incidence of plaque rupture in ST-elevation acute myocardial infarction.

OBJECTIVE: Several studies in experimental animals have shown that statins stabilize atheromatous plaques by increasing fibrous-cap thickness. However, direct evidence linking the use of statins to the incidence of plaque rupture in humans is lacking. We investigated whether statin treatment before the onset of ST-elevation myocardial infarction (STEMI) influences the incidence of plaque rupture detected by intravascular ultrasound (IVUS). METHODS: The study enrolled 458 patients with STEMI who were admitted within 6h from symptom onset. IVUS interrogation was performed before percutaneous coronary intervention. RESULTS: Plaque ruptures were detected in 262 patients (57%). Patients with statin pretreatment (n=68) had a lower incidence of plaque rupture than those without (37% vs. 61%, p<0.001). Univariate analysis revealed that smoking (p=0.003), lower high-density lipoprotein cholesterol (p=0.001), and a lack of statin pretreatment (p<0.001) were associated with a higher incidence of plaque rupture. Multivariate logistic regression analysis identified statin pretreatment as a negative determinant of plaque rupture independent of age, gender, coronary risk factors, and all other medications (odds ratio 0.35; 95% CI 0.19-0.66, p=0.001). Positive remodeling was also associated with plaque rupture (p<0.001), and the relationship between statin pretreatment and a lower incidence of plaque rupture persisted after adjustment for positive remodeling (odds ratio 0.42; 95% CI 0.22-0.80, p=0.009). CONCLUSIONS: Statin treatment before the onset of STEMI is associated with a lower incidence of plaque rupture, suggesting that the prevention of plaque rupture may be a crucial mechanism underlying clinical benefits associated with statins.

Impact of high-responsiveness to dual antiplatelet therapy on bleeding complications in patients receiving drug-eluting stents.

BACKGROUND: Few studies have examined whether high-responsiveness to antiplatelet therapy is associated with an increased risk of bleeding in patients receiving dual antiplatelet therapy. METHODS AND RESULTS: Elective drug-eluting stent implantation was performed in 184 patients treated with aspirin and a thienopyridine (200 mg/day of ticlopidine or 75 mg/day of clopidogrel). The subjects were divided into 3 groups according to post-treatment platelet reactivity before stenting as measured by the response to adenosine diphosphate: the 1(st) quartile group was defined as high-responders, the 4(th) as low-responders, and the other 2 quartiles as middle-responders. Major bleeding occurred more frequently in high-responders than in middle- or low-responders during an average of 16 months' follow-up (15 vs 4, 2%, P=0.02). High-responsiveness was the independent predictor of major bleeding (odds ratio 4.26, P=0.03). Adverse cardiac events were less frequent in high- and middle-responders than in low-responders (24, 16 vs 37%, P=0.02). Middle-responders had better net clinical outcomes, defined as the sum of major bleeding and adverse cardiac events, than did high- or low-responders (21 vs 39, 39%, P=0.02). CONCLUSIONS: In the present study high-responsiveness to antiplatelet therapy was associated with an increased risk of bleeding with no reduction in adverse cardiac events. Measuring platelet reactivity may be useful for risk stratification according to bleeding complications, as well as adverse cardiac events, in patients treated with drug-eluting stents.