Evaluation of oxygen uptake adjusted by skeletal muscle mass in cardiovascular disease patients with type 2 diabetes.

[Purpose] We aimed to evaluate oxygen uptake adjusted by total skeletal muscle mass in patients with cardiovascular disease with or without type 2 diabetes mellitus. [Participants and Methods] The participants included 54 males ≥50 years of age without heart failure who underwent cardiopulmonary exercise testing during cardiac rehabilitation. We divided the participants into two groups: patients with type 2 diabetes mellitus (DM group) and patients without type 2 diabetes mellitus (NDM group). [Results] We found no significant differences in age, weight, fat mass, or skeletal muscle mass between the groups. There were also no differences in cardiac function, body composition, and heart rate response. The DM group showed significantly lower peak oxygen uptake values adjusted by skeletal muscle mass, despite the absence of significant differences in skeletal muscle mass. A significant positive correlation was found between peak oxygen uptake and age, weight, and skeletal muscle mass. Stepwise regression analysis revealed that age, skeletal muscle mass, and medical history of diabetes were independent predictors of absolute peak oxygen uptake. [Conclusion] Peak oxygen uptake adjusted by skeletal muscle mass in patients with cardiovascular disease and type 2 diabetes mellitus is lower than that in those without type 2 diabetes mellitus.

Effect of Exercise Training on Body Temperature in the Elderly: A Retrospective Cohort Study.

BACKGROUND: This study evaluated the effect of exercise training on body temperature and clarified the relationship between body temperature and body composition in the elderly. METHODS: In this retrospective cohort study, a total of 91 elderly participants performed aerobic and anaerobic exercise training twice a week for 2 years. Non-contact infrared thermometer and bioelectrical impedance analysis were performed at baseline and at 2 years. RESULTS: Mean age of study participants was 81.0 years. The participants were divided into two groups by baseline body temperature of 36.3 °C; lower body temperature group (n = 67) and normal body temperature group (n = 24). Body temperature rose significantly after exercise training in the lower body temperature group (36.04 ± 0.11 °C to 36.30 ± 0.13 °C, p < 0.0001), whereas there was no significant difference in the normal body temperature group (36.35 ± 0.07 °C to 36.36 ± 0.13 °C, p = 0.39). A positive correlation was observed between the amount of change in body temperature and baseline body temperature (r = -0.68, p < 0.0001). Increase in skeletal muscle mass was an independent variable related to the rise in body temperature by the multivariate logistic regression analysis (odds ratio: 4.77, 95% confidence interval: 1.29-17.70, p = 0.02). CONCLUSIONS: Exercise training raised body temperature in the elderly, especially those with lower baseline body temperature.

Perioperative exercise capacity in chronic liver injury patients with hepatocellular carcinoma undergoing hepatectomy.

Dynamic assessment of preoperative exercise capacity may be a useful predictor of postoperative prognosis. We aimed to clarify whether perioperative exercise capacity was related to long-term survival in hepatocellular carcinoma patients with chronic liver injury undergoing hepatectomy. One hundred-six patients with hepatocellular carcinoma underwent pre- and postoperative cardiopulmonary exercise testing to determine their anaerobic threshold, defined as the point between carbon dioxide production and oxygen consumption per unit of time. Testing involved 35 items including blood biochemistry analysis, in-vivo component analysis, dual-energy X-ray absorptiometry, and cardiopulmonary exercise testing preoperatively and 6 months postoperatively. We classified patients with anaerobic threshold ≥ 90% 6 months postoperatively compared with the preoperative level as the maintenance group (n = 78) and patients with anaerobic threshold < 90% as the decrease group (n = 28). Five-year recurrence-free survival rates were 39.9% vs. 9.9% (maintenance vs. decrease group) (hazard ratio: 1.87 [95% confidence interval: 1.12-3.13]; P = 0.018). Five-year overall survival rates were maintenance: 81.9%, and decrease: 61.7% (hazard ratio: 2.95 [95% confidence interval: 1.37-6.33]; P = 0.006). Multivariable Cox proportional hazards models showed that perioperative maintenance of anaerobic threshold was an independent prognostic indicator for both recurrence-free- and overall survival. Although the mean anaerobic threshold from preoperative to postoperative month 6 decreased in the exercise-not-implemented group, the exercise-implemented group experienced increased anaerobic threshold, on average, at postoperative month 6. The significant prognostic factor affecting postoperative survival for chronic liver injury patients with HCC undergoing hepatectomy was maintenance of anaerobic threshold up to 6 months postoperatively.

Efficacy of Oxycodone for Dyspnea in End-stage Heart Failure with Renal Insufficiency.

A 67-year-old man with dilated cardiomyopathy and renal insufficiency was admitted to our hospital with dyspnea secondary to end-stage heart failure. We introduced oxycodone for medically refractory dyspnea instead of morphine because of the patient's renal insufficiency. After the administration of oxycodone, his dyspnea was alleviated without any adverse opioid effects, such as respiratory depression. After treating his heart failure, he was able to leave the intensive care unit. Oxycodone may therefore be a reliable agent for the treatment of dyspnea in patients with end-stage heart failure and renal insufficiency.

Loss of skeletal muscle mass in patients with chronic liver disease is related to decrease in bone mineral density and exercise tolerance.

AIM: This study aimed to identify the relationship between loss of skeletal muscle mass and clinical factors such as osteoporosis in patients with chronic liver disease. METHODS: The subjects were 112 patients (85 men and 27 women) with hepatocellular carcinoma who were scheduled to undergo hepatectomy. Skeletal muscle reduction was diagnosed according to the cut-off level of the skeletal mass index (SMI) for Asians (men <7.0 kg/m2 , women <5.4 kg/m2 ). Osteoporosis was diagnosed according to T-score ≤-2.5 standard deviation. The SMI and T-score were assessed using the results of dual-energy X-ray absorption. Peak oxygen consumption (PeakVO2 ), an index of exercise tolerance, was evaluated using the cardiopulmonary exercise test. The characteristics of patients with low SMI (low SMI group) were compared with those of patients whose SMI was not low (control group). Outcomes are presented as median (interquartile range). RESULTS: The T-score was significantly lower in the low SMI group (control vs. low SMI -1.1 [1.8] vs. -1.6 [1.9], P = 0.049). T-score positively correlated with SMI (r = 0.409, P < 0.0001). PeakVO2 was significantly decreased in the low SMI group (17.7 [6.3] vs. 14.4 [4.5], P = 0.006). In multivariate logistic regression analysis, T-score (odds ratio [OR], 3.508; 95% confidence interval [CI], 1.074-11.456; P = 0.038) and PeakVO2 (OR, 3.512; 95% CI, 1.114-11.066; P = 0.032) were significantly related to SMI, independent of age and sex. CONCLUSIONS: Skeletal muscle reduction in chronic liver disease is closely related to exercise tolerance and osteoporosis, and these factors are believed to be associated with physical inactivity in daily life.

Effect of exercise-based cardiac rehabilitation on non-culprit mild coronary plaques in the culprit coronary artery of patients with acute coronary syndrome.

Approximately, 70 % of acute myocardial infarctions are known to develop from mild atherosclerotic lesions. Therefore, it is important to evaluate mild coronary plaques to prevent acute coronary syndrome (ACS). The aim of the present study was to investigate the effects of exercise-based cardiac rehabilitation (CR) on mild coronary atherosclerosis in non-culprit lesions in patients with ACS. Forty-one men with ACS who underwent emergency percutaneous coronary interventions and completed a 6-month follow-up were divided into CR and non-CR groups. Quantitative coronary angiography (QCA) was performed using the automatic edge detection program. The target lesion was a mild stenotic segment (10-50 % stenosis) at the distal site of the culprit lesion, and the segment to be analyzed was determined at a segment length ranging from 10 to 15 mm. The plaque area was significantly decreased in the CR group after 6 months, but was significantly increased in the non-CR group (P < 0.05). The low-density lipoprotein (LDL) cholesterol, LDL/high-density lipoprotein (HDL) ratio and high-sensitivity C-reactive protein (Hs-CRP) levels were significantly reduced in both groups (P < 0.01). Peak VO2 in the CR group was significantly increased (P < 0.01). Changes in the plaque area correlated with those in Hs-CRP in both groups, while that association with those in HDL-C was observed in only CR group. Stepwise regression analysis revealed the decrease in Hs-CRP as an independent predictor of plaque area regression in the CR group. CR prevented the progression of mild coronary atherosclerosis in patients with ACS.

Effect of Intramuscular Adipose Tissue Content on Prognosis in Patients Undergoing Hepatocellular Carcinoma Resection.

BACKGROUND: It has recently been reported that myosteatosis, the infiltration of fat in skeletal muscle, is associated with insulin resistance and type 2 diabetes mellitus. The present study investigated the effect of skeletal muscle fat accumulation on short- and long-term outcomes following partial hepatectomy for hepatocellular carcinoma (HCC) and aimed to identify prognostic factors. METHODS: The records of 141 HCC patients who underwent hepatectomy were retrospectively reviewed. Clinicopathological and outcome data from 71 patients with high intramuscular adipose tissue content (IMAC) were compared with those from 70 patients with low IMAC. RESULTS: The 5-year overall survival rate was 46% among patients with high IMAC and 75% among those with low IMAC. The 5-year disease-free survival rates in these groups were 18 and 38%, respectively. Multivariate analysis revealed that high IMAC was predictive of an unfavorable prognosis. High IMAC was significantly correlated with liver dysfunction, higher intraoperative blood loss, the need for blood transfusion, and comorbid diabetes mellitus. CONCLUSIONS: Greater fat accumulation in skeletal muscle was predictive of worse overall survival after partial hepatectomy in patients with HCC, even with adjustment for other known predictors. The identification of patients with greater skeletal muscle fat accumulation before hepatectomy could permit early preventive strategies to maintain muscle quality and thus improve prognosis and patient selection for hepatectomy.

Intracoronary followed by intravenous administration of the short-acting ß-blocker landiolol prevents myocardial injury in the face of elective percutaneous coronary intervention.

BACKGROUND: Myocardial injury during elective percutaneous coronary intervention (PCI) is associated with higher subsequent cardiac events and mortality. ß-Blockers have been used to reduce myocardial injury during ischemia and reperfusion. We investigated whether intracoronary followed by intravenous administration of the short-acting ß-blocker landiolol prevents myocardial injury in the face of elective PCI. METHODS AND RESULTS: Patients undergoing elective PCI (n=70) were randomly assigned to the landiolol (n=35) or control (n=35) group. Landiolol or saline was administered into target vessels through a balloon catheter for 1min before and after first balloon inflation followed by continuous intravenous administration for 6h after PCI. The incidence of myocardial injury defined by cardiac troponin-I (cTnI) >/=0.05 ng/ml was 79% of the patients in the control group compared to 56% in the landiolol group (p=0.04). The cTnI level at 24h after PCI tended to be lower in the landiolol group (0.57 ± 1.14 versus 1.27 ± 2.48 ng/ml; p=0.07), while the CK-MB level was not significantly different between the landiolol and control groups. The incidence of peri-procedural myocardial infarction defined by cTnI >/=0.12 ng/ml was significantly (p=0.02) lower in the landiolol group (41%) compared to the control group (70%). There was no incidence of coronary spasm, hypotension, bradycardia or heart failure during and after PCI in the two groups. CONCLUSIONS: Brief intracoronary followed by continuous intravenous administration of landiolol is safe and effective for myocardial protection in the face of elective PCI.

Differences in the mode of presentation for acute coronary syndrome by pre-hospitalization medication, in relation to coronary risk factors, East-Osaka acute coronary syndrome (EACS) registry.

BACKGROUND: Pre-hospitalization medication such as aspirin and nitrates has been shown to affect the mode of presentation in acute coronary syndrome (ACS). However, it is not formally assessed whether other cardiovascular medications may be contributed to the differences in the mode of presentation, especially in relation to coronary risk factors. METHODS AND RESULTS: We conducted a registration study of patients (M/F 850/323) with either ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina (UA), and examined the differences in the mode of presentation, pre-hospitalization medication, and coronary risk factors. The ratio of the incidence of STEMI and NSTEMI/UA was significantly reduced in patients having pre-hospitalization medication with aspirin, nitrates or statins, but not with other medications such as beta-blockers in multivariate analysis. Pre-hospitalization medication with aspirin and nitrates was significantly associated with the same reduction of the ratio in patients with male gender, hypertension, diabetes mellitus and a history of coronary artery disease. However, in patients who smoked, were obese and hypercholesterolemic, pre-hospitalization medication with nitrates was significantly associated with the reduced ratio. The ratio was significantly low in patients with males and hypercholesterolemia treated with statins before admission. CONCLUSION: Depending on their coronary risk factors, pre-hospitalization medication with aspirin, nitrates or statins was associated with a different presentation and evolution of ACS.

Efficacy of intracoronary administration of a short-acting ß-blocker landiolol during reperfusion in pigs.

BACKGROUND: Although ß-blockers are used to prevent myocardial ischemia/reperfusion injury, the risk of heart failure has limited ß-blocker therapy in patients with acute myocardial infarction. This study evaluated efficacy of intracoronary administration of the short-acting ß-blocker, landiolol, during reperfusion in pigs with acute myocardial ischemia. METHODS AND RESULTS: In the non-ischemic model landiolol administered into the left anterior descending coronary artery (LAD) inhibited in a dose-dependent fashion segmental wall thickening (SWT) in the anterior LV wall without altering SWT in the posterior LV wall and without prolonged depression of global LV function except for the highest dose. In the ischemic model with 60 min LAD occlusion followed by reperfusion the medium dose landiolol administered into the LAD 1 min before and for 10 min during reperfusion inhibited initial recovery of SWT in the anterior LV wall but improved SWT in this region and global LV function late after reperfusion. Ultrastructural studies showed inhibition of sub-sarcolemmal bleb formation by treatment with landiolol 10 min after reperfusion associated with the inhibition of CK-MB release and the reduction of infarct size. There was no significant difference in CK-MB release and infarct size between landiolol treatment for 10 min and 180 min during reperfusion. CONCLUSIONS: Selective and brief intracoronary administration of landiolol during reperfusion enhances myocardial salvage without causing deterioration of global LV function.

Retrograde fast pathway ablation with the EnSite NavX mapping system for slow-fast atrioventricular node reentrant tachycardia and a prolonged PR interval during sinus rhythm.

An 84-year-old male had experienced palpitations. He was transported to our hospital for treatment of palpitations. A 12-lead electrocardiogram (ECG) showed regular tachycardia with a wide QRS complex of 153 bpm, and the P wave was not clear. The ECG after the tachycardia stopped showed a sinus rhythm, and there was a prolonged PR interval of 312 ms and complete right bundle branch block. We recorded a prolonged AH interval (235 ms) in electrophysiology study (EPS). As for the St-A interval (185 ms) by consecutive pacing from the right ventricular apex, it was short in comparison with the anterograde conduction. As a result of detailed EPS, we diagnosed the tachycardia as slow-fast atrioventricular nodal reentrant tachycardia. The anterograde conduction depended on the slow pathway (SP), and the fast pathway (FP) was considered to have only retrograde conduction. It was thought that a complete atrioventricular block been caused by the SP ablation. Therefore we carried out FP ablation with three-dimensional computed tomography and the EnSite NavX mapping system (St. Jude Medical, St Paul, MN, USA), which was superior in space resolution power, and were able to effect a radical cure without complications.

The case of successful catheter ablation using only the approach from the upper part of the subject's body, with meandering aorta and implanted IVC filter.

A 79-year-old female had paroxysmal supraventricular tachycardia. However, she was implanted with an inferior vena cava filter and her descending aorta had significant meandering. It was thought that the insertion of the catheters would be difficult from the femoral vessels. Therefore we inserted electrode catheters from the right subclavian vein and internal jugular vein. As a result of an electrophysiology study, we diagnosed atrioventricular reciprocating tachycardia with a left lateral concealed accessory pathway (AP). An ablation catheter was introduced retrogradely through the left brachial artery and it was pushed forward under the mitral valve. Furthermore, it was put into the part where the earliest retrograde atrial deflection was recorded under the right ventricular apex pacing, and we succeeded in ablation of the AP. All catheters were inserted only from the upper part of the person's body. As for catheter operability, electric potential, operation time, and fluoroscopy time, there was no change in the case of either approach from the femoral vessels. Because we did not puncture the inguinal region, the patient was able to return to her ward on foot after the operation. In addition, we were able to perform a radical cure without complications.

Percutaneous coronary intervention for left main trunk ostial stenosis in a patient with Takayasu's arteritis.

Takayasu's arteritis with coronary artery involvement is a rare event especially in men. We will report on a male case of Takayasu's arteritis undergoing stent implantation for left main trunk (LMT) ostial stenosis. The case was that of a 25-year-old man who had been diagnosed with Takayasu's arteritis but there was no significant large vessel involvement. He presented with effort angina and a multidetector computed tomography (MDCT) revealed severe ostial stenosis in the LMT. A coronary angiography confirmed this finding and a virtual histology intravascular ultrasound (VH-IVUS) showed fibrous thickening of the intima and media with little necrotic lipid core and calcification. We performed a bare metal stent implantation for this lesion. No restenosis was found in the MDCT at the 6 month follow-up. Our experience suggests that the VH-IVUS is useful for examining the gross structure and component of the coronary vascular wall and for determining the choice of treatment in patients with Takayasu's arteritis.

Comparison of neointimal morphology of in-stent restenosis with sirolimus-eluting stents versus bare metal stents: virtual histology-intravascular ultrasound analysis.

Sirolimus-eluting stents (SES) have reduced the incidence of restenosis and target lesion revascularization compared to bare metal stents (BMS). However, inhibition of endothelialization and neointimal formation after SES implantation may produce vulnerable plaques. The present study compared the neointimal morphology of in-stent restenosis (ISR) between SES and BMS using virtual histology-intravascular ultrasound (VH-IVUS). Thirty ISR lesions (SES n = 15, BMS n = 15) demonstrated by coronary angiography in 30 patients with stable angina pectoris were analyzed with VH-IVUS between 6 months to 3 years after stent implantation. Tissue maps were reconstructed from radiofrequency data using VH-IVUS software. ISR lesions after SES implantation consisted of a significantly increased necrotic core (NC) compared to BMS (12.9 vs. 5.6% of neointimal volume, p < 0.01). However, the NC in ISR lesions after SES implantation was covered with a thick fibrous cap. An increase in the size of NC covered with a thick fibrous cap is a characteristic morphological feature of ISR after SES implantation. Further studies are needed to clarify whether such a morphological change is related to the attenuation of stent thrombosis after SES implantation.

Three-dimensional echocardiographic assessment of left ventricular function in takotsubo cardiomyopathy.

We evaluated left ventricular (LV) function by three-dimensional echocardiography (3DE) in a patient with takotsubo cardiomyopathy (TC). An 82-year-old man was admitted to our hospital with a suspicion of acute myocardial infarction but was diagnosed as TC by coronary angiography and left ventriculography (LVG). Three-dimensional echocardiography showed circular asynergy from the midventricle to the apex associated with hyperkinesis of the base and volumetric data very close to those obtained by LVG. Thus, 3DE is a useful tool in evaluating regional wall motion abnormalities and LV volume in patients with TC.

Increased expression of tumor necrosis factor-alpha converting enzyme and tumor necrosis factor-alpha in peripheral blood mononuclear cells in patients with advanced congestive heart failure.

BACKGROUND: Tumor necrosis factor-alpha converting enzyme (TACE) has recently been identified as a metalloproteinase-disintegrin, which converts pro-tumor necrosis factor-alpha (TNF-alpha) to the mature form, and is an important mediator in the pathogenesis of CHF. AIMS: In order to establish the importance of TACE in the regulation of TNF-alpha synthesis in peripheral blood mononuclear cells (PBMC), we analyzed mRNAs and protein-positive cells of both TACE and TNF-alpha in PBMC obtained from patients with congestive heart failure (CHF). METHODS AND RESULTS: PBMC were obtained from 46 patients with CHF and 22 controls. PBMC were activated by phorbol 12-myristate 13-acetate and ionomycin and assessed for TACE and TNF-alpha mRNAs by real-time RT-PCR, intracellular TACE and TNF-alpha levels by flow cytometry, and TNF-alpha secretion by supernatant ELISA. Levels of TACE and TNF-alpha mRNAs, intracellular TACE and TNF-alpha, and supernatant TNF-alpha were higher in CHF than in controls (P<0.001). There was a positive correlation between TACE and TNF-alpha levels in CHF patients (mRNA: r=0.60, P<0.001, intracellular protein levels: r=0.76, P<0.001). When the CHF group was divided into two subgroups by NYHA functional class (I and II vs. III and IV), levels of TACE and TNF-alpha were significantly higher in severe CHF patients (NYHA III or IV) than in mild CHF patients (NYHA I or II) (mRNA: P<0.001; intracellular protein levels: P<0.001). CONCLUSION: These results demonstrate that in patients with CHF, and especially those with severe CHF, TACE expression in PBMC increases with TNF-alpha expression. These observations suggest that TACE in PBMC is an important regulator of TNF-alpha maturation, meaning that TACE may be a potential target for the inhibition of cellular TNF-alpha production in CHF.

Expression of Toll-like receptor 4 is associated with enteroviral replication in human myocarditis.

Previous studies have demonstrated that inflammatory cytokine expression associated with enteroviral (EV) infection may play an important role in human myocarditis. However, the mechanism of the host immune response against viral pathogens has not been fully understood. The aim of the present study was to determine whether Toll-like receptor 4 (TLR4) and EV RNA are present in human myocarditis. Endomyocardial biopsy samples were obtained from 44 patients with myocarditis and five controls. Levels of plus- and minus-strand EV RNAs and TLR4 mRNA were measured by real-time reverse transcriptase-PCR. Immunohistochemical analysis was performed to identify the cellular source of TLR4 and the EV capsid protein VP1. EV RNA was present in 21 patients with myocarditis and these patients were defined as having either active viral replication ( n =15) or latent viral persistence ( n =6). Neither strand of EV RNA was detected in controls. TLR4 mRNA expression levels were higher in myocarditis patients than in controls (TLR4/glyceraldehyde-3-phosphate dehydrogenase ratio 1.48+/-0.17 compared with 0.08+/-0.06, P <0.001). A positive correlation was found between EV RNA and TLR4 levels (plus-strand vs TLR4: r =0.66, P <0.001; minus-strand vs TLR4: r =0.48, P <0.001). TLR4 immunostaining was observed in infiltrating cells and myocytes in patients with myocarditis. The EV capsid protein VP1 was also found in myocytes. The myocarditis group with EV replication and high levels of TLR4 showed significantly lower systolic function. The present study has shown that increased expression of TLR4 is associated with EV replication and that these RNA levels are related to cardiac dysfunction in human myocarditis.

Aldosterone synthase (CYP11B2) expression and myocardial fibrosis in the failing human heart.

The pathway of tissue aldosterone production may exist in the heart, and may be an important contributory factor to myocardial fibrosis and cardiac remodelling in the failing heart. CYP11B2 (aldosterone synthase) catalyses the final step of aldosterone production. The aim of the present study was to determine whether CYP11B2 and CYP11B1 (11beta-hydroxylase) are expressed in myocardial tissues, and whether these enzymes contribute to collagen accumulation and myocardial dysfunction in the failing human heart. Endomyocardial tissues were obtained from 23 patients with chronic heart failure (CHF) and 10 controls. CYP11B2 and CYP11B1 mRNA levels were measured by real-time quantitative reverse transcriptase-PCR. The myocardial collagen volume fraction (CVF) was determined by digital planimetry. CYP11B2 mRNA expression was greater in the CHF group than in the controls (P<0.05), while CYP11B1 mRNA was barely expressed in either group. There was a positive correlation between CYP11B2 mRNA levels and CVF (r=0.64, P=0.001). CYP11B2 mRNA was particularly highly expressed in subgroups of CHF patients with a large left ventricular end-systolic diameter (>55 mm) or a low left ventricular ejection fraction (<30%). CYP11B2 mRNA expression and CVF were lower in a CHF subgroup treated with a combination of spironolactone and angiotensin-converting enzyme inhibitors (ACEIs) than in a subgroup not treated with these drugs. In conclusion, this study has shown that increased myocardial expression of CYP11B2 mRNA is associated with increased myocardial fibrosis and with the severity of left ventricular dysfunction in human CHF. In addition, CYP11B2 expression and cardiac fibrosis are found to be decreased in CHF patients on drug therapy comprising spironolactone combined with ACEIs.