Background The implementation of cardiac rehabilitation (CR) after acute myocardial infarction (AMI) has not been fully investigated in Japan, so a nationwide survey of hospitals was conducted. Methods and Results Questionnaires were sent in 2004 to a total of 1,875 hospitals in Japan, including all the 859 Japanese Circulation Society (JCS)-authorized cardiology-training hospitals (THs), 311 JCS-associated hospitals (AH), and 705 randomly sampled non-THs (NTHs). The response rate was 59% (1,106/1,875). The percentages of hospitals treating hospitalized AMI patients were 97% in 526 TH, 85% in 194 AH, and 20% in 339 NTH. Although the rates of implementation of emergency percutaneous coronary intervention were very high (92%, 56%, and 4%, respectively), the rates of implementation of recovery phase CR were low (20%, 8%, and 2%, respectively). In addition, patient education programs (23%, 13% and 2%) and formulated exercise prescriptions based on exercise testing (16%, 7% and 1%) were poorly implemented. More importantly, only 9%, 2% and 0% of these hospitals had outpatient CR programs. From these data, the nationwide participation rate in outpatient CR after AMI in Japan was estimated to be only 3.8-7.6%. Conclusion This first nationwide survey demonstrated that, in contrast to the broad dissemination of acute phase invasive treatment for AMI, the implementation of recovery phase CR, especially outpatient CR, is extremely poor in Japan. In addition, patient education programs and exercise prescription based on exercise testing are only poorly implemented. (Circ J 2007; 71: 173 - 179)

View full abstract

Background Progress in reperfusion therapy for acute myocardial infarction (AMI) has greatly reduced acute phase mortality, but few data exist regarding the time trends in left ventricular (LV) remodeling in hospital survivors of AMI. Methods and Results The study enrolled 813 patients with AMI who had received reperfusion therapy and survived to hospital discharge. The patients were divided into chronological groups: first treatment received between 1989 and 1992, n=196; 1993 and 1995, n=193; 1996 and 1998, n=211; and 1999 and 2002, n=213. A comparison was made of LV ejection fraction (LVEF) and LV end-diastolic volume index (LVEDVI) at 6 months after symptom onset. Along with the temporal improvements reperfusion therapy, LVEF and LVEDVI improved over time (55±14, 58±13, 59±13, 61±13%, p<0.001; 98±30, 94±27, 90±31, 76±27 ml/m², p<0.0001). Multiregression analysis revealed that shortening of the door-to-Thrombolysis In Myocardial Infarction (TIMI)-3 time (time interval from arrival at the emergency room until patients achieved TIMI-3 flow) and achieving substantial TIMI-3 flow were independent predictors for LV remodeling. Conclusion Although this was a retrospective analysis, the results demonstrated that the change in reperfusion therapy aiming at complete reperfusion at an earlier stage after AMI onset has contributed to improving post-MI remodeling. (Circ J 2007; 71: 180 - 185)

View full abstract

Background Elevated C-reactive protein (CRP) is associated with adverse outcomes in non-ST-segment elevation acute coronary syndromes (NSTE-ACS); however, the prognostic significance of serum amyloid A (SAA), also an important inflammatory marker, remains unclear. Methods and Results The ability of SAA, in combination with CRP, to predict clinical outcomes was evaluated in 277 patients with NSTE-ACS. Patients were classified according to the presence or absence of elevated SAA (>0.8 mg/dl) and elevated high-sensitivity CRP (>0.200 mg/dl) on admission: group 1, both SAA and CRP normal (n=133); group 2, SAA normal, but CRP elevated (n=30); group 3, SAA elevated, but CRP normal (n=28); and group 4, both SAA and CRP elevated (n=86). In groups 1, 2, 3, and 4, the rates of combined endpoints including death, (re)infarction, or urgent target-vessel revascularization at 30 days were 8%, 3%, 25%, and 23%, respectively (p=0.002). Multivariate analysis showed that as compared with group 1, the odds ratios for combined endpoints in groups 2, 3, and 4 were 0.50 (p=0.30), 1.95 (p=0.038), and 1.86 (p=0.044), respectively. Conclusions Regardless of the level of CRP, elevated SAA is associated with adverse 30-day outcomes in patients with NSTE-ACS, so SAA is a better predictor of clinical outcome than CRP in these patients. (Circ J 2007; 71: 186 - 190)

View full abstract

Background Subclinical hypothyroidism, defined as high serum thyroid-stimulating hormone (TSH) levels and normal serum free-triiodothyronine (fT3) and serum free-thyroxine (fT4) levels, is a common medical problem among the elderly, but it is unclear whether it should be treated with thyroid hormone replacement therapy. Methods and Results A cross-sectional study of 3,607 participants in a community health survey in Suita, in the northern part of Osaka, was performed. Participants were categorized into 5 groups: normal, hyperthyroidism, hypothyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism. The association between each group and various phenotypes was examined, in relation to cardiovascular disease and metabolic syndromes. Serum TSH levels increased and fT3 and fT4 levels decreased with age. A total of 14.6% of subjects aged 70-80 years and 20.1% of subjects aged older than 80 years were classified as having subclinical hypothyroidism. Subclinical hypothyroidism was not associated with glycol-hemoglobin A1c, body mass index, pulse rate, hypertension, total cholesterol, high-density lipoprotein cholesterol or triglyceride levels or intima - media thickness. It was only associated with higher fasting blood glucose and glycol-hemoglobin A1c levels compared with euthyroidism. Conclusions The present observation does not support the need for treatment of subclinical hypothyroidism or subclinical hyperthyroidism. (Circ J 2007; 71: 191 - 195)

View full abstract

Background Therapeutic angiogenesis using cell transplantation (TACT) is a treatment strategy for no-option patients with critical limb ischemia (CLI). However, because one-third of treated patients fail to respond, the present study was an exploration of the characteristics of responders and non-responders to this treatment regimen. Methods and Results Seven CLI patients (3 with Buerger's disease, 4 with arteriosclerosis obliterans undergoing chronic hemodialysis (ASO-HD)) were treated according to the TACT protocol (n=6: bone marrow-mononuclear cells (MNCs); n=1: peripheral blood-MNCs). Subjective symptoms (visual analog scale) and objective findings (extent of ulcer, ankle - brachial pressure index, transcutaneous oxygen pressure, thermography and angiography) were assessed. Numbers of transplanted CD34⁺, CD133⁺ and CD34⁺CD133⁺ cells were counted. Changes in circulating CD34⁺ and CD133⁺ cell numbers were also examined before and after the treatment. All responders (n=3) had Buerger's disease, and ASO-HD patients did not respond well. Among the responders, the numbers of circulating CD34⁺ and CD133⁺ cells persistently increased for 1 month after the treatment, but not in non-responders. Conclusions The TACT regimen improved CLI in patients with Buerger's disease but not in those with ASO-HD in this small study. In responders, post procedural circulating CD34⁺ and CD133⁺ cells persistently increased for 1 month (ClinicalTrials.gov Identifier: NCT00145262, TACT-NAGOYA). (Circ J 2007; 71: 196 - 201)

View full abstract

Background The effect of acute hyperglycemia (AHG) during the oral glucose tolerance test (OGTT) on coronary microvascular function was evaluated, as well as the associations among the changes in coronary microvascular function, oxidative stress, and sympathetic tone. Methods and Results Transthoracic Doppler echocardiography and OGTT were performed in 24 subjects with atherosclerotic risk factors (61±9 years). The coronary flow velocity before and during the infusion of adenosine (CFV_hyp), plasma levels of thiobarbituric acid-reactive substances (TBARS), and the low-frequency/high-frequency power (LF/HF) ratio yielded by power spectral analysis of heart rate variability were measured before and at 1 h during 75-g OGTT. AHG significantly decreased the CFV_hyp, and increased the TBARS and LF/HF. Multiple linear regression analysis revealed that the percent changes in the CFV_hyp were significantly associated with the percent changes in the LF/HF ratio (β=-0.43, p<0.05). Conclusion In subjects with atherosclerotic risk factors who may be considered likely to have atherosclerotic arterial damage, AHG seems to induce concomitant coronary microvascular dysfunction, increased oxidative stress, and sympathetic activation. Coronary microvascular dysfunction, therefore, appears to be closely related to sympathetic activation. (Circ J 2007; 71: 202 - 206)

View full abstract

Background A retrospective study was performed to determine the appropriateness of aortic root remodeling with aortic annuloplasty (m-Yacoub operation). Methods and Results A group of 60 patients with aortic valve disease with concomitant dilated or dissected ascending aorta, who underwent surgery between 1997 and 2003, were evaluated. Nineteen patients whose aortic valves were well preserved (mean age: 57.8±13.2 years) underwent the m-Yacoub operation with or without aortic valve leaflet suspension. The average follow-up period was 34.5±19.0 months. There were no operative or hospital deaths. Preoperatively, 16 patients had grade 4 aortic regurgitation (AR), 2 had grade 3 AR, and 1 had grade 1 AR. At the latest follow-up, 1 patient had grade 2 AR, 11 had grade 1, and 7 had grade 0. At 5-year follow-up the survival rate was 100±0.0%, and the reoperation-free rate was 82.5±11.3%. Conclusion Where it is possible to preserve the aortic valve, the m-Yacoub operation is an attractive option. (Circ J 2007; 71: 207 - 210)

View full abstract

Background Pregnancy after mechanical heart valve replacement is highly risky for both mother and child because of the aggravation of maternal heart function and adverse effects of anticoagulation therapy. In Japan, however, the risks and pregnancy outcomes in women with prosthetic mechanical heart valve replacement remain to be elucidated. Methods and Results In the present study 16 pregnancies in 12 women with prosthetic mechanical heart valve replacement were identified between 1983 and 2005. At 6-13 weeks of gestational age, warfarin, an anticoagulant agent, was changed to heparin and administration was continuously adjusted according to the activated partial thromboplastin time level up to the time of delivery. Major maternal complications and pregnancy outcomes were retrospectively investigated. The valve replaced was mitral (n=7), tricuspid (n=7), and aortic (n=2). Eight (50%) of 16 had cesarean live births. One case was delivered at full term, and 7 cases were delivered preterm (26-36 weeks) because of maternal indications. Two babies died in the neonatal period. Therapeutic abortion was performed in 3 cases, 4 cases ended in early miscarriage, and 1 case ended in intrauterine fetal death (30 weeks). Three mothers developed valve (mitral, tricuspid, aortic) thrombosis. There was 1 maternal death from heart failure. Conclusions Pregnancy after mechanical heart valve replacement requires strict control of coagulation. Special attention should be paid to the occurrence of complications during anticoagulation therapy. (Circ J 2007; 71: 211 - 213)

View full abstract

Background A higher plasma concentration of highly-sensitive C-reactive protein (hs-CRP) has been found in patients with atrial fibrillation (AF). In addition, low-density lipoprotein (LDL)-associated platelet-activating factor acetylhydrolase (L-PAF-AH) is associated with inflammation. Therefore, the association between AF and PAF-AH was examined. Methods and Results Eighty subjects who were not taking aspirin or statin were investigated, and classified into paroxysmal AF (n=41) and normal sinus rhythm (NSR, n=39) groups. The lipid profile was analyzed by capillary isotachophoresis (cITP), plasma hs-CRP, plasma PAF-AH, high-density lipoprotein (HDL)-associated (H-PAF-AH), and L-PAF-AH. Although there were no significant differences in total cholesterol, HDL, LDL, hs-CRP, or plasma PAF-AH between the 2 groups, L-PAF-AH and the L-PAF-AH/H-PAF-AH ratio in the paroxysmal AF group were both significantly higher than in the NSR group. Interestingly, the ratio of L-PAF-AH to H-PAF-AH positively correlated with the left atrial diameter in all subjects. Although there were no differences in plasma lipoprotein subfractions, as characterized by cITP, slow-migrating LDL positively correlated with L-PAF-AH in both groups. Conclusions The distribution of PAF-AH was associated with paroxysmal AF and may be a marker of inflammation in patients with paroxysmal AF. Antiinflammatory and antioxidant therapy that targets these factors might be effective for preventing paroxysmal AF. (Circ J 2007; 71: 214 - 219)

View full abstract

Background Sirolimus inhibits endothelial cell proliferation in vitro, but although the sirolimus-eluting stent (SES) is widely used because of the very low rates of in-stent restenosis, the influence of SES on coronary endothelial vasomotor function in humans is not well known. Methods and Results The present study included 21 patients treated with SES, and 12 patients treated with conventional bare metal stent (BMS). Endothelium-dependent vasomotor function was evaluated 6 months after stent implantation, using intracoronary acetylcholine infusion. Changes in diameter at the 5-mm proximal and distal edges of the stent, and at the control segment were assessed by quantitative coronary angiography. To evaluate native endothelial function, an intracoronary acetylcholine test was performed before stenting. In the 21 SES patients acetylcholine infusion at 10^-8 mol/L and 10^-7 mol/L produced significant vasoconstriction in the proximal stent segment (-11.3±10.3%, and -14.1±11.3%, respectively) and the distal stent segment (-13.7±9.3%, and -17.5±12.5%, respectively). In contrast, in the 12 BMS patients, acetylcholine infusion at the same concentrations did not produce a vasoconstrictive response in the proximal stent segment (5.0±8.2% and 4.9±9.1%, respectively) or the distal stent segment (4.2±7.6% and 5.1±7.7%, respectively). Intracoronary nitroglycerin induced a similar grade of vasodilation in the peri-stent area in both groups. Local endothelial function before SES implantation showed no vasoconstrictive response. Conclusions In contrast to vasodilation in BMS patients, SES implantation in the peri-stent area resulted in a vasoconstrictive response to acetylcholine. SES implantation may impair endothelial function in humans. (Circ J 2007; 71: 220 - 225)

View full abstract

Background Although drug-eluting stents dramatically reduce revascularization after percutaneous coronary intervention (PCI), it is still unclear whether they increase the risk of stent thrombosis. Late stent thrombosis (>30 days) was a very rare complication after bare metal stent implantation. Four cases of confirmed late angiographic stent thrombosis (LAST) after sirolimus-eluting stent (SES) implantation are presented and the incidence, promoting factors and outcomes of such cases in Japan, where clopidogrel has not been approved, are described. Methods and Results Between September 2004 and March 2006, 725 patients underwent PCI with SES implantation and 679 patients (94%) were clinically followed up (median 271 days). There were 4 cases (0.6%) of LAST (at 60, 180, 215, and 508 days, respectively) after elective SES implantation resulting in myocardial infarction. Three cases occurred soon after antiplatelet therapy discontinuation 3 patients died after LAST events. The incidence of LAST was 0.6%. Conclusions LAST is a rare complication, even after SES implantation, at least in patients with appropriate antiplatelet therapy. However, as it can lead to fatal complications, it must be taken into account, especially when antiplatelet therapy is discontinued. (Circ J 2007; 71: 226 - 228)

View full abstract

Background The aim of this study was to measure the patient entrance skin dose (ESD) during percutaneous coronary intervention (PCI) for chronic total occlusion (CTO), and assess the factors that affect it. Methods and Results Radiosensitive indicators were used to measure ESDs during 23 procedures. Multiple regression analysis identified the strength of the linear relationship of the dependent variable (the natural logarithm of the maximum ESD) with the set of multiple independent variables (the natural logarithm of both the patient and angiographic data). The methods for estimating the maximum ESD and the estimated ESDs were compared with the actual ESDs. The average maximum ESD for all the patients was 2.7±1.5 Gy (median: 2.6 Gy). The natural logarithm of the maximum ESD correlated well with the natural logarithm of body mass index (BMI; p=0.0112), total fluoroscopic time (TFT; p=0.0002), and Frame Fixation Rate (p=0.0014). For the higher Frame Fixation Rate group, there were significant correlations between the BMI² × TFT value and maximum ESD (r=0.972, p<0.0001), and the TFT and maximum ESD (r=0.968, p<0.0001). There were no significant correlations for the lower Frame Fixation Rate group. Conclusions In PCI for CTO, the BMI² × TFT value or TFT is a good predictor of radiation skin injury risk, when the beam angulation is not changed frequently. It is important to change the beam angulation to control ESD during a prolonged procedure. (Circ J 2007; 71: 229 - 233)

View full abstract

Background Several reports have suggested a possible link between bronchial asthma and coronary spasm, but the possibility of a relationship in coronary spastic angina (CSA) has not been clarified. Methods and Results Airway responsiveness to methacholine and coronary spasticity to acetylcholine were examined in 42 patients with CSA and 36 patients with chest pain syndrome (CP). Furthermore, 18 control subjects were examined and their airway responsiveness compared with that of the CSA and CP patients. The incidence of airway hyperresponsiveness was significantly higher in the CSA group (74%) than in the CP (19%) and control (17%) groups (p<0.0001). The geometric mean of the log minimum dose (Dmin), defined as the cumulative dose at the point at which respiratory conductance began to decrease, was significantly lower in the CSA group (0.75 log units) than in the CP (1.20 log units) and control (1.38 log units) groups (p=0.004). Conclusion These results demonstrate that acetylcholine-induced coronary spasticity is significantly related to methacholine-induced airway responsiveness in patients with CSA. A generalized hyperresponsiveness of the vascular and nonvascular smooth muscles, including that through cholinergic mechanisms, may exist in patients with CSA. (Circ J 2007; 71: 234 - 241)

View full abstract

Background Fast Fourier transform (FFT) analysis is a popular method of spectral analysis of atrial fibrillation cycle lengths (AFCL). Autocorrelation function (ACF) analysis is also available, so the aim of this study was to elucidate the relationship between FFT and ACF analyses in the spectral analysis of AFCLs. Methods and Results A total of 75 atrial fibrillation (AF) data from 39 patients were subjected to analysis. The dominant frequencies (DFs) from 4 different spectral resolutions of the FFT and peak AFCL from the ACF analysis were compared. In the FFT analysis using rectified signals, the DF was influenced by spectral resolution, no matter how the signals were tapered by the Hanning or Hamming window or filtered with the low-pass filter. There was a significant relationship between the DF from each spectral resolution and the peak AFCL. The DF from the 4,096-point FFT analysis had the strongest relationship to the peak AFCL with the smallest difference, when using 30-s AF data. In a study of the different lengths of the atrial fibrillation data, the DF also had a strong correlation to the peak AFCL with a small difference. Conclusions The peak AFCL obtained from ACF analysis was not of the same quality as that from FFT analysis, but had the same value as the DF from FFT analysis. (Circ J 2007; 71: 242 - 251)

View full abstract

Background Because metabolic syndrome is associated with cardiovascular diseases, its association with the risk of paroxysmal atrial fibrillation (PAF) and/or atrial flutter (PAFL) was examined in the present study. Methods and Results A prospective analysis was performed in 592 consecutive hospitalized patients without obvious structural heart diseases. Sinus rhythm was confirmed by electrocardiography in all patients. PAF/PAFL occurred in 32 (5%) and metabolic syndrome was present in 127 (21%) of the patients enrolled. PAF/PAFL occurred in 12 (9%) of the patients with metabolic syndrome, but only 20 (4%) of patients without metabolic syndrome (p=0.02). Multivariate logistic regression analysis showed that metabolic syndrome was a significant risk factor for PAF/PAFL that was independent of left atrial diameter (>44 mm) or age (>70 years) (odds ratio (OR) 2.8, 95% confidence interval (CI) 1.3-6.2, p<0.01). Among the 5 components of the metabolic syndrome, body mass index ≥25 kg/m² was the most strongly associated with PAF/PAFL (OR; 3.0, 95% CI 1.2-7.4, p=0.02). Conclusions Metabolic syndrome is highly associated with PAF/PAFL in patients without structural heart diseases and obesity may be an underlying mechanism for the higher prevalence. (Circ J 2007; 71: 252 - 255)

View full abstract

Background Patients with hypertrophic cardiomyopathy (HCM) sometimes develop subendocardial ischemia (SEI) in the left ventricle (LV). In the present study it was examined whether volumetric variables obtained by gated single-photon emission computed tomography (SPECT) are useful in detecting exercise-induced SEI in patients with HCM. Methods and Results Exercise ^99mTc-tetrofosmin myocardial scintigraphy was performed in 26 HCM patients having non-obstruction and mild hypertrophy with a ventricular septal thickness ≤20 mm. SEI was quantified using software developed previously, and the results were correlated with volumetric variables obtained using Quantitative Gated SPECT software. Exercise-induced percentage change in LV end-systolic volume was higher in 9 HCM patients with SEI (25.8±3.1%) than in 17 patients without (10.0±2.5%, p=0.009), although the percentage change in LV end-diastolic volume was similar in the 2 groups. The receiver-operator characteristics curve of the percentage changes in LV end-systolic volume for the detection of SEI showed that the optimal cutoff was 17%. This cutoff point yielded a good diagnostic value for the presence of SEI with a sensitivity of 89%, specificity 82%, and likelihood ratio 5.04. Conclusions Gated SPECT technique is useful in detecting SEI during exercise in a select population of HCM patients. (Circ J 2007; 71: 256 - 260)

View full abstract

Background The vascular type of Ehlers-Danlos syndrome (vEDS, EDS type IV; MIM#130050) is an autosomal dominantly inherited disorder that results from mutations in the genes for type III procollagen (COL3A1). Affected individuals with vEDS are at risk of arterial rupture, aneurysm, and/or dissection; gastrointestinal perforation or rupture; and uterine rupture during pregnancy, which may lead to sudden death. Methods and Results Three unrelated Japanese individuals who exhibited symptoms of vEDS were analyzed. In order to identify mutations in the patients' RNA, one 3.8-kb reverse transcriptase polymerase chain reaction product containing the triple-helical domain of COL3A1 was prepared from cultured skin fibroblasts and then was sequenced directly. Three heterozygous mutations were identified; specifically, 2 novel missense base substitutions (Gly220Trp, Gly448Glu) in the (Gly-X-Y)n repeat of the triple-helical domain and a known splicing donor mutation of intron 20 (G+1, IVS20) of COL3A1. The genotype-phenotype correlations in Japanese vEDS individuals with COL3A1 mutations were also investigated. Conclusion There was no association between the type of complications in vEDS and the related COL3A1 mutation found. After the genetic diagnosis of COL3A1, the establishment of both a network among medical specialists, including clinical geneticists to perform genetic counseling, and long-term follow-up systems of vEDS may help to improve the management of vascular and visceral complications. (Circ J 2007; 71: 261 - 265)

View full abstract

Background Elevated plasma homocysteine (Hcy) concentrations are associated with an increased risk of vascular disease. Hcy is known to inhibit endothelial cell proliferation in vitro. The purpose of the present study was to investigate the role of plasma Hcy concentrations on development of collateral circulation in single-vessel chronic total occlusion. Methods and Results Collateral status was determined by Rentrop's classification. Of 817 patients, 56 cases of pure single-vessel chronic total occlusion were studied. Plasma Hcy concentrations in patients with single-vessel total coronary occlusion were higher compared with controls (17.3 ±12.6 μmol/L vs 10.9±4.9 μmol/L, p=0.015). There was no significant difference in plasma Hcy concentrations of the good and poor collateral groups (17.2±13.7 μmol/L vs 15.3±9.3 μmol/L, p=0.834). Plasma Hcy concentrations in individual Rentrop subclasses 0, 1, 2 and 3 were as follows: 15.9 ±9.1, 16.3±12.4, 17.1±14.1 and 20.1±13.5 μmol/L (p=0.893). There was a positive linear correlation between Rentrop subclass and angina pectoris duration (r=0.41, p=0.003). Angina pectoris duration was the only independent variable affecting the development of coronary collaterals in the present study (odds ratio [confidence interval]: 1.85 [1.12-2.91], p=0.014). Conclusion Patients with single-vessel chronic total occlusion had higher plasma Hcy concentrations than controls, but similar Hcy concentrations when compared according to the presence of poor or good coronary collaterals. There is a lack of association between plasma Hcy concentration and coronary collateral status in the current study. (Circ J 2007; 71: 266 - 270)

View full abstract

Background There have been few multicenter studies using intravascular ultrasound (IVUS) to assess the process of atherosclerosis in a Japanese population with hypercholesterolemia that is being treated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors for control of low-density lipoprotein-cholesterol. Methods and Results An open-label multicenter study is planned to evaluate with IVUS whether treatment with rosuvastatin for 76 weeks results in regression of coronary artery atheroma volume in patients who have coronary heart disease (CHD) and hypercholesterolemia. Sample size is 200 subjects with CHD who are to undergo percutaneous coronary intervention. The planned duration is between October 2005 and October 2008. Conclusions The COSMOS study will be the first multicenter cardiovascular study in a Japanese population and may provide new evidence on the effects of rosuvastatin on the progression of coronary atherosclerotic lesions. (Circ J 2007; 71: 271 -275)

View full abstract

Background The Gaq protein-coupled receptor (GPCR) signaling pathway, which includes diacylglycerol (DAG) and protein kinase C (PKC), plays a critical role in the development of cardiac hypertrophy and heart failure. DAG kinase (DGK) phosphorylates DAG and controls cellular DAG levels, thus acting as a regulator of GPCR signaling. It has been previously reported that DGK inhibited GPCR agonist-induced activation of the DAG-PKC signaling and subsequent cardiomyocyte hypertrophy, so the purpose of this study was to examine whether DGK modifies the development of cardiac hypertrophy induced by pressure overload. Methods and Results Thoracic transverse aortic constriction (TAC) was created in transgenic mice with cardiac-specific overexpression of DGKξ (DGKξ-TG) and wild-type (WT) mice. Increases in heart weight at 4 weeks after TAC were attenuated in DGKξ-TG mice compared with WT mice. Increases in interventricular septal thickness, dilatation of the left ventricular cavity, and decreases in left ventricular systolic function in WT mice were observed with echocardiography at 4 weeks after TAC surgery. However, these structural and functional changes after TAC were attenuated in DGKξ-TG mice. In WT mice, cardiac fibrosis and up-regulation of profibrotic genes, such as transforming growth factor-β₁, collagen type I, and collagen type III, were observed at 4 weeks after TAC. However, cardiac fibrosis and gene induction of type I and type III collagens, but not transforming growth factor-β₁, were blocked in DGKξ-TG mice. Conclusion These results are the first in vivo evidence that DGKξ suppresses cardiac hypertrophy and fibrosis and prevents impaired left ventricular systolic function caused by pressure overload. (Circ J 2007; 71: 276 - 282)

View full abstract

Popliteal artery occlusion is a rare vascular complication in athletes and has not been previously documented in baseball players. A 21-year-old male baseball player presented with a 10-month history of progressive claudication because of repeated trauma-induced popliteal artery occlusion from frequently practicing stealing bases by sliding down onto his right leg. He was found to have a transient deficiency in both protein C and protein S. The patient underwent percutaneous transluminal recanalization angioplasty followed by anticoagulation therapy, with good results. This case illustrates the importance of awareness of this potential complication in baseball athletes, work-up for a hypercoagulable state and the feasibility of angioplasty therapy in the management of ischemic limbs after trauma. (Circ J 2007; 71: 283 - 285)

View full abstract

Background The predominant mechanism of early failure of saphenous vein grafts (SVG) after coronary bypass remains unclear, so angioscopy was used to identify the morphological changes. Methods and Results Of the 31 SVGs assessed 15 had both yellow plaque and thrombi, whereas in the remaining 16 SVGs the intima was clear white. The serum low-density lipoprotein cholesterol level was significantly higher in the diseased SVG group. Eight patients of the normal SVG group were prescribed ticlopidine, compared with only 1 from the diseased SVG group (p=0.015). Conclusions This is the first direct demonstration of yellow plaque and/or thrombosis in SVGs by intravascular angioscopy. In addition to the importance of prescribing statins, it might be vital to also add ticlopidine to aspirin therapy. (Circ J 2007; 71: 286 - 287)

View full abstract