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We report a case of aortic perforation caused by the staple line formed during a wedge resection for lung cancer. Six hours after an uneventful wedge resection, sudden frank drainage of blood from the chest tube occurred. A reoperation was performed, and we found bleeding from the aorta. After suturing the bleeding spot on the aorta, we found that the stapling line of the lung rode on the aorta with longitudinal contact. We speculated that the stapling line scratched the aorta in synchrony with the patient's breathing and injured the aorta.

Background: Residual aneurysms after graft replacement are rare, but they can be detrimental if they are saccular and large. The etiology of residual aneurysms remains unknown, and their management is controversial. One treatment option is late open surgical conversion; however, postoperative respiratory complications resulting from the dissection of pleural adhesions, which is frequently necessary with this approach, are often unavoidable. Case presentation: Herein, we report a case of open surgical repair of a residual distal aortic arch aneurysm that occurred after total arch replacement and thoracic endovascular aortic repair. Contrast-enhanced magnetic resonance imaging was not possible in this case due to the patient’s severe renal dysfunction; however, contrast-enhanced computed tomography using minimal contrast did not detect remarkable leakage through the graft or stent graft into the aneurysm. Late open surgical conversion using video-assisted thoracic surgery was performed by thoracic surgeons, and the adhesion between the aortic wall and the lung was safely and effectively dissected. Because there was no significant pulsation or evidence of feeding arteries in the aortic wall, the aortic wall was opened carefully. No bleeding or backflow from any branch arteries into the aneurysm was noted, so the aortic wall was ligated with continuous sutures. The patient recovered without experiencing any major complications. Conclusions: This case report demonstrates that video-assisted thoracic surgery is safe and effective for late open conversion in cases of residual aneurysm; furthermore, this case suggests that video-assisted thoracic surgery may be particularly beneficial for the dissection of adhesions between the aortic wall and lung in these cases.

Background: Few studies have investigated the importance of glycemic control in patients with diabetes mellitus (DM) for reducing the incidence of late target lesion revascularization (TLR) after implantation of new-generation drug-eluting stents (DES). Methods and Results: We retrospectively identified 1,568 patients who underwent new-generation DES implantation. Patients were divided into 3 groups based on diabetic status and glycemic control 1 year after the procedure: those without DM (non-DM group; n=1,058) and those with DM at follow-up with either good (HbA1c

Clinical evidence demonstrating the impact of statins for preventing late target lesion revascularization (TLR) after newer-generation drug-eluting stent implantation and differences in the effect of statins on late TLR according to pre-interventional vessel remodeling and vessel size is limited. We retrospectively evaluated 1193 de novo lesions in 720 patients who underwent everolimus-eluting stent implantation using intravascular ultrasound from January 2010 to December 2012. The primary endpoint was late TLR. Lesions were divided into the statin group (n = 825) and non-statin group (n = 368). The incidence of late TLR was significantly lower in the statin than non-statin group (1.7% vs. 5.2%, respectively; p = 0.001), and within the statin group, it was significantly lower in the follow-up low-density lipoprotein cholesterol (LDL-C) p = 0.006). Furthermore, in positive remodeling lesions and non-small vessel size lesions, the incidence of late TLR was significantly lower in the statin than non-statin group (1.6% vs. 8.5% and 1.3% vs. 5.3%, respectively; p = 0.001 and p = 0.004). Lowering the LDL-C level using statins was more effective for preventing late TLR after everolimus-eluting stent implantation. Evaluating pre-interventional vessel remodeling patterns and vessel size might be helpful to stratify lesions at high risk of late TLR.

Background We sometimes experience postoperative surgical site infection (SSI) at the chest tube drainage site (CDS) after thoracotomy. The incidence of and risk factors for SSI at the CDS have remained unclear. Methods We conducted a prospective study to determine the incidence and risk factors for SSI at the CDS. We analyzed 99 patients who underwent lobectomy or segmentectomy for pulmonary malignant lesions. Results There were 56 males and 43 females with an average age of 71 years. The postoperative drainage period was 2-15 days. Bacterial species were detected in secretions in 18 of 99 cases (18.2%). Older age was a risk factor for the detection of bacteria at the timing of chest tube removal. Eighteen cases (18.2%) were diagnosed with presence of SSI at the CDS at the timing of staple or suture removal. A pathological diagnosis of squamous cell carcinoma was regarded as a candidate risk factor for SSI. Eleven of 18 SSI patients showed delayed wound healing. A higher level of HbA1c was found in patients with delayed wound healing. Enterococcus faecalis infection may influence the development of complex SSI. Conclusions We identified the bacterial profiles, incidence of and risk factors for SSI at the CDS. More intense preoperative glycemic control and an understanding of the bacterial profile and may be useful for reducing the incidence of SSI chest tube drainage sites (CDS).

A 19-year-old woman developed hypotension and abdominal distension during lumbar discectomy. Computed tomography revealed a right common artery injury and a large retroperitoneal hematoma. She was transferred to our hospital and brought to an angiography room directly. Endovascular balloon occlusion of the aorta was performed by cardiologists while surgeons were preparing for surgery. With the hemodynamics stabilized, the injured artery was repaired. In such a case, closing the artery as soon as possible, whether by clamping or by balloon occlusion, is vital. The ability to respond with a "Heart Team" is essential for a small-manpower hospital to rescue a patient with a serious condition.

There is still no clear guideline for surgical treatment for patients with medically refractory trigeminal neuralgia (TN). When it comes to which surgical treatment to choose, microvascular decompression (MVD) or Gamma Knife surgery (GKS), we should know the long-term outcome of each treatment. We analyzed 179 patients undergoing MVD and 52 patients undergoing GKS followed for 1 year or longer. We evaluated the patient’s neurological status including pain relief, complications and recurrence. Results were assessed with Barrow Neurological Institute (BNI) pain intensity and facial numbness scores. Overall outcomes were compared between the two groups based on pain relief and complications. BNI pain intensity and facial numbness scores at the final visit were significantly lower in the MVD group than in the GKS group (P

Malignant pleural mesothelioma (MPM), an asbestos‐related occupational disease, is an aggressive and incurable tumor of the thoracic cavity. Despite recent advances in MPM treatment, overall survival of patients with MPM is very low. Recent studies have implicated that PI3K/Akt signaling is involved in MPM cell survival and development. To investigate the effects of Akt inhibitors on MPM cell survival, we examined the effects of nine selective Akt inhibitors, namely, afuresertib, Akti‐1/2, AZD5363, GSK690693, ipatasertib, MK‐2206, perifosine, PHT‐427, and TIC10, on six MPM cell lines, namely, ACC‐MESO‐4, Y‐MESO‐8A, MSTO‐211H, NCI‐H28, NCI‐H290, and NCI‐H2052, and a normal mesothelial cell line MeT‐5A. Comparison of IC 50 values of the Akt inhibitors showed that afuresertib, an ATP‐competitive specific Akt inhibitor, exerted tumor‐specific effects on MPM cells. Afuresertib significantly increased caspase‐3 and caspase‐7 activities and apoptotic cell number among ACC‐MESO‐4 and MSTO‐211H cells. Moreover, afuresertib strongly arrested the cell cycle in the G1 phase. Western blotting analysis showed that afuresertib increased the expression of p21WAF 1/ CIP 1 and decreased the phosphorylation of Akt substrates, including GSK‐3β and FOXO family proteins. These results suggest that afuresertib‐induced p21 expression promotes G1 phase arrest by inducing FOXO activity. Furthermore, afuresertib significantly enhanced cisplatin‐induced cytotoxicity. Interestingly, results of gene set enrichment analysis showed that afuresertib modulated the expression E2F1 and MYC, which are associated with fibroblast core serum response. Together, these results suggest that afuresertib is a useful anticancer drug for treating patients with MPM.

Everolimus-eluting stent (EES) is effective for treating in-stent restenosis (ISR). However, the long-term incidence of target lesion revascularization (TLR) is unknown. Further, the role of post-intervention minimal stent area (MSA) measured by intravascular ultrasound (IVUS) in TLR is unknown in this setting.Overall, 223 ISR lesions (192 patients) that were treated with EES between 2010 and 2016 were analyzed retrospectively. Lesions were divided into two groups according to the post-intervention MSA [ ≤ 5.3 mm: 72 lesions (67 patients), and5.3 mm: 151 lesions (138 patients)]. The cut-off point was determined on the basis of receiver operating characteristic curve analysis.The cumulative 5-year incidence of TLR was significantly higher in the group with MSA of 5.3 mm or less than in the group with MSA more than 5.3 mm (15.8 and 7.2%, P = 0.01). After adjusting for confounders, the excess risk of the group with MSA of 5.3 mm or less relative to the group with MSA more than 5.3 mm for TLR remained significant [hazard ratio: 3.07, 95% confidence interval (CI): 1.17-8.51, P = 0.02]. Using multivariate logistic regression analysis, we identified female sex (odds ratio: 2.39, 95% CI: 1.06-5.49, P = 0.04) and stent size of 3.0 mm or less (odds ratio: 13.43, 95% CI: 6.23-32.38, P0.0001) as independent predictors of MSA of 5.3 mm or less.EES implantation for ISR was associated with an acceptable rate of TLR through long-term follow-up. Postintervention MSA of 5.3 mm or less was associated independently with a higher risk for TLR.

Background Data are scarce on the role of aortic valve area (AVA) to identify those patients with asymptomatic severe aortic stenosis (AS) who are at high risk of adverse events. We sought to explore the prognostic impact of AVA in asymptomatic patients with severe AS in a large observational database. Methods and Results Among 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the present study included 1309 conservatively managed asymptomatic patients with left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on AVA (group 1: AVA >0.80 cm2, N=645; group 2: 0.8 cm2 ≥AVA >0.6 cm2, N=465; and group 3: AVA ≤0.6 cm2, N=199). The prevalence of very severe AS patients (peak aortic jet velocity ≥5 m/s or mean aortic pressure gradient ≥60 mm Hg) was 2.0%, 5.8%, and 26.1% in groups 1, 2, and 3, respectively. The cumulative 5‐year incidence of AVR was not different across the 3 groups (39.7%, 43.7%, and 39.9%; P=0.43). The cumulative 5‐year incidence of the primary outcome measure (a composite of aortic valve–related death or heart failure hospitalization) was incrementally higher with decreasing AVA (24.1%, 29.1%, and 48.1%; P, See Editorial by Tribouilloy et al

Background: Catamenial pneumothorax (CP) is defined as repeated pneumothorax related to menses and thoracic endometriosis. We performed a retrospective analysis of nine patients with CP to determine the clinical features as well as the effects of treatment and recurrence rates. Methods: A retrospective review was conducted of the clinical and pathologic data in all CP patients undergoing treatment at our institution. Nine patients underwent treatment for CP. Of these, six underwent surgical treatment 8 times. Results: The median age was 36 years. Six patients had experienced delivery. The laterality of the pneumothorax was right in all patients. Pelvic endometriosis was diagnosed in five patients. Six patients underwent surgical treatment. Partial resection of the lung was performed in four patients and partial resection of the diaphragm in five. Of these, both resections were performed in four patients. A pathological diagnosis of endometriosis was achieved in only three patients. The observation period was 16.7 months. In the six patients with surgical resection, five experienced recurrence at various intervals. Onset of pneumothorax occurred pre- or menstrual period in most cases. Conclusions: The diagnosis and treatment of CP is not easy. A multidisciplinary approach and skillful management are required. Recurrence of CP is common following a temporary cure of pneumothorax by surgical treatment.

Purpose: Video-assisted thoracic surgery (VATS) techniques have been widely used for resection of mediastinal tumors. This study investigated the usefulness of the subxiphoid approach in thoracoscopic thymectomy. Methods: In all, 36 patients with anterior mediastinal tumor underwent thymectomy using the subxiphoid approach in two Japanese institutions. These patients were retrospectively reviewed and analyzed. Results: There were 16 females and 20 males with a mean age of 57 years. Five patients underwent partial thymectomy (PT), 27 underwent total or subtotal thymectomy, and 4 underwent thymectomy with combined resection (CR) of the surrounding organs or tissues. The mean maximum tumor diameter, amount of resected tissue, and blood loss were 4.1 cm, 72.5 g, and 20.6 g, respectively. More than half of tumors were diagnosed as thymoma (n = 19). The operation time was prolonged with a greater volume of thymectomy. The duration of chest tube drainage and postoperative stay were 1.7 ± 1.0 days and 5.9 ± 7.6 days, respectively. Four patients suffered intraoperative and postoperative complications, as follows: bleeding of the innominate vein, bleeding of the internal thoracic vein, crisis of myasthenia gravis (MG), pericarditis, and phrenic nerve paralysis. There were no mortalities after surgery. Conclusion: Subxiphoid thoracoscopic thymectomy might be a safe and useful approach for mediastinal tumors.

The aim of this study was to evaluate the prognostic impact of left ventricular ejection fraction (LVEF) in patients with severe aortic stenosis (AS).The prognostic impact of LVEF in severe AS remains controversial.Among 3,815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the present study population consisted of 3,794 patients after excluding 21 patients without LVEF data. Patients were divided into 4 groups according to LVEF at index echocardiography (50%, 50% to 59%, 60% to 69%, and ≥70%; conservative strategy: n = 388, n = 390, n = 1,025, and n = 800; initial aortic valve replacement strategy: n = 206, n = 170, n = 375, and n = 440). Echocardiographic data were site reported, and there was no echocardiography core laboratory.In the conservative group, the cumulative 5-year incidence of the primary outcome measure (a composite of aortic valve-related death or heart failure hospitalization) was significantly higher in patients with LVEFs 50% and 50% to 59% than in those with LVEFs 60% to 69% and ≥70% (72.3%, 58.4%, 38.7%, and 35.0%, respectively, p 0.001), whereas in the initial aortic valve replacement group, the negative effect of low LVEF was markedly attenuated (20.2%, 20.3%, 17.7%, and 12.4%, respectively, p = 0.03). After adjusting for confounders, LVEF 50% (hazard ratio: 1.82; 95% confidence interval: 1.44 to 2.28; p 0.001) and 50% to 59% (hazard ratio: 1.77; 95% confidence interval: 1.42 to 2.20; p 0.001) but not 60% to 69% (hazard ratio: 1.14; 95% confidence interval: 0.94 to 1.39; p = 0.17) were independently associated with poorer outcomes compared with LVEF ≥70% (reference) in the conservative group. In the initial aortic valve replacement group, the adjusted risk for the primary outcome measure was not significantly different across the 4 LVEF groups.This study demonstrates that survival in patients with severe AS is impaired when LVEF is 60%, and these findings have implications for decision making with regard to the timing of surgical intervention.

Background There are limited data regarding the risk stratification based on peak aortic jet velocity (Vmax) in patients with severe aortic stenosis ( AS ). Methods and Results Among 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the study population consisted of 1075 conservatively managed patients with Vmax ≥4.0 m/s and left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on Vmax (group 1, 4.0 ≤ Vmax AS ‐related events (aortic valve–related death or heart failure hospitalization) was incrementally higher with increasing Vmax (entire population; 38.0%, 49.4%, and 62.8%, P P =0.008; and asymptomatic patients; 29.4%, 38.9%, and 47.7%, P =0.005). After adjusting for confounders, the excess risk of group 2 and group 3 relative to group 1 for AS ‐related events remained significant (hazard ratio, 1.39; 95% CI , 1.07–1.81; P =0.02, and hazard ratio, 1.53; 95% CI , 1.17–2.00; P =0.002, respectively). The effect size of group 3 relative to group 1 for AS ‐related events in asymptomatic patients (N=479) was similar to that in symptomatic patients (N=596; hazard ratio, 1.59; 95% CI , 1.01–2.52; P =0.047, and hazard ratio, 1.67; 95% CI , 1.16–2.40, P =0.008, respectively), and there was no significant overall interaction between the symptomatic status and the effect of the Vmax categories on AS ‐related events (interaction, P =0.88). Conclusions In conservatively managed severe AS patients with preserved left ventricular ejection fraction, increasing Vmax was associated with incrementally higher risk for AS ‐related events. However, the cumulative 5‐year incidence of the AS ‐related events remained very high even in asymptomatic patients with less greater Vmax.

Objective To determine the association between plasma brain natriuretic peptide (BNP) level in patients with heart failure (HF) and physical frailty as well as with each domain of physical frailty. Methods Two hundred and six outpatients of cardiovascular medicine aged 60 years and older who had been hospitalized for HF or had been given a prescription medication for HF were included. Physical frailty was assessed using the following five domains: slowness, weakness, exhaustion, low activity, and shrinking, according to the Cardiovascular Health Study. Patients were divided into nonfrailty and frailty groups according to frailty scores. Plasma BNP level was measured. The 6-min walk test was performed to measure endurance. Results Plasma BNP was significantly different between the two groups (frailty group: 158.0 ± 214.7 pg/mL, nonfrailty group: 65.2 ± 88.0 pg/mL, P < 0.01). Multivariate logistic regression analysis revealed log-transformed plasma BNP (Log BNP) was significantly associated with physical frailty (OR: 1.68, 95% CI: 1.11–2.56), and Log BNP was significantly associated with the slowness domain (walking speed < 1.0 m/s) of physical frailty (OR: 1.75, 95% CI: 1.15–2.67). Additionally, Log BNP was negatively correlated to the 6-minute walk distance (6MWD) (ρ = −0.37, P < 0.01), while 6MWD was positively correlated to walking speed (ρ = 0.66, P < 0.01). Conclusions Plasma BNP level was related to physical frailty, especially in the slowness domain. Endurance may intervene in the associations between plasma BNP level and walking speed.

Background: Effects of statin therapy on cardiac sympathetic nerve activity in patients with chronic heart failure (CHF) have not previously been evaluated. Methods and Results: To compare the effects of lipophilic atorvastatin and hydrophilic rosuvastatin on cardiac sympathetic nerve activity in CHF patients with dilated cardiomyopathy (DCM), 63 stable outpatients with DCM, who were already receiving standard therapy for CHF, were randomized to atorvastatin (n=32) or rosuvastatin (n=31). We evaluated cardiac sympathetic nerve activity by cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy, hemodynamic parameters and neurohumoral factors before and after 6 months of treatment. There were no differences in the baseline characteristics of the 2 groups. In the rosuvastatin group, there were no changes in MIBG parameters, left ventricular ejection fraction or plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) after 6 months of treatment. In contrast, the atorvastatin group showed a significant increase in the delayed heart/mediastinum count ratio (2.18±0.4 vs. 2.36±0.4, P

Background: The aim of the present study was to interpret B-type natriuretic peptide (BNP) level in outpatients with stable chronic heart failure (CHF); it is important to clarify whether the change in BNP represents disease progression or a range of biological variation. Methods and Results: To compare biological variation in BNP and biological variation in factors of the renin-angiotensin-aldosterone system (RAS) in stable CHF patients with dilated cardiomyopathy (DCM), the BNP plasma levels and RAS factors were measured in 115 stable outpatients with DCM. According to stepwise multivariate analysis, plasma BNP at baseline (P=0.005), presence of atrial fibrillation (P=0.015), and a high biological variation in plasma renin concentration (PRC; P=0.002) were significant independent dominant factors related to a high biological variation in BNP. Although there was no change in body weight or blood pressure during the 2-month study period, the % change in hematocrit was negatively correlated with % change in BNP (r=-0.327, P=0.0008), and positively correlated with % change in PRC (r=0.671, P=0.001). Conclusions: There was a significant relationship between biological variation in BNP and biological variation in PRC, suggesting that the physiological interaction between the natriuretic peptide system and RAS may contribute to the biological variation in plasma BNP in stable outpatients with DCM. (Circ J 2011; 75: 1897-1904)

Background It has been reported that mineralocorticoid receptor antagonist improves the prognosis of chronic heart failure (CHF). Recently, hemoglobin A1c (HbA 1c ) levels have been reported to be an independent risk factor for mortality in CHF, suggesting the important role of insulin resistance in CHF. We compared the metabolic effect of a selective mineralocorticoid receptor blocker eplerenone with spironolactone in CHF patients. Methods One hundred seven stable outpatients with mild CHF, who were already receiving standard therapy for CHF, were randomized (1:2) to spironolactone (25 mg/d) or eplerenone (50 mg/d). Plasma levels of B-type natriuretic peptide, adiponectin, HbA 1c and cortisol were measured before and after 4 months treatment with spironolactone or eplerenone. Results There were no differences in baseline characteristics including hemodynamic parameters and plasma levels of biomarkers between 2 groups. In both groups, plasma B-type natriuretic peptide levels were significantly decreased and plasma aldosterone levels were significantly increased after 4 months. In patients receiving spironolactone (n = 34), plasma adiponectin levels were significantly decreased (12.6 ± 1.4-11.2 ± 1.3 μg/mL, P 1c and cortisol levels were significantly increased (5.61 ± 0.1-5.8 ± 0.1%, P P = .003, respectively). In patients receiving spironolactone, there was a significant positive correlation between the change in cortisol and the change in HbA 1c ( r = 0.489, P = .003). In contrast, in patients receiving eplerenone (n = 73), plasma levels of adiponectin, HbA 1c and cortisol did not change. Conclusion These findings indicated that the metabolic effect of eplerenone differed from that of spironolactone and that eplerenone had a superior metabolic effect especially on HbA 1c in CHF patients.

Aims To compare the effects of lipophilic simvastatin and hydrophilic rosuvastatin on plasma adiponectin and glycated haemoglobin A1c (HbA1c) levels in patients with non-ischaemic chronic heart failure (NICHF). Methods and results Seventy-one stable outpatients with NICHF, who were already receiving standard therapy for CHF, were randomized to simvastatin (n = 35) or rosuvastatin (n = 36). Plasma levels of brain natriuretic peptide (BNP), total adiponectin, high-sensitive C-reactive protein, HbA1c, and oxidized low-density lipoprotein (oxLDL), a marker of oxidative stress, were measured before and 4 months after treatment with simvastatin or rosuvastatin. There was no difference in the baseline characteristics including left ventricular ejection fraction (LVEF) and biochemical parameters between the two groups. In both groups, plasma BNP levels and LVEF did not change after 4 months. Plasma levels of adiponectin and oxLDL did not change and HbA1c level was slightly increased (6.0 ± 0.9 vs. 6.1 ± 0.9%, P = 0.053) in the simvastatin group. In contrast, plasma adiponectin level was significantly increased (12.3 ± 7.3 vs. 14.0 ± 8.2 µg/mL, P = 0.012) concomitant with a significant reduction in oxLDL and HbA1c (oxLDL: 8.8 ± 4.7 vs. 7.6 ± 4.7 U/mL, P = 0.0059; HbA1c: 6.0 ± 0.7 vs. 5.9 ± 0.7%, P = 0.002) in the rosuvastatin group. Conclusion These findings suggest that hydrophilic rosuvastatin but not lipophilic simvastatin increases adiponectin and decreases HbA1c levels in patients with NICHF.

A certain percentage of aldosterone (ALD) breakthrough generally occurs in patients with hypertension and chronic heart failure and is an important issue during long-term treatment with angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB). It has been reported that efonidipine decreases the plasma levels of ALD. However, the long-term effects of efonidipine on the plasma levels of ALD and the left ventricular mass index (LVMI) remain unknown in patients with hypertension. Sixty stable outpatients with essential hypertension who had received amlodipine and ACE-I or ARB for more than 1 year were randomized into two groups (amlodipine group (n=30): continuous amlodipine treatment at a stable dose; efonidipine group (n=30): amlodipine (5 mg day(-1)) was changed to efonidipine at a dose of 40 mg day(-1)). There was no difference in their baseline characteristics including the LVMI and plasma levels of ALD. In the amlodipine group, there were no significant changes in blood pressure, LVMI or plasma levels of ALD for 18 months. In the efonidipine group, blood pressure did not change after replacement of amlodipine with efonidipine, although there was a significant decrease in the plasma levels of ALD after 6 months. The decrease in ALD was sustained for 18 months and LVMI was significantly decreased after 18 months (121+/-25 vs. 114+/-21 g m(-2), P0.05). There was a significant correlation between the changes in LVMI and % changes of ALD in the efonidipine group. These findings indicate that the effect of efonidipine on the suppression of plasma ALD was sustained for at least 18 months and that long-term efonidipine therapy decreases LVMI in patients with essential hypertension.

Background: The effect of the dose of carvedilol on cardiac sympathetic nerve activity (CSA) and mortality remain uncertain in patients with chronic heart failure (CHF). Methods and Results: To compare the dose of carvedilol and the transcardiac gradient of norepinephrine (NE), a biomarker of CSA, and prognosis in patients with CHF, hemodynamic parameters and plasma levels of NE, N-terminal brain natriuretic peptide (NT-proBNP) in the aortic root and coronary sinus were measured in 107 patients with systolic CHF who received carvedilol. Patients were divided into 2 groups [group I: low dose (

Background: It is reported that adiponectin has a cardioprotective effect and is decreased in type 2 diabetes mellitus (DM). Methods and Results: The effect of carperitide (atrial natriuretic peptide: ANP) on plasma adiponectin levels was evaluated in acute decompensated heart failure (ADHF) patients with and without DM. In 47 patients (DM: n=11) who were admitted with ADHF, blood samples were collected before and 7 days after administration of carperitide. The plasma levels of ANP, brain natriuretic peptide (BNP), aldosterone and adiponectin were measured. Plasma adiponectin levels were significantly increased (17.6 ±1.5 to 19.6 ±1.8 μg/ml, P=0.0003) concomitant with the increase in ANP and decrease in BNP 7 days after carperitide infusion. Although adiponectin levels before treatment were slightly lower in ADHF patients with DM, the % increase in adiponectin levels was significantly greater in ADHF patients with DM than in those without DM (26.7 vs 6.6%, P=0.007). In the stepwise multivariate analyses, a higher plasma aldosterone levels before treatment (P=0.04) and DM (P=0.01) were significant independent predictors of a greater % increase in adiponectin levels after treatment with carperitide. Conclusions: Carperitide infusion increases the plasma adiponectin level, especially in ADHF patients with DM. (Circ J 2009; 73: 2264-2269)

Background Cardiac troponin I (cTnI) is a useful biomarker in patients with chronic heart failure (CHF), and a highly sensitive cTnI (hs-cTnI) commercial assay has become available. However, the prognostic role of serial measurements of hs-cTnI in stable outpatients with CHF remains unknown. Methods At entry to the study, we evaluated 95 stable outpatients with nonischemic CHF showing a serum hs-cTnI (Centaur TnI-Ultra [Siemens Medical Solution Diagnostics, New York, NY], lower limit of detection 0.006 ng/mL) value ≥0.006 ng/mL. To evaluate the role of repetitive measurements of hs-cTnI, we performed echocardiography and measured serum levels of cTnI and N-terminal proBNP at baseline and 6 months later and then prospectively followed up these patients for 4.25 years. Results During long-term follow-up, there were 27 cardiac deaths. On multivariate analyses, high plasma N-terminal pro–brain natriuretic peptide (≥711 pg/mL, P = .0008), high serum hs-cTnI at baseline (≥0.03 ng/mL, P = .0011), and an increase in hs-cTnI (Δhs-cTnI ≥0 ng/mL, P = .022) after 6 months were independent significant prognostic predictors. The hazard ratio for mortality of patients with high hs-cTnI (≥0.03 ng/mL) and an increase in hs-cTnI (Δhs-cTnI ≥0 ng/mL) was 3.59 (95% CI 1.3-9.9, P = .014) compared with that of those with high hs-cTnI (≥0.03 ng/mL) and a decrease in hs-cTnI ( Δ hs-cTnI Conclusions These findings indicated that not only the serum concentration of hs-cTnI at baseline but also an increase in hs-cTnI were independent and useful prognostic predictors in patients with nonischemic CHF.

Background: Cardiac troponin T (cTnT) is useful biomarker in patients with chronic heart failure (CHF). However, its clinical use is limited by the low sensitivity of the conventional commercial assay system. Recently, a highly sensitive cTnT (hs-cTnT) assay has become commercially available. Methods and Results: To compare the prognostic value of conventional cTnT and hs-cTnT in patients with nonischemic dilated cardiomyopathy (DCM), hemodynamic parameters and the serum levels of conventional cTnT, hs-cTnT and brain natriuretic peptide (BNP) were measured in 85 consecutive CHF patients with nonischemic DCM and then these patients were followed for a mean of 4.1 years. During long-term follow up, there were 20 cardiac deaths. In 85 DCM patients, conventional cTnT was elevated (≥0.03ng/ml) in 4 patients (5%) and hs-cTnT was elevated (≥0.01ng/ml) in 46 patients (54%). In non-survivors (n=20), conventional cTnT was elevated (≥0.03ng/ml) in 2 patients (2%) and hs-cTnT was elevated (≥0.01ng/ml) in 17 patients (85%). In the stepwise multivariate analyses, a high plasma level of BNP (P=0.002), low left ventricular ejection fraction (

Background: To evaluate the biological variation and prognostic value of brain natriuretic peptide (BNP) for stable outpatients with nonischemic chronic heart failure (NICHF). Methods and Results: Biological variation in BNP was evaluated using an automated assay system in 140 outpatients with NICHF. The stable clinical condition during the 2-month study period was defined as unchanged NYHA and unchanged left ventricular ejection fraction; therefore, 7 patients were excluded during the 2 months. Thereafter, 133 patients were prospectively followed and the relationship between cardiac events and the plasma BNP concentrations (at baseline and after 2 months) were evaluated as well as the changes in BNP. The biological variation in BNP (2-month interval) was calculated as 22.3%. During a mean follow-up period of 42 months, 26 patients had cardiac events. According to stepwise multivariate analyses, plasma BNP after 2 months (P=0.0002) and % change in BNP (P=0.0067) were significant independent predictors of cardiac events. Conclusions: These findings indicated that a combination of the absolute value of BNP after 2 months and % increase in BNP (2-month interval) is useful for predicting cardiac events in stable outpatients with NICHF. (Circ J 2011; 75: 341-347)

It has been reported that mineralocorticoid receptor antagonist improves the prognosis of chronic heart failure (CHF). Recently, hemoglobin A₁(c) (HbA₁(c)) levels have been reported to be an independent risk factor for mortality in CHF, suggesting the important role of insulin resistance in CHF. We compared the metabolic effect of a selective mineralocorticoid receptor blocker eplerenone with spironolactone in CHF patients.One hundred seven stable outpatients with mild CHF, who were already receiving standard therapy for CHF, were randomized (1:2) to spironolactone (25 mg/d) or eplerenone (50 mg/d). Plasma levels of B-type natriuretic peptide, adiponectin, HbA₁(c) and cortisol were measured before and after 4 months treatment with spironolactone or eplerenone.There were no differences in baseline characteristics including hemodynamic parameters and plasma levels of biomarkers between 2 groups. In both groups, plasma B-type natriuretic peptide levels were significantly decreased and plasma aldosterone levels were significantly increased after 4 months. In patients receiving spironolactone (n = 34), plasma adiponectin levels were significantly decreased (12.6 ± 1.4-11.2 ± 1.3 μg/mL, P.0001) and HbA₁(c) and cortisol levels were significantly increased (5.61 ± 0.1-5.8 ± 0.1%, P.0001, 11.3 ± 0.8-14.7 ± 1.3 μg/dL, P = .003, respectively). In patients receiving spironolactone, there was a significant positive correlation between the change in cortisol and the change in HbA₁(c) (r = 0.489, P = .003). In contrast, in patients receiving eplerenone (n = 73), plasma levels of adiponectin, HbA₁(c) and cortisol did not change.These findings indicated that the metabolic effect of eplerenone differed from that of spironolactone and that eplerenone had a superior metabolic effect especially on HbA₁(c) in CHF patients.

In general, treatment with most angiotensin receptor blockers (ARBs) increases plasma angiotensin II (Ang II) level because of a lack of negative feedback on renin activity. Olmesartan is a potential ARB inducing activation of angiotensin-converting enzyme 2 (ACE2) that hydrolyzes Ang II to Ang 1-7, and has shown a beneficial effect on ventricular remodeling. Indeed, a previous study reported that olmesartan treatment resulted in decreased plasma levels of Ang II and aldosterone. However, there has not yet been a study showing the relationship of chronic effects of olmesartan on Ang II and the left ventricular mass index (LVMI) in comparison with those of other ARB.A total of 50 stable outpatients with essential hypertension who had received candesartan for more than 1 year were randomized into two groups: control group (n=25): continuous candesartan treatment at a stable dose; and olmesartan group (n=25): candesartan (8 mg day(-1)) was changed to olmesartan given at a dose of 20 mg day(-1). There was no difference in the baseline characteristics between the two groups. In the control group, there were no significant changes in blood pressure, LVMI or biomarkers during 12 months of study. In the olmesartan group, blood pressure did not change and plasma levels of Ang II decreased during 12 months of study, whereas LVMI was significantly decreased after 12 months (135+/-36 vs. 123+/-29 g m(-2); P

Background— The pathophysiological role of cortisol, which binds to the mineralocorticoid receptor with an affinity equal to that of aldosterone (ALD), may be influenced by oxidative stress in patients with chronic heart failure. We evaluated cardiac event prediction using cortisol levels in chronic heart failure, in comparison with ALD, adrenocorticotropic hormone, and brain natriuretic peptide (BNP), and the impact of oxidative stress. Methods and Results— We measured the plasma levels of biomarkers such as BNP, ALD, adrenocorticotropic hormone, serum cortisol, and oxidized low-density lipoprotein (oxLDL), a biomarker of oxidative stress, in 319 consecutive symptomatic patients with chronic heart failure, and we followed these patients for a mean period of 33 months. During the follow-up period, 29 patients had cardiac events (death or hospitalization). Plasma levels of BNP, ALD, adrenocorticotropic hormone, oxLDL, and serum cortisol (16.8�1.8 μg/dL versus 12.4�0.3 μg/dL, P =0.01) were significantly higher in patients with cardiac events than in those without cardiac events. On stepwise multivariate analyses, high levels of BNP ( P =0.0003), renin ( P =0.002), cortisol ( P =0.02), and oxLDL ( P =0.002) were independent predictors of cardiac events, but ALD and adrenocorticotropic hormone levels were not. In patients with serum cortisol ≥12.5 μg/dL, the hazard ratio of cardiac events in patients with oxLDL ≥12 U/mL was 3.5 compared with that in patients with oxLDL P =0.008). Conclusions— These findings indicate that serum cortisol levels were a complementary and incremental cardiac event risk predictor in combination with BNP in patients with chronic heart failure and that cardiac event prediction based on cortisol levels was influenced by oxidative stress.

The effect of the dose of carvedilol on cardiac sympathetic nerve activity (CSA) and mortality remain uncertain in patients with chronic heart failure (CHF).To compare the dose of carvedilol and the transcardiac gradient of norepinephrine (NE), a biomarker of CSA, and prognosis in patients with CHF, hemodynamic parameters and plasma levels of NE, N-terminal brain natriuretic peptide (NT-proBNP) in the aortic root and coronary sinus were measured in 107 patients with systolic CHF who received carvedilol. Patients were divided into 2 groups [group I: low dose (10 mg/day, n=41) and group II: high dose (or=10 mg/day, n=66)]. There was no difference between the 2 groups for the hemodynamic parameters. The dose of carvedilol did not correlate with plasma NE, but was significantly correlated with the transcardiac increase in NE. During a median follow-up of 4.3 years, 13 patients died of cardiac disease. In the Cox stepwise multivariate analyses, a high level of transcardiac increase in NE (P0.001), high level of plasma log NT-proBNP (P=0.004) and low dose of carvedilol (P=0.012) were significant independent predictors.The carvedilol dose is important for the management of CSA and prognosis in patients with systolic CHF.

Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) are useful biomarkers in patients with chronic heart failure (CHF). However, the clinical use has limitations due to the low sensitivity of a conventional commercial assay system. Recently, a high sensitive-cTnI (hs-cTnI) commercial assay has become available.To compare the prognostic value of cTnT and hs-cTnI, we measured hemodynamic parameters and serum levels of cTnT, hs-cTnI and N-terminal pro-brain natriuretic peptide (NT-proBNP)in 258 consecutive CHF patients and then followed these patients for a mean period of 2.6 years. In both assays of cTnT and hs-cTnI, the lowest concentration at which the coeffi cient of variation wasor =10% were 0.03 ng/mL, respectively. Therefore, in the present study, an elevated cTnT or cTnI test was defined as a level ofor =0.03 ng/mL.During long-term follow up, there were 20 cardiac deaths. In 258 CHF patients, serum cTnT were elevated (or =0.03 ng/mL) in 32 patients (12%) and serum hs-cTnI was elevated (or =0.03 ng/mL) in 112 patients (43%). On stepwise multivariate analyses, high plasma NT-proBNP (or =627 pg/mL, P = .0063) and hs-cTnI (or =0.03 ng/mL) (P = .016) were independent significant prognostic predictors but cTnT (or =0.03 ng/mL) was not. The hazard ratio for mortality of patients with high plasma NT-proBNP (or =627 pg/mL) and hs-cTnI (or =0.03 ng/mL) was 5.74 (95% CI, 2.33-14.28, P.0001) compared to that of those with low NT-proBNP (627 pg/mL) or hs-cTnI (0.03 ng/mL).These findings indicate that a high plasma concentration of hs-cTnI is an independent and useful prognostic predictor in patients with CHF.

Background: Patients with a high plasma adiponectin have a poor prognosis in chronic heart failure (CHF). Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are reported to increase the plasma adiponectin concentration, but the effect of β-blockers on plasma adiponectin in patients with CHF remains unknown. Methods and Results: Blood samples were collected at before and 6 months after administration of carvedilol in 44 CHF patients. The hemodynamic parameters, echocardiography, plasma concentrations of brain natriuretic peptide (BNP), norepinephrine and adiponectin were measured. Six months after treatment, there were significantly decreased plasma concentrations of adiponectin (15.8 ±1.4 to 11.0 ±1.1 μg/ml, P

Abnormal cardiac sympathetic nerve activity (CSA) plays an important role in the pathophysiology of CHF. However, no previous study has compared the transcardiac gradient of norepinephrine (NE) and the prognosis of patients with chronic heart failure (CHF). To evaluate the prognostic role of the transcardiac gradient of NE in patients with CHF. We measured hemodynamic parameters and plasma levels of NE, brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in the aortic root (AO) and coronary sinus (CS) in 356 consecutive patients with CHF. During a median follow-up of 3.5 years, 40 patients died. Transcardiac gradients of BNP (273±276 vs. 472±433 pg/mL, p123 I- metaiodobenzylguanidine (MIBG) could be performed, transcardiac increase in NE (ΔNE) was correlated with the washout rate (r=0.398, p=0.0009) and was a superior predictor of mortality than MIBG parameters. Patients were divided into four groups based on the cut-off levels for ΔNE and plasma NT-proBNP, and Kaplan-Meier survival curves were constructed (Figure ). The transcardiac increase in NE, as a biomarker of CSA, is an independent and useful prognostic predictor for evaluating the prognosis of CHF patients.