Immunochemical fecal occult blood tests predict dual antiplatelet therapy discontinuation after coronary stenting.

OBJECTIVE: The discontinuation of dual antiplatelet therapy (DAPT) increases the risk of stent thrombosis after coronary stenting. Some patients must discontinue DAPT due to gastrointestinal (GI) tract disease; however, the type of examination that is most useful for detecting GI tract diseases has not been fully evaluated. The purpose of this study was to clarify whether the immunochemical fecal occult blood test (iFOBT) can be used to predict GI tract disease-related DAPT discontinuation following stent implantation in patients with coronary artery disease. METHODS: A total of 181 consecutive DAPT-naïve patients who underwent coronary stenting were divided into two groups according to the results of iFOBTs: a positive iFOBT group (n=32) and a negative iFOBT group (n=149). During the 12-month follow-up period, the DAPT discontinuation rate was lower in the negative iFOBT group than in the positive iFOBT group (3.4 vs. 18.8%, p=0.005). Kaplan-Meier event-free curves showed that the DAPT discontinuation rate in the negative iFOBT group was lower than that observed in the positive iFOBT group (log-rank test: p=0.001). Logistic and Cox regression analyses showed that a positive iFOBT result was the strongest predictor of the risk of DAPT discontinuation after coronary stenting. CONCLUSION: A positive iFOBT result is associated with DAPT discontinuation following coronary stenting.

Impaired renal function is a major determinant of left ventricular diastolic dysfunction: assessment by stress myocardial perfusion imaging.

OBJECTIVE: Relationships between myocardial scintigraphic parameters and renal function have not been fully determined. We investigated correlations between estimated glomerular filtration rate (eGFR) and left ventricular (LV) diastolic function using stress electrocardiographic (ECG)-gated myocardial single photon emission computed tomography (SPECT). METHODS: We enrolled 136 consecutive patients with suspected coronary artery disease (CAD) who were assessed using technetium-99m stress ECG-gated myocardial SPECT. We evaluated SPECT images using 17-segment defect scores graded on a 5-point scale, summed stress score, summed rest score and summed difference score (SDS). The parameters for assessing LV diastolic function were peak filling rate (PFR), 1/3 mean filling rate and time to peak filling. The CAD was defined as SDS ≥2. Chronic kidney disease (CKD) was defined as eGFR <60 mL/min/1.73 m(2). Patients were assigned to the following four groups (no CAD/no CKD: control group, n = 68; CAD/no CKD: CAD group, n = 24; no CAD/CKD: CKD group, n = 34; CAD/CKD: CAD + CKD group, n = 10). RESULTS: The PFR was significantly impaired after stress in the CKD and CAD + CKD groups compared with controls (p < 0.001 for both). Furthermore, PFR at rest positively correlated with eGFR (r = 0.29, p < 0.001) and inversely correlated with SDS (r = -0.18, p < 0.05). Multivariate stepwise regression analysis independently associated eGFR with PFR (ß coefficient = 0.260, p = 0.002). CONCLUSIONS: Our data suggest that impaired renal function is a significant determinant of LV diastolic dysfunction in patients with suspected CAD.

Questionnaire survey on the continuity of home oxygen therapy after a disaster with power outages.

BACKGROUND: After the Great East Japan Earthquake, oxygen-dependent patients in areas experiencing power outages could not continue home oxygen therapy (HOT) without oxygen cylinders. The purpose of this study was to examine use of oxygen cylinders in areas experiencing power outages and the effects of HOT interruption on patients' health. METHODS: Questionnaires were mailed to 1106 oxygen-dependent patients and HOT-prescribing physicians in Akita, near the disaster-stricken area. We investigated patients' actions when unable to use an oxygen concentrator and classified the patients based on oxygen cylinder use. Patients who experienced an interruption of or reduction in oxygen flow rate by their own judgment were assigned to the "interruption" and "reduction" groups, respectively; those who maintained their usual flow rate were assigned to the "continuation" group. Differences were tested using analysis of variance and the χ2 tests. RESULTS: In total, 599 patients responded to the questionnaire. Oxygen cylinders were supplied to 574 patients (95.8%) before their oxygen cylinders were depleted. Comparison of the continuation (n=356), reduction (n=64), and interruption (n=154) groups showed significant differences in family structure (p=0.004), underlying disease (p=0.014), oxygen flow rate (p<0.001), situation regarding use (p<0.001), knowledge of HOT (p<0.001), and anxiety about oxygen supply (p<0.001). There were no differences in changes in physical condition. CONCLUSIONS: Most patients could receive oxygen cylinders after the disaster. Some patients discontinued their usual oxygen therapy, but their overall health status was not affected.

Adaptive servo-ventilation therapy improves cardiac sympathetic nerve activity in patients with heart failure.

AIMS: This study investigated whether abnormal cardiac sympathetic nerve activity (SNA) is associated with the severity of central sleep apnoea (CSA) and whether adaptive servo-ventilation (ASV) therapy can improve cardiac SNA in heart failure (HF) patients with predominant CSA. METHODS AND RESULTS: Overnight polysomnography was conducted to diagnose CSA. Cardiac SNA was analysed by [123I]metaiodobenzylguanidine scintigraphy in 26 consecutive HF patients with predominant CSA. Of the 26 patients, 10 agreed to ASV therapy. Cardiac SNA was analysed 6 months after initiating ASV based on a non-randomized protocol. The apnoea-hypopnoea index and central apnoea index were significantly correlated with the washout rate (WR) and a delayed heart to mediastinal (H/M) ratio, suggesting that SNA is associated with abnormal breathing patterns. The WR, H/M ratio, plasma BNP level, and LVEF were significantly improved (WR, 40.0 ± 11.6% vs. 34.6 ± 11.4%, P = 0.046; H/M ratio, 1.5 ± 0.1 vs.1.8 ± 0.3, P = 0.013; ln BNP, 5.4 ± 1.0 vs. 4.6 ± 1.2, P = 0.007; and LVEF, 43.8 ± 10.4% vs. 47.0 ± 10.6%, P < 0.001) in the ASV group patients, but not in the non-ASV group patients. Multiple linear regression analyses showed that a decreased WR was strongly associated with an increased LVEF (coefficient = -0.454, P = 0.013). CONCLUSIONS: Abnormal cardiac SNA could be significantly correlated with the severity of CSA in HF patients. ASV therapy might improve cardiac function in these patients by partially mediating cardiac SNA regulation.

Comparison of anti-inflammatory effects and high-density lipoprotein cholesterol levels between therapy with quadruple-dose rosuvastatin and rosuvastatin combined with ezetimibe.

BACKGROUND: Statins are frequently administered to reduce low-density lipoprotein cholesterol (LDL-C) and vascular inflammation, because LDL-C and high sensitive C-reactive protein (hs-CRP) are associated with high risk for cardiovascular events. When statins do not reduce LDL-C to desired levels in high-risk patients with coronary artery disease (CAD), ezetimibe can be added or the statin dose can be increased. However, which strategy is more effective for treating patients with CAD has not been established. The present study compares anti-inflammatory effects and lipid profiles in patients with CAD and similar LDL-C levels who were treated by increasing the statin dose or by adding ezetimibe to the original rosuvastatin dose to determine the optimal treatment for such patients. METHODS: 46 patients with high-risk CAD and LDL-C and hs-CRP levels of >70 mg/dL and >1.0 mg/L, respectively, that were not improved by 4 weeks of rosuvastatin (2.5 mg/day) were randomly assigned to receive 10 mg (R10, n = 24) of rosuvastatin or 2.5 mg/day of rosuvastatin combined with 10 mg/day of ezetimibe (R2.5/E10, n = 22) for 12 weeks. The primary endpoint was a change in hs-CRP. RESULTS: Baseline characteristics did not significantly differ between the groups. At 12 weeks, LDL-C and inflammatory markers (hs-CRP, interleukin-6, tumour necrosis factor-alpha and pentraxin 3) also did not significantly differ between the two groups (LDL-C: R10 vs. R2.5/E10: -19.4 ± 14.2 vs. -22.4 ± 14.3 mg/dL). However, high-density lipoprotein cholesterol (HDL-C) was significantly improved in the R10, compared with R2.5/E10 group (4.6 ± 5.9 vs. 0.0 ± 6.7 mg/dL; p < 0.05). CONCLUSION: Both enhanced therapies exerted similar anti-inflammatory effects under an equal LDL-C reduction in patients with high-risk CAD despite 2.5 mg/day of rosuvastatin. However, R10 elevated HDL-C more effectively than R2.5/E10. TRIAL REGISTRATION: UMIN000003746.

Candesartan improves impaired endothelial function in the human coronary artery.

BACKGROUND: Endothelial dysfunction is closely related to cardiovascular events. Several studies have documented that angiotensin II type 1 receptor blockers (ARB) improve peripheral endothelial dysfunction. However, the effect of ARB on coronary endothelial function remains elusive. The purpose of this study was to ascertain the beneficial effects of ARB on human coronary artery endothelial function. METHODS AND RESULTS: Twenty-seven patients were randomly assigned to either the candesartan group (n=14) or the control group (n=13) and followed for 12 months. Coronary blood flow velocity was measured in the left anterior descending artery without stenosis using an intracoronary Doppler-tipped guide-wire. We evaluated coronary endothelial function as the coronary blood flow velocity reserve (CFR), which was defined as the percent change in the coronary blood flow velocity after an intracoronary acetylcholine infusion. At baseline, the CFR in both groups was below 300%, implying that these patients had endothelial dysfunction. After treatment with candesartan for 6 months, the CFR increased significantly from 199 ± 20 to 337 ± 27% (P<0.001), whereas the CFR did not change in the control group (194 ± 32 vs. 185 ± 41%, P=0.52). During 12 months of observation, the cardiovascular event-free survival rate of the patients with an increased CFR was significantly greater than the rate in patients with a decreased CFR (P=0.02). Moreover, the cardiovascular event-free survival rate was greater in the candesartan group than in the control group (P=0.04). CONCLUSION: Our results suggest that candesartan improves coronary endothelial dysfunction of human coronary arteries and may prevent cardiac events.

Impact of obesity on plasma B-type natriuretic peptide levels in Japanese community-based subjects.

The plasma B-type natriuretic peptide (BNP) concentration was recently shown to be inversely correlated with body mass index (BMI). However, very few attempts have been made to associate abdominal obesity and BNP in the Japanese general population. Here, we conducted a cross-sectional study, and examined 339 male and 429 female residents without heart disease in a rural Japanese community who received an annual health checkup in 2006. BNP was inversely associated with both BMI and abdominal circumference (AC) in the age-adjusted regression analysis (p < 0.05). Following adjustment for traditional risk factors, multiple regression analysis revealed that BNP was negatively correlated with AC (p < 0.05), but not BMI. Although metabolic syndrome was not associated with BNP levels, AC had an influence on low BNP levels in the multiple regression analysis using both AC and BMI concurrently (p < 0.05 for AC and p > 0.60 for BMI). These effects were more prominent in men than in women. Collectively, plasma BNP levels are inversely related with obesity, as measured by AC, in Japanese community-based subjects.

Low mean corpuscular hemoglobin level is a predictor of discontinuation of antiplatelet therapy in patients with acute coronary syndrome.

OBJECTIVE: Premature discontinuation of antiplatelet therapy (APT) increases the risk of thrombosis in patients who have undergone placement of a drug-eluting stent for acute coronary syndrome (ACS). The goal of the present study was to identify predictors of patients who would prematurely discontinue APT following stent implantation. METHODS: One-hundred and sixty-one ACS patients who underwent percutaneous coronary intervention in our institution between November 2004 and September 2008 were enrolled in this study. RESULTS: Over the 12-month follow-up period, 18 patients (11.2%) discontinued APT. Among baseline demographic and laboratory variables, multivariate analysis revealed that mean corpuscular hemoglobin (MCH) level was an independent risk factor for APT discontinuation (OR: 0.738, p=0.017). Kaplan-Meier survival analysis showed that the incidence of APT discontinuation was significantly higher in patients with low MCH (<30.0 pg) than in patients with high MCH (≥30.0 pg) (p=0.0006). CONCLUSION: Low baseline MCH level was a predictor of APT discontinuation in ACS patients. Thus, careful consideration should be made before employing a drug-eluting stent in patients with low MCH levels.

Endothelial progenitor cells are associated with response to chemotherapy in human non-small-cell lung cancer.

PURPOSE: Bone marrow-derived endothelial progenitor cells (EPCs) play an important role in angiogenesis and tumor growth. However, the clinical relevance of EPCs in non-small-cell lung cancer (NSCLC) remains unclear. Recently, some reports suggested that EPCs correlate with clinical behavior of cancer patients. We assessed the hypothesis that EPCs correlate with efficient of therapy, prognosis, and clinicopathological factors, and EPCs may offer a possible biomarker for treatment outcome in NSCLC. METHODS: EPCs labeled with CD34, CD133, and vascular endothelial growth factor receptor-2 (VEGFR-2) antibodies were counted by flow cytometry in the peripheral blood of 31 NSCLC patients. We categorized two groups of NSCLC patients according to circulating EPC numbers. We examined age, pathological stage, histological type, Fluoro-D: -glucose Positron emission tomography (FDG-PET), response to therapy, progression-free survival, and tumor size of NSCLC patients and investigated whether these factors correlate with EPC counts. RESULTS: Circulating EPC numbers before antitumor therapy were increased in NSCLC patients compared with healthy controls (P < 0.05). In NSCLC patients, therapy was significantly effective in low circulating EPC group compared with that of high (P < 0.05). Furthermore, the low EPC group showed significantly longer progression-free survival times than that of high (P < 0.05). However, no significant associations with age, gender, histological type, pathological stage, or FDG-PET were detected. CONCLUSION: Peripheral blood levels of bone marrow-derived EPCs are significantly increased in patients with NSCLC and correlate with response to chemotherapy. EPCs may offer a possible biomarker for efficient of treatment and prognosis.

The prevalence of apical wall motion abnormalities in patients with long-term right ventricular apical pacing.

BACKGROUND: Long-term right ventricular apical pacing (RVAP) can lead to adverse clinical outcomes. Although left ventricular (LV) dyssynchrony is the major causative factor, other potential mechanisms are not fully understood. We sought to clarify whether RVAP elicits apical wall motion abnormalities that contribute to LV contractile dysfunction. METHODS: We studied annual echocardiographic data over a 5-year period after pacemaker implantation (PMI) for 74 patients who underwent RVAP. The patients were divided into two groups according to the percentage of ventricular pacing: right ventricular (RV) pacing < 50% and RV pacing ≥ 50%. We assessed LV ejection fraction, LV end-diastolic volume, and left atrial dimension. To assess regional wall motion abnormalities, the wall motion score index was calculated. RESULTS: LV wall motion abnormality was observed in 64% of the subjects and was more pronounced in apical segments than in other segments. At 2 years after PMI, brain natriuretic peptide levels were significantly higher in the group with RV pacing ≥ 50% than in the group with RV pacing < 50%. The subjects with RV pacing ≥ 50% had higher LV end-diastolic dimension and lower ejection fraction at 3 years after PMI. CONCLUSION: Long-term RVAP elicits apical wall motion abnormalities that could in part contribute to LV contractile dysfunction.

Beneficial effects of adaptive servo ventilation in patients with chronic heart failure.

BACKGROUND: Sleep-disordered breathing (SDB) is thought to be a state of inflammation caused by hypoxic stress. Whether adaptive servo ventilation (ASV) attenuates the inflammatory response and improves the cardiac function of patients with congestive heart failure (CHF) accompanied by SDB was not been investigated. METHODS AND RESULTS: Seventeen inpatients with New York Heart Association (NYHA) II or III underwent polysomnography. There was a positive correlation between the apnea hypopnea index and high-sensitivity C-reactive protein (hs-CRP) level (r=0.753, P=0.016). The patients were divided into ASV (n=10) and non-ASV groups (n=7), and CHF-parameters were measured before and after ASV treatment. Improvement was noted for the NYHA class in the ASV group but not in the non-ASV group. In contrast to the non-ASV group, the level of brain natriuretic peptide (BNP), ejection fraction, and hs-CRP levels in the ASV group significantly improved (BNP, 212.1 ± 181.2 to 77.3 ± 54.0 pg/ml [P<0.05]; ejection fraction, 43.5 ± 6.4 to 53.3 ± 6.1% [P=0.002]; hs-CRP, 0.85 ± 0.58 to 0.21 ± 0.19 mg/dl, [P=0.008]). The increase in ejection fraction was correlated with a decrease in the hs-CRP level (r=-0.753, P=0.001). CONCLUSIONS: Anti-inflammatory effects of ASV are important contributors for improving cardiac function in patients with CHF accompanied by SDB.

Double transgenic mice crossed GFP-LC3 transgenic mice with alphaMyHC-mCherry-LC3 transgenic mice are a new and useful tool to examine the role of autophagy in the heart.

BACKGROUND: The involvement of autophagy in heart disease has been reported. Transgenic mice expressing GFP-LC3 have been a useful tool in detecting autophagosomes systemically. It is difficult to differentiate increased formation of autophagosomes from decreased clearance of autophagosomes in the heart using GFP-LC3 mice. METHODS AND RESULTS: We generated transgenic mice expressing mCherry-LC3 under alphaMyHC promoter and crossed the mice with transgenic mice expressing GFP-LC3. The deference of resistance to acidic conditions between GFP and mCherry overcame the limitation. CONCLUSIONS: This method is an innovative approach to examine the role of autophagy and to analyze autophagosome maturation in cardiomyocytes. (Circ J 2010; 74: 203 - 206).

Cardioprotective effect of an L/N-type calcium channel blocker in patients with hypertensive heart disease.

BACKGROUND: Left ventricular (LV) diastolic dysfunction is related to increased cardiac sympathetic activity. We investigated the effect of cilnidipine, an L/N-type calcium channel blocker, on LV diastolic function and cardiac sympathetic activity in patients with hypertensive heart disease (HHD) using radionuclide myocardial imaging. METHODS AND RESULTS: Thirty-two frame electrocardiography (ECG) -gated (99m)Tc-sestamibi (MIBI) myocardial single photon emission computed tomography (SPECT), and (123)I-metaiodobenzylguanidine (MIBG) imaging were performed before and 6 months after drug administration in 32 outpatients with HHD. Sixteen of the patients were treated with cilnidipine and the other 16 were treated with nifedipine retard. The parameters for assessing LV diastolic function evaluated using ECG-gated (99m)Tc-MIBI SPECT were peak filling rate (PFR), first-third filling rate (1/3FR), and time to peak filling (TPF). Cardiac sympathetic activity was assessed as early and delayed heart to mediastinum (H/M) ratios and a washout rate (WR), using (123)I-MIBG imaging. The PFR and 1/3FR significantly increased after 6 months of treatment with cilnidipine (p<0.05 for both), but did not with nifedipine retard. The H/M ratios significantly increased (p<0.05 for both) in conjunction with a decreased WR (p<0.05) in the cilnidipine group. Moreover, a significant positive correlation was seen between the rate of change in PFR and the rate of change in early and delayed H/M ratios in the cilnidipine group (p<0.05 for both). The same results were obtained for the relationship between the rate of change in 1/3FR and the rate of change in H/M ratios (p<0.05 for both). However, no such relationship was seen in the nifedipine group. CONCLUSION: These data indicate that cilnidipine seems to suppress cardiac sympathetic overactivity via blockade of N-type calcium channels and improves LV diastolic function in patients with HHD.

Association between perceived stress and plasma B-type natriuretic peptide concentrations.

BACKGROUND: Many patients with heart disease continue to have cardiac events despite receiving optimal treatments for traditional risk factors. Consequently, non-traditional risk factors for heart disease, such as perceived stress, have attracted attention. Associations between perceived stress and plasma B-type natriuretic peptide (BNP) were explored, while controlling for traditional heart disease risk factors. METHODS AND RESULTS: This cross-sectional study examined 360 male and 446 female (age, >40 years) residents of a rural Japanese community who received annual health checkups in 2006. A lifestyle questionnaire was used to obtain information regarding perceived stress and medical history, and routine anthropometric and blood pressure measurements and a laboratory assessment of cardiovascular risk factors, including plasma BNP concentrations and an electrocardiogram, were done. After adjusting for traditional heart disease risk factors, multiple regression analysis showed that perceived stress was associated with BNP concentrations, particularly in women (F=6.12, P=0.026). In addition, multiple tests using Bonferroni's procedure showed that BNP concentrations decreased with perceived stress level in men and women. Similar trends were observed in the sub-analyses of subjects with and without known heart disease. CONCLUSIONS: Perceived stress in our study was negatively associated with plasma BNP concentrations, independently of traditional heart disease risk factors.

Usefulness of plasma BNP levels as a marker of left ventricular wall stress in obese individuals.

Plasma brain natriuretic peptide (BNP) level is known to reflect left ventricular wall stress (LVWS). Recent studies have shown that obese individuals have lower BNP levels. However, the usefulness of BNP level as a marker of LVWS in obese individuals remains unclear. This study examined whether BNP reflects LVWS even in obese individuals.This study enrolled 136 hospital inpatients who had suffered chronic heart failure (NYHA class I or II), or who had undergone a thorough examination for angina pectoris. On the basis of body mass index (BMI), we divided the inpatients into nonobese (< 25) and obese (> or = 25) groups. All BNP measurements, cardiac catheterizations, and echocardiographic examinations were carried out within 24 hours. Although no significant differences were found between the two groups in the hemodynamic parameters examined, including end-diastolic LVWS (LV-EDWS) and end-systolic LVWS (LV-ESWS), BNP levels were significantly lower in the obese group compared to the nonobese group. In the nonobese group, a definite correlation between LV-EDWS or LV-ESWS and BNP (r = 0.43, r = 0.46, respectively) was observed, whereas no correlation was found between LV-EDWS or LV-ESWS and BNP in the obese group (r = -0.09, r = 0.06, respectively). To explore the mechanism for suppressed BNP levels in obese individuals, the correlation of BNP with biochemical markers was analyzed. Statistical significance was found only between adiponectin and BNP (r = 0.44), implying that BNP or adiponectin might influence the plasma levels of the other.In conclusion, BNP levels cannot be used as a marker of LVWS in obese individuals.

Successful outcome in a pregnant woman with isolated noncompaction of the left ventricular myocardium.

A 24-year-old pregnant woman was referred to our hospital for the evaluation of her cardiac function. An electrocardiogram showed Wolff-Parkinson-White syndrome. Echocardiography revealed prominent trabeculation and deep intertrabecular recesses at the left ventricular apex and mid-portion of the inferior and lateral wall, with an impaired ejection fraction. She was diagnosed as having an isolated noncompaction of the ventricular myocardium (INVM). As the pregnancy progressed, severe restrictive hemodynamics became apparent. In consideration of the fetal growth, we decided to deliver the fetus by cesarean section at 32 weeks gestation; the patient successfully delivered a female infant. Interestingly, echocardiography demonstrated INVM in both the child and mother. This report is the first description of a successful pregnancy in a patient with familial INVM.