Few reports have focused on whether old diabetic patients had worse outcomes compared to old nondiabetics after coronary artery bypass grafting (CABG). This study aimed to evaluate the outcomes of old diabetic patients compared to old nondiabetics following isolated CABG.
From January 2004 to December 2008, the relevant pre-, intra-, and postoperative materials of all CABG patients over 65 years of age in our center were investigated and analyzed retrospectively. In this study, diabetes is defined as the need for oral medication or insulin. A total of 140 diabetic patients over 65 years of age were entered in the study, accounting for 31.7% of the total population. Diabetic patients over 65 years of age were less likely to have undergone previous percutaneous coronary intervention (P < 0.0001) and more likely to undergo CPB (P = 0.03) during CABG as compared to nondiabetics over 65 years of age. Univariate analysis and multivariate logistic regression analysis showed diabetic patients over 65 years of age only had a higher rate of deep sternal wound infection (OR = 2.76, 95%CI 1.22-7.83, P = 0.002), while sharing almost similar rates among other morbidities and mortality as compared to nondiabetic patients over 65 years of age.
Excellent results following CABG may be expected in old diabetic patients.

View full abstract

Triflusal is a derivative of acetylsalicylic acid but it exhibits different pharmacological and pharmacokinetic properties. The object of this study was to evaluate the efficacy of additional use of triflusal in patients who underwent drug-eluting stent implantation.
First, we prospectively tested platelet function with a rapid platelet function analyzer (VerifyNow®-Aspirin) in patients with stable angina (male, age, 61.6 ± 8.3, body weight, 69.3 ± 11.2 kg) who maintained dual (aspirin 100 mg and clopidogrel 75 mg per day, n = 23) or triple (aspirin 100 mg, clopidogrel 75 mg, and triflusal 300 mg per day, n = 23) therapy for more than one month. They were randomly assigned to a group. The triple group showed superior inhibition of arachidonic acid induced platelet aggregation compared to the dual group (420.2 ± 47.7 ARU versus 465.0 ± 71.2 ARU, P = 0.016). Second, we compared composite outcomes (death, myocardial infarction, and nonhemorrhagic stroke) after drug-eluting stent (DES) implantation between the dual (n = 1474) and triple (n = 433) groups in the prospective Seoul National University Hospital drug-eluting stent (SNUH-DES) cohort. The triple group had more current smokers, male patients, and patients with a previous history of revascularization. Also, the triple group underwent more complex interventions such as left main, chronic total occlusion, long lesion, and restenotic lesion than the dual group. In spite of their higher risk profiles, the triple group patients showed comparable composite outcomes (19 cases, 4.4%) to those of the dual group ones (41 cases, 2.8%) (P = 0.12).
The triflusal-based triple antiplatelet therapy achieved superior platelet inhibition compared to the dual therapy ex vivo and it could be applied after complex intervention with DES.

View full abstract

The aim of the study was to compare the course of myocardial infarction in women versus men in Upper Silesia, an industrial region in the south of Poland.
The study comprised 1003 patients with either ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI). The patients were divided into group 1 (300 females) and group 2 (control, 703 males). The groups differed significantly with respect to age, incidence of hypertension, diabetes, and smoking. In group 1 STEMI occurred significantly less frequently than NSTEMI. Taking this into account, we divided the studied cohort into group A (STEMI patients) and group B (NSTEMI patients), each subdivided into women and men.
In the 30 day long follow-up, group 1 patients had significantly lower creatine kinase activity, higher occurrence of ventricular tachycardia, lower percentage of intra-aortic balloon pump use, and longer hospital stay compared with group 2. Group 1 was characterized by significantly higher mortality and target lesion reocclusion (TLR).
The medical course of myocardial infarction in women is similar to that in men, as is the treatment of acute coronary syndrome. In our study, patients from both groups underwent invasive examination with consecutive interventional treatment with similar frequency. However, this finding is not reflected in the outcomes. Women had higher risks of death and TLR in 30 day follow-up. Taking this into consideration, we should attempt to identify the factors responsible for this situation by expanding the analysis to a larger population to allow firm conclusions to be drawn.

View full abstract

The cost-effectiveness of drug-eluting stents (DES) has been evaluated in the United States and Europe, however, there is little information from Japan. The present study evaluated the cost-effectiveness of sirolimus-eluting stents (SES) in Japan. In-hospital and follow-up costs of 25 consecutive patients undergoing SES implantation in a de novo lesion were evaluated. A control group for comparison was composed of 25 consecutive patients undergoing bare metal stent (BMS) implantation in a de novo lesion before the introduction of SES. There was no significant difference in resource use between the SES and BMS groups. Procedural cost (¥1,049,200 ± 208,793 versus ¥896,590 ± 117,984, P = 0.01) was higher in the SES group than in the BMS group because of the higher reimbursement price of SES (¥378,000 versus ¥258,000). In-hospital cost (¥1,202,891 ± 208,793 versus ¥1,050,280 ± 177,984, P < 0.01) was higher in patients treated with SES. Less target lesion revascularization (4% versus 20%, P = 0.2) in patients with SES reduced the difference; aggregate 1-year cost was not significantly different (¥1,479,481 ± 284,343 versus ¥1,463,640 ± 495,803, P = 0.9). It is concluded that SES may be cost-effective even in Japan.

View full abstract

Sarcoidosis is a systemic granulomatous disorder whose prognosis worsens when the heart is involved, and early diagnosis is important. Endomyocardial biopsy is the most helpful diagnostic examination, but suffers from low sensitivity and low specificity. Microvolt T wave alternans (MVTWA) is utilized in noninvasive examinations to detect beat-to-beat changes in the shape of the T wave at the microvolt level. Such beat-to-beat T wave changes arise from beat-to-beat changes in the transmural gradient of action potential duration. We speculate that the granulomatous changes of cardiac sarcoidosis produce cell-to-cell uncoupling and augment the transmural gradients of action potential duration.
To examine the clinical significance of MVTWA in the prediction of cardiac involvement in sarcoidosis patients, we obtained MVTWA in a total of 35 sarcoidosis patients with and without cardiac involvement. All patients underwent electrocardiography (ECG), ambulatory electrocardiography, chest radiography, transthoracic echocardiography, and MVTWA examination using a CH 2000 system. We diagnosed cardiac sarcoidosis in 7 patients according to the accepted diagnostic criteria. MVTWA was detected in 6 out of 7 cardiac sarcoidosis patients (85.7%) as opposed to in 2 out of 28 patients without cardiac involvement (7.1%). The difference between the two groups was statistically significant (P < 0.001). The sensitivity and specificity of MVTWA in cardiac sarcoidosis detection were 85.7% and 92.8%, respectively. The positive and negative predictive values were 75% and 96.3%, respectively, with an overall accuracy of 91.4%.
Noninvasive examination of MVTWA using a CH 2000 is a useful diagnostic tool for detecting cardiac involvement in patients with sarcoidosis.

View full abstract

The occurrence of ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy (DCM) who are treated with an implantable cardioverter-defibrillator (ICD) for primary or secondary prevention is not fully understood.
In this nonrandomized, two-centre, observational study we analyzed the occurrence of ventricular arrhythmias in a total of 105 DCM patients (age, 53 ± 13 years) treated with an ICD. Fifty-one patients with a left ventricular ejection fraction ≤ 35% did not have prior sustained ventricular arrhythmias (primary prevention). The secondary prevention group consisted of 54 patients with documented sustained ventricular tachycardia (n = 25) or aborted sudden cardiac death (n = 29). During 32 ± 7 months follow-up the number of patients with appropriate defibrillator therapies (n = 51) was comparable between the two groups (HR 0.79, 95% CI 0.454 to 1.361, P = 0.389). Importantly, less primary prevention patients experienced appropriate ICD shocks for any arrhythmic event (HR 0.35, 95% CI 0.186 to 0.777, P = 0.008), as well as appropriate ICD shocks for ventricular fibrillation (HR 0.31, 95% CI 0.167 to 0.737, P = 0.006). In contrast, antitachycardia pacing was more often observed in the primary prevention group (HR 2.75, 95% CI 1.031 to 6.238, P = 0.043). Two primary prevention and 6 secondary prevention patients received multiple ICD therapies in consequence of incessant ventricular tachycardia.
The characteristics of ventricular arrhythmias in patients with DCM who are treated with an ICD for primary or secondary prevention vary according to the underlying indication. Therefore, different device programming according to the patient’s history might improve ventricular tachyarrhythmia management.

View full abstract

The aim of this study was to evaluate the relationship between renal resistive index and inflammation in untreated hypertensive patients. Sixty-one hypertensive patients (male/female: 38/23, aged 45.8 ± 8.3 years, and mean hypertension duration 28.2 ± 35.6 months) and 40 (male/female: 23/17, aged 42.7 ± 8.5 years) healthy control subjects were included in the study. Renal resistive index was positively correlated with age (P = 0.016, r = 0.308), pulse pressure (P = 0.022, r = 0.294), C-reactive protein (P = 0.00, r = 0.757), urinary albumin excretion (P = 0.003, r = 0.371) and negatively correlated with creatinine clearance (P = 0.042, r = -0.262) in the hypertensive group. The hypertensive group was further divided in two groups according to the renal resistive index; < 0.60 and > 0.60. In the > 0.60 group, age (48.0 ± 7.3 versus 42.8 ± 8.9 years, P = 0.01) and C-reactive protein levels (7.4 ± 1.5 versus 4.0 ± 1.6 mg/L, P = 0.01) were higher, and creatinine clearance (95.5 ± 22.1 versus 109.1 ± 25.3 mL/min, P = 0.04) was lower than the < 0.60 group. Renal resistive index was higher in the nondippers than the dippers (0.61 ± 0.04 versus 0.58 ± 0.03, P = 0.003). Renal resistive index is associated with inflammation and may be a useful marker, together with albuminuria, in hypertensive patients when evaluating hypertensive renal damage.

View full abstract

Cardiac function during exercise is assumed to be important in determining exercise tolerance. The aims of this study were to evaluate changes in left ventricular diastolic function (LVDF) during exercise and its effect on exercise tolerance assessed by a noninvasive method, exercise-stress tissue Doppler echocardiography. Twenty-six men with sinus rhythm (controls, hypertension, and cardiomyopathy) underwent cardiopulmonary exercise testing. To assess LVDF during exercise, exercise-stress Doppler echocardiography was performed with a constant workload at rest, and at 50%, 100%, and 120% of anaerobic threshold (AT). Doppler variables related to LVDF increased significantly as the workload increased (P < 0.05). Resting E’correlated significantly with AT (r = 0.424, P = 0.0308) and peak VO₂ (r = 0.471, P = 0.0152). However, the difference in E’between rest and 120% AT (ΔE’) was closely correlated with AT (r = 0.744, P < 0.0001) and peak VO₂ (r = 0.748, P < 0.0001). Moreover, ΔE’was correlated independently with AT (P = 0.0321) and peak VO₂ (P = 0.0192) by multiple regression analysis. These results suggest that the ability to increase LVDF during exercise is an important factor in determining exercise tolerance.

View full abstract

The anatomical relationship between left ventricular pacing site and the anterior papillary muscle (A-PM) may have a major influence on the improvement of mitral regurgitation (MR) in cardiac resynchronization therapy (CRT). The aims of the present study were to assess the anatomical relationship between coronary veins and papillary muscles in patients with and without heart failure (HF), and to examine its contribution to the response to CRT. Sixty-one patients (36 patients with HF, 25 patients without HF) who underwent multi-detector computed tomography were studied. We measured the angle between the anterior papillary muscle and coronary veins (Ang. 1) and the angle between the anterior edge of the left ventricular free wall and A-PM (Ang. 2). Angle 1 of the posterolateral vein in the patients with HF was significantly smaller than those without HF (54.9 ± 11.1, 68.7 ± 15.8 degrees, respectively, P = 0.02). Supportively, Angle 2 of patients with HF was larger than that of patients without HF (100 ± 13.0, 87.3 ± 10.7 degrees, respectively, P < 0.01). Significant decreases in left ventricular end-diastolic diameter, the grade of MR, and brain natriuretic peptide level after 6 months of CRT were observed (P < 0.01, P = 0.04, P < 0.01, respectively) in patients with severe A-PM displacement (Ang. 2 > 100 degrees), but not in patients with Ang. 2 < 100 degrees. A-PM tends to be located in a more posterior wall in patients with HF. Displacement of A-PM may have a potential role as a predictor of the response to CRT.

View full abstract

This study investigated the effects on cardiomyocyte differentiation of embryonic stem cells by the overexpression of the transcription factor, Pitx2c, and examined the effects of transplantation of these differentiated cells on cardiac function in a mouse model of myocardial infarction.
Pitx2c overexpressing embryonic stem cells were characterized for cardiac differentiation by immunocytochemistry, RNA analysis, and electrophysiology. Differentiated cells were transplanted by directed injection into the infarcted murine myocardium and functional measurements of blood pressure, contractility, and relaxation were performed. Histochemistry and FISH analysis performed on these mice confirmed the engraftment and cardiac nature of the transplanted cells.
Pitx2c overexpressing embryonic stem cells robustly differentiated into spontaneously contracting cells which acquired cardiac protein markers and exhibited action potentials resembling that of cardiomyocytes. These cells could also be synchronized to an external pacemaker. Significant improvements (P < 0.01) in blood pressure (56%), contractility (57%), and relaxation (59%) were observed in infarcted mice with transplants of these differentiated cells but not in mice which were transplanted with control cells. The Pitx2c overexpressing cells secrete paracrine factors which when adsorbed onto a heparinated gel and injected into the infarcted myocardium produce a comparable and significant (P < 0.01) functional recovery.
Pitx2c overexpression is a valuable method for producing cardiomyocytes from embryonic stem cells, and transplantation of these cardiomyocytes into infracted myocardium restores cardiac function through multiple mechanisms.

View full abstract

Erythropoietin (Epo) is a hormone which regulates erythrocyte production. It has recently become known that Epo enhances angiogenesis. However, since shear stress is an initiator of arteriogenesis, this increase with Epo may be due to increased shear stress from erythrocytosis. To clarify this, we compared the effects of Epo on both angiogenesis and arteriogenesis. Myocardial infarction was induced by LAD ligation in Wistar rats (Epo, G-CSF and control). Epo (1,000 IU/kg) was administered immediately after ligation of the LAD. G-CSF was administered at 100 μg/kg/day for 5 days after the coronary ligation. Four weeks later, coronary angiography was performed using synchrotron radiation coronary micro-angiography with a Langendorff apparatus. The number of vessels was investigated by microscopy. The numbers of capillaries and arterioles (> 100 μm in diameter) were measured. Microscopical examination: Capillary density in the twilight zone was 95 ± 19 in the control group, 126 ± 24 in the G-CSF group, and 142 ± 32 in the EPO group (control versus Epo: P < 0.005, control versus G-CSF: P < 0.05). Arteriole numbers were 4.3 ± 0.2 in the control group, 6.9 ± 1.0 in the G-CSF, and 11.8 ± 0.6 in the Epo group (control versus Epo: P < 0.00001, G-CSF versus Epo: P < 0.00001, control versus G-CSF: P < 0.00001). The ratios of arterioles and capillaries were 0.048 ± 0.013 in the control group, 0.057 ± 0.016 in the G-CSF group, and 0.088 ± 0.019 in the Epo group (control versus Epo: P < 0.0005, G-CSF versus Epo: P < 0.05). Angiography: The number of crossing arterioles in the 2 mm lattice was 5.4 ± 1.7 in the Epo group and 3.8 +/-0.4 in the control group (P < 0.05). The gray scale values for the evaluation of capillaries was 128 ± 3.7 and 119 ± 2.1 in the Epo and control groups, respectively (P < 0.00005). Epo enhanced arterioles more significantly than it did capillaries in this infarcted rat heart model.

View full abstract

The postulated relationship between nonbiodegradable polymers and late stent thrombosis has led to a concerted effort to seek alternative biodegradable polymers for drug delivery. The purpose of this study was to evaluate the long-term effects of novel sirolimus-eluting stents (SES) with biodegradable polylactic-co-glycolic acid (PLGA) polymer on neointimal thickening in a porcine coronary model. Three types of stents were implanted in different coronary arteries of the same mini-swine: bare cobalt-chromium stents (BMS); PLGA-coated-only stents (PCOS); and PLGA-coated, sirolimus-eluting stents (PCSES). A total of 26 animals underwent successful placement of 78 oversized stents (each stent-group, n = 26) in the coronary arteries with histopathologic analysis and Western blot at 28 days, 3 months, or 1 year. At 28 days and 3 months, the mean neointimal area was about two-fold lower in PCSES versus BMS or PCOS. At 1 year, the mean intimal area was similar for PCSES (1.76 ± 0.28 mm²) and BMS (2.06 ± 0.23 mm², P = 0.051). Western blot analysis demonstrated decreased expression of p27^kip1 in the vessel wall 3 months after PCSES implantation as compared with 28 days. PCSES effectively reduced in-stent neointimal formation for the first 3 months in this porcine coronary model. Beyond 3 months, neointimal proliferation was not substantially inhibited by PCSES. The observed delayed neointimal hyperplasia with PCSES may be partly related to the potential side effects of sirolimus and/or late insufficient arterial drug levels.

View full abstract

A 74-year-old female with a diagnosis of idiopathic dilated cardiomyopathy and ventricular tachycardia died suddenly 9 years after an implantation of an implantable cardioverter-defibrillator (ICD). The destructive removal of an ICD generator and the leads by an uninformed coroner resulted in the loss of the fragile electrograms during the terminal episodes of VT/VF and caused severe charring on the surface of the ICD generator.
In order to observe the conditions in which the shock deliveries occurred during the noise detection, we programmed the ICD to deliver the maximum shock energy via a programmer while keeping continuous contact between the device surface and shock lead. The maximum shock energy of 31 Joules produced significant sparks from the surface of the ICD.
To avoid the loss of data from an ICD and injury to the patient, widespread notification and education through appropriate scientific societies about the functions of ICDs are highly recommended.

View full abstract

We experienced an 81 year-old man with heart failure and macrocytic anemia. His serum ferritin level was extremely high (> 3,000 ng/mL). Echocardiography showed a normal left ventricular (LV) ejection fraction (EF), although the total ejection isovolume index (TEI index) was markedly elevated (0.60). In a cardiac catheterization study, cardiac index, pulmonary arterial wedge pressure, LV wall motion, and coronary arteries were shown to be normal. However, atrial pacing demonstrated a negative force-frequency relationship (a decrease in arterial blood pressure with higher pacing rates). Pathological study showed hemosiderin accumulation in his liver, but not in his myocardial tissue. As earlier studies have reported that iron may play an important role in oxidative cell damage and that this ion can enter cardiomyocytes through L-type Ca²⁺ channels, we started an iron chelating agent (deferoxamine) and a calcium channel blocker (verapamil) in this case. Eighteen months later, his serum ferritin levels fell significantly without any changes in anemia. The TEI index was normalized (0.21) and the atrial pacing provoked a less negative force-frequency relationship. Thus, this combination treatment may be effective in iron overload cardiomyopathy at its early stage, when LV diastolic dysfunction is dominant and LV systolic dysfunction is only latent.

View full abstract